Pandemics and Global Health 1685072283, 9781685072285

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INFECTIOUS DISEASES AND MICROBIOLOGY

PANDEMICS AND GLOBAL HEALTH

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INFECTIOUS DISEASES AND MICROBIOLOGY

PANDEMICS AND GLOBAL HEALTH

NITHA BALAN AND

MANUEL THOMAS EDITORS

Copyright © 2022 by Nova Science Publishers, Inc. DOI: https://doi.org/10.52305/ZHSY1605 All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. We have partnered with Copyright Clearance Center to make it easy for you to obtain permissions to reuse content from this publication. Simply navigate to this publication’s page on Nova’s website and locate the “Get Permission” button below the title description. This button is linked directly to the title’s permission page on copyright.com. Alternatively, you can visit copyright.com and search by title, ISBN, or ISSN. For further questions about using the service on copyright.com, please contact: Copyright Clearance Center Phone: +1-(978) 750-8400 Fax: +1-(978) 750-4470

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NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the Publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book.

Library of Congress Cataloging-in-Publication Data Names: Balan, Nitha, editor. | Thomas, Manuel (Research consultant), editor. Title: Pandemics and global health / Nitha Balan, PhD, Assistant Professor, Department of Microbiology, Sree Ayyappa College, Eramallikkara, Chengannur, Kerala, India, Manuel Thomas, PhD, Research Consultant, UniBiosys Biotech Research Labs, Kerala, India, editors. Description: New York : Nova Science Publishers, [2022] | Series: Infectious diseases and microbiology | Includes bibliographical references and index. | Identifiers: LCCN 2021050244 (print) | LCCN 2021050245 (ebook) | ISBN 9781685072285 (hardcover) | ISBN 9781685072612 (adobe pdf) Subjects: LCSH: Epidemics--History. | Communicable diseases--History. | World health--Diseases--History. Classification: LCC RA649 .P363 2022 (print) | LCC RA649 (ebook) | DDC 614.4--dc23/eng/20211013 LC record available at https://lccn.loc.gov/2021050244 LC ebook record available at https://lccn.loc.gov/2021050245

Published by Nova Science Publishers, Inc. † New York

Contents

Preface

........................................................................................ ix

Chapter 1

Pandemics and Global Health in the 21st Century ......................................................... 1 Nitha Balan and Manuel Thomas

Chapter 2

Epidemics and Pandemics: The Kerala Model ........ 11 Rogimon P. Thomas, Sreeja Raj, V. Vinod and Kannan V. Manian

Chapter 3

Human Diaspora and Pandemics: A Review in the Context of COVID-19 ..................... 31 Shaibu Jacob, P. S. Ajith, M. B. Arya, David Abin, Rogimon P. Thomas and Joby Paul

Chapter 4

The Role of Vaccines in Public Health ...................... 73 Ann Susan Mathew, Shelmi Antony and Jayesh Antony

Chapter 5

A Review on COVID-19 Vaccines ........................... 107 Lakshmi Bhaskaran

Chapter 6

Vaccination and Public Health ................................ 119 Geena George and Hema Vijayan

Chapter 7

Pandemics: A Travel through Historic Times ........ 127 C. Mamatha

vi

Contents

Chapter 8

Tumultuous Epidemics in India: A Historic Overview.................................................. 143 Nisha Pallath

Chapter 9

Rise of Microbes and Pandemics in Shaping Human Civilization ................................................... 157 M. Hayarnnisa, Ann Mary Jacob and S. M. Merlin

Chapter 10

COVID-19 Pandemic: A Boon or Bane for Nature ...................................... 169 Asha Ramachandran

Chapter 11

Mental Health Issues in COVID-19 ......................... 181 Hridya Vijay and Nitha Balan

Chapter 12

The Impact of COVID-19 on Youngsters ............... 195 Joby Jose and Shaiju K. Sebastian

Chapter 13

The Pandemic and Its Impacts with a Special Focus on COVID-19 Situation in India ................... 207 Prem Jose Vazhacharickal, Jiby John Mathew and N. K. Sajeshkumar

Chapter 14

The Pandemic AIDS.................................................. 243 Tharakupeedikayil Abdul Majeed Sajeena

Chapter 15

The Plague Pandemic................................................ 259 Thushara Balakrishnan

Chapter 16

Future Pandemics: Agents, Potential and Impacts ................................. 287 Sunaina Valappay Cheenatukandy

Chapter 17

SARS-CoV-2 and Diabetics ...................................... 313 Sweety Gopinath

Chapter 18

Pandemics and Ethnomedicine ................................ 327 Tojo Jose and Sebastian Antony

Contents

vii

Chapter 19

Identification of Active Plant Constituents to Inhibit SARS-CoV-2 by Molecular Docking Studies: A Comprehensive Review ........... 341 M. Deepak, C. T. Sulaiman, Indira Balachandran and Subhash Chandran K. Parameswaran

Chapter 20

Pandemics in European Literature: A Review ....... 353 Temina Cyriac

Chapter 21

Impact of COVID-19 and Lockdown on India’s Foreign Trade.......................................... 367 Jinu Joseph

About the Editors ................................................................................ 377 Index

..................................................................................... 379

PREFACE Knowledge of public health and pandemics is pivotal, as the emergence, re-emergence, and outbreak of diseases have plagued mankind from time immemorial. The past few decades have witnessed a deluge of infectious diseases, many of which involve novel pathogens with umimaginable morbidity and mortality. Furthermore, knowledge of public health equips the public with well articulated opinions regarding crucial health issues that appear daily in the media. The COVID-19 pandemic in particular imperils the public health arena globally. This book, Pandemics and Global Health, portrays the history of pandemics, the current realm and future outlooks. Nitha Balan MSc., PhD Manuel Thomas MSc., PhD

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 1

PANDEMICS AND GLOBAL HEALTH IN THE 21ST CENTURY Nitha Balan1, PhD and Manuel Thomas2, PhD 1

Department of Microbiology, Sree Ayyappa College Eramallikkara, Chengannur, Kerala, India 2 UniBiosys Biotech Research Labs, South Kalamassery, Kochi, Kerala, India

ABSTRACT Pandemics are disease outbreaks which affect several countries and can cause major health, social and economic risks. In March 2020 World Health Organization declared Covid-19 as a pandemic, which has become a Public Health Emergency of International Concern (PHEIC). The disease has spread throughout the world mainly due to the inadequate preparedness for the global health security. Increased population mobility, rapid urbanization, climate change, weak surveillance and limited laboratory diagnostic capacity and increased human-animal interaction are also contributed to the emergence and rapid spread of pandemics which also exposed the pitfalls in the current 

Corresponding Author’s Email: [email protected].

2

Nitha Balan and Manuel Thomas public health global caricature. COVID 19 pandemic revelaed the clear picture of the failure of our global helath infrastructure.The diseases demonastrates that helath security is a collective response which need adequate technical capacity, improve current global security we need a proper authority, responsiveness, expertise, evaluation, finacing etc. The currenr pandemic situation opens an opportunity to combine knowledge and skills together to rejuvenate global public health system.

Keywords: pandemics, global health, epidemics, outbreaks, public health

INTRODUCTION Disease outbreaks and associated drastic aftermaths have wreaked havoc since the beginning of mankind. Throughout the history, poverty, inequality and social determinants of health paves the way for the transmission of infectious diseases and existing health disparities or inequalities can further contribute to unequal burdens of morbidity and mortality irrespective of geographic region (Quinn and Kumar, 2014). The past few decades have witnessed rapid emergence of infectious diseases, creating a serious threat to global public health where Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) Human Influenza A (H5N1), Pandemic Influenza A (H1N1), Ebola virus and Hanta virus are the major agents (Oswalia and Vasdev 2021). It should be noted that the human and economic toll of these and future agents are quite uncertain and unimaginable and thus a reinforcement of global public health system are pivotal for a better future.

REASONS BEHIND EMERGENCE AND REEMERGENCE OF INFECTIOUS DISEASES An emerging infectious disease (EID) is one that has appeared and affected a population for the first time, or has existed previously but is rapidly increasing, either in terms of the number of new cases within a

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population, or its spread to new geographical areas (WHO, 2005). The reappearance of a previously known infection after a period of disappearance or decline in incidence is known as re-emergence (Ranga et al., 1997). The major predisposing factors in the emergence and reemergence of diseases are human, environmental, ecological and pathogen factors which play a vital role in perpetuating novel emerging pathogens. Moreover, changes in vector populations, human association with reservoir hosts and appearance of new pathogen variants with high potential in transmission are also considered as keyfactors. According to Bedford, et al., (2019) emergence of epidemics will become more tragic, frequent, complex, harder to prevent and contain rapidly changing ecology, urbanization, climate change, increased travel and fragile public health systems prevailing in lion-part of the countries. Microorganisms are talented in infecting and causing diseases among humans facing a significant and concerted threat to public health from time immemorial. These threats are amplified due to an array of factors like climate change, increased international travel, immune host response, changes in vector population etc. Constant mutation and adaptation make the microbial world drug resistant which results in many disease outbreaks. The past few decades have witnessed an overwhelming increase in the incidence of endemic diseases, epidemics, and pandemics.

ENDEMIC (GREEK EN MEANING IN AND DEMOS MEANING PEOPLE) Endemic diseases are diseases present permanently in a region or population. Generally, it is used to describe a disease that is present at an approximately constant level within a society or country. Each country may have a disease that is unique like Caribbean Dengue in Caribbean region (Brandling-Bennett and Penheiro, 1996) and Kyasanur Forest disease (KFD) in Karnataka, India (Murhekar et al., 2015).

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EPIDEMIC (GREEK EPI MEANING UPON OR ABOVE AND DEMOS MEANING PEOPLE) Epidemic disease is an outbreak that affects many people at one time and can spread through one or several communities within a short span of time. When the term epidemic is used in connection with infectious diseases it is due to the sudden rise of cases usually resulting from a new infectious agent or an existing agent with mutation or expansion of geographic range (Chakrabort, 2015). The term epidemic is similar to outbreak but is commonly used to describe an unusual frequency of illness in a group of people that is not explained by expected seasonal increases (TELL ME, 2014). On the other hand, epidemics can follow predictable patterns and these trends among population.

PANDEMIC (GREEK PAN MEANING ALL AND DEMOS MEANING PEOPLE) A pandemic occur when a new infectious agent, or a reemerging one, spreads across multiple continents, or even worldwide. According to the classical epidemiological definition, a pandemic is defined as “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people” (Last, 2001). Significant features of a pandemic are given below:     

Affects a wider geographical area, often global Infects a very large number of people Often caused by a new pathogen or a new strain of a pathogen that has been dormant for many years Spreads quickly in humans as there is little to no existing immunity Can cause a high number of deaths

Pandemics and Global Health in the 21st Century 

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Because of the need to control the spread of the disease, there is often social perturbation, tempestuousness, anarchy, and crippling impact on economy

STAGES OF A PANDEMIC WHO has acknowledged six phases that should be followed before declaring a disease as pandemic (WHO 2009). Phase 1 represents a low risk and phase 6 is a full-blown pandemic:   

  

Phase 1 - a virus is seen in animals but has not been shown to infections in humans Phase 2 - a known animal virus has caused an infection in humans Phase 3 - scattered or isolated incidence of cases or small clusters of the disease occurring in humans; possible cases of human-tohuman transmission but not at a level to cause community-level outbreaks Phase 4 - human to human transmission at a rate that causes an outbreak in communities Phase 5 - the spread of the disease between humans is now evident in more than one country Phase 6 - community-level outbreaks are in at least one additional country other than that seen in phase 5

Once Phase 6 is reached preparation should be made for a global pandemic. Each phase has an array of actions needed to be followed to facilitate transparency and awareness among public health professionals and general public.

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PANDEMICS AND GLOBAL HEALTH The global history of emerging or re-emerging infectious disease pandemics has proclaimed that they have appeared every decade but now, the frequency between epidemics/pandemics are alarmingly shorter as evident with Severe Acute Respiratory Syndrome (SARS) in 2003, Influenza A H1N5 (bird flu) in 2007, H1N1 (swine flu) in 2009, Middle East Respiratory Syndrome (MERS) in 2012 and Ebola in 2014 and the most recent member COVID 19 (Jones et al., 2008; FAO, 2020). Lion part of the developing countries has difficulties in improving public health systems at par with developed countries. Gostin and Friedman (2015) have suggested a new global health framework with vigorous and dynamic national health systems as its cornerstone and a sceptered WHO at its vertex. The establishment of UN Mission for Emergency Ebola Response (UNMEER) in 2014 is the first UN mission to respond to public health emergencies (Ebola Response, 2021). The global health architecture is increasingly under deep strain, largely due to recent, ongoing, and potential global health crises like the COVID 19. The Ebola crisis has revealed serious flaws in the capability of the national and international system to prevent and respond to these junctures. It should be noted that the health, development, and security challenges are tightly interwoven nexus and thus a multilateral system anchored in the United Nations will address these issues without any discrepancy among fellow members.

CLIMATE CHANGE AND DISEASE EMERGENCE Climate is considered as an epitope of health and any climate constrains has resulted in shifts in pattern, range and intensity of infectious diseases, while weather affects the timing and power of outbreaks. Epstein et al., (1998) reported that longterm warming trend boosts geographic expansion of several diseases, while extreme weather events are engendering ‘clusters’ of disease outbreaks. A warming and

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unstable climate paves the way for global emergence, resurgence and redistribution of infectious agents with epidemic proportions (Leaf, 1989). The emergence and re-emergence of neglected tropical diseases are expected in several countries where the lives of millions of people especially in developing countries will be at risk. El-Sayed and Kamel (2020) amalgamated the role of climate change in the spread of infectious agents and their vectors including viral, bacterial and parasitic diseases. Nava et al., (2017) noted that environmental changes have a deluge of impact on the emergence and reemergence of infectious diseases, mostly in countries with high biodiversity and severe dissonant socio-economic and environmental issues.

CONCLUSION Recent COVID 19 pandemic portrayed the hindrances in institutional silos for sound and holistic policymaking, smooth implementation, and operational capacity among national and international public health arena. The national and international developments in managing the pandemic clearly depicted an international system that is insufficiently prepared for an outbreak and reacts sluggishly to an outbreak which steps up to a global health security threat. From the beginning of mankind itself episodes of ailments outraged mankind and COVID 19 is a recent member. Thus, mounting an effective and rapid response mechanism to pandemics is the need of the hour to leapfrog not only local and national efforts but also international cooperation which embodies global solidarity and collective responsibility for forbidding and combating pandemic disease threats.

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REFERENCES Bedford, J., Farrar, J., Ihekweazu, C. Kang, G., Koopmans, M. and Nkengasong, J. (2019). A new twenty-first century science for effective epidemic response. Nature 575:130-136. Brandling-Bennett, A. D., Penheiro, F. (1996). Infectious diseases in Latin America and the Caribbean: are they really emerging and increasing? Emerging infectious diseases. 2(1):59. Chakrabort, R. (2015). Epidemics. Encyclopedia of Global Bioethics. doi 10.1007/978-3-319-05544-2_174-3. Ebola Response. (2021). UN Mission for Ebola Emergency Response (UNMEER). https://ebolaresponse.un.org/un-mission-ebola-emergen cy-response-unmeer. (Accessed on 27.06.2021). El-Sayed, A. and Kamel. (2020). Climatic changes and their role in emergence and re-emergence of diseases. Environmental Science and Pollution Research. 28:1-17. Epstein, P. R., Diaz, H. F., Elias, S., Grabherr, G., Graham, N. E., Martens, W. J. M., Mosley-Thompson, E. and Susskind E. J. (1998). Biological and physical signs of climate change: focus on mosquitoborne disease. Bull. Am. Meteorol. Soc. 78:409-417. FAO. (2020). Global emergence of infectious diseases: links with wild meat consumption, ecosystem disruption, habitat degradation and biodiversity loss. Rome. https://doi.org/10.4060/ca9456en. (Accessed on 27.06.2021). Gostin, L. O., Friedman, E. A. (2015). A retrospective and prospective analysis of the West African Ebola virus disease epidemic: robust national health systems at the foundation and an empowerd WHO at the apex. Lancet. 385:1902-1909. Jones, K. E., Patel, N. G., Levy, M. A., Storeygard, A., Balk, D., Gittleman, J. L. and Daszak, (2008). Global Trends in Emerging Infectious Diseases. Nature. 451(7181):990-3. Last, J. M. (2001). A dictionary of epidemiology. Oxford University Press, Inc., New York, New York.

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Leaf, A. 1989. Potential health effects of global climate and environmental changes. N. Engl. J. Med. 321:1577-1583. Murhekar, M. V., Kasabi, G. S., Mehendale, S. M., Mourya, D. T., Yadav, P. D. and Tandale, B. V. (2015). On the transmission pattern of Kyasanur Forest disease (KFD) in India. Infectious Diseases of Poverty. 4:37. Nava, A., Shimabukuro, J. S., Chmura, A. A., Luz, S. L. B. (2017). The Impact of Global Environmental Changes on Infectious Disease Emergence with a Focus on Risks for Brazil. ILAR Journal. 58(3):393-400. Oswalia J. and Vasdev K. (2021). Emerging and re-emerging infectious diseases - Past, present and beyond. MOJ Biol. Med. 6(1):5-8. Quinn, S. C. and Kumar, S. (2014). Health inequalities and infectious disease epidemics: A challenge for global health security. Biosecurity and Bioterrorism: Biodefense Strategy, Practice and Science. 12(5):263-273. Ranga.S., Trivedi.N., Khuranan, S. K., Thergaonkar, A., Talib, V. H. (1997). Emerging and reemerging infections. Indain Journal of Pathology & Microbiology,40(4): 569-81. TELL ME. (2014). Transparent communication in Epidemics: Learning Lessons from experience, delivering effective Messages, providing Evidence. https://www. tellmeproject.eu/sites/default/files/Dossier% 201%20-%20Epidemics%20and%20pand emics%20%20General%20 guidelines.pdf. (Accessed on 27.06.2021). Walton, J., Beeson, P. B., Scott, R. B. (Eds.). (1986). Epidemic. The Oxford companion to medicine, 1, A-M, 351. Oxford: Oxford University Press. World Health Organization, Regional Office for South-East Asia. Combating Emerging Infectious Diseases in the South-East Asia Region. New Delhi: WHO-SEARO; 2005. World Health Organization. (2009). Pandemic influenza preparedness and response: a WHO guidance document. Geneva: World Health Organization. 2009.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 2

EPIDEMICS AND PANDEMICS: THE KERALA MODEL Rogimon P. Thomas1,, PhD, Sreeja Raj2, V. Vinod3, PhD and Kannan V. Manian4, PhD 1

Department of Botany, CMS College Kottayam (Autonomous), Kerala, India 2 Department of Biotechnology, St. Berchmans College (Autonomous), Changanacherry, Kerala, India 3 College of Medicine, University of Florida, Gainesville, Florida, USA 4 University of Rochester Medical Centre, Rochester, New York, USA

ABSTRACT Infectious diseases are always keyed out by either epidemic or a pandemic. These are the words used for describing a disease outbreak. But, an epidemic and a pandemic describe different stages of disease in society. An epidemic is a disease outbreak that affects many individuals 

Corresponding Author’s Email: [email protected].

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Rogimon P. Thomas, Sreeja Raj, V. Vinod et al. in an area, or a population and will affect many people concurrently and spread across different communities within a short period. Epidemic involves not only infectious diseases but all that deteriorates the health of a society and can follow predictable patterns and these trends are often used to monitor, predict, and control the spread of the infection. A pandemic is an epidemic that moves across the borders of different nations. Pandemic affects the wider geographical area and affects people around the world. The causative agent, probably a virus might infect people, spread faster among communities, and may result in a huge global death toll. The world since December 2019 is in the grips of the Covid-19 virus. In this paper, an attempt has been made to pinpoint and highlight the efforts made by the state of Kerala in tackling the pandemic of all times, Covid 19.

Keywords: COVID-19, epidemic, pandemic, Kerala

PANDEMICS AND EPIDEMICS: AN INTRODUCTION Pandemics have always shaped civilizations. An epidemic becomes a pandemic when it moves across the boundaries of a place or a country (Physiopedia, 2020). Starting from the smallpox epidemic, moving through plague, SARS, Ebola, Zika and finally Covid-19 outbreaks, man has always been fighting with the microorganisms. Each epidemic helps mankind redefine the limits of technologies and medical science and develop novel methods of immunisation and treatment strategies. More and more pandemics keep evolving along with the changing lives of human lives. Smallpox and the Spanish Flu had the most Global death tolls. Each time a pandemic outbreak occurs; mankind finds a way to beat the causative organism. Though a pandemic is always disheartening, it brings the world together to fight. Today we have invented vaccines for Covid-19 infections, but still, the battle of mankind and the microbial world will continue forever. This chapter portrays the efficient strategies adopted by the state of Kerala that drew the appreciation of the global community.

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COVID-19 VIRUS: ORIGIN AND CHARACTERISTICS COVID-19 was declared a 'Public Health Emergency of International Concern' by World Health Organization on 30th January 2020 (WHO, 2020). The novel coronavirus infection was first reported in China's Wuhan, the capital city of Hubei Province in the People’s Republic of China on 31st December 2019. After that, the disease started to spread across the globe. Though the government took measures to contain the spread, the disease became a pandemic. The causative agent of this novel coronavirus infection is SARSCov2 (Severe Acute Respiratory Syndrome-Corona virus 2) of genus beta-corona virus. It is characterized as a mild to severe respiratory droplet infection, transmitted chiefly by contact with infectious material (such as respiratory droplets, or with objects or surfaces contaminated by the causative virus). The droplets from the respiratory tract of an infected individual are transmitted onto a mucosal surface (e.g., mouth, nose) or conjunctiva of a susceptible person, or transmitted onto environmental surfaces (Aarathi et al., 2020). The disease spread through person to person transmission. The major symptoms of the disease include severe fever, shortness of breath, cough, sore throat, loss of taste and smell, nausea, vomiting and diarrhoea (Cascellaet al., 2020). The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection (Huang et al., 2019). The transmission of COVID-19 occurs in four phases, namely first appearance through travellers who tested positive, then local spread, followed by community spread and finally, widespread outbreak of a pandemic (Upadhyay, 2020). Since the first occurrence of COVID-19 outside China in Thailand on 13th January 2020, even nations with effective health care systems and elaborate health care administration like the UK and the USA have quickly slipped from the stage of local spread to community transmission. Analysis of data from many countries shows extremely rapid escalation from the second stage of transmission to the third, often within weeks (Choolayil et al., 2021).

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KERALA: DEMOGRAPHY AND LOCAL SETTING Kerala, God's own country, the land of coconut and spices, is the thirteenth largest state in India in terms of population has 33,387,677 inhabitants as per the 2011 census (Ministry of Home Affairs, 2011; MoHFW, 2017). Simply Population density, affluent non-resident Keralites and thriving tourism all raise the risk for an outbreak in Kerala (Sulaiman et al., 2020). Kerala's airports cater to the travel needs of millions of passengers annually, in and around the world. The situation was crucial for Kerala as it is a small state with a dense population. It homes 35 million people makes it 819 people per square kilometre, eight most densely states in India. Kerala is known for its social development indicators like infant mortality rate, literacy rates, sex ratio and human development indices even though it is having a low per capita income. International travelling is a part of Kerala culture, which is connected to the rest of the world through four airports that serve around 17 million passengers annually.

EPIDEMICS IN KERALA Back in the 1800s appeared one of the most alarming epidemics in Kerala history, Cholera. The then ruler of Travancore, Maharani GouriParvathyBayi started preparing for containment of the disease right when it started wreaking havoc in Bengal in the year 1819. Maharani had managed to distribute preventive medicines among the statesmen before the epidemic came to Kerala. Along with Cholera, the people of Kerala were also fighting Malaria and Smallpox during those days. The rulers of Travancore realized that local treatment methods were ineffective against the combined effects caused by the three epidemics. They then started offering allopathic treatment to the people along with local methods. During Kerala's fight with the Coronavirus, a shigella virus outbreak was reported in Kozhikode district in the third week of December 2020.

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Shigellosis, or more commonly referred to simply as a shigella infection, is an acute invasive enteric infection caused by bacteria belonging to the genus Shigella. It is “clinically manifested by diarrhoea that is frequently bloody,” according to the World Health Organization (WHO). The state had managed to contain the disease even though it created panic among the people.

NIPAH OUTBREAKS: A LEARNING EXPERIENCE TO KERALA Kerala survived two Nipah virus outbreaks in the recent past which gave Kerala an upper hand in tackling the situation. The first reports came from the district Kozhikode, of a person with symptoms of encephalitis. Nipah virus infection (NiV), which belongs to Henipavirus, is a pathogenic zoonotic disease. (WHO, 2018). The natural reservoirs of the virus are fruit bats of the genus Pteropus, and the virus has been isolated from bat urine and partially eaten fruits in Malaysia (Chua et al., 2002). Some patients present with acute respiratory distress syndrome and mortality ranges from 40% to 70%. Eighteen cases were confirmed from the districts of Kozhikode and Malappuram. The disease had a high mortality rate and spreads through person-to-person contact. Two outbreaks of the Nipah Virus gave the state a learning experience.It managed to train people to manage an immediate crisis, identify and mitigate threat situations. The skills of tracing and tracking, supportive management of highly infective critical patients, analysis of data to determine how the epidemic is progressing, prevention of healthcare-associated infections, psychosocial support to persons who are under quarantine or on treatment, working with media to avoid panic, and managing misinformation campaigns were picked up by the system during the first outbreak and rehearsed during the second. The results of the hard works of the health care system made people trust them. The ample experience during the Nipah times equipped the authorities to

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manage the first wave of COVID-19 effectively (Sadanandan, 2020). Early identification, isolation of suspected people and laboratory confirmations helped the healthcare system in containing the outbreak.

NOVEL CORONAVIRUS IN KERALA In India, Kerala was the first state affected by Covid-19, and the first coronavirus case was confirmed in the Thrissur district on 30th January 2020 (Jayesh et al., 2020). Two students who returned from China were identified infected. All those infected people recovered and were tested negative by 20th February 2020. Kerala successfully managed to treat the infected efficiently. Six new cases were reported in Kerala by the beginning of March 2020. This became the second wave of Covid-19 infections in Kerala. By the second wave, the number of infections in Kerala began to rise as the authorities expected. The state had already prepared for addressing the situation.

HOW DID KERALA TACKLE THE PANDEMIC? Kerala Government strategized various measures to be adopted including the operating procedures for aggressive testing, contact tracing, quarantining and treatments.

Close Monitoring and Screening Kerala anticipated the threat because of the Keralites living across the world that keeps travelling in and around. Kerala started its preparations when the disease was reported in China and Southeast Asia. A strict system was enforced for close monitoring and screening of people coming into the state by all means from abroad and within India.

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Early Diagnosis of Passengers from Abroad Kerala has around 2.4 million of its people living as emigrants in different countries, especially in Middle Eastern Countries (Economic Review, 2016). Most of the Covid-19 cases reported in Kerala were among those returned from abroad and other states, and the rest were through person-to-person transmission. People coming from abroad were screened for Covid-19 symptoms at the airports as a preliminary step. Those with symptoms were immediately shifted to Covid-19 specialised hospitals for proper treatment. Asymptomatic passengers were advised to remain on home quarantine and avoid travelling until the period of quarantine ends. They were strictly monitored through phone calls. In case they needed immediate attention; they were shifted to appropriate treatment centres, tested for infection and treated if found positive. A ‘sanitised corridor’ protocol was followed for the travellers arriving at the portal of entry to their concerned quarantine destinations with special double-chambered taxis. People found with symptoms were identified and moved to Covid-19 speciality hospitals for further treatment. They were also tested for infection and observed until they are free from the symptoms. The government created a portal call “Covid-19 Jagratha,” a comprehensive solution for real-time surveillance, care and support for people affected/quarantined by Covid-19. Covid-19 Jagratha portal provides all services for the public in case of emergency and provides information related to Covid-19 in a streamlined manner.

Screening at State Borders Once the nationwide lockdown was revoked and cross border movement was initiated, natives of Kerala those who were stranded across the country were asked to register in the Covid-19 Jagratha portal to obtain travel passes. Multiple screening teams were deployed along the state borders to monitor the entry of people. Each team comprised of a

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senior police official, a paramedical staff and a local volunteer. Every vehicle was monitored, details of passengers were collected and their body temperatures were recorded. This was also done at railway stations and airports (Times of India, 2020).

Quarantine System and Testing Along with the world, Kerala started practising social distancing, quarantine, and self-isolation. According to CDC, social distancing also called physical distancing meaning to keep space between yourself and other people outside of your home (at least two metres). Quarantine ensures strict isolation of infected and people suspected of symptoms. Isolation is effectively done either by self-isolation at home or Government authorised Quarantine centres (CDC, 2020).

Sentinel Surveillance Sentinel surveillance is the monitoring of the rate of occurrence of a disease in a population in collaboration with doctors, laboratories, public health departments etc. A sentinel surveillance system was instituted in Kerala. The population was stratified into 5 categories: Group 1 – Patients in the general population with Acute Respiratory Infection (ARI) but NOT a COVID suspect. Group 2 – Health Care Workers in Non-COVID settings Group 3 – Persons with high social exposure: These persons were further categorized into the following; Food delivery persons, Community Volunteers for COVID, police personnel in enforcement of lockdown, provisions shop vendors ration shop, wholesale fruits or vegetable vendors. Group 4 – Category A COVID -19 Suspects: These categories of persons are those COVID suspects having sore throat or cough or rhinitis

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or diarrhoea and do not require testing unless there is a change in their category. Group 5 – Guest workers: Generally, are those persons from other states who have come to Kerala for labour (Department of Health & Family Welfare, Government of Kerala). Sentinel surveillance included random testing done in the community. It was done using RT-PCR (reverse transcriptase-polymerase chain reaction) test (GoK Dashboard, 2020). Kerala Police and other local bodies were entrusted with this duty.

Incessant Treatment Facilities for the Needy The Government of Kerala took extra efforts to provide treatment facilities to patients suffering from diseases other than Covid-19 infection, like haemophilia, thalassaemia and haemodialysis and so on. A triage system, a method of prioritizing patients' systematically according to how urgent they need care and treatment, was set up at all hospitals. Those patients showing symptoms of Covid-19 were isolated and tested.

Educating the Society The major challenge the government faced was to educate the general public about the epidemic and how to go through it. The government launched a campaign called “Break the Chain” to practice social distancing and maintain personal hygiene to limit the spread of the disease to the community level. All the institutions, ATMs, buses etc were asked to maintain sanitary precautions. People were encouraged to use sanitisers, wash their hands frequently to stop the spread of the virus. The Government of Kerala implemented a lockdown even before the Central government announced the nationwide lockdown. Public gatherings including religious and non-religious gatherings were banned.

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All schools and colleges except for medical colleges were closed. All festival gatherings were banned. Movie theatres and shopping malls were closed down. Only those shops selling essential items were allowed to open within the prescribed time duration, the rest of them were kept closed. All government functions were postponed. All inter-state, interdistrict, international travel was stopped (Anilkumar, 2020). People were compulsorily asked to wear face masks and avoid travel unless otherwise, it is an emergency. Inter-district travel was restricted. Emergency travel was allowed only with authorised travel passes from authorities. All the educational institutions were asked to remain closed. Offices were asked to work with minimal staff and work from home was encouraged wherever possible. The public transport system was stopped across the state.

Print, Visual and Social Media Campaigns The print, visual and social media played a pivotal role in dispersing the messages, instructions, releasing route maps of Covid-19 cases among common people. Relevant and accurate information was shared by the authorities through media to reach the public. Messages regarding the spread and prevention were made caller tune by the Telecom companies so that we would hear a message while we make a call. The Government of Kerala published many training videos for health workers on YouTube and also to promote public awareness about handwashing techniques, social distancing norms, home quarantine etc. The Kerala police also played a crucial role in campaigns and awareness by making and socialising awareness videos to circulate the message “Stay home” via the "Break the chain" campaign. Videos in languages other than Malayalam were also made to provide awareness messages among the guest workers. The government also took measures to counteract the spread of false information.

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Managing Guest Workers Kerala houses about 2.5 million migrant labourers from other states of India. They are officially designated as Guest workers. Several labour camps were set to accommodate all the guest workers of the state. Camps were set up by the Kerala government to accommodate more than 3.5 lakh guest workers. Guards with multilingual knowledge were posted in labour camps for effective communication with migrant labourers. Committees were constituted to take note and address the grievances and make necessary arrangements for all basic amenities and food in collaboration with CSR (Corporate Social Responsibility), LSG (Local Self Government) and other Non-Governmental Organisations. The camps were provided with all basic amenities and recreation facilities. As the guest workers disliked the traditional Kerala food provided by ‘Kudumbashree’, the desired choice of food like chapati, pickle, North Indian Dal curry and Khichdi was provided along with milk supply daily (Economic Times, 2020). A helpline number was also created to address the grievances of the guest workers. Awareness messages in all languages were given to the guest workers to ensure their safety. Timely checking was done to monitor the health of the people by the healthcare workers in collaboration with the labour department. Tele-counselling services were arranged for highly stressed workers by counsellors from TISS (Tata Institute of Social Sciences) (Official Website of Kerala Police, 2020).

INFRASTRUCTURES ENGAGED IN SUPPORTING THE HEALTHCARE SYSTEM COVID Specialised Treatment Centres The State Government had converted most of the government hospitals into Covid hospitals. There were 28 hospitals exclusively dedicated for the treatment of Covid- 19 patients. Hospitals were advised

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to postpone all surgeries unless otherwise they are of utmost importance and people were asked to visit hospitals only in emergencies. Covid-19 isolation wards were separated so that there will be no contact between those infected and the general public. Covid First-Line Treatment Centres were set up to manage the outbreak regionally. All mild and moderate cases are treated in these centres and severe cases are referred to Covid hospitals (Health & Family Welfare Dept., 2020). Covid-care centres were also established to provide a home for people who do not have facilities for quarantine at home. These centres were provided with ample security and all basic amenities.

Disha and Norka District Intervention System for Health Awareness or DISHA is a 24x7 helpline number launched in 2013 under the National Health Mission and Government of Kerala. The 16-member team is called in during crises. They had been actively involved in the outreach work of the recent floods in Kerala, the Nipah outbreak, the Ockhi cyclone and so on ("DISHA," 2013). Disha team played a crucial role in managing distress calls from the people. They managed to provide 24x7 psychosocial support to the people in need. The team also had doctors who were available to answer the queries of the people. Department of Non-Resident Keralites Affairs (NORKA), the division managing the affairs of Keralites staying outside the state, has been in the process of bringing expatriates back with priority given to pregnant women, people who need medical assistance, the elderly and people with an expired visa. Over 3 lakh non-resident Keralites have registered on Norka so far (Mathrubhumi, 2020).

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MANPOWER SUPPORT SYSTEM INVOLVED Kerala Police The lockdown, containment, and surveillance actions imposed by Kerala Police were noteworthy. To monitor lockdown enforcement, drones and exclusive women police bullet patrol teams have been deployed. Active monitoring was enforced at railway stations and airports. To confine the movement of the general public, a geo-fencing app was set up and checkpoints were set up along with mobile and foot patrolling. Interstate and inter-district borders were sealed off. Police were accountable for supplying essential travel passes through an online pass system. Kerala Police developed a "Road Vigil app for monitoring the movement of vehicles during lockdown period (Official Website of Kerala Police, 2020).

Asha Workers and Kudumbashree Accredited Social Health Activists (ASHAs), who are community health volunteers, approximate one for every 1000 to1500 population (Menon et al., 2020). ASHA workers were entrusted with the duty of informing if anyone violated the quarantine regulations. They, along with the health workers, conducted regular household surveys. Also, they were entrusted with communicating information to the public. ‘Kudumbashree’ units are part of women empowerment programmes of the Government of Kerala. The programme was launched in the year 1997. ‘Kudumbashree units’ in Kerala, a women self-help group under the leadership of Local Self Government, is one of the largest women empowering projects in the country. They were involved in the production of safety equipment, cook and provide food for the needy, serve the elderly and other needy persons. Community Kitchen initiative is regarded as one of the notable services rendered by Kudumbashree units.

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Volunteering Services People with experience in relief operations during the flood and other crises joined hands even during the covid-19 emergency. Volunteers were catered with proper directions through registered apps and videos (GoK Dashboard, 2020). They were involved in supplying food, medicines, groceries and also assisting people in need.

PRESENT SCENARIO OF THE STATE During the early stages, the state had received international acclaim in controlling the virus. The number of infections began to rise in July and reached a peak almost by October. Despite the hard work, the state reported the highest number of cases in India with a high-test positivity rate during February 2021. As the test positivity rate keeps vacillating, the Government have decided to ramp up the testing through Government laboratories to achieve 1 lakh Covid-19 tests per day, in which 75,000 tests should be RT PCR (GoK, Heath & Family Welfare (F) Department, 2021). Infection transmissions occurred mainly through the intermingling of people. To slow down the rate of transmission, the Government had initiated a “Back to the Basics” campaign in response to the current context of the upward trend of positive cases. The campaign entails strategies for the prevention and control of Covid-19 in a renewed manner. The campaign aims to revive and adhere to all the Covid-19 prevention measures laid down by the Government. The ‘OttakallaOppamundu’ is a program launched by the government for providing Psychosocial support to the people in quarantine, isolation, school children and other categories of the population as well as to the community in general. The test positivity rate in the state is 10.6 per cent as of 1st February 2021 (Weekly Bulletin, 2021). The rate has dropped to 3.05 per cent by the second week of March 2021. This reduction is achieved by the diligent efforts of the Government, including the increase in testing those suspected with symptoms.

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The Government of India almost completed the mission of Vaccination drive across India for its 3 crore Health workers and Frontline workers starting from 16th January 2021. The next set of people in queue is the 27-crore people who are of age above 50 and those below 50 years of age and co-morbidities. Covishield from Serum Institute of India which is based on the Oxford AstraZeneca vaccine and Covaxin by Bharat Biotech is being administered to the people (The Hindu, 2021). The Government of Kerala constituted the State Steering Committee, State task Force, District Task Force and Block Task Force for policy initiatives and coordination and implementation of COVID-19 vaccine introduction (GoK, HFW, 2021). The State began its second phase of COVID-19 vaccination on 1st March 2021. The Health Department has communicated that those aged 60 years and above and others aged between 45 and 59 years with co-morbidities can register during this phase. Private hospitals are also included in administering the Covid vaccine to the General Public. Those who are eligible for the vaccination in this phase can register themselves on the government's portal, Co-WIN (a digital platform that was formed for real-time monitoring of COVID19 vaccine delivery) for the same (Times Now news, 2021). In Kerala, around 300 private hospitals have been identified for the second phase. These hospitals can charge up to Rs 250 for a single dose. Government authorisedcentres will provide the vaccine to the public free of cost.

CONCLUSION Kerala is like any other state and has nothing extraordinary. The state has managed and coordinated all the available facilities to tackle the situation. Kerala's efficient health care system, the Police, the Local selfGovernment bodies, NGOs, self-help groups and voluntary workers, all joined hands for the state to fight the Covid-19 virus. Also, the learning experience from the past floods and Nipah outbreak aided the state in managing the scenario. Till the beginning of the second wave, Kerala was successful in containing the disease. But at a later stage, the authorities

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and the public were less vigilant of the preventive measures, and it resulted in the heightening of Covid cases. The present situation in Kerala has implications for the nation at large. Hence it is the nation’s responsibility, not just of the state, to launch all possible measures in controlling the COVID- 19 situations in Kerala. The Union health ministry and other relevant ministries must back up the Kerala government in a big way to bring down the number of cases. The state requires re-defining its past strategies and scheming and fashioning new plans and strategies to go back to normal. Kerala has always maintained a position of leadership in the vaccine compliance list of the universal immunisationprogramme. Vaccination must be done in a priority-based manner such as; the maximum number of at-risk individuals, which includes health care workers, other front line workers, and individuals older than 50 and those below 50 years who have comorbidities. A collaborative effort of all the current strategies will show a decline in the number of COVID cases in a controllable manner.

REFERENCES Aiyappa, V (2020). ‘Kerala Police: A Model Policing Paradigm in Handling COVID-19’. One India. https://www.oneindia.com/india/ kerala-police-a-model-policing-paradigm-in-handling-covid-13075490.html (accessed January 2021). Ajayakumar, Aarathi., Mehar Shagufta, Ayesha., Joseph, Roselent (2020). COVID-19 management andcontrol: The Kerala story. Internship. Society For Community Health Awareness, Research And Action (Sochara), Bengaluru. Anilkumar (2020). Kerala Lockdown: Kerala to go under lockdown till March 31 | Thiruvananthapuram News-Times of India [WWW Document]. Times India. URL https://timesofindia.indiatimes.com/ city/thiruvananthapuram/kerala-to-go-under-lockdown-till-march31/articleshow/ 74778886.cms (accessed January 2021).

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Bisht, R. & Menon, S. (2020) 'ASHA Workers Are Indispensable. So Why Are They the Least of Our Concerns?'. The Wire. https:// thewire.in/rights/asha-workers-coronavirus(accessed January 2021). Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S.C., Di Napoli, R. (2020). Features, Evaluation and Treatment Coronavirus (COVID19), in StatPearls. StatPearls Publishing, Treasure Island (FL). CDC, 2020a. Coronavirus Disease 2019 (COVID-19) [WWW Document]. Cent. Dis. Control Prev. URL https:// www.cdc.gov/ coronavirus/2019-ncov/php/principles-contact-tracing.html (accessed 5.25.20). CDC, 2020b. Coronavirus Disease 2019 (COVID-19) [WWW Document]. Cent. Dis. Control Prev. URL https://www.cdc.gov/ coronavirus/2019-ncov/prevent-getting-sick/social-distancing.html (accessed 5.28.20). Choolayil, A. C.,and Putran, L. (2021).COVID-19, The Local and the Global: Lessons from Kerala. 41 (January 2020), 7–21. https://doi. org/10.1177/0262728020966102. Economic Times (2020). Amid lockdown, migrant workers a content lot in Kerala [WWW Document]. Econ. Times. URL https:// economic times.indiatimes.com/news/politics-and-nation/amid-lockdownmigrant-workers-a-content-lot-in-kerala/articleshow/75243908.cms (accessed 25 February 2021). ENVIS Centre Kerala. State of Environment and Related Issues: Health. http://www.kerenvis.nic.in/Database/HEALTH_813.aspx (accessed July 2020). GoK Dashboard [WWW Document]. URL https://dashboard.kerala.gov. in/index.php (accessed 25 February 2021). GoK Dashboard [WWW Document]. URL https://health.kerala.gov.in/ weeklyBulltin.html.(accessed25 February 2021). GoK Dashboard [WWW Document]. URL https://dhs. kerala.gov.in/2021/02/25/25-02-2021/(accessed 25 February 2021). Huang C., Wang Y., Li X., et al. (2020).Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet,

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395:497-506. [PMID: 31986264] doi:10.1016/S0140-6736(20)30 183-5. Menon, J. C., Rakesh, P. S., John, D., Thachathodiyl, R., Banerjee, A., Ps, R., andJohn, D. (2020). What was right about Kerala's response to the COVID-19 pandemic ? 1–5. https://doi.org/10.1136/bmjgh2020-003212. Parry, Nicholas (2020).Shigella outbreak at medical camp in Kerala, Health Issues India, 24 December 2020, https://www.healthissues india.com/2020/12/24/shigella-outbreak-at-medical-camp-in-kerala/ [accessed 26 February 2021]. Physiopedia contributors (2020). 'Endemics, Epidemics and Pandemics', Physiopedia, https://www.physio-pedia.com/index.php?title=Endem ics,_Epidemics_and_Pandemics&oldid=261904> [accessed 25 February 2021]. Reid, D. (2020). ‘India Confirms its First Coronavirus Case’. CNBC. https://www.cnbc.com/2020/01/30/India-confirms-first-case-of-thecoronavirus.html. Sadanandan, R. (2020). Kerala's Response to COVID ‑ 19. 189–191. https://doi.org/10.4103/ijph.IJPH. Sulaiman, K. M., Muhammad, T., Muhammad Rishad, A. P. and Afsal, K. (2020). Trace, quarantine, test, isolate and treat: A Kerala model of Covid-19 response. MedRxiv, 49, 120–131. https://doi.org/10. 1101/2020.06.15.20132308. The Hindu (2020). Coronavirus | India approves COVID-19 vaccines Covishield and Covaxin for emergency use. [WWW Document]. URL https://www.thehindu.com/news/national/drug-controllergeneral-approves-covishield-and-covaxin-in-india-for-emergencyuse/article33485539.ece(accessed 27February 2021). The Hindu (2020). Coronavirus | First phase of vaccination to start on January 16. [WWW Document]. URL https://www.thehindu.com/ news/national/india-to-start-covid-19-vaccination-drive-on-jan16/article33536670.ece (accessed 27February 2021). Times Now News (2021).COVID-19 vaccination for 60+, comorbid people from March 1: How to use Co-WIN App to register yourself.

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[WWW Document]. URL https://www.timesnownews.com/ india/ article/covid-19-vaccination-for-60-comorbid-people-from. Unnithan, P.S.G. (2020). 'Kerala Reports First Confirmed Coronavirus Case in India. India Today. https://www.indiatoday.in/india/story/ kerala-reports-first-confirmednovel-coronavirus-case-in-india1641593-2020-01-30. Upadhyay, A. (2020) Coronavirus Outbreak Explained: What Are the Different Stages of corvid-19 Transmission. https://swachhindia.ndtv. com/what-are-the-different-stages-ofcovid-19-transmission-expertsexplain-43036. WHO (2020, July 2) Responding to COVID-19—Learnings from Kerala. https://www.who.int/india/news/feature-stories/detail/responding-tocovid-19---learnings-from-kerala.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 3

HUMAN DIASPORA AND PANDEMICS: A REVIEW IN THE CONTEXT OF COVID-19 Shaibu Jacob1,*, P. S. Ajith2, M. B. Arya2, David Abin3, Rogimon P. Thomas4, PhD and Joby Paul1, PhD Department of Botany, St. Thomas’ College (Autonomous), Thrissur, Kerala, India 2 Bodhi Cultural Centre, Indian Science Research Academy (ISRA), Adimali, Idukki, Kerala, India 3 Trinity Adventist Academy, Mavelikkara, Alappuzha, Kerala, India 4 Department of Botany, CMS College (Autonomous), Kottayam, Kerala, India 1

ABSTRACT The human diaspora started from the beginning of civilization but its intensity and speed were enhanced or induced by the advancement in the travel sector. Pandemics during human history indicated that diaspora is the main vector/ tool of spreading among the millions. In this context, this chapter is focused to understand the perspective and *

Corresponding Author’s Email: [email protected].

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Shaibu Jacob, P. S. Ajith, M. B. Arya et al. conscious level of nations in the following four questions. 1. Is there any satisfactory technological advancement to identify the pandemic diseases of international travelers in the context of the developed stage of diaspora? 2. How the advanced technological development catalyzed the intensity and speed of dispersal mechanism of pandemic disease outbreaks like COVID-19? 3. Is there any apt security against pandemics among nations and how will it be formed? It was observed that, during the COVID-19 period, the immediate response of science and technology was not sufficient to ensure the security of the people in the context of diaspora. Even though nations had successfully developed bio-weapons through technological advancement, they had failed to guarantee security consciousness to their people. The diaspora of the present century is facing the extreme challenge of pandemic diseases because of the poor predictive mechanism on the evolution of microbes in the climatic changing scenario.

Keywords: pandemic, technological advancement, diaspora, virtual vector

INTRODUCTION The World Health Organization (WHO) has alarmed the current outbreak of the novel coronavirus (COVID-19) as a global pandemic (Lau et al. 2020). All nations were frightened due to its accelerated dispersion among the continents. It could make a drastic decline in the social and economic development of the world. Medical technology advancement has been stressful to stop the transboundary dispersal but in contrast, aviation technology acted as a ‘virtual vector’ of coronavirus. As a result of the lack of intelligent measure and policies, migrants of different countries turn to panic and that lead to the rush return to the homeland which ultimately leads to the diffusion of the virus in every continent literally. The attack of the virus named COVID-19 started in Wuhan in December 2019 and it spread to the rest of China and then to the whole world (Kraemer et al. 2020). The causative organism of this pandemic is Coronavirus, distributed in humans, mammals, and birds can cause

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respiratory, intestinal, hepatic, and nervous system diseases (Perlman et al. 2020). Due to its variable incubation period, it was difficult to identify its rapid spreading (Poletto et al. 2014) and it overrides the age barriers of people. Due to its virulence and air transmission mechanism, approximately 119,609,831 people were infected and a death toll of 2,651,700 lives around the world as of 13th March 2021. The period of COVID-19 is historically relevant in the context of Human diaspora because this pandemic affected adversely in all levels of migration and its allied sector especially, low-income job migrants. Around the spreading range, the highest number of migrants including countries affected this pandemic in the high level of range and due to this fall down the international migrants and remittances such as 31% and 37% respectively by this pandemic (GMDAC analysis based on UN DESA, 2020; World Bank, 2020a; WHO, 2021). COVID 19 pandemic affected the transboundary migrants and the international migrants account for 3.4% of the world population, especially the international migrants of these 20 nations, between 11 March 2020 to 22 February 2021 (IOM, 2021). The economic emergency induced by COVID‐19 could be long, bottomless, and inescapable when observed through an emigration lens. An exponential development happened in the case of law and policies making against COVID-19 such as lockdown breakage of transboundary journey distancing etc were led to an economic depression in worldwide. Host nations faced supplementary challenges in many sectors, such as health and agriculture that depended on the obtainability of migrant workers. Migrants faced the threat of infection and also the possible loss of employment, wages, and health insurance coverage (World Bank, 2020). India is an important nation of origin for international immigrants with about 17 million emigrants according to the latest assessments released by the United Nations (2019). Every year a large number of people from India go abroad for overseas employment and study purposes. This chapter analyses the migration status of international and national scenario, state-level accounts in the context of COVID-19 and

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also try to point out the connection of aviation and COVID-19 spread. This analysis elucidates a clear virtual connection among migrants, aviation, and covid-19.

CORONAVIRUS PANDEMIC IN THE WORLD The ability to spread the pattern of the coronavirus can hold 210 nations of the world and hit around two million people worldwide [Appendix -1]. Without following covid prevention measures like social distancing and lack of abdicating instruments leads to more adverse conditions among migrants in the United States of America (Tharoor, 2020). The coronavirus disease 2019 (COVID-19) pandemic is the key challenge that healthcare systems around the world are presently facing (WHO 2021). The coronavirus disease 19 (COVID-19) is a highly infectious and pathogenic viral infection caused by unembellished acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, and blow-out around the world (Shereen et al. 2020). The novel coronavirus (termed 2019-nCoV) was testified in December 2019 from the genomic screening of clinical samples from patients with viral Pneumonia in Wuhan, China. The primary viral pneumonia patients were found to be epidemiologically linked to the Huanan seafood marketplace in Wuhan City, Hubei Province, China, where other non-aquatic animals, such as bats, pangolins, and rabbits, were on sale before the outbreak (Dietz et al. 2019, Tan et al. 2020, Zhu et al. 2020, Sofi et al. 2020). Through the use of next-generation sequencing, a new human infecting coronavirus, provisionally called the 2019 novel coronavirus (2019nCoV), was identified. Subsequently, on February 11, 2020, an outbreak or disease previously known as “novel coronavirus” or 2019-nCoV was officially renamed as C-O-V-I-D-19 or COVID-19, and the causal virus was named as “severe acute respiratory syndrome-related coronavirus 2” or SARS-CoV-2 (Sofi et al. 2020, WHO 2020) and this virus spread around the world (210 nations) by the movement of human and a drastic decline happened in the all-developmental sectors in the world.

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CORONAVIRUS HIT INTENSITY INDUCED BY POPULATION DISPERSAL INTENSITY Migration, urban population growth, and high population density are considered major factors (Connolly et al. 2020) for the spreading of pandemics. China has experienced large-scale migration in recent decades (Shen 2018; Chan 2014). Return migration range of early 2020 can assume to assess the migration to the Hubai province between 20102015 (Jianfa, 2020). Many travelers came back to their native place by the declaration of lockdown by the Chinese government before the spring holiday. Within 30 days coronavirus spread over from Wuhan to every province in China in 2019 (Gao et al. 2020). After that, it was confirmed outside on 13th January 2020 in Bangkok (Thailand) (WHO, 2020, Gennaro et al, 2020) On the 2nd March 2020, 67 territories outside mainland China had reported 8565 confirmed cases of COVID-19 with 132 deaths, as well as substantial community transmission were seen in several countries worldwide, including Iran and Italy and it was declared a global pandemic by the WHO on the 11th March 2020 (Hsu, et al. 2020, Gennaro et al. 2020). The number of confirmed cases has been constantly increased worldwide and after Asian and European regions, a steep increase was being observed in low-income countries (WHO, 2020). Based on the migration status, Wuhan had verboten all transport in and out of the city as of 10:00 on January 23, 2020, this is maybe the largest quarantine/movement constraint in human history to avert infectious disease spread (Tian et al. 2020). It could maintain control over hundreds of millions of Chinese residents, including 9 million Wuhan residents’ reduction of inter and intra-city movements. Due to the Wuhan lock-down (Yuan et al. 2020), Read et al. (2020) proposed that travel restrictions from and to Wuhan city are unlikely to be effective in halting transmission across China; with a 99% effective reduction in travel led to reducing 24.9% on February. There they had a 10-day delay in between infection and detection, which means that about a 5-day incubation period and an average 5- day delay from symptom commencement to

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detection of a case (Imai et al. 2020; Yang et al. 2020; Li et al. 2020). Around five million migrants turn back to their native destination before lockdown and they consider as potential disease spreaders. Case distribution and its correlation with population emigration from Wuhan in the early epidemic are of great importance for early warning and prevention of future outbreaks (Chen et al. 2020). The outbreak in China was largely under control by the end of March 2020. Kraemer et al. (2020) found a positive correlation between the COVID-19 cases and the population flow from Wuhan.

PRESENT SCENARIO OF COVID-19 IN THE WORLD The sum of confirmed cases is increasing every day with the obtainability of swift testing kits. This pandemic is going to impact harshly in the socio-economic and psychological aspects. COVID-19 is being considered as overwhelming as the World influenza epidemic of 1918 (Jahangir et al. 2020). The light of the above table can illustrate the following contents about the spread of this disease from one nation to another. According to the following table, 118852593 cases were reported in the world while this time and 94379293 recovery cases were also reported by WHO but 2635511 deaths were reported all over the world on 8thMarch 2021 (Table 1). Table 1. Present scenario of COVID-19 in the world Sl. No. 1 2 3 4 5 6 7

Country, Other Afghanistan Albania Algeria Andorra Angola Anguilla Antigua and Barbuda

Total Cases 55901 114840 114681 11130 21161 18 882

Total Deaths 2451 1986 3026 112 516 23

Total Recovered 49499 77498 79428 10708 19761 18 489

Active Cases 3951 35356 32227 310 884 0 370

Total Population 39528110 2875623 44394002 77350 33562497 15095 98488

Human Diaspora and Pandemics Sl. No. 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47

Country, Other Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Brazil British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cabo Verde Cambodia Cameroon Canada CAR Caribbean Netherlands Cayman Islands Chad Channel Islands Chile China Colombia Comoros Congo Costa Rica

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Total Cases 2169694 176286 8227 29090 484916 238383 8642 128428 554156 3353 298960 794605 12355 6501 731 868 256462 140990

Total Deaths 53359 3239 77 909 8798 3262 185 476 8502 37 2070 22347 316 81 12 1 11884 5410

Total Recovered 1961640 165441 7929 26218 450862 230244 7483 121776 507920 3002 289622 53888 11962 5552 690 866 200900 119904

Active Cases 154695 7606 221 1963 25256 4877 974 6176 37734 314 7268 718370 77 868 29 1 43678 15676

Total Population 45481402 2967070 107079 25703415 9041847 10202123 395831 1741774 165818974 287618 9447173 11624438 402577 12340011 62119 777454 11782447 3266670

32912 11205972 153

413 270917 1

27765 9913739 131

4734 1021316 21

2384149 213601044 30370

192 269579 12230 2369 15892 1163 36794 896739 5023 622

3 10999 143 3 155 1 566 22335 63 6

183 220049 11886 773 15236 597 32936 843962 4920 470

6 38531 201 1593 501 565 3292 30442 40 146

440363 6912161 21294381 12132125 560143 16877961 26997350 37970105 4887367 26391

460 4231 4043 867949 90018 2285960 3611 9329 207832

2 149 86 21206 4636 60773 146 131 2848

430 3729 3955 818337 85201 2187473 3427 7514 188151

28 353 2 28406 181 37714 38 1684 16833

66253 16747259 174967 19229245 1439323776 51256145 882282 5610902 5126156

38

Shaibu Jacob, P. S. Ajith, M. B. Arya et al. Table 1. (Continued)

Sl. No. 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83

Country, Other Croatia Cuba Curaçao Cyprus Czechia Denmark Diamond Princess Djibouti Dominica Dominican Republic DRC Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Eswatini Ethiopia Faeroe Islands Falkland Islands Fiji Finland France French Guiana French Polynesia Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe

Total Cases 248838 59157 4862 38065 1365724 218660 712

Total Deaths 5635 361 22 235 22624 2384 13

Total Recovered 238914 54084 4686 2057 1178832 208020 699

Active Cases 4289 4712 154 35773 164268 8256 0

Total Population 4087715 11321834 164556 1213418 10722709 5806286

6227 151 244923

63 3204

5950 138 200284

214 13 41435

997869 72109 10922800

26738 296841 188361 61814 6371

712 16105 11128 1935 96

22432 256009 145418 58440 5739

3594 24727 31815 1439 536

91416350 17827025 103657333 6508788 1434345

2988 80929 17203 169878 660 54 66 64609 3963165 16693 18509 16313 4792 274045 2537043 86737 4259 214661 31 148 10614

7 686 658 2466 1

2538 57716 15513 140035 657 54 57 46000 269019 9995 4842 14374 4203 267421 2337000 81299 4139 179672 31 147 2242

443 22527 1032 27377 2 0 7 17833 3604581 6611 13526 1846 436 3002 126679 4782 27 28052 0 0 8210

3580149 1327152 1168432 116909397 48991 3549 900923 5546668 65373300 303969 282028 2261642 2462978 3983867 83968953 31517045 33684 10387775 56838 112883 400171

2 776 89565 87 141 93 153 3622 73364 656 93 6937 1 162

Human Diaspora and Pandemics Sl. No. 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124

Country, Other Guatemala Guinea Guinea-Bissau Guyana Haiti Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Isle of Man Israel Italy Ivory Coast Jamaica Japan Jordan Kazakhstan Kenya Kuwait Kyrgyzstan Laos Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta

Total Cases 180393 17208 3327 8928 12594 175442 11151 489172 6070 11305877 1403722 1723470 745642 224588 1091 812823 3149017 36028 28968 443001 457151 220770 111185 204388 86692 48 92274 405407 10525 2026 142671 2596 203992 57056 48 20155 32614 319364 21144 8710 25640

Total Deaths 6522 101 51 205 250 4301 203 16497 29 158325 38049 61016 13671 4499 25 5955 101184 206 475 8402 5169 2821 1899 1144 1476 1737 5180 309 85 2340 55 3363 673 300 1077 1200 64 358 341

Total Recovered 166410 15403 2696 8211 9967 68350 10694 344267 6023 10947162 1224603 1471179 674345 23364 422 770156 2550483 32966 14781 422542 382949 204129 87994 189155 83718 42 82665 318800 3922 1898 129706 2519 190131 53453 47 19543 24381 300620 18534 6452 22176

39 Active Cases 7461 1704 580 512 2377 102791 254 128408 18 200390 141070 191275 57626 196725 644 36712 497350 2856 13712 12057 69033 13820 21292 14089 1498 6 7872 81427 6294 43 10625 22 10498 2930 1 312 7156 17544 2546 1900 3123

Total Population 18142761 13375898 1999803 789171 11498123 10012743 7538891 9643370 342770 1389345702 275514280 84732072 40839991 4975737 85343 9197590 60400305 26824609 2970088 126208366 10272869 18931182 54581787 4313950 6598061 7348083 1871712 6804268 2153952 5138962 6935506 38204 2695875 632967 655418 28177203 19467533 32651098 547074 20648538 442355

40

Shaibu Jacob, P. S. Ajith, M. B. Arya et al. Table 1. (Continued)

Sl. No. 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160

Country, Other Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Micronesia Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique MS Zaandam Myanmar Namibia Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria North Macedonia Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Poland Portugal

Total Cases 4

Total Deaths

Total Recovered 4

Active Cases 0

Total Population 59465

6928 17385 664 18604 2144558 1 200124 2062 3561 82029 20 487286 63645 9 142114 40631 275070 1138796 74 2416 6537 4848 159646 109262

47 442 10 129 192488

6783 207 62 15511 266074 0 20793 161 710 9052 1 4843 14318 0 7191 2077 942 N/A 16 85 2137 192 17670 9845

375064 4733102 1273226 277314 129865108 115853 4027473 39434 3314526 628121 4994 37211482 31852751

26 175 179 1993 3244

98 16736 592 2964 1685996 1 175111 1875 2847 71864 18 473738 48616 7 131722 38104 271116 N/A 58 2305 4225 4477 139983 96173

77601 145257 597497 203669 346301 1819

632 1600 13377 2211 5957 21

66014 135227 566493 181452 333675 846

10955 8430 17627 20006 6669 952

5450455 5195338 223831323 5182511 4361396 9063183

174013 1387457 607048 1849424 812575

3387 48323 12608 46373 16635

144144 1294623 546671 1516540 744196

26482 44511 47769 286511 51744

7192788 33287453 110583559 37817932 10176124

4220 26 4 1113 1 8705 711 2 3201 450 3012 15998

54661300 2572457 29496163 17161066 287388 5002100 6678765 24801718 209630676 2083315

Human Diaspora and Pandemics Sl. No. 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196

Country, Other Qatar Romania Russia Rwanda Réunion South Korea Saint Kitts and Nevis Saint Lucia Saint Martin Saint Pierre Miquelon Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten Slovakia Slovenia Solomon Islands Somalia South Africa South Sudan Spain Sri Lanka St. Barth St. Vincent Grenadines Sudan Suriname Sweden Switzerland Syria Taiwan

41

Total Cases 168829 845352 4360823 19846 13801 94198 41

Total Deaths 264 21252 90734 271 71 1652

Total Recovered 157242 774277 3959533 18118 12389 84675 41

Active Cases 11323 49823 310556 1457 1341 7871 0

Total Population 2807805 19148700 145977728 13171603 899717 51299687 53458

3941 1571 24

47 12

3722 1399 24

172 160 0

184206 39118 5774

2 3511 1696

1 474 282

199323 33980 221949

3 4062 2010

77 32

381348 36195 503291 3032 3928 60070 2077 331571 198234 18

6551 935 4644 15 79 29 27 8244 3918

371850 31467 400347 2809 2769 59939 2034 255300 183848 16

2947 3793 98300 208 1080 102 16 68027 10468 2

35186108 17045174 8712992 98767 8088085 5882050 43211 5461470 2079136 698395

8820 1524174 9205 3178442 86685 638 1674

338 51015 103 71961 515 1 8

4079 1445979 7906 2823433 83561 462 1114

4403 27180 1196 283048 2609 175 552

16195700 59822837 11283999 46767300 21475225 9898 111183

28766 8990 707192 569312 16187 978

1915 175 13111 10088 1079 10

23268 8498 N/A 526511 10625 936

3583 317 N/A 32713 4483 32

44549353 590252 10142695 8698250 17791224 23846563

42

Shaibu Jacob, P. S. Ajith, M. B. Arya et al. Table 1. (Continued)

Sl. No. 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221

Country, Other Tajikistan Tanzania Thailand Timor-Leste Togo Trinidad and Tobago Tunisia Turkey Turks and Caicos UAE Uganda UK Ukraine Uruguay USA Uzbekistan Vanuatu Vatican City Venezuela Vietnam Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe

Total Cases 13308 509 26598 159 7737 7743

Total Deaths 90 21 85 92 140

Total Recovered 13218 183 26000 94 6534 7509

Active Cases 0 305 513 65 1111 94

Total Population 9684201 60894519 69920970 1335655 8411398 1402618

239368 2821943 2190

8292 29227 15

205719 2649862 2071

25357 142854 104

11903738 84963623 39077

419996 40520 4241677 1425522 66484 29866708 80347 3 27 143796 2533 129

1369 334 125168 27685 678 542274 622

399803 15095 3348489 1210246 57134 20640756 79051 1 15 135869 2048 7

18824 25091 768020 187591 8672 8683678 674 2 12 6520 450 122

9972587 46724486 68132056 43551614 3482043 332341490 33802407 312053 802 28380156 97941814 11102

10 2627 83913 36341

1 661 1148 1489

8 1452 80027 33953

1 514 2738 899

607375 30275469 18735154 15011546

1407 35

A Virtual Relationship of Airport and COVID-19 in the World The different response is principally due to the detail that the COVID-19 crisis has quickly spread globally. The majority of countries in the world implemented travel restrictions, lockdowns and other measures to prevent the spreading of corona virus (Monmousseau et al. 2020, Suzumura et al., 2020, White House, 2020, European Council,

Human Diaspora and Pandemics

43

2020, Iacus et al. (2020). Italy was the first country to enforce a national lockdown (World Atlas, 2020) from March 9th, 2020 to February 21st, 2020 an initial measure confining only the northern region of Lodi (Monmousseau et al. 2020). Followed by the EU officially closed the external borders of 26 of its member states to nearly all non-EU residents on March 17th, 2020 (New York Times 2020, Monmousseau et al. 2020). The top five nations with the largest number of infected people were the USA, Brazil, Russian Federation, India and UK (WHO, 2020. Bindu and Indu, 2020). Airports Council International (ACI) prophesied that COVID-19 can wipe out two-fifths of passenger traffic and half of the airport incomes in 2020 (ACI, 2020). The International Civil Aviation Organization (ICAO) assessment that during the first half of 2020, compared to their original forecast, showed an overall reduction of 47% to 58% of seats offered by airlines and face loss of around 112 to 135 billion USD (ICAO, 2020. Sanchez et al. 2020). Comprehensive information on air traffic between international airports has been demonstrated to be useful in retrospectively authenticating and prospectively envisaging case emergence in other countries. For the ongoing COVID-19 epidemic, 24 countries had authoritatively described cases by the first week of February 2019. All of the first reports in these countries had travel antiquity to China (mostly to Wuhan city of Hubei province) and also, they assess the global importation risk of novel coronavirus disease (COVID-19) for other countries based on travel to China (Adiga et al. 2020). Brockmann (2020), clearly demonstrated the risk factor of COVID-19 in the context of pandemic disaster by the aviation industry of the world and they consider the time and distance from the epicenter of COVID-19. According to Adiga et al. (2020) COVID-19 pandemic spread induced by the aviation sector could be simply imagined by the transportation network of around 4000 airports in the world (Adiga et al. 2020). Brockmann (2020) observed the potential of this pandemic by using 2019 data from the International Air Transport Association (IATA) and identified all cities in China that received at least 100000 airline passengers from Wuhan during February through April 2019. In a

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Shaibu Jacob, P. S. Ajith, M. B. Arya et al.

scenario where these cities might experience local epidemics, analyzed the volumes of airline passengers to international destinations from February to April 2019 and reported that around 50 international cities contribute the number of migrants to the mainland of China. And another necessary observation is that the analyzed international airline passenger trips from the following 10 cities: Wuhan, Beijing, Shanghai, Kunming, Chengdu, Xiamen, Haikou, Guangzhou, Shenzhen and Hong Kong. The migrants return from the city by using connecting flights e.g., Taipei (1359253), Bangkok (1232307), Tokyo (1086105), Seoul (1008960) and Singapore (751 064). 90% of the passengers were received by Asia, with London, the UK ranked 10th in volume (252 127). Other nations include Paris (142724 passengers) and Moscow (114925 passengers). Sydney (242577) passengers, while Los Angeles (184808), New York (148133) and San Francisco (140556) received the highest volumes to North American destinations. Cairo (62470) is the one and only migrants received nation in Africa (50 destinations). Table 2. Key facts and figures from the World Migration Report, 2000 and 2020 Key facts-World migration reports Estimated number of international migrants Estimated proportion of world population who are migrants Estimated proportion of female international migrants Estimated proportion of international migrants who are children Region with the highest proportion of international migrants Country with the highest proportion of international migrants Number of migrant workers Global international remittances (USD) Number of refugees Number of internally displaced persons Number of stateless persons Source: PhD. Research Bureau, PHDCCI compiled from IOM.

2000 Report 150 million 2.80% 47.50% 16.00% Oceania UAE 126 billion 14 million 21 million -

2020 Report 272 million 3.50% 47.90% 13.90% Oceania UAE 164 million 689 billion 25.9 million 41.3 million 3.9 million

In the case of a pandemic, flights are the major speedy spreading carrier in technologically advanced travel. Because the topmost affected countries have more potential to spread disease to the other region

Human Diaspora and Pandemics

45

because of the high number of airport and air services. Good health incorporates mental, social and physical comfort. The field of migration and health encompasses health apprehensions arising from human agility, such as the transmission of transferrable diseases, and should engross with all aspects of well-being in the framework of migration and with totally who are affected, including families of migrants and the public fitness of communities with whom migrants interrelate during all phases of the migration journey (World migration report 2020) (Table 2).

A VIRTUAL RELATIONSHIP OF COVID-19, AVIATION AND MIGRATION IN THE INDIAN CONTEXT Epidemic in India Epidemic waves affected people and also their humanity. The return of migrants may bring disease into the native region and the same occasion happened in the 1980s in the case of HIV/AIDs and the population became risk (Maharatna, 2014, BBC, 2020, Bhagat et al. 2020). In a different period, pandemic disease adversely affected people’s life as well as the global economy. Migrants may be the carriers of diseases or a part of a disease outbreak because of their borderless long journey. Different period’s pandemic diseases adversely affected migration and also the global economy. Such examples of the pandemic are Smallpox epidemic (1974), Cholera (1910-1911, Death- 8,00,000), Spanish Flu (1918 – 1920, Death-17-18 million Indians), Plague in Surat (1994), SARS (2002- 2004), Dengue and Chikungunya Outbreak (2006), Swine flu outbreak (2014-2015, Death-2000 Indians), Nipah Virus outbreak (2018) and the very end of 2019 COVID, 19 emerged. COVID19 has rapidly spread worldwide by travelers or migrants coming from the epicentre of the outbreak or countries with reported cases. COVID-19 has been confirmed on all continents, including in the European Union

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Shaibu Jacob, P. S. Ajith, M. B. Arya et al.

(EU) countries and has already caused victims in the EU. European Centre for Prevention and Control assessed the risk for people travelling within the EU as high, especially from the United Kingdom, France, Germany, Italy, Spain and the Netherlands. The world spread of COVID19 pandemic disease also largely affected the workers due to the shutdown of factories and workplaces in India. Millions of migrant workers also faced issues like loss in their income, food scarcity and uncertainty about the future. However, necessary steps have been taken by the government with the support of citizens and are trying to reduce socioeconomic impact.

Lockdown and Interstate Migration Lockdown is essential to prevent pandemics and pollution but before the implementation necessary apt arrangements should cover otherwise it will badly affect poor people. According to the Shahas (2020) study revealed that migrants from north-central India show that the majority of the workers were the daily wage earners and they faced many adverse conditions such as lack of food, shelter, no identity card and angry from police and local people because of a notion of feeling against the covid spread. (India Today, 2020). In India, mass return migration to the homeland could be seen by challenging all difficulties. The very effort to stave off the pandemic turned into one of the greatest human tragedies in India’s recent history (Bhagat et al. 2020). Migrant workers stood as the backbone of the Indian economy. There were permanent and semi-permanent workers (15 million and 194 million) among the migrants (482 million) in India (Keshri and Bhagat, 2012). For life sustenance, many of them came to the urban sector for employment and contribute a significant account in urban population (50%) and interstate migrants also have an essential role in it (1/5 of the urban population). Around 53 million came from the rural sector and tried to take part in urban development. Out of 53 million-plus cities, eight of them are mega-cities with a population of 5 million and more

Human Diaspora and Pandemics

47

(Bhagat et al. 2020). In general, in-migration rates were higher in highincome states such as Delhi, Goa, Haryana, Punjab, Maharashtra, Gujarat and Karnataka, whereas low-income states such as Bihar, Uttar Pradesh, Jharkhand, Rajasthan and Odisha reported relatively higher rates of outmigration (Bhagat et al. 2020). Due to the absence of transportation facilities, millions of migrant labours started their exodus to their native places. States like Delhi, Uttar Pradesh, Rajasthan, Karnataka and Bihar have looked into the situation and had arranged transport buses to help the workers reach their homes. But this massive transportation had resulted in a problematic situation and increased misunderstanding between the states. As this was a violation of and a threat to the benefits of lockdown and was risky for them and people in the villages, the Government of India gave a licensed order to seal all borders and make necessary arrangements like temporary shelters, food, clothes etc. (Press Trust of India, 2020; Government of India, 2020).

The Indian Diaspora According to the United Nations (2019), there have 17 million international migrants from India and also the top remittance (USD 78.6 billion) received nation (World Migration Report 2020). Indian migrants mainly focused on the United States of America, Malaysia, Saudi Arabia, the U.A.E, United Kingdom, South Africa, Canada, Singapore, Kuwait, Oman, Qatar, Thailand, and New Zealand. But some skilled, semiskilled and students focused on USA, UK, Canada, Australia etc., where labour and employment laws are well defined and emigrants’ interests are well protected under the local law, a considerable proportion of the emigrants from India are less educated and less or semi-skilled workers migrating to Gulf countries. According to the United Nation, around 3% of the world population migrated from poor to rich countries, poor to poor countries, rich to rich countries and rich to poor countries by political and economic existence.

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Shaibu Jacob, P. S. Ajith, M. B. Arya et al.

Indian diaspora that constitutes an important and exclusive force in some reverences blow-out across all six continents and 125 nations. Table 3. The present situation of COVID-19 in India Sl.No.

Name of the states/UT

Active cases 1 Andaman and Nicobar Islands 7 2 Andhra Pradesh 998 3 Arunachal Pradesh 3 4 Assam 1627 5 Bihar 313 6 Chandigarh 710 7 Chhattisgarh 2820 8 Dadra and Nagar Haveli and Daman and Diu 12 9 Delhi 1803 10 Goa 688 11 Gujarat 3140 12 Haryana 2031 13 Himachal Pradesh 614 14 Jammu and Kashmir 892 15 Jharkhand 463 16 Karnataka 6881 17 Kerala 41162 18 Ladakh 44 19 Lakshadweep 158 20 Madhya Pradesh 3606 21 Maharashtra 99205 22 Manipur 28 23 Meghalaya 13 24 Mizoram 8 25 Nagaland 20 26 Odisha 747 27 Puducherry 176 28 Punjab 7497 29 Rajasthan 1755 30 Sikkim 50 31 Tamil Nadu 3997 32 Telangana 1807 33 Tripura 30 34 Uttarakhand 632 35 Uttar Pradesh 1647 36 West Bengal 3163 Total 188747 Source: Ministry of health and family welfare (08 March 2021).

No. of people affected 4955 882520 16780 214947 260899 21253 307642 3402 628377 53922 265831 267433 57507 124190 118703 935772 1031865 9657 327 257166 2068044 28890 13811 4410 12106 335080 39022 174967 316988 5989 838606 296562 33003 95095 593895 563182 10882798

Confirmed death 62 7174 56 1094 1546 355 3858 2 10921 799 4415 3056 997 1962 1093 12362 4300 130 1 3871 52478 373 148 10 91 1917 670 5927 2789 135 12518 1642 391 1695 8737 10278 157853

Human Diaspora and Pandemics

49

Over the past two centuries, India has reached the world’s most diverse migration history. The Indian diaspora has a promoter for economic development in both within India as well as the migrated nations. Indian diaspora has its own scope; an expatriate is migrated to the foreign land from their own territories. Around 20 million Indian people are spread over the globe, and it constitutes an important strengthening of the world culture.

How Is COVID-19 Hitting India? The first case of COVID-19 surfaced in India on January 30, 2020, and following out-break the lockdown in the entire country was announced on 24th March for a period of 21 days (Bhagat et al. 2020). Kerala has the top migration rate among other Indian states (Bhagat et al. 2013). The lockdown directly affects the migrants and states economies of all nations (The Indian Express, 2020). To mitigate the effect of the lockdown on the vulnerable groups, the Government of India on 26 March 2020, announced a 70-lakh crore package under the Pradhan Mantri Gareeb KalyanYojana. Both governments decided to spend 52000 crores of the Building and Construction Workers Welfare Fund for relief work. (DBT) (DHNS, 2020; Government of India, 2020). The Ministry of health and family welfare (08 March 2021) had revealed a clear picture of the COVID-19 affected states/UT and its range. According to this 188747, active cases and 10882798 people of India were affected by COVID-19. By coronavirus attack 157853 life was lost in India. All details are illustrated in the following Table 3.

COVID-19 and Return Migration in the Indian Context Considering the COVID-19 affected countries, India stands on the top 5 infected nations in the world. However, India has taken effective measures to regulate the pandemic and boost the economy. However, the

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Shaibu Jacob, P. S. Ajith, M. B. Arya et al.

sudden stoppage of movements of people and the suspension of travel has drastically influenced the tourism and aviation industry in India (Bindu and Indu, 2020). The government of India has taken necessary precautions for preventing the COVID-19 outbreak so the nationwide lockdown was implemented on 25th March that was extended to 7th June 2020 and on 13 March 2020, all visas were suspended except diplomatic and other official visas (Chanana, 2020). In India, the borders were sealed to break down borderless travel by lockdown (Bindu and Indu, 2020). As the initiative of central and states governments, many of the migrants came back to their home land. In this mission, two- way approach was done by concerned governments with the help of the Indian navy and airlines. The first mission was taken by the Indian navy named ‘SamudraSetu’ and the second mission is Vande Bharath Mission (VBM).

‘Samudra Setu’ and Return Migration In India ‘Samudra Setu’ is the first program to initiate for evacuating Indian migrants from other nations and it was completed on May 5, 2020. By this attempt around 3992 Indian migrants were reached their homeland. In this operation participated four ships of the Indian Navy named Shardul, Magar, Jalashwa and Airavat and travelled around 23,000 km. The details are given in the table (Table 4). Table 4. COVID-19 and ‘Samudra Setu’ undertaken by Indian Navy Name of Date Port of the Ship Embarked Embarkation Jalashwa 08-May Malѐ Magar 10-May Malѐ Jalashwa 15-May Malѐ Jalashwa 01-Jun Colombo Jalashwa 05-Jun Malѐ Shardul 08-Jun Bandar Abbas Airavat 20-Jun Malѐ Jalashwa 25-Jun Bandar Abbas Source: Official web site of Indian Navy.

Number of Citizens 698 202 588 686 700 233 198 687

Date Disembarked 10-May 12-May 17-May 02-Jun 07-Jun 11-Jun 23-Jun 01-Jul

Port of Disembarkation Kochi Kochi Kochi Tuticorin Tuticorin Porbandar Tuticorin Tuticorin

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Vande Bharat Mission The second phase of the return migration named Vande Bharat Mission was initiated on 7th May 2020 and is enduring in June 2020 (Ministry of Civil Aviation, 2020). Air India, Air India Express, and Indigo became part of it. As per MoCA, by June 23rd, 2020, a total of 681 inbound flights brought back 1, 29,339 passengers to India while a total of 686 outbound flights carried 45,095 passengers to their respective countries. On March 22, the international flights were suspended by India, followed by domestic air transport services on 24th March (Table 5). Table 5. Return to the homeland through VBM VBM No. No. % Of passengers in Phase of flights of Passengers the total VBM 1 84 15296 0.6 2 260 50744 1.99 2+ 186 3412 0.13 2++ 132 5005 0.19 3 553 103906 4.08 4 1082 198193 7.79 5 1104 194792 7.66 6 1289 227938 8.96 7 1441 261108 10.27 8 1651 299360 11.77 8+ 1508 278948 10.97 9 1697 323129 12.71 9+ 1481 282849 11.12 10 1557 297371 11.69 Source: Ministry of External Affairs, Government of India.

From No. of nations 12 47 15 8 41 29 28 29 26 28 29 27 26 28

Total No of states 11 17 16 11 20 19 16 18 15 12 14 14 15 15

% Of States 37.93 58.62 55.17 27.58 68.96 65.51 55.17 62.06 51.72 41.37 48.27 48.27 51.72 51.72

MIGRATION FROM INDIA Today there have assessed around 3.4% of the world population is migrants. Globalization, demographic alterations, conflicts, earnings inequalities and climate change encourage many workers, and their

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Shaibu Jacob, P. S. Ajith, M. B. Arya et al.

families to cross boundaries in search of employment and safety. India is a foremost country of origin and transit, as well as a popular terminus, for workers crossways international borders. There are 30 million Indians migrants but 9% of the Indian migrants were focused on the gulf region. In the context of eligibility90% of the migrants are included in low and semi-skilled workers but limited data is available in this sector. That is, labour migration data is available mostly for workers who have to register for emigration clearance (Wadhawan 2018). As far as the majority of Indian migrants are concerned, they depend on the pull factor in that point of view, the Indian migrants have specific corridors.

Diaspora of Kerala towards COVID-19 and Vande Baharat Mission COVID-19 in Kerala Context The first case of coronavirus was reported in Kerala on January 30, 2020. Only three were reported in the first phase. The patients were properly quarantined in the hospital and treated. No other persons were affected by them. The second phase of COVİD-19 was started by Italian migrants who allegedly escaped from the airport testing facility. By the end of March, the number of active cases crossed a hundred. Kerala then resorted to complete lockdown. The next day, the Government of India also pronounced country-wide lockdown until April 15 which later extended multiple times until May 31 (Jayesh and Sreedharan 2020). On March 23, Kerala announced a state-wide lockdown until March 31 (India Today, 2020). A day later, the central government announced a nationwide 21-day lockdown until April 15 (CGO 2020). And also extended the lockdown until May 3, which further extended until May 31 (Jayesh and Sreedharan 2020). Kerala government makes prevention against COVID-19 through social mobilization under the leadership of Kerala health ministry. This process can be done in light of the experience of Nipa outbreaks in 2018 (Sadanandan 2020). Kerala became the model for a comprehensive

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strategy made and implemented against COVID-19 pandemic, in this context world attention initially turned to Kerala. (Issac & Sadanandan, 2020; Rajan, 2020c; Vijayan, 2020). Around 5 million migrants work outside the state among these 2.5 million works in COVID-19 affected nations like gulf countries (Jalan and Sen 2020). The way of approach of the Kerala government against COVID-19 can be considered as a benchmark for how the public health department can be utilized properly (Jayesh and Sreedharan 2020). Kerala captured the attention of Worldwide Media and was appreciated for the efficient management of COVID-19 (Jayesh and Sreedharan 2020, CGO 2020, KGO 2020). The present situation of Kerala in the context of COVID-19 is illustrated in the following table. According to it, there are 37150 active cases, and the total case reported in Kerala is 1081055. The efficient health work could cure 1116281 no: of persons and the total number of persons in quarantine are 166107. Unfortunately, 4328 deaths were reported by COVID-19. The following statics are based on the Kerala government updates until 09-03-2021. The district-wise details are illustrated in Table 6. Table 6. COVID-19 statistics of Karla by govt. updates (until 09-03-2021) Sl. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Total

Name of the District EKM PTA KLM TSR KKD KNR KTM PKD KKD ALP MPM IDK TVM WYD

Active cases 6185 3198 3099 3071 3038 2757 2581 2313 2139 1953 1884 1730 1704 1498 37150

Total death 428 114 319 460 464 292 202 178 97 375 425 37 849 88 4328

Total reported 125962 57947 88858 100713 122718 55064 80992 60181 30109 79657 119653 27840 103906 27455 1081055

Total cured 119323 54627 85417 97165 199189 51985 78201 54680 27865 77303 117325 26068 101268 25865 1116281

Quarantine d 18496 7199 12737 19119 18411 11853 10679 5625 7572 11878 17120 3329 17822 4267 166107

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Kerala migrants came back by the timely decision of both Kerala Chief Minister and Prime Minister of India. Kerala migrants were faced with many difficulties and unsafe conditions in gulf countries so this decision becomes more beneficial to them. Bringing them back at the time was a priority and the evacuation of Indians began after the push from the state government and various diaspora organizations in the first week of May through Navy vessels and later through the Vande Bharat flights (Rajan 2020).

Migration Trend of Keralite from 1998 to 2018 The quest for a better life and economic opportunities within and outside a region continues to be the principal reason for migratory movements in the world. United Nations stated that around 244 million migrants (3.4% of the world population) (“Migration,” 2017). Migration can make development in the employment sector through giving more opportunities and showed the potential growth in the standard of living (Khadria, 2010). Migration could reduce poverty and make development in different sectors such as agrarian reforms, trade union activities, social welfare etc. (Zachariah et al. 2001). Indian diaspora study reveals that labourers in non-agricultural sectors constituted the largest proportion of emigrants from Kerala, 27.4 percent of the total. After the Gulf region, the migrants gave the priority to the United States of America and accommodate around 5.7% of emigrants. Before the COVID-19 periods, according to the economic review of Kerala 2019 and CDC report revealed the statistics of migration from 1998 to 2018 (CDC, 2019). Return Migration by Indian Navy in COVID-19 Period Operation Samudra Setu conducted by the Indian government under the leadership of the Indian navy was launched on 05/05/2020 for evacuating Indian citizens from another country as part of it successfully bringing back 3,992 Indian migrants to the homeland in the context of COVID-19 Pandemic. In this operation, Indian Naval Ships Jalashwa, and Airavat, Shardul and Magar participated in fulfilling this target by 55

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days travel (23000 km). Indian navy already has this sort of experience in the past. eg. Operation Sukoon in 2006 and Operation Rahat in 2015 (Indian Navy 2020). Three vessels disembarked in Kochi by carrying 1488 migrants from different nations (Table7). Table 7. Return migration by Indian navy in the COVID-19 period Name of the Ship

Port of Embarkation

Jalashwa Male Magar Male Jalashwa Male Total number of persons

Number of Citizens

Date Disembarked

Port of Disembarkation

698 202 588 1488

10-May 12-May 17-May

Kochi Kochi Kochi

Vande Bharat Mission in Kerala Considering the return migration and COVID-19 statistics, it was observed a significant connection but unfortunately, there was no clear data of migrant’s COVID-19 rate and spreading relation about them. But we know the second phase of coronavirus outbreaks directly caused migrants to travel to their homeland from Italy to Pathanamthitta. This kind of inquiry is essential to prevent future pandemics and its easy tackling.

Phase of VBM

No of flights

% of flights in each phase

% of flights in VBM

No of return migrants

% of migrants

%of passengers in the total VBM

No of nations

Table 8. Vande Bharat Mission in Kerala

1 2 2+ 2++ 3 4 5 6 7 8 8+ 9 9+ 10

17 46 85 54 81 282 232 267 354 402 424 455 404 407

20.23 17.6 45.69 40.9 14.64 26.06 21.01 20.71 24.46 24.34 28.11 26.81 27.27 26.14

0.12 0.32 0.6 0.38 0.57 2.01 1.65 1.9 2.52 2.86 3.02 3.24 2.88 2.9

2913 8631 14961 3515 14091 48909 36139 40574 59435 67452 72230 80058 71068 72023

19.04 16.99 43.77 70.22 14.64 24.67 18.55 17.8 22.76 22.53 25.89 24.77 25.12 24.21

0.11 0.003 0.58 0.13 0.55 1.92 1.42 1.59 2.33 0.02 2.84 3.14 2.79 0.28

7 7 7 8 21 16 12 11 12 10 9 9 9 4

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Figure 1. Correlation between total reported COVID-19 cases and number of international airports in different countries.

CONCLUSION The World Health Organization had revealed the first case of COVID-19 reported date of each country. According to this report, almost all countries reported the first case of COVID-19 had around 50 days above the gap (Appendix-1). It indicates that well-planned preventive measures can break the spread of COVID-19 like a pandemic, but it happened only through a static movement of people, especially in the case of migrants. Around 3.7% of the world’s population is under the account of migration. Only zero percent international and interstate migration can reduce the intensive spread of pandemics like COVID-19. The technological advancement in the travel sector helps to fulfill the notion of return migration, especially through the aviation sector. If considering the air distance from Wuhan to all nations can reach within 24 hours by using the aviation sector (Average flight speed 500km/h) details are given in appendix -1. In statistical analysis have a significant Correlation between total reported cases and the International Airports.

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This perspective of study can be used to reduce the intensity of future pandemics.

ACKNOWLEDGMENTS The authors are thankful to the Principal and Head of the Department of Botany, St. Thomas’ College (Autonomous) Thrissur, Kerala for facilities. The authors also express their gratitude to the Librarian, St Thomas’ College (Autonomous) Thrissur, for literature and Anooja M Bala and Biji Jacob Oommen for constructive comments on the manuscripts.

APPENDIX 1. CONSOLIDATED DATA OF COVID-19 CASES IN RELATIONS WITH AIRPORTS, DISTANCE AND DAYS AFTER THE REPORT FROM CHINA Country USA India Brazil Russia UK France Spain Italy Turkey Germany Colombia Argentina Mexico Poland Iran South Africa Ukraine Indonesia

Total Cases 29866708 11305877 11205972 4360823 4241677 3963165 3178442 3149017 2821943 2537043 2285960 2169694 2144558 1849424 1723470 1524174 1425522 1403722

No of Airports 503 132 288 139 144 136 59 77 53 103 168 101 100 15 64 90 38 205

Air distance from Wuhan 12201.97 3572.33 17567.81 6430.43 8875.03 8908.12 9864.42 8666.49 7210.75 8032.24 16003.03 19193.43 13406.05 7577.65 5779.15 11082.99 7018.07 4163.29

Days after report from China 50 60 86 61 61 54 61 60 100 57 96 93 89 94 80 95 93 92

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Country Peru Czechia Netherlands Canada Chile Romania Israel Portugal Belgium Iraq Sweden Philippines Pakistan Switzerland Bangladesh Serbia Hungary Morocco Austria Jordan Japan UAE Lebanon Saudi Arabia Panama Slovakia Malaysia Belarus Ecuador Nepal Georgia Bulgaria Bolivia Croatia Dominican Republic Tunisia Azerbaijan Ireland Kazakhstan Denmark

Total Cases 1387457 1365724 1138796 896739 867949 845352 812823 812575 794605 745642 707192 607048 597497 569312 554156 503291 489172 487286 484916 457151 443001 419996 405407 381348 346301 331571 319364 298960 296841 275070 274045 269579 256462 248838 244923 239368 238383 224588 220770 218660

No of Airports 39 11 15 18 45 18 15 25 10 13 65 70 62 11 15 6 6 25 9 5 99 9 2 35 40 8 66 7 25 43 4 14 37 10 13 9 4 21 24 20

Air distance from Wuhan 17649.51 17886.53 8538.39 11504.27 19451.36 7552.58 7338.4 10337.07 8663.58 6472.89 7453.97 1906.44 3869.6 8713.54 2475.02 7945.51 7918.19 10543.1 8062.85 7266.17 2432.12 5878.7 7225.5 6588.05 15377.16 8017.19 3322.82 7104.18 16378.57 2822.26 6190.75 7833.87 18430.25 8210.6 14542.32 9131.63 5806.03 9067.46 4182.34 7920.62

Days after report from China 96 91 88 55 93 87 82 92 64 85 61 60 87 86 98 96 94 92 86 92 46 59 82 92 99 96 55 89 90 53 87 98 100 86 91 92 89 90 103 88

Human Diaspora and Pandemics Country Greece Costa Rica Kuwait Lithuania Moldova Slovenia Egypt Guatemala Armenia Honduras Paraguay Ethiopia Qatar Nigeria Oman Venezuela Libya Myanmar Bosnia and Herzegovina Bahrain Albania Algeria Kenya North Macedonia S. Korea Latvia China Ghana Kyrgyzstan Sri Lanka Zambia Montenegro Estonia Uzbekistan Norway Uruguay Finland Mozambique El Salvador Singapore Cuba Luxembourg Afghanistan

Total Cases 214661 207832 204388 203992 200124 198234 188361 180393 176286 175442 174013 169878 168829 159646 145257 143796 142671 142114 140990 128428 114840 114681 111185 109262 94198 92274 90018 86737 86692 86685 83913 82029 80929 80347 77601 66484 64609 63645 61814 60070 59157 57056 55901

No of Airports 46 29 2 5 2 3 26 20 2 35 14 53 3 22 10 65 18 41 4 3 1 36 38 2 28 3 191 5 2 22 21 3 5 12 59 13 30 42 1 3 10 1 26

Air distance from Wuhan 8021.16 15105.74 6288.62 7218.24 7253.54 8298.89 7762.63 14330.34 6253.52 14540.76 19026.49 8116.37 6114.1 11064.44 5511.16 15444.91 1918.13 2177.41 8138.47 6165.47 8160.79 9656.94 8882.76 13331.46 11121.51 7210.3 1057.09 11988.24 3751.27 4443.61 10499.65 8146.92 7092.01 4170.06 7802.34 19001.7 7059.66 10716.44 14488.7 3437.42 13783.97 8634.58 4214

59 Days after report from China 87 96 85 89 97 94 75 103 91 101 97 103 90 88 85 103 113 113 95 85 98 86 103 87 50 92 0 103 108 57 108 107 88 105 87 103 59 112 108 53 101 90 85

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Country Namibia Uganda Cyprus Cameroon Zimbabwe Senegal Ivory Coast Botswana Malawi Jamaica Sudan Thailand Malta Angola Maldives Madagascar Rwanda French Polynesia Mauritania Guinea Eswatini French Guiana Gabon Syria Cabo Verde Réunion Tajikistan Haiti Belize Burkina Faso Hong Kong Andorra Guadeloupe Lesotho Congo South Sudan Suriname Guyana Somalia Mali

Total Cases 40631 40520 38065 36794 36341 36195 36028 32912 32614 28968 28766 26598 25640 21161 21144 20155 19846 18509 17385 17208 17203 16693 16313 16187 15892 13801 13308 12594 12355 12230 11151 11130 10614 10525 9329 9205 8990 8928 8820 8710

No of Airports 29 12 7 22 13 14 34 16 11 7 25 47 3 38 5 62 5 46 22 11 2 6 42 7 3 2 2 6 19 27 2 1 10 17 25 25 12 30 21 12

Air distance from Wuhan 11913.03 9194.78 7356.24 11000.93 10383.48 12803.63 11915.98 11224.42 9913.84 14488.6 8358.08 2342.58 8853.51 11557.1 5179.38 9003.91 9563.78 11561.08 12427.19 12899.27 11079.93 15816.27 11399.75 7172.53 13234.06 8495.56 4214.72 14506.68 14152.91 11662.34 14540.76 9379.73 14818.5 11335.89 11108.94 9032.27 15814 15779.9 7883.28 12196.05

Days after report from China 104 110 99 96 110 92 101 120 123 100 103 43 97 109 97 110 104 101 104 103 104 94 103 112 110 101 151 109 113 100 52 92 103 164 104 126 103 101 106 115

Human Diaspora and Pandemics Country Bahamas Aruba Trinidad and Tobago Togo Martinique Nicaragua Benin Equatorial Guinea Djibouti Iceland CAR Curaçao Niger Gambia Gibraltar Chad Saint Lucia Sierra Leone Comoros Mongolia Barbados Guinea-Bissau Seychelles Eritrea Yemen Vietnam New Zealand Burundi Turks and Caicos Sint Maarten Monaco Liberia Sao Tome and Principe Papua New Guinea St. Vincent Grenadines Taiwan Antigua and Barbuda Bhutan Bermuda Mauritius Faeroe Islands Tanzania Cayman Islands

Total Cases 8642 8227 7743 7737 6928 6537 6501 6371 6227 6070 5023 4862 4848 4792 4259 4231 3941 3928 3611 3561 3353 3327 3032 2988 2627 2533 2416 2369 2190 2077 2062 2026 2010 1819 1674 978 882 868 731 664 660 509 460

No of Airports 41 1 3 2 1 9 6 2 5 38 24 1 7 1 1 19 2 11 5 19 1 3 6 4 26 33 62 3 7 1 1 16 3 27 2 22 2 1 2 2 1 29 3

Air distance from Wuhan 13706.37 15199.27 15407.36 11820.33 14965.87 14782.09 11670.9 11265.59 7556.96 8810.07 3259.98 15254.21 11269.58 12833.79 10284.94 10184.75 15030.6 12932.12 8912.26 2026.96 15112.57 12879.43 7362.75 7764.59 7261.45 1354.61 10117.21 9712.38 14198.45 14602 8910.12 12880.37 8118.36 5672.93 15109.74 945.48 14694.71 2416.48 13022.86 8281.37 8457.4 9269.63 14221.64

61 Days after report from China 105 103 102 96 95 108 106 104 108 89 104 103 109 107 93 109 103 121 151 100 107 115 104 111 131 53 89 121 89 106 127 110 91 57 109 51 103 96 108 108 94 106 103

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Country

Total Cases Brunei 192 British Virgin Islands 153 Dominica 151 Grenada 148 Wallis and Futuna 129 New Caledonia 74 Fiji 66 Falkland Islands 54 Macao 48 Laos 48 Saint Kitts and Nevis 41 Greenland 31 Saint Pierre Miquelon 24 Anguilla 18 Solomon Islands 18 Marshall Islands 4 Vanuatu 3 Samoa 3 Source: WHO and Prokerala, 2021.

No of Airports 1 6 2 2 2 15 32 2 1 24 2 33 2 1 41 35 32 5

Air distance from Wuhan 2858.68 14564.63 14891.81 15255.2 8881.81 8094.15 8737.5 17579.17 935.64 1831.75 14681.6 9404.81 11359.71 14581.79 6599.04 6470.4 7889.71 9310.65

Days after report from China 99 115 112 112 320 108 109 124 52 113 115 106 126 116 307 332 346 353

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https://www.bloombergquint.com/law-and-policy/covid-19-fear-andpanicbiggerproblem-than-coronavirus-says-sc-seeks-report-fromgovt-on-steps-takentoprevent-migration-of-workers. Rajan, S. I. (2020). “Migrants at a crossroads: COVID-19 and challenges to migration, Migration and Development, 9(3) 323-330, DOI: 10.1080/21632324.2020.1826201. https://doi.org/10.1080/21632324.2020.1826201. Read, J. M., Bridgen, J. R. E., Cummings, D A T., Ho, A. & Jewell, C. P. (2020). “Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions.” medRxiv 2020.01.23.20018549. https://doi.org/10.1101/2020.01.23.20018549. Sadanandan, R. (2020). “Kerala’s response to COVID-19.” Indian J Public Health. https://www.ijph.in/text. asp?2020/64/6/99/285594. Sahas, J. (2020). “Voices of the Invisible Citizens: A Rapid Assessment on the Impact of COVID-19 Lockdown on Internal Migrant Workers.” April, New Delhi. Sancheza, P S., Dortac, A.V. & Cugueró, N. (2020). “An early assessment of the impact of COVID-19 on air transport: Just another crisis or the end of aviation as we know it?” Journal of Transport Geography, 86:102749. https://doi.org/10.1016/j.jtrangeo. 2020. 102749. Shen, J. & Lin, L. (2020). “The different effects of the determinants of urbanisation on state‐sponsored and spontaneous urbanisation in Fujian Province of China.” Population space and place. https://doi.org/10.1002/psp.2364. Shereen, M. A., Khanan, S., Kazmi, A., Bashir, N. &Siddiquea, R. (2020). “COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses.” Journal of Advanced Research. 24, 91-98. https://doi.org/10.1016/j.jare.2020.03.005. Suzumura, T., Kanezashi, H., Dholakia, M., Ishii, E., Napagao, S. A., Pérez-Arnal, R., & Garcia-Gasulla, D. (2020). “The Impact of COVID-19 on Flight Networks.” arXiv preprint arXiv 2006.02950. Tan, B.Y.Q., Chew N.W.S., Lee G.K.H., Jing M., Goh Y., Yeo L.L.L. (2020). “Psychological impact of the COVID-19 pandemic on health

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Care Workers in Singapore.” Ann. Intern. Med. 173:317–320. doi: 10.7326/M20-1083. Tharoor, s. (2020). “Migrants are the unsung heroes of the pandemic.” https://www.washingtonpost.com/world/2020/04/03/migrants-areunsung-heroes-pandemic/. The Indian Express. (2020). “Coronavirus deepens struggles for migrant workers in Gulf countries.” 14th April 2020, Available at: https://indianexpress.com/article/coronavirus/coronavirus-deepensstruggles formigrants-in-persian-gulf-63616. Tian, X., Li, C., Huang, A., Xia, S., Lu, S., Shi, Z., Lu, L., Jiang, S., Yang, Z., Wu, Y. & Ying, T. (2020). “Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody.” bioRxiv. United Nations, Department of Economic and Social Affairs, Population Division (United Nations, 2019). Whitehouse, (2020). “Proclamation - suspension of entry as immigrants and nonimmigrants of certain additional persons who pose a risk of transmitting 2019 novel coronavirus.” https://www.whitehouse.gov/ presidential-actions/proclamation-suspension-entry-immigrantsnonimmigrantscertain-additional-persons-pose-risk-transmitting2019-novel-coronavirus./ WHO (2020). WHO Coronovirus Diseases (COVID-19) Dashboard. Retrieved June 23, 2020, from https://covid19.who.int/?gclid=CjwK CAjwxLH3BRApEiwAqX9arc_CvnQ4Jqcil3sjAHO1Iz1mQJLuox8h QdKT5FukPRtnr1hh8dXG2BoCYIoQAvD_ BwE. World Health Organization Coronavirus Disease 2019 Situation Report. https://www.who.int/docs/default-source/coronaviruse/situationreports/20200326-sitrep-66-covid-19.pdf?sfvrsn=9e5b8b48_2. World Health Organization Novel Coronavirus (2019-nCoV), Situation Report https://www.who.int/docs/default-source/coronaviruse/ situation-reports/20200121-sitrep-1-2019- ncov.pdf. World Health Organization. (2003). “Summary of probable SARS cases with onset of illness.” http://www.who.int/csr/sars/country/table 2004_04_21/en/index.html.

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World Health Organization. Coronavirus never before seen in humans is the cause of SARS– update 31. Geneva: The Organization; 2003. World Migration Report. (2020). “IOM World Migration Report.” International Organization for Migration. (490: 9789290687894. I: https://doi.org/10.18356/b1710e30-en. Yang. J., Zhenga, Y., Goua, X., Pu, K., Chena, Z., Guoa, Q., Ji, R., Wang, H., Wanga, Y., & Zhou, Y. (2020). “Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis.” International Journal of Infectious Diseases. 94. 91–95. https://doi.org/10.1016/j.ijid.2020. 03.017. Yuan, Z., Xiao, Y., Dai, Z., Huang, J. & Chen, Y. (2020). “A simple model to assess Wuhan lock-down effect and region efforts during COVID-19 epidemic in China Mainland.” medRxiv. https://doi.org/ 10.1101/2020. 02.29.20029561 Zacharias, M. & Roff, J. (2001). “Who Adds More Value to Marine Conservation Efforts?” Conservation Biology, 15(5), 1456-1458. http://www.jstor.org/stable/3061504.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 4

THE ROLE OF VACCINES IN PUBLIC HEALTH Ann Susan Mathew1, Shelmi Antony2, PhD and Jayesh Antony1,*, PhD 1

Department of Zoology, St. Thomas College, Palai, Kerala, India 2 Department of Zoology, Assumption College, Changanacherry, Kerala, India

ABSTRACT The development and usage of vaccines depend on the assessment of their benefits and risks, primarily by regulatory bodies as well as by physicians and patients. The immunization programs have helped to increase life expectancy, reduce parental fears of life-threatening childhood diseases, eradication of certain destructive epidemics from the community, and pecuniary savings by prevention of disabilities and diseases. Different types of vaccines are currently in use against various life-threatening diseases and those which have the potential of emerging in previously unaffected regions of the world. For certain globally infectious diseases like Yellow Fever, Japanese Encephalitis, Dengue, * Corresponding Author’s Email: [email protected].

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Ann Susan Mathew, Shelmi Antony and Jayesh Antony Influenza, Pneumonia, Rotaviral Gastroenteritis and Hepatitis B, effective human vaccines have already been developed, while for Gonorrhoea, Melioidosis and Tuberculosis (apart from the BCG vaccine) several effective vaccines are in development. Research advancements and most modern technologies are being applied in the development of several modern vaccines through the support of proteomics, genomics, comparative genomics, structural vaccinology, transcriptomics, mRNA based technologies and most recently vaccinomics. The rate of vaccine refusal or delay has been reported to increase in developed countries due to several reasons, leading to variation in vaccine coverage rates and reemergence of vaccinepreventable diseases. Use of combination vaccines increases vaccination rates, provide better coverage and timeliness of vaccination, improve the efficiency of healthcare practice, and reduce costs for the healthcare system. Veterinary vaccines are important for animal health and welfare, food production and public health by preventing animal diseases, reducing transmission of zoonotic and food borne infections to people and finally by enhancing the efficiency of food production. According to WHO, the pandemic COVID-19 is a serious threat to our health and well-being. Recently different countries have developed and are still developing several vaccines in order to combat this lifethreatening disease. Currently, while widespread vaccination is the only strategy that is effective in preventing the transmission of COVID-19, questions remain about the degree and duration of protection that will be offered from the COVID-19 vaccines. Recent studies report the emergence of an anti-vaccination culture among public and its spread through social media, which consequently may result in reduction of herd immunity and the spread of infectious diseases.

Keywords: vaccines, public health, modern vaccines, childhood vaccines, COVID-19, pandemic

INTRODUCTION National immunization programs along with scientific and pharmaceutical enterprises have developed vaccines which help human beings to get protection from various childhood diseases and several other life-threatening diseases. The development and usage of vaccines depend on the assessment of their benefits and risks, primarily by regulatory bodies as well as by physicians and patients (Jerry & Aaron

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2020). Several vaccines against smallpox, measles and polio have transformed public health, while others like malaria and HIV have failed to work. Rotaviral and 1976 influenza vaccine were later proved to have several unpredicted adverse effects. The immunization programs have helped in increasing life expectancy, reduce parental fears of lifethreatening childhood diseases, eradication of certain destructive epidemics from the community, and pecuniary savings by prevention of disabilities and diseases. Vaccine efficacy and safety assessed from phase III trials are the most important factors evaluated before approving licensure. Efficacy and effectiveness are different terminologies as far as vaccines are considered. ‘Efficacy’ is the real action of a formulation under controlled conditions, while ‘effectiveness’ refers to its performance in the epidemic affected individuals (Wilder-Smith et al., 2017). Possibly the most astonishing achievement in the history of vaccine development and immunization is the worldwide eradication of smallpox, the first human disease to be eradicated from the planet. Later vaccines were developed against a large number of universal childhood diseases including rubella, measles, whooping cough, mumps, diarrhea, chickenpox and rotavirus. Additionally, protective immunity was induced in children through immunization against several life-threatening diseases like diphtheria, poliomyelitis, or bacterial meningitis caused by Haemophilus influenza type b or Streptococcus pneumonia. Vaccines also protect the humankind from Human Papilloma Virus [HPV] related cancers, Hepatitis B and congenital rubella syndrome (Anne Schuchat 2011). A global health partnership known as Global Alliance for Vaccines and Immunization (GAVI) was created in 2000 to economically safeguard and speed up the delivery of new and improved vaccines to children in the poor countries. This alliance merges activities from UNICEF, World Health Organization, World Bank, Bill & Melinda Gates Foundation, vaccine industries from various countries, research and technical agencies, civil societies, and other private philanthropists (William Muraskin 2004).

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VALUE OF CHILDHOOD COMBINATION VACCINES Although more than 2 to 3 million deaths are prevented and about 750,000 children are saved from disability each year worldwide through vaccination against childhood diseases such as tetanus, pertussis, diphtheria, poliomyelitis, hepatitis B and bacterial meningitis, the rates of vaccine refusal or delay have been found to increase in developed countries which has led to disparity in vaccine coverage rates and reemergence of vaccine-preventable diseases (World Health Organization 2005). The multiple injections during each visit are one of the major reasons for this refusal rate which has resulted in disquiet among health care personals and parents. The administration of combination vaccines and multiple antigens in lower number of injections, increase vaccination rates, provide better coverage, improve the efficiency of healthcare practice, and reduce financial burden on the healthcare system. The first pediatric hexavalent vaccine, InfanrixHexa (Glaxo SmithKline) marketed in 2000, immunizes against hepatitis B, poliomyelitis, tetanus, acellular pertussis, diphtheria and Haemophilus influenzae type B antigens (European Medicines Agency 2010) followed by another vaccine by Hexyon in 2013 against the same diseases. A good immunogenic and safety profile of combination vaccines is attested through extensive evaluation of the clinical evidence on the safety and immunogenicity of these vaccines (Dhillon S 2010; Plotkin et al., 2011; Lyseng and Dhillon 2012; McCormack 2013). In addition, combination vaccines improve timeliness of vaccine administration, reduce hospital visits, decrease the cost burden of injection-related pain, reduce time spent by parents at the healthcare centers and ease charting time and inventory management for healthcare providers. Several studies have reported an improved coverage rate with the use of combination vaccines which is considered to be an effective evaluation strategy of an immunization program. The major challenges of developing combination vaccines include physical incompatibility of different antigens and compatibility of antigens with pH, the types of adjuvants, tonicity of the formulation,

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buffers and preservatives (Van Hoof 2001). Other challenges include demonstration of equal performance between each combination vaccine and its individual monovalent components and economic disadvantage for physician practices (Khaled et al., 2015).

IMPORTANCE OF VETERINARY VACCINES TO ANIMAL HEALTH AND PUBLIC HEALTH Veterinary vaccines are important for public and animal health as well as in food production by preventing animal disease and reducing the transmission of zoonotic and food-borne infections to humans. A successful animal vaccine in the history of veterinary vaccines is the rabies vaccine, without which people would hesitate to keep a pet in their houses. The use of Rabies vaccines for wild and domestic animals has mostly extinguished human rabies in developed countries (James 2011).

TYPES OF VACCINES Vaccine development and its use have become one of the major achievements in the field of medicine. There are many approaches to vaccine development and the different types of vaccines currently in use include Live attenuated vaccines, Conjugate vaccines, DNA vaccines, Subunit vaccines, Inactivated vaccines, Recombinant vector vaccines and Toxoid vaccines. Some effective vaccination strategies against certain globally infectious diseases are listed in Table 1.

FLAVIVIRUS VACCINES Flaviviruses are Arthropod-borne viruses which have been associated with human diseases of major public health concern like Dengue fever,

Rotatrix BCG (Bacillus Calmette-Guerin) vaccine Recombivax HB

Rotavirus

Tuberculosis

Hepatitis B

Prevenar7 Prevenar13 RotaTeq

Recombinant vaccine

Live attenuated Split virion, inactivated vaccine Quadrivalent, inactivated vaccine Unconjugated polysaccharide vaccine Conjugate vaccine Conjugate vaccine Pentavalent, attenuated vaccine Monovalent, live attenuated vaccine Live attenuated

Dengvaxia Quadrivalent influenza vaccine (QIV) Fluarix Tetra

Pneumonia Pneumonia Rotavirus

Inactivated vaccine

SA 14-14-2

Pneumovax23

Live attenuated vaccine Chimeric live vaccine

Vaccine type

Vaccine Candidate/ trade name YFV 17D IMOJEV

Pneumonia

Influenza

Disease/ Pathogen Yellow fever Japanese encephalitis Japanese encephalitis Dengue Influenza

Merck

Albert Calmette & Camille Guerin

GlaxoSmithKline

Pfizer Pfizer Merck

Merck

GlaxoSmithKline

Sanofi Pasteur Sanofi Pasteur

Intercell

Developer/ supplier Max Theiler Sanofi Pasteur

From 6 months and above

Within 24 hours after birth

8 weeks and above

2 years and older 2 years and older From 6-12 weeks

2 years and older

From 6 months

9 years and older From 6 months

17 years and older

From 6-8 months From 9 months

Age indications

Completed

Completed

Completed

Completed Completed Completed

Completed

Completed

Completed Completed

Completed

Clinical trial status Completed Completed

Beran 2008

Principi and Esposito 2015

Nuorti and Whitney 2010 Paradiso 2011 Paradiso 2011 Ruiz-Palacios et al., 2006 Vesikari et al., 2007

Dos et al., 2019

Hadingero et al., 2015 Mathieu et al., 2016

Tauber et al., 2007

Monath et al., 2008 Guy et al., 2010

Reference

Table1. Details of different types of vaccines developed by various manufacturers against the major global life-threatening diseases

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Yellow fever, Japanese encephalitis and tick-borne encephalitis. Zika virus, the most recent explosive epidemic agent also belongs to the flaviviridae family. The epidemic capability of Flavivirus can be related to numerous factors like the characteristics of the arthropod vectors, the creation of ideal vector breeding habitats due to improperly planned urbanization, changes in environmental conditions, the worldwide spreading out of vectors and increased global travel (Pierson and Diamond 2020). Flaviviruses are enveloped, positive stranded RNA virus and they contain three main structural proteins; Capsid (C), Envelope (E), and Membrane protein (M).The Envelope protein or E protein is a threedomain structure which facilitates virus entry and multiplication in host cells. The virus neutralizing antibodies usually target the E protein and thus help prevent infection (Pierson et al., 2008). Developed by Max Theiler in 1937, YFV 17D is the most successful live-attenuated viral vaccine in the history of viral vaccines. The vaccine has a great record of protecting over 98% of the vaccines from yellow fever for at least 10 years (Gardner and Ryman 2010). Despite this, some severe vaccine associated adverse effects have been reported. SA14-14-2 is an extensively used effective vaccine for Japanese encephalitis virus in Asia and India (Halstead and Jacobson 2008). Another Chimeric live attenuated vaccine (IMOJEV, formerly known as CHIMERIVAX-JE) containing the prM and E protein, was developed by Sanofi Pasteur (France) for Japanese encephalitis virus. Administration of this vaccine has led to increased immunogenicity in the vaccines without safety concerns (Guy 2010).

DENGUE VIRUS VACCINES The dengue serocomplex is composed of 4 serotypes. Infection by any one of these serotypes immunizes against homotypic re-infection. But with a secondary heterotypic infection, it only provides a transient protection. Moreover, according to epidemiological observations a heterotypic re-infection can be associated with an elevated risk of severe

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disease (Guzman et al., 2010). Hence the major obstacle in the design and development of a vaccine is that an incomplete protective immunity against all virus serotypes might elevate the risk of severe disease in a subsequent natural infection. As a result, the aim is to develop a vaccine that can elicit a neutralizing response against all the viral serotypes and possess an excellent profile of tolerability. The tetravalent Dengvaxia from Sanofi Pastuer was the first live attenuated vaccine licensed against dengue virus in 2016. It was approved for use by FDA in 2019 but recommended for use only in individuals between 9-16 years of age who had prior dengue infection and are living in endemic areas (Hadinegoro et al., 2015).

GONORRHOEA AND GONOCOCCAL VACCINES The sexual and reproductive health of people are severely affected by sexually transmitted infections like gonorrhoea world-wide (Unemo et al., 2019). The bacterium, Neisseria gonorrhoeae (the gonococcus), is the causative agent of this infection (Rowley et al., 2019). As no gonococcal vaccine is available, the control and prevention of the disease depend majorly on the promotion of safe sexual behaviors and timely diagnosis and treatment. The World Health Organization targets to bring down 90% of gonorrhoea incidence by 2030 and WHO’s strategy includes the development of a gonococcal vaccine that might help to fight antimicrobial resistance [AMR] and is biologically feasible (World Health Organization 2016). Certain key populations are at higher risk of being affected including men who have sex with men (MSM), young people, migrants and sex workers (Kirkcaldy et al., 2019). Another public health concern related to Gonorrhoea is the development of high levels of AMR (antimicrobial resistance). N. gonorrhoeae has acquired or developed AMR to numerous antibiotics through different mechanisms. This offers high risk to the public health since the pathogen is manifesting high resistance to all recommended antimicrobials including Cephalosporin, Azithromycin and Ceftriaxone.

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The tremendous increase in global gonorrhoea cases and the associated risk of antimicrobial resistance points out the fact that the existing treatments are insufficient for controlling gonorrhoea and the immediate need to develop a biologically feasible vaccine. Natural infection with N. gonorrhoeae does not immunize an individual towards subsequent re-infections even with the same strain. Recently there has been a decline in the number of gonorrhoea cases in many countries after the administration with a Meningococcal group B outer membrane vesicle (OMV) vaccine (marketed under the trade name MeNZB) against N. meningitidis, a close relative of N. gonorrhoeae (Petousis-Harris et al., 2017). Another licensed vaccine 4CMenB (trade name BE XSERO; Glaxo SmithKline), a four-component meningococcal serogroup B vaccine was found to recognize gonococcal antigens and was found to successfully eliminate N. gonorrhoeae infection from mouse model. Meningococcal OMV Vaccines, Gonococcal OMV vaccines, a lipopolysaccharide epitope vaccine, and protein subunit vaccines are some of the promising vaccine candidates under evaluation. The increasing awareness related to gonococcal AMR and the recent increase in the number of gonorrhoea and syphilis cases in certain countries have led to the urgent need of development of an effective gonococcal vaccine (Workowski and Bolan 2015).

INFLUENZA VACCINE Influenza is a fast-spreading respiratory tract infection caused by the highly infectious influenza viruses. Influenza often occurs as global outbreaks, especially during the winter season and is the cause of increased number of deaths among high-risk populations like elderly people, pregnant women, children, people affected by some other underlying disease conditions and health care providers (Uhart et al., 2016). Twentieth century witnessed three influenza pandemics: the 1918 Spanish flu (H1N1 Pandemic), the 1957 H2N2 pandemic and the 1968

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H3N2 Pandemic. They usually affect the upper respiratory tract. The epidemic nature of influenza is due to its continuous antigenic changes (Mohsen 2017). The influenza virus is a single-stranded RNA virus which bears 2 major surface glycoproteins: Hemagglutinin and Neuraminidase. The very large number of these glycoprotein subtypes is a major reason for its persistent antigenic variations (Palese 2004). Several types of influenza vaccines are available, like live-attenuated vaccines and inactivated vaccines having different strains of the virus. The strains have to be frequently changed because of the continuous antigenic drifts. The recent vaccines contain three (TIV-Trivalent influenza vaccine) or four (QIV-Quadrivalent influenza vaccine) strains. The most commonly used trivalent vaccine consists of 2 influenza A strains (H1N1 and H3N2) and one lineage of Influenza B virus (Yamagata or Victoria). The different lineages of influenza B co-circulate or differ in circulation according to changes in season. In some seasons either one of the lineages predominate the other. Hence, when a vaccine mismatch occurs, the response against the heterotypic B virus is tremendously reduced, which leads to a reduction in the benefits of the vaccine and can lead to more deaths and hospitalizations than expected (Silva et al., 2014). As a result, Quadrivalent influenza vaccines that include an additional influenza B strain, have been developed for reducing the mismatch of vaccine and would help to prevent the uncertainty of the B strain in circulation and would thus help in the control of infections caused by influenza B. QIV usage has significantly reduced the viral infection and hospitalizations (Reed et al., 2012).

MELIOIDOSIS BIODEFENSE VACCINE The gram-negative bacterium Burkholderia pseudomallei causes Melioidosis, an emerging infectious disease which is highly endemic in 48 countries and an additional 34 countries where it is not reported previously (Wiersinga et al., 2018). Additionally, B. psuedomalleig is regarded as a prospective biological weapon (Rotz et al., 2002). In case

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of a deliberate or intentional release, the most likely mode of dispersal would be via infectious respiratory aerosols. Since the pathogen is tolerant to most of the commonly used antibiotics, the treatment can be difficult. The most effective method to tackle this problem is to develop a vaccine that can help to prevent the global incidence of Melioidosis (Currie 2015). Countries like Thailand and Australia consider the use of Biodefense vaccines, as they have been estimated to have more incidence of the endemic Melioidosis infections (Limmathurotsakul and Peacock 2011). Melioidosis infections are more common among people with diabetes mellitus, kidney failure or chronic lung disease (Limmathurotsakul et al., 2010). A vaccine which provides a lifelong protection against the pathogen and its diverse strains is considered to be an ideal vaccine. A wide range of vaccine candidates are being examined like live attenuated vaccines (Atkins et al., 2002), inactivated whole cell vaccines (Peacock et al., 2012), subunit vaccines (Rezaei et al., 2010), plasmid DNA vaccine (Liu 2006) and Dendritic cell vaccine.

PNEUMOCOCCAL VACCINES Streptococcus pneumoniae (Pneumococcus) is a gram- positive bacterium that can cause major global public health problems. Pneumococcal infections can occur in all populations, but it is more common in elderly people, younger children and people with asthma or COPD etc. Pneumococcus also can cause mucosal diseases as well as invasive pneumococcal diseases (IPD) (Pittet and Posfay-Barbe 2012). A polysaccharide vaccine and a conjugate vaccine are being currently used against Pneumococcus. PNEUMOVAX 23 is a polyvalent polysaccharide pneumococcal vaccine which can prevent 23 serotypes of the bacterium. The vaccine provides protective immunization against pneumococcal infections through B-cell response. It is approved for use in persons who are at an increased risk for pneumococcal infections or have other

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underlying medical conditions like immunosuppression, chronic lung, heart or liver diseases, etc. (Nuorti et al., 2010). The pneumococcal polysaccharide vaccine elicits only weak immune response in children above 2 years of age. Hence conjugated pneumococcal vaccines (PCV) were developed. The conjugated vaccine was developed by Pfizer in 2000 under the trade name Prevenar 7 (PCV 7). It contains a carrier protein conjugated with polysaccharides from 7 serotypes and is capable of inducing both T-cell and B-cell responses. But there has been a prevalence of serotypes that were not included in this vaccine which is known as serotype replacement (Isaacman et al., 2010). In 2010, Pfizer developed an extended version of PCV 7 called Prevenar 13 (PCV 13) with most of the emerging serotypes causing IPD in developing countries (Gessner et al., 2010). The vaccination of young children was found to induce a parallel reduction in pneumococcal infections in their unvaccinated siblings (children below the age of 2) and when infected or acquired, the pathogen clearance also occurred at a faster rate in the unvaccinated siblings (Givon-Lavi et al., 2003). In conclusion, pneumococcal diseases still remain a global public health concern, especially in young children. Development of vaccines has tremendously helped in bringing down the IPD cases globally. Hence vaccine availability and proper immunization, particularly of children should be given priority.

ROTAVIRUS VACCINES Rotaviral gastroenteritis is a global public health problem affecting almost all children below the age of 5. It is the major cause of hospitalizations among children. The manifestations of the disease include severe diarrhoea, vomiting and fever (Bernstein 2009). Two rotavirus vaccines, RotaTeq developed by Merck and Rotarix by Glaxo SmithKline Biologicals have been included in routine immunization programmes and have been approved to use in many countries. In addition to their high efficacy, both the vaccines were also successful in

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reducing the rate of hospitalizations by 42% in many countries across the globe (Vesikari et al., 2007). Another indirect benefit of vaccinating a proportion of the population is that it helps to decrease the risk of disease among unvaccinated individuals who belong to the same community. Rotatrix, a monovalent P (subtype) G1 vaccine was found to provide cross-protection against some commonly circulating strains (G1, G3, G4, and G9) with an efficacy ranging between 82-96%. On the other hand Rotatrix was found to be less effective against infections caused by G2 strain of the virus. According to scientific reports and certain safety trials, the RotaTeq vaccine was found to be highly effective against G1-G4 and G9 serotypes (Vesikari et al., 2006).

TUBERCULOSIS VACCINE Tuberculosis (TB) is a contagious infection, which is one of the leading causes of death from a curable infectious disease. It is caused by the bacterium Mycobacterium tuberculosis which most frequently affects the lungs. Every year approximately 8 million people are getting affected by TB and almost 2 million deaths occur globally (World Health Organization 2002). Despite all the research works on vaccine development, the Mycobacterium bovis Bacillus Calmette-Gurein (BCG) Vaccine remains the only licensed TB vaccine available. BCG is usually administered as a neonatal vaccine and it is found to elicit only weak immune responses in adults (Colditz et al., 1994). Thus, the development of an effective TB vaccine has become a global public health priority. The vaccine candidates under development and clinical evaluation include naked DNA vaccines, subunit vaccines and live attenuated vaccines. Most of the vaccines are under pre-clinical trials. There are 2 categories of TB vaccines under trial: Pre exposure and post exposure vaccines (Lietman and Blower SM 2000). Several years after the development of the BCG Vaccine, there is a ray of hope as huge number of prospective vaccine candidates are in the final stages of clinical trials. All these will hopefully lead to a new era in TB vaccine development and

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help in effectively reducing the disease incidence and the mortality rates globally.

HEPATITIS VACCINE Hepatitis B virus or HBV is a virus having worldwide distribution that is capable of causing a potentially life-threatening liver infection, leading to death mainly from liver cirrhosis and hepatocellular carcinoma (HCC). The only reservoir of HBV is Humans. It is commonly transmitted during childbirth from mother to child as well as through various body fluids, mainly semen and vaginal fluid (Goldstein et al., 2005). There is no specific treatment for HBV. Administration of Hepatitis B vaccine is the only effective preventive measure against the virus. In 1986 the plasma-derived vaccine was replaced with recombinant hepatitis B vaccines. HBsAg is an active component of hepatitis B recombinant vaccine. Monovalent formulations of the vaccine are available and also fixed combinations with other vaccines like DTP, Haemophilus influenza type B, hepatitis A and Polio are also available (Beran 2008). The WHO recommends that all infants receive the monovalent vaccine soon after birth, while to complete the course two or three doses should be administered at least 4 weeks apart. The timely birth dose helps to prevent mother-to-child transmission. The vaccine has been found to have high protective efficacy and there has been a drastic drop in the number of children chronically infected with HBV when compared to the pre-vaccine era. Individuals with allergic reactions were found to have severe adverse effects while receiving the hepatitis B vaccine. The vaccine is safe for pre-mature infants, HIV-positive individuals and pregnant women (Cornejo-Juárez et al., 2006).

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MODERN VACCINES Vaccines are an efficient prophylactic strategy which is used for protecting against various life-threatening infectious diseases and in increasing the life expectancy of humans. To be introduced and approved, a vaccine must obviously be effective and the efficacy is reviewed from time to time. Research advancements and most modern Table 2. Vaccines developed using various modern technologies Pathogen

Clinical manifestations Dengue fever

Modern technology used in vaccine research Genomics, Proteomics

West Nile fever, encephalitis, meningitis Pneumonia, middle ear infections, and meningitis

Proteomics

Mycobacterium tuberculosis

tuberculosis

Comparative genomics, proteomics, transcriptomics (DNA microarray)

Influenza A virus

Fever, nasal congestion, fatigue Gastrointestinal bleeding, bloating, nausea Fever, maculopapular rash, conjunctivitis Fever, fatigue

Structural vaccinology

Dengue virus

West Nile virus

Streptococcus pneumonia

Hepatitis C virus Zika virus

Influenza virus

Reverse vaccinology, functional genomics, proteomics, transcriptomics (DNA microarray)

Status of Reference vaccine Discovery Kanlaya et al., 2009 studies and Sanchez-Burgos et al., 2010 Discovery Pastorino et al., 2009 studies and Tan et al., 2010 Preclinical studies/ Discovery studies

Giefing et al.,2008; Hiller et al., 2007; Morsczeck et al., 2008; Song et al., 2008a; Wizemann et al., 2001 and Song et al., 2008b Preclinical Cockle et al., 2002; studies/ Giri et al., 2010; Discovery Kato-Maeda et al., studies 2001; Stewart et al., 2002 Preclinical Laursen et al., 2018 studies

Structural vaccinology

Discovery Ishtiaq and LaaPoh studies 2019

mRNA-Lipid nanoparticle based technology

Preclinical Pardi et al., 2017 studies

Self-amplified mRNA & nonreplicating mRNA technology

Clinical trials

Brazzoli et al., 2016

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techniques have led to newer strategies for effective vaccine development (Table 2). These advancements in vaccine development can be attributed to several factors like; 1) the lack of effective treatment for some globally destructive infectious diseases 2) prevalence of multiple drug resistance in microorganisms and 3) enhancing the safety of conventional vaccines. Different modern techniques are being used in vaccine development like:

RNA-BASED TECHNOLOGIES Nucleic Acid vaccine development is found to be safer and time saving, since it is done without the growth of highly infectious pathogenic microorganisms. They are found to be more effective in curbing rapidly spreading infectious diseases when compared to the live attenuated and inactivated vaccines. Although DNA vaccines are a promising candidate for modern vaccine development, they are not found to have enough potency in early clinical trials. When compared to DNA and viral vectored vaccines, the mRNA Vaccine was found to be more advantageous (Cuiling et al., 2019).

GENOMICS-BASED ANTIGEN SELECTION Vaccinomics is the application of genomics and bioinformatics to vaccine development. There has been an incredible growth in genome sequencing information, after completion of the first genome sequencing (in Haemophilus influenzae). Genomics has immensely contributed to modern biology by providing access to entire genetic information, increasing our knowledge of gene networks, gene sequencing and revealing genomic diversity. Computational biology helps to reduce various experimental techniques and facilitate protein analyses. Genomics data have made the identification and selection of antigens more convenient without the need to cultivate pathogens using biochemical techniques (Fraser et al., 2000).

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STRUCTURAL VACCINOLOGY It is a modern approach in vaccine development which involves the determination of the structure of antigen-antibody complex, remodeling of the epitope or antigen and then incorporating it into an effective and safe vaccine (Ishtiaq and LaaPoh 2019).

PROTEOMICS BASED ANTIGEN SELECTION APPROACHES Proteomics investigates the protein expression profile in living cells, which is highly crucial for vaccine research. New proteomics techniques are able to differentiate between surface and cytoplasmic proteins. Since surface antigens are more accessible to the immune system, the data produced by these techniques are crucial in the selection of a suitable vaccine candidate (Cullen et al., 2005). Mass spectroscopy of the surface digested proteins of bacteria helps to identify the ‘surfome’ or surface proteins. Secreted proteins (Secretome) are also viable vaccine candidates in addition to surface exposed antigens (Ravipaty and Reilly 2010).

TRANSCRIPTOMICS It deals with the study of transcriptosomes, the complete set of RNA transcripts produced in a specific cell or under specific circumstances, through methods such as DNA microarray analysis. The genes expressed upon infection or in response to particular virulence factors or antigens are identified and used for the process of vaccine selection and thus aid in vaccine development (El-Etr et al., 2004). New emerging viruses have made it necessary to develop vaccines using modern techniques that might be more effective in preventing the spread of diseases and also improving the efficacy of traditional vaccine which are currently in use. New technologies and better understanding of the immune system and

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immune responses have led to a new era in the field of vaccine development and immunization.

COVID-19 VACCINES COVID-19, a pandemic caused by corona virus SARS-CoV-2 is a life- threatening disease. The World Health Organization declared its outbreak on March 11th, 2020, and suggested all nations worldwide to take “urgent and aggressive” action (World health organization 2020). All the affected countries took extensive measures to curb the spread of the disease and treated the pandemic as a global health crisis (Dryhurst et al., 2020) (Faasse and Newby 2020) (Kwok et al., 2020) (Park et al., 2020) (Wise et al., 2020) (Linda et al., 2021). Recently different countries have developed several vaccines in order to combat this threatening disease (Table 3). There are only three FDA approved vaccines currently available, under Emergency Use Authorization. They are Pfizer-BioNTech [mRNA], Moderna [mRNA] and Johnsen & Johnsen’s Janssen [Viral vector]. Covaxin, manufactured by Bharat Biotech and Covishield manufactured by Serum Institute of India are the two vaccines approved in India to be used for covid 19 vaccination, both of which successfully completed phase 2/3 clinical trials. Besides these, there are a couple of vaccines in India which are under different phases of the clinical trials. They include ZyCov-Di, being developed by ZydusCadila company; HGCO19, India's first mRNA vaccine made by Genova and HDT Biotech Corporation; another nasal vaccine by Bharat BioTech; the Sputnik V vaccine candidate by Dr Reddy's Lab and Gamaleya National Centre in Russia and a second vaccine being developed by Serum Institute of India and Novavax, an American vaccine development company (Centers for disease control and prevention 2021;World health organization 2021 and BBC 2021).

Bharat Biotech Serum Institute of India

Covaxin

Covishield [OxfordAstraZeneca vaccine]

AZD1222

BNT162b2

Janssen Pharmaceuticals Viral vector Companies of Johnson & Johnson Pfizer, Inc., and mRNA BioNTech AstraZeneca plc Viral vector

JNJ-78436735

weakened version of adenovirus from chimpanzees, modified to look like coronavirus

killed coronaviruses

mRNA

Moderna TX, Inc.

mRNA-1273

Type of Vaccine

Manufacturer

Name

Vaccine administration site/route Shot in the muscle of the upper arm Shot in the muscle of the upper arm

Shot in the muscle of the upper arm Two doses given with Intramuscular an interval of 8 to 12 weeks. two doses are given Shot in the muscle of four weeks apart the upper arm two doses given Shot in the muscle of between four and 12 the upper arm weeks apart

2 shots, 21 days apart

2 shots, one month (28 days) apart 1 shot

No. of shots

Not Approved

Not Approved

Approved

Approved

Approved

FDA approval status Approved

Covishield

Covaxin

Oxford/AstraZeneca

Pfizer-BioNTech

Johnson & Johnson’s Janssen

Name used in community Moderna

Table 3. Different vaccines developed in USA and India against the novel corona virus, SARS-CoV-2, which causes the pandemic COVID-19

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A vaccination program will be successful only when the public accepts vaccines. A key determinant in vaccine acceptance is the risk associated with the disease against which the vaccine is developed (Betsch et al., 2018) (Thomson et al., 2016). Recent studies have proved that majority of the people would accept the vaccine (Detoc et al., 2021) (Dodd et al., 2020) (Freeman et al., 2020) (Malik et al., 2020) (NeumannBohme et al., 2020) while according to about 25% reports, they would not (The COCONEL Group 2020). Since vaccines against COVID-19 are still in the early developmental stages or under clinical evaluation, information about the safety of the vaccines is limited. Currently, while widespread vaccination is the only strategy that is effective in preventing the transmission of COVID-19, questions remain about the degree and duration of protection that will be offered from the COVID-19 vaccines (Altmann et al., 2020; Elise et al., 2021).

ANTI-VACCINATION ATTITUDE AMONG PUBLIC A very clear example of anti-vaccination attitude was the reemergence of the highly contagious respiratory disease, Measles in US in 2014, which was believed to be eradicated from the country in 2000. 90% of these cases were reported in unvaccinated people or those with unknown vaccination status. The reasons for the rebound are the concerns about vaccine side effects as well as the emergence of an anti-vaccination culture (Anna 2010). It was also found that a relentless vaccine criticism movement has been spread through social media rapidly (Jennifer et al., 2020). Another study proved that those parents opting to exempt their children from vaccination and benefited from herd immunity have most probably received the information from various online platforms (Daniel et al., 2005; Tanushree et al., 2016). Studies have shown that majority of the sexually active men and women are exposed to HPV during some stages of their life (Weaver 2006). HPV infection is the major cause of cervical cancer and the associated widespread deaths worldwide. So, vaccination of young girls against one or several papillomaviruses (HPV)

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is recommended to prevent cervical cancer, vaginal cancer, etc (Barthès et al., 2020). Lack of knowledge or misbeliefs among young girls were found to be the major reason for insufficient vaccination coverage in many countries. In France HPV vaccination coverage has never exceeded 30% (Barthès et al., 2020), while in other countries such as the United Kingdom, Australia, or Portugal the vaccination coverage rates ware above 80% (Barthès et al., 2020). The increase in vaccine hesitancy leads to decreased vaccination coverage in several countries. Studies conducted in pregnant women toward pediatric vaccinations reveal their anxiety and misconceptions towards vaccine efficiency and safety, which further reduce their faith in immunization. This concern about vaccine safety has led many people to seek alternate vaccination programs, or decide to delay or even decline vaccination, all of which consequently result in reduction of herd immunity and the spread of infectious diseases (Larson et al., 2016; Raude et al., 2016; Phadke et al., 2016; Annalisa et al., 2020).

CONCLUSION Vaccination has been an effective strategy in protecting the human race from many life-threatening diseases like Polio, Smallpox, Pertussis, etc. An effective vaccine is the result of a series of sophisticated and careful scientific processes that ensure the quality of each shot administered. Pandemics like influenza, COVID-19, etc. have swept through human population and caused millions of deaths worldwide. They pose a challenge to vaccine development as vaccine production and widespread supply demand time. And also, with the emergence of new strains, new vaccines have to be developed. The science of vaccinology together with the tools of public health would help to better combat infections and prevent the spread of diseases.

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ACKNOWLEDGMENTS We thank Gibin Raja George, Assistant Professor in English, St. Thomas College, Palai for his technical help in the preparation of the manuscript.

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Reed C., Meltzer M. I., Finelli L., Fiore A. 2012. “Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine.” Vaccine 30:1993-8. Rezaei N., Siadat S. D., Aghamohammadi A., Moin M., Pourpak Z. 2010. “Serum bactericidal antibody response 1 year after meningococcal polysaccharide Vaccination of patients with common variable immunodeficiency.” Clin Vaccine Immunol 17: 524–530. Rotz L. D., Khan A. S., Lillibridge S. R., Ostroff S. M., Hughes J. M. 202. “Public health assessment of potential biological terrorism agents.” Emerg Infect Dis 8:225-230. Rowley J., Vander Hoorn S., Korenromp E., Low N., Unemo M., AbuRaddad L. J., et al. 2019 “Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016.” Bull World Health Organ 97(8):548–62. Ruiz-Palacios G. M., Perez-Schael I., Velazquez F. R. 2006. “Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis” Engl J Med 354:11–22. Salmon, Daniel A., Lawrence H. Moulton, Saad B. Omer, M. Patricia deHart, Shannon Stokley, and Neal A. Halsey. 2005 “Factors Associated with Refusal of Childhood Vaccines among Parents of School-Aged Children: A Case-Control Study.” Archives of Pediatrics & Adolescent Medicine 159 (5): 470–76. Sanchez-Burgos, G., Ramos-Castañeda, J., Cedillo-Rivera, R., and Dumonteil, E. 2010 “Immunogenicity of novel Dengue virus epitopes identified by bioinformatic analysis.” Virus Res 153:113–120. Schuchat, Anne. 2011 “Human vaccines and their importance to public health.” Procedia in Vaccinology 5: 120–126. Silva M. L., Perrier L., Spath H. M., Grog I., Mosnier A., Havet N., Cohen JM. 2014 “Economic burden of seasonal influenza B in France during winter 2010-2011” BMC Public Health 14:56. Song, X. M., Connor, W., Hokamp, K., Babiuk, L. A., and Potter, A. A. 2008 “Streptococcus pneumonia early response genes to human lung epithelial cells.” BMC Res Notes 1, 64.

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Song, X. M., Connor, W., Jalal, S., Hokamp, K., and Potter, A. A. 2008 “Microarray analysis of Streptococcus pneumonia gene expression changes to human lung epithelial cells.” Can J Microbiol 54: 189– 200. Stewart, G. R., Wernisch, L., Stabler, R., Mangan, J. A., Hinds, J., Laing, K. G. 2002. “Dissection of the heat-shock response in Mycobacterium tuberculosis using mutants and microarrays.” Microbiology 148:3129–3138. Tan, P. L., Jacobson, R. M., Poland, G. A., Jacobsen, S. J., and Pankratz, V. S. 2001 “Twin studies of immunogenicity-determining the genetic contribution to vaccine failure.” Vaccine 19:2434–2439. TanushreeMitra, Scott Counts, James W. Pennebaker. 2016 “Understanding Anti-Vaccination Attitudes in Social Media. Proceedings of the Tenth International AAAI Conference on Web and Social Media (ICWSM 2016). 269-278. Tauber E., Kollaritsch H., Korinek M., Rendi-Wagner P., Jilma B, Firbas C. 2007. “Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese Encephalitis vaccine: a non-inferiority, phase III, randomized controlled trial.” Lancet 370(9602):1847–53. The COCONEL Group. 2020. “A future vaccination campaign against COVID-19 at risk of vaccine hesitancy and politicization.” The Lancet Infectious Diseases, 20(7):769–770.https://doi.org/10.1016/ S1473-3099(20)30426-6. Thomson, A., Robinson, K., & Vallée-Tourangeau, G. 2016. “The 5As: A practical taxonomy for the determinants of vaccine uptake.” Vaccine, 34(8):1018–1024 https://doi.org/10.1016/j.vaccine.2015. 11.065. Unemo M., Lahra M. M., Cole M., Galarza P., Ndowa F., Martin I., et al. 2019 “World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts.” Sex Health https://doi.org/10.1071/SH19023. Van Hoof J. 2001 “Manufacturing issues related to combining different antigens: an industry perspective.” Clin Infect Dis 33:S346-S350.

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Vesikari T., Karvonen A., Prymula R. 2007 “Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study.” Lancet 370:1757–63. Vesikari T., Matson D. O., Dennehy P. 2006. “Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.” N Engl J Med 354:23–33. Weaver B. A. 2006. “Epidemiology and natural history of genital human papillomavirus infection.” J Am Osteopath Assoc 106:2–8. WHO 2020 “WHO Director-General’s opening remarks at the media briefing on COVID-19” last modified on 11 march 2020 https://www. who.int/dg/speeches/detail/who-director-general-s-opening-remarksat-the-media-briefing-on-covid-19—11-march-2020. Wiersinga, W., Virk, H., Torres, A. 2018. “Melioidosis” Nat Rev Dis Primers 4: 171-07. Wilder-Smith, A., I. Longini, P. L. Zuber, T. Bärnighausen, W. J. Edmunds, N. Dean, V. Masserey Spicher, M. R. Benissa and B. D. Gessner. 2017 “The public health value of vaccines beyond efficacy: methods, measures and outcomes.” BMC Medicine 15:138, 1-9. William Muraskin. 2004 “The Global Alliance for Vaccines and Immunization: Is It a New Model for Effective Public–Private Cooperation in International Public Health?” American Journal of Public Health. 94:1922-1927. Wise, T., Zbozinek, T. D., Michelini, G., Hagan, C. C., & Mobbs, D.2020. “Changes in risk perception and self-reported protective behavior during the first week of the COVID-19 pandemic in the United States.” Royal Society Open Science, 7 https://doi. org/10.1098/rsos.200742. Wizemann, T. M., Heinrichs, J. H., Adamou, J. E., Erwin, A. L., Kunsch, C., Choi, G. H. 2001. “Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumonia infection.” Infect Immun 69:1593–1598.

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Workowski K. A. & Bolan G. A. 2015. “Centres for disease control and prevention. Sexually transmitted diseases treatment guidelines.” MMWR. 64:1-137. World Health Organization. 2016. “Global health sector strategy on sexually Transmitted infections.” last modified July 2016. https:// www.who.int/reproductivehealth/publications/rtis/ghss-stis/ en/. World Health Organization. 2021 “Coronavirus disease (COVID-19): Vaccines” Last modified on (19 February 2021). https://www.who. int/news-room/q-a-detail/coronavirus-disease(covid19)vaccines?ad groupsurvey={adgroup survey}&gclid= EAIaIQobChMI97jemIyq7w IVkYNLBR0lMwMUEAAYASAAEgJOWvD_BwE. World Health Organization. WHO Report 2002: global tuberculosis control. Surveillance, planning, financing. Geneva: The Organization; (2002). World Health Organization.2005. “Global Immunization Vision and Strategy” last modified: May 2005 http://whqlibdoc.who. int/hq/ 2005/WHO_IVB_ 05.05.pdf. 2005.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 5

A REVIEW ON COVID-19 VACCINES Lakshmi Bhaskaran*, PhD Department of Microbiology and Biotechnology, Sree Maneklal. M. Patel Institute of Sciences and Research, Gandhinagar, Gujarat, India

ABSTRACT COVID-19 is caused by SARS-COV-2 RNA viruses. Vaccines to prevent the COVID-19 are perhaps the best hope for ending the pandemic. Scientists across the globe are working on this vaccine. There are 23 approved corona vaccines, 56 vaccines in development. Vaccine type includes mRNA vaccine, inactivated vaccine, peptide vaccine, adenovirus vaccines developed by different agencies have been approved and some of them are waiting for approval. This review article focuses on different types of vaccines, how they are developed and what are the challenges in developing vaccines against a pandemic disease.

Keywords: vaccine, attenuated, killed, mRNA, subunit particles, COVAXIN, Pfizer, ZyCoV-D *

Corresponding Author’s Email: [email protected].; Assistant Professor.

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INTRODUCTION Vaccines are given to prevent infectious diseases and are given to millions of babies, children, adolescents and adults and it’s critical that they must be demonstrated to be safe and effective. Vaccines have prevented countless cases of disease and disability and have saved millions of lives (BJC, Newsroom, 2021). There are five different stages in the development of a vaccine. These include exploratory stage, preclinical stage, clinical development, regulatory review and approval, manufacturing and quality control (WHO,2014). Clinical development has a four-phase process (Angela, 2011). During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded, and the vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety. Many vaccines undergo Phase IV formal, ongoing studies after the vaccine is approved and licensed. In public health emergencies such as a pandemic, the development process may be atypical or expedited. Ensuring the safety and effectiveness of vaccines is of top priorities of the World health organization (WHO) and Food and Drug Administration (FDA, 2020). COVID-19 vaccine is a vaccine intended to provide acquired immunity against Covid-19. WHO is working in collaboration with scientists, businesses, and global health organizations through the ACT accelerator to speed up the pandemic response where a safe and effective vaccine is found. FDA recognizes the gravity of public health emergencies and the importance of facilitating availability as soon as possible, to prevent COVID-19. Emergency Use Authorization (EUA) allow the use of unapproved medical products, or unapproved use of approved medical products in an emergency to diagnose, treat or prevent serious or life threatening diseases or conditions when certain criteria have been met, including that there are no adequate, approved, and available alternatives (FDA,2020). As of December 16th, 2020, there are 56 COVID-19 candidate vaccines in clinical evaluation. Of which 13 are in Phase III

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trials, and there are another 166 candidate vaccines in pre-clinical evaluation. (WHO, 2020) A list of some of the candidate vaccines developed against COVID-19 by different countries using different platforms is shown in Table 1. The vaccines developed by different countries use different platforms like replicating, non replicating, protein subunit, DNA, virus like particle, inactivated viruses and attenuated viruses, etc. Most of the vaccine target age groups above twelve. The following are the details of some of the vaccines developed by different countries.

COVAXIN BBV152 (also known as Covaxin) is an inactivated virus based COVID-19 vaccine being developed by Bharat Biotech (BBIL) in collaboration with the Indian Council of Medical Research (Raches Ella, 2021). COVAXIN, India’s indigenous vaccine was the first vaccine to get regulatory approvals for clinical trials. The vaccine makes use of an inactive version of a virus to spike up the production of antibodies in the host body. The vaccine is developed using the virus strain isolated at the ICMR’s National Institute of Virology (NIV). The strain has been successfully transferred from NIV to BBIL (Livemint. 9 May 2020). In phase I, the vaccine was tested on 375 volunteers. The second phase included around 750 volunteers (The Indian Express. 25 July 2020) and conducted a double-blind randomized controlled phase. A wellestablished Vero cell manufacturing platform, with proven safety in other licensed live and inactivated vaccines, aided in the rapid development of BBV152. Vaccines were administered on a two-dose intramuscularly. The secondary outcomes were immunogenicity based on the anti-IgG S1 response (detected with an enzyme-linked immunosorbent assay or ELISA, and wild-type virus neutralization or microneutralization and plaque reduction neutralisation assays). Cell-mediated responses were also evaluated.

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ZYCOV-D Ahmedabad-(India, Gujarat) based pharma giant, Zydus Cadila announced its novel vaccine candidate ZyCOV-D (Outlook News 20, Nov, 2020). Extensive research for the same was done in coordination with medical laboratories in the USA and Europe for the same. The company is testing two versions of its vaccine, one which makes use of molecular DNA to elicit an immune response, while the other uses a live measles viral strain to provide protection. The Phase-II study of ZyCoVD had been conducted in over 1,000 healthy adult volunteers as part of the adaptive Phase I/II dose escalation, multi-centric, randomized, double-blind placebo controlled study. The vaccine was found to be safe and immunogenic. The trial has been reviewed by an independent Data Safety Monitoring Board (DSMB), and reports have been submitted to the Central Drugs Standard Control Organization (CDSCO) for the update on the safety outcome. Zydus Cadila has successfully established that its DNA vaccine platform shows much improved vaccine stability, thus requiring lower cold chain requirements. This makes the vaccine ideal for access in the remotest regions of the country. Administered through the intradermal route, it also allows for the ease of administration. Further, the platform also provides ease of manufacturing the vaccine with minimal biosafety requirements (BSL-1).

SERUM INSTITUTE OF INDIA’S COVISHIELD VACCINE Covishield vaccine developed by Oxford University and AstraZeneca, which is being manufactured in India by Pune-based Serum Institute. COVISHIELD Known as ChAdOx1 nCoV-19 or AZD1222, the vaccine is based on a weakened version of a common cold virus or the adenovirus that is found in chimpanzees (as Angana Chakrabarti, on the print, 3, Jan. 2021). This viral vector contains the genetic material of the SARS-CoV-2 spike protein - protrusions present on the outer surface of

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the virus that help it bind with the human cell. As is with most vaccines, the Oxford-AstraZeneca version produces the mimic spike protein that then triggers an immunological reaction, which would effectively prime the immune system. From phase 1 trials of the vaccine, researchers had concluded that two doses of the vaccine, a month apart, would offer the best protection. But a dosing error in the third phase of the clinical trials led to participants receiving a half-dose and then a full dose, which proved to be 90 percent effective. In the case of those who received two full doses, the efficacy was 62 percent. Drugs Controller General of India VG Somani stated that the overall efficacy of the AstraZeneca/Oxford vaccine was found to be 70.42 percent - well below vaccines from Pfizer and Moderna, but above the 50 percent threshold set by many regulators. Covishield is Serum Institute of India’s version of the OxfordAstraZeneca vaccine that had been in the works for several months. Oxford-AstraZeneca vaccine is being touted as the “poor man’s vaccine” as it can be transported and stored at 2 degrees Celsius to 8 degrees Celsius for up to six months (Chakrabarti, 2021).

LIVE ATTENUATED VACCINES Live attenuated vaccines are a type of vaccine which is made from a weakened version of the original microorganism. When injected into the host, it does multiply; however, it is not strong enough to cause disease. The human immune system can identify the virus quickly and generate large amounts of antibodies against it. Thus, making the person immune to the microbe (Angela, 2011).

SPUTNIK The vaccine is named after the first Soviet space satellite. The launch of Sputnik-1 in 1957 reinvigorated space research around the world,

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creating a so called “Sputnik moment” for the global community. Sputnik V is the world’s first registered vaccine based on a well-studied human adenoviral vector-based platform (Times Now Digital, Feb 03, 2021). It currently ranks among the top-10 candidate vaccines in the World Health Organization’s (WHO) list. The idea is to use two types of adenoviral vectors - Ad5 and Ad26 - in the COVID-19 vaccine. In this way, they trick the body, which has developed immunity against the first type of vector and boost the effectiveness of the vaccine with the second shot using a different vector. Clinical trials of Sputnik V have been announced in the UAE, India, Venezuela and Belarus. The Sputnik V vaccine’s efficacy is confirmed at 91.4% based on data analysis of the final control point of clinical trials. The Sputnik V vaccine efficacy against severe cases of Covid-19 is 100%. With its two-vector approach, Russia’s renowned Gamaleya Centre had also developed and registered a vaccine against the Ebola fever.

PFIZERS-BIONTECH COVID-19 VACCINE Pfizers-BioNTech is manufactured by Pfizer Inc. They are mRNA/lipid nanoparticles vaccine administered as a two-dose regimen, 21 days apart (As Jonathan Corum and Carl Zimmer on New York Times 21, Jan, 2021). The vaccine contains a synthetic, small piece of the SARS-COV-2 genetic material (mRNA) that instructs cells in the body to make the virus distinctive “Spike.” When vaccinated, the body produces copies of spike protein which alone does not cause disease and the immune system learns to react defensively, producing an immune response against SARS COV-2. Protein and two specified doses of each authorized vaccine at specified intervals.

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MODERNA VACCINE Moderna contains messenger RNA (mRNA) with instructions for producing a protein from SARS-COV-2, the virus that causes COVID19. It does not contain the virus itself and cannot cause COVID-19. Moderna wraps the mRNA in oily bubbles made of lipid nanoparticles. Table 1. Sl. No.

Platform

1

NonReplicating Viral Vector

Type of candidate vaccine recombinant adeno virus expressing Truncated S protein (rADV-S)

2

Replicating Viral Vector

Recombinant measles virus Spike protein

University Health Network, Canada; Center for Disease Control and Prevention (CDC)

3

Replicating Viral Vector

MV-SARS recombinant measles virus vaccine expressing SARS CoV antigen

Institute Pasteur

receptor binding domain (RBD) of the SARSCoV spike (S)protein

Baylor College Medicine; Sabin; New York Blood Center (NYBC); University of Texas Medical Branch (UTMB); Walter Reed Army Institute of Research (WRAIR); National Institute of Allergy and Infectious Diseases (NIAID)

4

5 6 7

Protein Subunit

Protein Subunit Virus-like Particle Inactivated Virus

SARS recombinant spike protein plus deltainulin SARSVLPs S protein and influenza M1 protein

Developer

International Vaccine Institute(IVI)

Vaxine Pty Ltd, Australia Novavax

rSARS CoV-E*

CNB-CSIC; University of Iowa

8

DNA

DNA prime-protein S437-459 and M1-20

Institute of Immuno Biology, Shanghai Medical College of Fudan University, China

9

DNA

SARS S DNA prime and HLA- A*0201 restricted peptides boost vaccine

Sun Yat-sen University, China

10

DNA

3a DNA vaccine

State Key Laboratory of Virology; Graduate University of Chinese Academy of Sciences

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Sl. No.

Platform

11

DNA

12

DNA

DNA S protein + DNA IL2

13

DNA

DNA vaccine pIRESISS-S1

14

DNA

M and N DNA vaccine

14

DNA

M and N DNA vaccine

15

NonReplicating Viral Vector

MVA S alone, or MVAS prime and Ad5-S boost

The Rockefeller University

16

NonReplicating Viral Vector

NC protein add-mixed with MALP-2 by intranasal route and boosting with MVA-NC by intramuscular route

Helmholtz Centre for Infection Research; Technical University Munich; German Center for Environmental Health

17

NonReplicating Viral Vector

Heterologous Adenoviral prime boost AdHu5 s AdC7-nS

University of Manitoba; University of Pennsylvania School of Medicine; Southern Research Institute; Fox Chase Cancer Institute

NonReplicating Viral Vector NonReplicating Viral Vector Protein Subunit

VEEV replicon particles expressing the SARS-CoV S

University of North Carolina at Chapel Hill, USA

Recombinant DI expressing S protein

National Institute of Infectious Diseases, Japan

Recombinant truncated S-N fusion protein

Beijing Institute of Genomics, China

Protein Subunit

Recombinant peptide N223 on liposomes

Saitama Medical University; Josai University; Nippon Oil and Fat Corporation; National Institute of Infectious Diseases, Japan

18

19

20

21

Type of candidate vaccine DNA vaccine VRCSRSDNA015-00-VP; Biojector used

Developer National Institute of Allergy and Infectious Diseases (NIAID) State Key Laboratory of Virology, University of Chinese Academy of Sciences Jilin University; Academy of Military Medical Sciences National Hospital Organization KinkiChuo Chest Medical Center; Osaka Prefectural Institute of Public Health; Jichi Medical School; The University of Hong Kong; National Taiwan University College of Medicine; National Institute of Infectious Diseases; Central Institute for Experimental Animals; Pharmaceutical Frontier Laboratory

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Sl. No.

Platform

Type of candidate vaccine

22

Protein Subunit

Recombinant TMtruncated S protein

23

Protein Subunit

Trimeric Spike protein

24

Virus-like Particle

25

Virus-like Particle

Chimeric VLP (S protein SARS plus E, M and N proteins of mouse hepatitis virus) Recombinant trimeric S protein

26

Inactivated Virus

purified inactivated Vero-cell SARS vaccine

27

Inactivated Virus

Formalin- and UV inactivated virus vaccine

Baxter Vaccines, Austria

28

Inactivated Virus

β-propiolactone inactivated virus vaccine

National Institute of Allergy and Infectious Diseases (NIAID); University of Virginia

Live Attenuated Virus Live Attenuated Virus

Live attenuated vaccine Nsp16 mutant lacking 2’-OMTase

University of North Carolina

Live attenuated SARSCoV MA-ΔExoN

University of North Carolina

ISCV

Sinovac Biotech Ltd (/Beijing Kexing Bio-product), Chinese Centre for Disease Control and Prevention; Chinese Academy of Medical Sciences

RABV-SARS

Thomas Jefferson University

whole virus

Sanofi

29

30

31

32 33

Inactivated Virus Inactivated Viral Vector Inactivated Virus

Developer Chinese Center for Disease Control and Prevention; Canadian Science Centre for Human and Animal Health HKU-Pasteur Research Centre; The University of Hong Kong; National Institutes of Health; Centers for Disease University of Texas Medical Branch (UTMB) The John Hopkins University School of Medicine, USA Institute of Microbiology and Epidemiology, National Vaccine and Serum Institute; Beijing Genomics Institute (BGI); Harbin Institute of Veterinary Medicine

The vaccine is given as two injections, usually into the muscle of the upper arm, 28 days apart. After injection, the vaccine particles bump into cells and fuse to them, releasing mRNA. The cell’s molecules read its sequence and build spike proteins. The mRNA from the vaccine is eventually destroyed by the cell, leaving no permanent trace. When a

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person is given the vaccine, some of their cells will read the mRNA instructions and temporarily produce the spike protein. The person’s immune system will then recognize this protein as foreign and produce antibodies and activate T cells to attack it. If later on, the person comes in contact with SARS-COV-2 virus, their immune system will recognise it and be ready to defend the body against it. Most importantly, Moderna’s vaccine can be stored in normal freezers and does not require a supercold transportation network, making it more accessible for smaller facilities and local communities (CDC, 4 March, 2021). Even though Pfizers and Moderna vaccines are messenger RNA vaccines, they’re really different messenger RNA molecules, they have different so-called lipid delivery systems, meaning the sort of fatty droplet in which the messenger RNA is located, i.e., why they have different storage and handling characteristics (FDA, 2020)

CONCLUSION COVID-19 caused by coronavirus 2 (SARS-CoV-2), which was first identified in December 2019 in Wuhan, China. The outbreak was declared a Public Health Emergency of International Concern in January 2020, and a pandemic in March 2020. From the time outbreak occurred, the development of a safe and effective vaccine is the top priority of many countries and also of CDC and WHO. Different vaccine candidates using different platforms are now available for use and many more are in the clinical trials. As the virus mutates rapidly, the scientists are also analysing the efficacy of the above listed vaccines against the mutated strain also. The recent data shows the benefits of the vaccine outweigh known harms and complications.

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REFERENCES Angela, C. (2021). Everything we know about covishield, one of 2 covid vaccines likely to get nod for use in India Covishield is Serum Institute of India’s version of the Oxford-AstraZeneca vaccine that had been in the works for several months. 3 January, 2021 https://theprint.in/theprint-essential/everything-we-know-aboutcovishield-one-of-2-covid-vaccines-likely-to-get-nod-for-use-inindia/577641/. Angela S Clem. Fundamentals of Vaccine Immunology. J. Glob. Infect. Dis. 3(1) 73-78,2011. Corum Jonathan and Zimmer Carl on New York Times, 21 Jan, 2021 https://www.nytimes.com/interactive/2021/health/how-covid-19vaccines-work.html. FDA. (2020). Covid-19 vaccine news and updates (https://www.fda.gov/ emergency-preparedness-and-response/coronavirus-disease-2019covid-19/covid-19-vaccines). ICMR teams up with Bharat Biotech to develop Covid-19 vaccine. Livemint. 9 May 2020. https://www.livemint.com/news/india/icmrteams-up-with-bharat-biotech-to-develop-covid-19-vaccine11589038719666.html). Raches Ella, Krishna Mohan Vadrevu, Harsh Jogdand, Sai Prasad, Siddharth Reddy, Vamshi Sarangi, Brunda Ganneru, Gajanan Sapkal, Pragya Yadav, Priya Abraham, Samiran Panda, Nivedita Gupta, Prabhakar Reddy, Savita Verma, Sanjay Kumar Rai, Chandramani Singh, Sagar Vivek Redkar, Chandra Sekhar Gillurkar, Jitendra Singh Kushwaha, Satyajit Mohapatra, Venkat Rao, Randeep Guleria, Krishna Ella, Balram Bhargava. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet, January,2021. https://doi.org/10. 1016/S1473-3099(21) 00070-0. Sputnik V COVID-19 vaccine shows 91.6% efficacy in phase 3 trials: Lancet study. Times Now Digital, Feb 03,2021. https://www.

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timesnownews.com/health/article/sputnik-v-covid-19-vaccine-shows91-6-efficacy-in-phase-3-trials-lancet-study/715278. WHO. 2014. Principles and considerations for adding a vaccine to a national immunization programme from decision to implementation and monitoring. https://apps.who.int/iris/handle/10665/111548. WHO. 2020. Update on COVID-19 vaccine development. https://www. who.int/docs/default-source/coronaviruse/risk-comms-updates/update 45-vaccines-developement.pdf?sfvrsn=13098bfc_5. World Health Organization, Geneva. Accessed on 10.06.2021)

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 6

VACCINATION AND PUBLIC HEALTH Geena George1,, PhD and Hema Vijayan2, PhD 1

Department of Botany, Nirmala College Muvattupuzha, Ernakulam, Kerala, India 2 Matrix Fine Sciences, Aurangabad, Maharashtra, India

ABSTRACT This review write-up outlines the core concepts in vaccine asepsis, such asicacy and effectiveness, vaccine failure, herd immunity, epidemiological shift and describes the application of this information both at program levels and in the practice by family physicians, paediatricians and epidemiologists. Universal disease elimination can be attained for pathogens that are constricted to human life. For eradication of epidemics, high levels of human immunity are required worldly, to make sure no ongoing spreading in our well-linked globe. Immunization has made major contribution to the public health. Infections like smallpox and rinderpest have been eliminated. Universal coverage of vaccination against many infectious diseases of children has been enhanced drastically since the commencent of WHO’s



Corresponding Author’s Email: [email protected]; Geena George, Assistant Professor, Department of Botany and Hema Vijayan, Senior Executive (R&D).

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Geena George and Hema Vijayan Immunization Programme in 1974 and of the universal Alliance for Vaccination and Immunization in 2000. Evolution of vaccines against infections like tuberculosis, malaria and HIV is challenging and procurements are still modest. Success against these diseases may require combination vaccinations, each content restorate a different branch of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets including diabetes, hypertension and Alzheimer’s disease. This review ends with proposals for the provision of systematic training and learning platforms in vaccine epidemiology to save millions of preventable mortality rate and improve health outcomes through life-course.

Keywords: immunization, epidemiology, infection mortality rate

INTRODUCTION A substance used to energizing the production of antibodies and giving immunity against diseases is developed from the causative agent of a disease, its products or a synthetic substitute, treated to act as an antigen without inducing the disease. Immunization is invariably recognized as one of the best policies to increase duration and quality of life during the last centuries (World Health Organization, 2020). Nevertheless, vaccination coverage rates are under the levels recommended to limit spread and to reduce the burden on health systems of vaccine-preventable diseases (Plans-Rubió, 2019). In several countries, vaccination acceptance is low because of misconceptions about the effectiveness and safety of vaccines (Costantino, et al., 2018). The vaccine hesitancy involves at least fifteen percentage of the population and even health workers have become doubtful vaccination sometimes.

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BACKGROUND INFORMATION Before the development of human vaccines, many people survived without experiencing a list of diseases including mumps, rubella, measles, whooping cough and chickenpox and rotavirus diarrhoea. In addition to these global diseases of childhood, thousands of kids each year suffered or succumbed to life threatening episodes of paralytic poliomyelitis, diphtheria, or bacterial meningitis caused by Haemophilus influenzae type b (Hib) or Streptococcus pneumonia (Roush and Murphy, 2007). The most extraordinary accomplishment related to immunization programs is the global eradication of smallpox. This is the first disease of humans to be extinguished from the universe through an intentional, organized, and massive undertaking of governments and nongovernmental organizations throughout the world. Before the advent of vaccines, some communicable diseases started declining precipitously in developed countries through improvements in sanitation, nutrition, housing conditions and improved indoor air quality. However, vaccination can often accelerate disease reduction even in the most impoverished communities before such advances are accomplished. For example, the Expanded Program on Immunization (EPI), introduced worldwide in 1974, provided the first basic infrastructure for children’s health services in many poor countries and has proved a suitable platform for addressing a variety of health needs. The history of immunization is incomplete without reporting the public health intervention that led to the practice of these vaccines for children globally. The EPI (Expanded Program of Immunization) was founded by WHO in 1974 with the focus on providing routine vaccines to all children by 1990 (World Health Assembly, 1974). Global policies for immunization against diphtheria, tetanus, measles, polio and tuberculosis were set out in 1977. The EPI includes hepatitis B, Hib and pneumococcal vaccines in many areas and by 2017, 85% of the global children received diphtheria, tetanus and measles vaccines (World Bank, 2019).

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IMPACT OF VACCINES The most remarkable impact of immunization has been to prevent diseases and mortality from serious infections that disproportionately affect children. Vaccines are estimated to prevent almost six million deaths per year and to save 386 million life years and 96 million disability-adjusted life years (DALYs) globally (Ehreth, 2003). The measures of vaccine impact contain, vaccine efficacy, the direct protection offered to a vaccinated group under optimal conditions e.g., trial settings or vaccine effectiveness, the direct and indirect effect of vaccines on the population in a real-life setting (Wilder-Smith et al., 2017). Numerical measure of vaccine effect therefore involves estimating the extent of morbidity and mortality prevented. In the United States in 2009, amongst an annual birth cohort vaccinated against 13 diseases it was estimated that nearly 20 million cases of disease and 42,000 deaths were prevented (Zhou et al., 2009). Infectious diseases that accounted for major mortality and morbidity in the early 20th Century in the United States showed over a 90% decline in incidence by 2017 from the prevaccine peak incidence (Roush and Murphy, 2007) due to high vaccine uptake of over 90% for the DTaP (diphtheria, tetanus, and acellular pertussis), MMR (measles, mumps and rubella) and polio vaccines. Infectious diseases reduction was seen across other high-income countries demonstrating the efficacy of vaccines when available and accessible.

FUTURE OF VACCINATION Immunization will one day be developed also against the major infections such as HIV, TB and malaria, although it is unpredictable to put forward a time and that eventually these infections will cease to be a major public health priority even if their stage of existence may not be eradicated completely. Ensuring the maximum benefit that immunization

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can provide against diseases will be achieved only if there is global, highlevel surveillance to detect the emergence of new potentially dangerous diseases and also to detect the emergence of strains resistant to the vaccines in routine use as quickly as possible so that countermeasures can be put into place. As the incidence of infectious diseases reduces and living standards improve across the developing universe, many developing countries are entering a transition period in which they have a residual challenge from infectious diseases such as HIV and tuberculosis, while at the same time encounter major challenges from emerging noninfectious diseases such as diabetes, cardiovascular disease and cancer. Does immunization have a role to play in ameliorating this increasing global burden of non-infectious diseases? Prevention of a substantial proportion of liver and cervical cancers should be achievable by ensuring universal hepatitis B and HPV vaccination and prevention of some stomach and nasopharyngeal cancers might be possible in communities where there is a high risk of these cancers by vaccination against Helicobacter pylori and Epstein Barr virus infections, respectively. Vaccination to prolong survival from other cancers, as recently demonstrated for prostate cancer, may become practicable, but highly personalized cancer immunotherapy is likely to be too expensive for universal use in even middle-income countries (Liu, 2011). Management of diabetes and hypertension is difficult in communities with limited access to healthcare and it is possible that immunization against these conditions could help by limiting the need for frequent contacts with the health system, although there is much work to be done before this approach could become a reality. Some progress is being made in developing vaccines which modulate the course of diabetes and hypertension (Bachmann and Jennings, 2011). Immunization against addiction, including smoking, is also feasible, although very high antibody level are required to achieve an effect (Maurer and Bachmann, 2007) and there are early results suggesting that immunization against Alzheimer’s might slow the progress of this situation. In the coming decades, immunization is likely to expand its significance beyond

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prevention of the common diseases of childhood which has been its main success so far.

VACCINE GROWTH The evolution process for vaccines is unique and also highly capital intensive and risky. The significance of safety with biologics, the vaccine industry is highly regulated. Vaccine development proceeds in an iterative fashion. Studies to discover new vaccine antigens and novel approaches to immunization usually take several years and costs tens of millions of dollars. Once a discovery is made, several improvements must be undertaken to reach the licensing stage. Those growths include process development, clinical development and assay development. In the interest of urgently developing safe and efficacious vaccines to tackle this pandemic, it is important that scientists in academia, industry, regulatory agencies and other government organizations collaborate and learn from each other. Challenging areas that could benefit from such collaborative efforts include understanding the critical priorities for vaccine development, urgently developing robust models for vaccine testing and finding ways to successfully deliver vaccines to billions of people around the world.

CONCLUSION One of the main challenges for public health, particularly for vaccinology, in the next decades is the contrast in vaccine hesitancy among the general population. In response to this phenomena, strong multidisciplinary alliances between health care professionals, providing evidence-based data on vaccine effectiveness and safety and on reduction of the burden of vaccine-preventable disease due to vaccinations offered, addressing vaccine hesitancy through innovative communication

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strategies and increasing opportunities to administer vaccines among the general population (at school, at work, at the hospital ward) and any such productive and prolific approaches should be considered by international and national health authorities and agencies as some of the possible strategies.

REFERENCES Bachmann M. F. and Jennings G. T. 2011. Therapeutic vaccines for chronic diseases: successes and technical challenges. Phil. Trans. R. Soc. B 366, 2815-2822. Costantino, C., Restivo, V., Tramuto, F., Casuccio, A., Vitale, F. 2018. Universal rotavirus vaccination program in Sicily: Reduction in health burden and cost despite low vaccination coverage. Hum. Vaccin. Immunother. 14, 2297-2302. Ehreth, J. 2003. The global value of vaccination. Vaccine 21, 596-600. Liu M. A. 2011. Cancer vaccines. Phil. Trans. R. Soc. B 366, 2823-2826. Maurer P. and Bachmann M. F. 2007. Vaccination against nicotine: an emerging therapy for tobacco dependence. Expert. Opin. Investig. Drugs 16, 1775-1783. Plans-Rubió, P. 2019. Low percentages of measles vaccination coverage with two doses of vaccine and low herd immunity levels explain measles incidence and persistence of measles in the European Union in 2017-2018. Eur. J. Clin. Microbiol. Infect. Dis. 38, 1719-1729. Roush S. W. and Murphy T. V. 2007. Vaccine-Preventable Disease Table Working Group. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA; 298:2155-63. Wilder-Smith, A., Longini, I., Zuber, P. L., Barnighausen, T., Edmunds, W. J., Dean, N. 2017. The public health value of vaccines beyond efficacy: methods, measures and outcomes. BMC Med. 15:138. doi: https://10.1186/s12916-017-0911-8.

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World Bank. 2019. Immunization, DPT (% of Children Ages 12-23 Months). Washington, DC: World Bank. World Health Assembly. 1974. The expanded programme on immunization: the 1974 resolution by the world health assembly. Assign. Child. 1985 87-88. World Health Organization. Vaccines and Vaccination. Available online: https://www.who.int/health-topics/vaccines-and-immunization (accessed on 8 September 2020). Zhou, F., Shefer, A., Wenger, J., Messonnier, M., Wang, L. Y., Lopez, A. 2009. Economic evaluation of the routine childhood immunization program in the United States. Pediatrics 133, 577-585.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 7

PANDEMICS: A TRAVEL THROUGH HISTORIC TIMES C. Mamatha*, PhD Department of Life Sciences, Jain University, Bangalore, India

ABSTRACT Pandemics have always co-existed with human race right from the historic times, thus, causing devastations. Understanding the history of pandemics has gained importance in the current times where humankind is struggling to fight off one of the worst pandemics ever, the COVID- 19. It has severely affected every sphere of human life; social, psychological, economic and behavioral. People all over the world has learned to live co-exist with the virus. From Plague to Cholera, Leprosy, Spanish Flu to SARS, pandemics have always ruled the world throughout historic times. The earliest pandemic in record happened in 430 BC and had its beginnings in Athens. By 165 AD, mankind was engulfed by the darkest times with the advent of the Plague which was the worst among pandemics ever occurred. It is also considered to have wiped off one third of the world’s population during the episode in the 1350. Plague actually changed the political history of *

Corresponding Author’s Email: [email protected].

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C. Mamatha the world by bringing the downfall of some of the most powerful empires. Unlike other pandemics, Plague resurfaced periodically and that is why it is considered as the worst pandemic of all.

Keywords: pandemic, history, plague

INTRODUCTION Pandemics have always played a major role in shaping human history and cultures as we know it now. Pandemic outbreaks have always decided outcomes of wars, wiped out entire cultures, wiped out huge parts of population and even paved way for innovations and advances in the field of science, economy and politics (Scheidel, 2017). One of the deadliest outbreaks ever reported was the Plague. Stemming from the Greek word plaga (strike or blow), the word plague is used interchangeably to describe a virulent contagious febrile disease caused by Yersinia pestis. For years together, the word was used as a synonym for any sudden outbreak of a disastrous evil or affliction (Hajar, 2012). The Latin terms are plaga and pestis which describes any kind of sickness. The best-known episodes of plagues to be recorded are the ones referred to in the religious scriptures which serve as the foundations to Abrahamic religions, starting with the Old Testament. In the Book of Exodus, there exists a description about a series of ten plagues which first struck the Egyptians and then the Israelites who were held captive by the Pharaoh, the ruler of Egypt. Even though what the book described seems more like occurrences of elements, there are references to some diseases which clearly shows infectious nature. Lice, diseased livestock, boils, and possible deaths of firstborn are mentioned as clear signs of some infections which then spread all around, causing devastations (Marr, 1996). There are similar references to the plagues in the Islamic tradition, in the Qur’an (Qur’an). In the Biblical context, outbreaks of pandemics are seen as a part of the nascent human societies and are said to have played a major part in the wiping out of humanity. In the Apocalypse or

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The Book of Revelations, it is said that seven bowls of God’s wrath will be poured on the Earth by angels and again some of the bowls are said to contain plague, which clearly implies the infectious nature of the disease. Therefore, one can clearly point out the fact that pandemics has always defined the lives of people worldwide from times immemorial and the depths of these are so deep that even the religious scriptures have descriptions about them. As per the Abrahamic spirituality, pandemics were considered as punishments given by the divine to punish humans for their sins.

THE ATHENIAN PLAGUE 430 BC The Athenian plague is a historically documented event which occurred in 430 B.C. It is said to have happened during the Peloponnesian War, fought between Athens and Sparta (Thucydides, 2017). The Athenian plague originated in Ethiopia, and then spread throughout Egypt and Greece. Initial symptoms of the plague were headaches, conjunctivitis, rash which covered the body, and fever. The victims would cough up blood, and suffer from extremely painful stomach cramps, followed by extreme vomiting (Thucydides, 2017). Infected individuals would generally die by the seventh or eighth day. Those who survived this stage might suffer from partial paralysis, amnesia, or blindness for the rest of their lives. Doctors and other caregivers frequently caught the disease and died with their patients in the process of healing them. This plague is said to have claimed the lives of almost 25% of the population in overcrowded city of Athens (Olson et al., 1996). The cause of the Athenian plague of 430 B.C. is still not clear. Many diseases, including bubonic plague, have been ruled out as possibilities but a recent theory postulates that typhoid fever may be a cause (Sabbatani and Fiorino, 2009). However, some epidemiologists now suggest that it may have been an Ebola viral hemorrhagic fever (Olson et al., 1996).

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THE ANTONINE PLAGUE Even Hippocrates, who is thought to have been a contemporary of the plague of Athens, has not recorded any accounts of the outbreak. But there was another outbreak which occurred a couple of centuries later, which was documented (Yapijakis, 2009). This outbreak known as The Antonine Plague of 165 AD was documented by the historic physician, Galen. This plague is supposedly caused due to smallpox infection, which was brought into the land by the soldiers returning from Seleucia (Fears, 2004). This particular ailment had affected Asia, Egypt and Italy before it entered the land. Unlike the plague of Athens, which was limited over a small geographical area, the Antonine Plague spread across the entire Roman Empire. This plague is said to have shaken the very integrity of the political, military and economic basis of the society and also wiped out as much as one third of the population (Sabbatani and Fiorino, 2009). Along with weakening the very roots of Rome, this plague is said to have renewed the spiritual and religious nature of Rome, leading to the inflow of novel religions, including Christianity. History has it that this plague brought about the fall of the Roman Empire in the West in the 5th Century.

THE JUSTINIAN PLAGUE The Justinian plague was the “original plague” pandemic caused by Yersinia pestis and it is thought to have originated in the 6th century AD either in Ethiopia, moving through Egypt, or in Central Asia, where it may have then traveled further. From the place of origin, this quickly spread to the Roman world and beyond. This plague is said to have spread due to business relations within various lands. Even the military forces are said to have spread the disease from Asia Minor to Africa, Italy and then to Western Europe. The Justinian epidemic is the earliest clearly documented plague outbreak (Horgan, 2014).

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Hallucinations were experienced prior to the outbreak of the illness, followed by the first symptoms of the disease; fever and fatigue. Soon afterwards, buboes appeared in the groin area or armpits, or occasionally beside the ears. The disease then progressed rapidly, killing its victims within days. The infected individuals would enter a delirious, lethargic state, and would refuse to eat or drink. Following this stage, the victims would appear mentally disturbed and so caring for them was a daunting task (Procopius, 1914). Many died painfully as their buboes gangrened while some others died vomiting blood. There were also cases, where the buboes grew to huge sizes, and then ruptured followed by suppuration. However, in such cases, the patient would usually recover and would have to live with the side effects with withered thighs and tongues. It was during this pandemic that death toll rose to very high levels within a very short time and all gravesites were overflew beyond capacity. With no burial grounds, people started throwing the bodies of victims out into the streets or piling them along the seashore to rot. The empire solved this problem by digging huge pits and collecting the corpses there. But even these pits soon overflowed (Procopius, 1914). Further the bodies were placed inside towers in the walls, which caused the whole city to stink. Streets were deserted, and all trades were abandoned. Food materials were hard to come by and people succumbed to death out of starvation and due to the disease itself. By 600, the population of the Empire had been reduced by 40% and even by 50% in some other parts (Procopius, 1914). It was at this point that the Christian tradition entered the realm of interpreting and understanding the events of this nature (Evagrius, 1846). They concluded that these pandemics were punishment for sins or the retribution for the induction of God’s wrath (Evans, 1976). This interpretation of the plague reappeared during many other phases which come by, including the Black Death. Meanwhile, as the Byzantine Empire became weakened in its physical, economic, and cultural infrastructure, the nomadic Arab tribes, moved through sparsely populated areas practicing a form of protective isolation and this set the

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stage for the rapid expansion of Islamism (Sabbatani et al., 2012, Sabbatani et al., 2012).

THE BLACK DEATH The global outbreak of bubonic plague is the one that originated in China in 1334 and it arrived in Europe in 1347. It had reduced a population of 450 million to 300 million within 50 years. The Black Death had claimed 60% of the population at the time (DeWitte 2014). Starting in China, the pandemic spread through Central Asia and Northern India following the trade route. The plague reached Sicily and within the next 5 years, spread to the entire continent, moving to Russia and the Middle East. The wave itself is said to have claimed 25 million lives (Encyclopaedia, 2018). The symptoms were horrifying and the disease had a mortality rate of 70% while that of pneumonic plague was close to 95%. It was by the 19th century that the causative agent was found to be Yersinia pestis (CDC, 2015). This strain tends to infect and overflow in the guts of oriental rat fleas (Xenopsylla cheopis) forcing them to regurgitate concentrated bacteria into the host while feeding. Such hosts then transmitted the disease further. Finally, it infects humans as the bubonic plague (Eisen and Gage, 2008). Humans can transfer the disease through droplets, thus leading to pneumonic plague. The mortality rate of the Black Death varied between geographical regions, sometimes skipping sparsely populated rural areas, but then extracting its toll in the densely populated urban areas, where population perished in excess of 50%, sometimes even up to 60% (Benedictow, 2012). The only remedies were inhalation of aromatic vapors from flowers or camphor. During the time there was a shortage of doctors which led to a proliferation. There was a mafia during the time who sold useless cures and amulets which claimed to offer magical protection (Hajar, 2012). The first known quarantine was in Ragusa in the year 1377, where all arrivals had to spend 30 days on the nearby island of Lokrum before

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entering the city. This period of 30 days, named trentine was later extended to 40 days, thus earning the name quarantine (Sehdev, 2002). Quarantine remains in effect in the present time as a highly regulated, nationally, and internationally governed public health measure available to combat contagions.

SPANISH FLU (1918- 1920) This pandemic occurred during the second decade of the 20th century and is considered as the first real form of pandemic and the first one to have occurred after the advent of modern medicine. The consequences of this pandemic were devastating throughout the globe (CDC, 1918). The causative agent was H1N1 strain of influenza virus (Antonovics et al., 1918). But ironically, despite the name Spanish flu, the real origin of this pandemic is unknown. The sources of origin may have been USA, China, Spain, France or even Austria. This global epidemic occurred in the middle of World War I, when advanced modes of travel including those for intercontinental travel were available and this perpetuated the uncertainties (CDC, 1918). It only took a few months for this virus to travel across the world. To make things worse, in Europe the massive military movements and overcrowding contributed to the massive spread with a fatality rate of about 50 to 100 million. The Spanish flu killed more people a year that the Black Death did in a century (Flecknoe, 2018). Another frightful aspect was that this killed more young and healthy individuals than other pandemics. The reason for this is said to be the triggering of a cytokine surge which overwhelmed and disrupted the immune system. To make things worse, the virus returned as a more deadly mutant strain, much more virulent than the original one, causing the second wave to become more uncontrollable (Simonsen, 1998). This pandemic is said to have affected the outcome of World War I (PriceSmith, 2008). This pandemic was also the first one with long-lingering effects which could be observed and quantified. The children born to

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women exposed to the virus had more physical ailments than those born to the ones not exposed (Almond, 2006). Many renowned politicians, artists and scientists succumbed to the disease while others who survived went on to have distinguished careers in arts and politics like Walt Disney, Franklin Roosevelt, Woodrow Wilson etc. (Whitford, 1987). But despite all the devastations the pandemic episode soon faded which led historians to call it ‘the forgotten pandemic.’

HIV PANDEMIC AIDS caused by the HIV virus was a slowly progressing global pandemic which cascaded through many decades of time, through different continents and affected different civilizations, bringing on new challenges with every new group it affected. The initial expansion of HIV was marked by its predominant spread among the gay population and by the high mortality rate, which lead to the marked social isolation and stigma. The HIV has affected about 40 million people globally (Cohen et al., 2008) and has caused about one million deaths worldwide (Wang et al., 2015). Statistics says that HIV infects 1.2 million people in the US and about 12,000 die every year (CDC, 2018). Even though HIV is a fairly slowly spreading pandemic, it has received formidable public health attention, both by national and by international administrations. Advances in medical treatment have turned HIV into a chronic condition manageable by medication. Also, this disease shed light onto the mental aspects of physical ailments (Psychiatry Bibliography). From the aspects of higher depression rates among the affected (Ciesla and Roberts, 2001) to the association with substance abuse and issues connected with stigma, guilt and shame this disease shed new light in the medical sector.

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SMALLPOX (1972) Smallpox has the fame of being one of the most frightening and contagious diseases in the history of the world. With its world-wide spread, killing a huge part of its victims (30%) and deforming the remaining, smallpox is one of the most severe pandemics to have affected the world. It is also one of the few pandemics to have been completely eradicated from the face of the earth (Tarantola and Henderson, 1895). The work of Edward Jenner in this regard is noteworthy and brings out the real implication of the process he developed. The pandemic had small origins in Yugoslavia, starting from a pilgrim who was returning from the Middle East developing skin eruptions. This was not diagnosed by the physicians which then caused the disease to spread (Ilic and Ilic, 2017). Mandatory revaccinations were introduced, and entire villages affected were cordoned off in quarantine. This outbreak saw 175 cases with 35 fatalities. These quick measures taken helped curb the disease within 2 months (O’Toole et al., 2003).

SARS Severe Acute Respiratory Syndrome (SARS) was the pandemic to have its first outbreak in the twenty-first century which received wide public attention. Caused by the SARS Corona virus (SARS-CoV), this originated in China and infected less than 10,000 individuals, mainly in China and Hong Kong and 251 cases in Canada (Toronto) (Smith, 2006). The mortality rate was 10% but luckily the outbreak was contained by the mid 2003 (WHO, 2003).

SWINE FLU OR H1N1/09 PANDEMIC The 2009 H1N1 pandemic was a reprise of the “Spanish flu” pandemic of 1918, but luckily the consequences were less devastating.

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As this was a re-assortment of the bird, swine, and human flu viruses; it was colloquially called as “swine flu” (Trifonov t al., 2009). It originated in Mexico in April 2009 and became a pandemic in weeks, ending by May 2010 (McNeil Jr, 2009). The death toll was calculated to be between 20,000 and 50,000. Even though the mortality rates were lower than the regular influenza ones, this was considered threatening as it infected healthy young adults, causing severe respiratory distress, similar to the H1N1 outbreak (Nguyen-Van-Tam et al., 2009).

EBOLA (2014- 2016) Ebola virus, which is endemic to Central and West Africa with fruit bats being the reservoir, caused an outbreak in a remote village in Guinea in December 2013. It spread mostly among families and managed to cause an outbreak in Sierra Leone and Libya with over 28,000 cases and 11,000 fatalities. A small number of cases were also registered in Nigeria and Mali, but these outbreaks were quickly contained (Kalra et al., 2014). However, the largest Ebola outbreak to date is the one which occurred in Texas in 2014 from a passenger from Libya who fell ill and died in Texas, thus spreading the disease to the two nurses who took care of him (Bell et al., 2015).

ZIKA (2015- 2016) Zika is a virus found in the Rhesus monkey in Uganda. The first outbreaks were small ones recorded in Micronesia and Brazil with symptoms such as flat pinkish rash, bloodshot eyes, fever, joint pain and headaches, resembling the dengue. This disease is mosquito borne but also is transmitted sexually. In the adult patients, Guillain-Barre syndrome were seen as a complication of the disease and severe microcephalia was seen in unborn children of infected mothers. In 2015,

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the disease transferred from Micronesia, across the Pacific, to Brazil, whence it continued to spread (Kindhauser et al., 2015). By 2016, the disease spread throughout South America, Central America, the Caribbean, and several states within the USA. However, this virus remains to be one of significant concern as there is no vaccine or treatment protocol.

CONCLUSION Pandemics has played a huge role in shaping the history of the world as we know it. As humans evolved, microorganisms evolved with us, which is evident from the episodes of pandemics seen in this era. Every time a pandemic struck, it affected human lives drastically and an entirely new lifestyle followed as an aftermath of a pandemic. It can be concluded that in the coming years as well, pandemics will continue to inflict human race. The only way to cope up is to be alert, observant and to be prepared for such situations.

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Benedictow O J. The black death 1346–1353: the complete history. Woodbridge: Boydell Press; 2012. p. 380. CDC: Remembering the 1918 influenza pandemic. https://www.cdc.gov/ features/1918-flu-pandemic/index.html. Accessed Oct 2018. Centers for Disease Control (CDC). 2015 Sept 24. FAQ: Plague. https:// www.cdc.gov/plague/faq/index.html. Retrieved October 2018. Ciesla J A, Roberts J E. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am. J. Psychiatry. 2001; 158(5):725–730. doi: 10.1176/appi.ajp.158.5.725. Cohen M S, Hellmann N, Levy J A, DeCock K, Lange J. The spread, treatment, and prevention of HIV-1: evolution of a global pandemic. J. Clin. Invest. 2008;118(4):1244–1254. doi: 10.1172/JCI34706. Dawood F S, Iuliano A D, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect. Dis. 2012; 12(9):687–695. doi: 10.1016/S1473-3099(12)70121-4. DeWitte S N. Mortality risk and survival in the aftermath of the medieval black death. PLoS One. 2014;9(5):e96513. doi: 10.1371/journal. pone.0096513. DeWitte S N. Mortality risk and survival in the aftermath of the medieval black death. PLoS One. 2014;9(5):e96513. doi: 10.1371/journal. pone.0096513 Eisen R J, Gage K L. Adaptive strategies of Yersinia pestis to persist during inter-epizootic and epizootic periods. Vet. Res. 2008;40(2):1. doi: 10.1051/vetres:2008039. Evagrius Scholasticus, Ecclesiastical history (AD431–594), trans. Walford E; 1846. Book 4. Chapter 29. http://www.tertullian.org/ fathers/evagrius_4_book4.htm#12. Evans J A S. The attitude of the secular historians of the age of Justinian towards the classical past. Traditio. 1976;32:164–165. doi: 10.1017/ S0362152900005572. Fears J R. The plague under Marcus Aurelius and the decline and fall of the Roman empire. Infect. Dis. Clin. N. Am. 2004;18(1):65–77. doi: 10.1016/S0891-5520(03)00089-8.

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Flecknoe D, Charles Wakefield B, Simmons A. Plagues & wars: the ‘Spanish flu’ pandemic as a lesson from history. Med. Confl. Surviv. 2018;34(2):61–68. doi: 10.1080/13623699.2018.1472892. Hajar R. The air of history (part II) medicine in the middle ages. Heart Views. 2012;13(4):158–162. doi: 10.4103/1995-705X.105744. Halliday S. Death and miasma in Victorian London: an obstinate belief. BMJ. 2001;323:1469. doi: 10.1136/bmj.323.7327.1469. Horgan J. Justinian’s Plague (541–542 CE). Ancient history encyclopedia; 2014 Dec 26. Retrieved from https://www.ancient.eu/ article/782/. Ilic M, Ilic I. The last major outbreak of smallpox (Yugoslavia, 1972): the importance of historical reminders. Travel Med. Infect. Dis. 2017; 17:69–70. doi: 10.1016/j.tmaid.2017.05.010. Kalra S, Kelkar D, Galwankar S C, Papadimos T J, Stawicki S P, Arquilla B, Hoey B A, Sharpe R P, Sabol D, Jahre J A. The emergence of ebola as a global health security threat: from ‘lessons learned’ to coordinated multilateral containment efforts. J. Global Infect. Dis. 2014;6(4):164–177. doi: 10.4103/0974-777X.145247. Kindhauser M K, Allen T, Frank V, Santhanaa R S, Dye C. Zika: the origin and spread of a mosquito-borne virus. Bull. World Health Organ. 2016; 10.2471/BLT.16.171082. Langmuir A D, Worthen T D, Solomon J, Ray C G, Petersen E. The Thucydides syndrome: a new hypothesis for the cause of the plague of Athens. N. Engl. J. Med. 1985;313:1027–1030. doi: 10.1056/ NEJ M1985101 73131618. Littman R J. The plague of Athens: epidemiology and paleopathology. Mt Sinai J. Med. 2009;76(5):456–467. doi: 10.1002/msj.20137. Marr J S, Malloy C D. An epidemiologic analysis of the ten plagues of Egypt. Caduceus. 1996;12(1):7–24. McNeil Jr D G. In new theory, swine flu started in Asia, not Mexico. The New York Times. 2009 June 23. Nguyen-Van-Tam J S, Openshaw P J M, Hashim A, et al. Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza:

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In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 8

TUMULTUOUS EPIDEMICS IN INDIA: A HISTORIC OVERVIEW Nisha Pallath*, PhD Department of Biosciences, MES College, Marampally, Ernakulam, Kerala, India

ABSTRACT India has witnessed a deluge of epidemics and pandemics throughout history which are characterized by unusual occurrence in a community or region with unimaginable ramifications. The key factors are malnutrition, lack of sanitation and lack of a proper public health system which contributes to rise of epidemic diseases in India. The country is prone to Cholera, Plague, Smallpox, Encephalitis, Swine flu, Nipah and the most recently COVID-19. Thus, it is necessary for the government to reorient health-centric holistic policies for health care assessment and service delivery. The emergence of COVID-19 pandemic has produced two different tales in India - historical epidemics/pandemics, pandemics of the colonial past, influenza in

*

Corresponding Author’s Email: [email protected]; Nisha Pallath, Assistant Professor, Department of Biosciences.

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Keywords: epidemics, India, pandemics, history, public health

INTRODUCTION The term epidemic a word derives from Homer’s Odyssey, which later took its medical meaning from the Epidemics, a treatise by Hippocrates. Before Hippocrates, epidemios, epidemeo, epidamos, and other variants had meanings related to the current definitions of “indigenous” or “endemic” (Martin et al., 2006). By the early 17th century, the terms endemic and epidemic were referred to contrasting conditions of population-level disease, with the endemic condition at low rates of occurrence and the widespread epidemic condition (Lodg, 1603). It is not uncommon for rapid and sudden outbreaks in India, and many articles identified the cause for these conditions to come about in such developing countries; lack of sanitation, malnutrition, and lack of a proper public health system (Rice et al., 2000; John et al., 2011).

EPIDEMICS Epidemics of infectious diseases are generally caused by several factors including a change in the ecology of the host population (e.g., increased stress or increase in the density of a vector species), a genetic change in the pathogen reservoir or the introduction of an emerging pathogen to a host population (by movement of pathogen or host). Generally, an epidemic occurs when host immunity is suddenly reduced in case of deeprooted pathogen or newly emerging novel pathogen and found that increased in the transmission threshold and endemic equilibrium (Epidemics, 2012).

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An epidemic may be restricted to one location it spreads to other continents or countries and affects a huge number of people, it may be termed as pandemic. The announcement of an epidemic usually requires a good understanding of a baseline rate of incidence of diseases, epidemics for certain diseases such as influenza are reaching some increase in incidence above this baseline (Green et al., 2002). A couple of cases IN very rare disease may be classified as an epidemic, while many cases of a common disease such as the common cold, fever would not. An epidemic can cause enormous damage through financial and economic losses in addition to impaired health and loss of life. The conditions which govern the outbreak of epidemics include infected foods, contaminated drinking water and the migration of some populations of animals, like rats, mosquitoes and others. Certain epidemics occur at definite seasons, like whooping-cough occurs in spring, measles in winter and in March. Influenza, the common cold, and other infections of the upper respiratory tract, such as sore throat, occur mainly in the winter. There is another variation, both the number of people affected and the number who die in successive epidemics: the severity of successive epidemics rises and falls over periods of five or ten years (Epidemics, 2012).

Types ●

Common source outbreak

In a common source outbreak epidemic, the affected individuals had an exposure to a common causative agent. If the exposure is singular and all of the affected individuals develop the disease over a single exposure and incubation course, it can be termed a point source outbreak. If the exposure was continuous or variable, it can be termed a continuous outbreak or intermittent outbreak, respectively.

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Propagated outbreak

In a propagated outbreak, the disease spreads from person-to-person. Affected individuals may become independent reservoirs leading to further exposures. Many epidemics will have characteristics of both common source and propagated outbreaks. For example, secondary person-to-person spread may occur after a common source of exposure or environmental vectors may spread a zoonotic disease agent.

Transmission Airborne transmission - Spread of infection by droplet nuclei or dust in the air. Without the intervention of winds or drafts the distance over which airborne infection takes place is short IE, 10 to 20 feet (Stawicki et al., 2020). ●

●

●

●

●

Arthropod transmission - Transmission by an insect, either mechanically through a contaminated proboscis or feet, or biologically by the growth of a pathogen in the arthropod. Biological transmission - This transmission Involving a biological process, e.g., passing a stage of development of the infectious agent in an intermediate host. Biological transmission - Involving a biological process, e.g., passing a stage of development of the infecting agent in an intermediate host. Contact transmission - The disease agent is transferred directly by chewing, biting, sucking, or indirectly by drinking of nonpotable water, inhalation of droplets, traveling in contaminated vehicles. Fecal-oral transmission - The infectious agent from the infected host’s feces and acquired by the susceptible host through the ingestion of contaminated material.

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Cyclopropagative transmission - The agent undergoes both development and multiplication in the transmitting vehicle. Developmental transmission - The agent undergoes some development in the transmission vehicle. Horizontal transmission - Lateral spread to others in the same group and at the same time, spread to contemporaries. Propagative transmission -The agent multiplies in the transmission vehicle. Vertical transmission - From one generation to the next by intrauterine infection of the fetus. Some retroviruses are transmitted in the germ line, i.e., their genetic material is integrated into the DNA of either the ovum or sperm.

CHOLERA PANDEMICS I-VI (1817-1899) The first major Cholera epidemic hit British-colonized India in 1817 where the first case was reported on 23rd August 1817. Then the epidemic was recurring with heavy death toll and crippling economic impacts - 2nd Cholera Pandemic (1829), 3rd Cholera Pandemic (1852), 4th Cholera Pandemic (1863), 5th Cholera Pandemic (1881) and 6th Cholera Pandemic (1899).

BOMBAY PLAGUE EPIDEMIC (1896) This plague began in September 1896 in colonial Bombay creating a lot of social and political frenzy which killed thousands and many people were forced out of the city (Ebrahim, 2016).

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POLIO EPIDEMIC (1970-1990) India was the worst affected by polio and the incidence of polio in India was very high in both urban and rural. The situation is better after compulsory Polio Vaccination program and after the introduction of the vaccine and concerted extensive vaccination drives, India was declared polio-free in January 2011 (John and Vashishth, 2013).

SMALLPOX EPIDEMIC (1974) Variola major or Variola minor are the main causative agents of Smallpox. According to the studies, 60% of the smallpox cases globally reported in India and was more virulent than the other parts of the world. India launched the National Smallpox Eradication Program (NSEP) to overcome this horrible situation but failed to attain the desired results. WHO along with the Soviet Union sent some medical assistance to India and in March 1977 India was free from smallpox. The smallpox epidemic of India was one of the worst smallpox epidemics of the 20th century and occurred three years (Bloom and Cadarette, 2019). Over 15,000 people contracted and died between January and May 1974. Most of the deaths from smallpox happen in Indian states of Orissa, Bihar, and West Bengal. In 1980, smallpox was certified as being eradicated from the world due to the WHO’s smallpox eradication program (Weinraub, 1974).

PLAGUE (1994) The pneumonic plague hit Surat in September 1994 and of the 5150 cases, 2793 (54.2%) were reported from Maharashtra, 1391 (27.0%) from Gujarat, 749 (14.5%) from Delhi, and 169 (3.3%) from the states of Andhra Pradesh, Haryana, Madhya Pradesh, Rajasthan, Uttar Pradesh, and West Bengal (MMWR, 1994).

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MENINGOCOCCAL MENINGITIS EPIDEMIC (2005) Meningococcal disease is seen in all parts of the country, though in low numbers, with outbreaks of the disease occurring from time to time. In early 2005, a sudden surge had been noted in meningococcemia and meningococcal meningitis cases which are reported from Delhi, surrounding Uttar Pradesh and Maharastra. Around 430 cases of meningococcal meningitis were reported as of June 2005. Case management, early detection through surveillance was aimed at prevention of spread (NCDC, 2009).

DENGUE OUTBREAK (2006) Dengue has been endemic in India from the nineteenth century, dengue haemorrhagic fever (DHF) was first reported in 1987. The outbreak began in early September of 2006 and the first case was reported from Delhi and then cases from Rajasthan, Kerala, Gujarat, Chandigarh, and Uttar Pradesh are noted (Mavalankar and Parvathy, 2007). In 2012 an outbreak occurred in India during which a total of 47,029 DF cases and 242 deaths were reported. In the last decade, dengue has attained a pan-India stature where outbreaks and deaths have been reported from majority of the states (NVBDCP, 2021).

CHIKUNGUNYA OUTBREAK (2006) Chikungunya virus (CHIKV) re-emergence in 2005, transmission has been documented in most of the Indian states with varied rates. Kumar et al. (2021) observed that the CHIKV transmission was higher in the southern, western, and northern regions of India than in the eastern and northeastern regions. However, a higher proportion of the population

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susceptible to CHIKV in the eastern and northeastern regions suggests a susceptibility of these regions to outbreaks in the future too.

GUJARAT HEPATITIS OUTBREAK (2009) In Gujarat many people in February 2009 were infected with Hepatitis B which caused by the transmission of the infected patient’s blood and body fluids. Local doctors of Gujarat were suspected of causing the outbreak with used and contaminated syringes. Hepatitis B outbreak was a cluster of hepatitis B cases that appeared in Modasa, northern Gujarat, India in 2009. Over 125 people were infected and up to 49 people died (Dash and Das, 2013).

ODISHA JAUNDICE OUTBREAK (2014-2015) Odisha witnessed an outbreak of Jaundice in September 2014, and this outbreak was suspected to be the contaminated water sources (Paul et al., 2015). According to various reports a total of 3,966 jaundice cases have been reported in various districts and Sambalpur town alone accounted for 2,945 cases (Deccan Herald, 2015).

SWINE FLU OUTBREAK (2014-2015) In 2014, several reports of the H1N1 virus started to emergence. Swine flu is like influenza virus and mainly affected states were Gujarat, Rajasthan, Delhi, Maharashtra and Telangana Even after several public awareness drives, by March 2015, about 33,000 cases were reported across the country and about 2000 people lost their lives (Murhekar and Mehendale, 2016).

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ENCEPHALITIS OUTBREAK (2017) In the year 2017, the city of Gorakhpur in Uttar Pradesh witnessed an increase in the number of children deaths, mainly due to mosquito bites. Children died of Japanese encephalitis and acute encephalitis syndrome and both of these viral infections cause brain inflammation and results in physical disabilities and even deaths. The outbreak began in early September 2016 accounted for 325 cases from 164 villages in the district by end of November, including 91 deaths. The cases were reported from 164 villages of the district. Most of the cases were children below 10 yr of age, mean age being three years. Common clinical symptoms included fever, recurrent vomiting, pain in abdomen, convulsions and loss of consciousness (Narain et al., 2017).

NIPAH VIRUS OUTBREAK (2018) In Kerala, Nipah Virus was reported in May 2018; an infection caused by guava fruit bats and was widespread within a few days. Kerala state government implemented several precautionary measures in order to downplay the spread of the Nipah virus. By the month of June, due to the preventive measures implemented, the outbreak was curbed. The outbreak was localized in Kozhikode and Malappuram districts of Kerala (Arunkumar et al., 2019).

MALARIA AND TB CONTINUE TO GRIP INDIA India continues to report thousands of cases of malaria and in 2018 alone, 228 million cases of malaria were reported globally, according to WHO. 85% of the cases were reported in 19 countries in Sub-Saharan Africa and India. Same is the case with deaths due to malaria. 2% of the global deaths due to malaria are reported in India. India also accounted

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for 3% of the total malaria cases in the world and 47% of the total Plasmodium vivax cases of malaria. Tuberculosis has resulted in the death of 4.4 Lakh people in 2018 alone according to National Tuberculosis Control Programme Report. One of India’s Sustainable Development Goals (SDG) target is to be TB free by 2025.

CORONAVIRUS (2019) COVID-19 (Coronavirus disease) is a new strain, has not been previously identified in humans before 2019. The major symptoms include respiratory distress, fever, cough, shortness of breath, etc. and lead to like pneumonial infections, severe acute respiratory problems and even death (Andersen et al., 2020). A total of 29,823,546 Coronavirus cases are reported from India with 385,167 deaths as on 19th June 2021. The Covid -19 pandemic hit the country by affecting every nook and corner.

CONCLUSION India has a long history of fight with epidemics and pandemics from time immemorial. Good medical care and efficient research have made it possible to fight every infection and luckily, the country was able to even eradicate a few. It can be pointed out that majority of the infectious diseases have become widespread due to the mere lack of sanitation and crowded environment. The typical tropical climate and seasonal rains are the major predisposing factors which influences vector population too in disease transmission dynamics. Changes in the population age structure, improvements in the nation’s economic status, shift in lifestyle and duality of disease burden testify to the demographic, development and health transition occurring in the country. Population stabilization, poverty alleviation, life-style modification, surveillance and control of

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communicable and non-communicable diseases constitute the major challenges demanding urgent attention today to curb future epidemics.

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John, T. J. and Vashishtha, V. M. (2013). Eradicating poliomyelitis: India’s journey from hyperendemic to polio-free status. Indian J. Med. Res. 137:881-894. Kumar, M. A., Kamaraj, P., Khan, S. A., Allam, R. R., Barde, P. V., Dwibedi, B., Kanungo, S., Mohan, U., Mohanty, S. S., Roy, S., Sagar, V., Savargaonkar, D., Tandale, B. V., Topno, R. K., Kumar, C. P. H., Sabarinathan, R., Kumar, V. S., Bitragunta, S., Grover, S. S., Lakshmi, P. V. M., Mishra, C. M., Sadhukhan, P., Sahoo, P. K., Singh, S. K., Chander Prakash Yadav, Elangovan Ramya Dinesh, Thiyagarajan Karunakaran, Chinnasamy Govindhasamy, Rajasekar, T. D., Jeyakumar, A., Suresh, A., Augustine, D., Kumar, P. A., Kumar, R., Dutta, S., Toteja, G. S., Gupta, N., Clapham, H. E., Mehendale, S. M. and Murhekar, (M. V. 2020). Seroprevalence of Chikungunya virus infection in India, 2017: a cross-sectional population-based serosurvey. Lancet Microbe. 2:e41-47. Lodge, T. 1603. A treatise of the plague: containing the nature, signs, and accidents of the same, with the certaine and absolute cure of the fevers, botches and carbuncles that raigne in these times. London: Edward White. Martin, Paul M. V., Martin-Granel, Estelle 2006. “2,500-year evolution of the term epidemic.” Emerging Infectious Diseases. 12 (6): 976-80. Mavalankar, Dileep, Priya Shastri and Parvathy Raman. “Chikungunya epidemic in India: a major public-health disaster.” The Lancet Infectious Diseases 7.5 (2007):306-307. McCall, Sherman, Vilensky, Joel A., Gilman, Sid, Taubenberger, Jeffery K. 2008. “The relationship between encephalitis lethargica and influenza: A critical analysis.” Journal of Neurovirology. 14 (3): 177185. MMWR. (1994). International Notes Update: Human Plague - India, 1994. Morbidity and Mortality Weekly Report. 43(39):722-723. Murhekar, M. and Mehendale, S. (2016). The 2015 influenza A (H1N1) pdm09 outbreak in India. Indian J. Med. Res. 143(6):821-823.

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NCDC. (2009). Meningococcal Disease: Need to remain alert. Monthly Newsletter of National Centre for Disease Control, Directorate General of Health Services, Government of India 13(3):01-08. NDTV Web Version, “More dengue, chikungunya cases reported,” 2006. NVBDCP. 2021. Dengue/DHF situation in India. ttps://nvbdcp.gov.in/ index4.php?lang=1&level=0&linkid=431&lid=3715. Accessed on 19.06.2021. Outbreak Investigation of Nipah Virus Disease in Kerala, India, 2018. Paul, S., Mahajan, P. B., Bhatia, V., Sahoo, J. R. and Hembram, D. K. (2015). Investigation of jaundice outbreak in a rural area of Odisha, India: Lessons learned and the way forward. Community Acquir. Infect. 2:131-136. Ravenholt, R. T., Foege, William, H. 1982. “1918 Influenza, Encephalitis Lethargica, Parkinsonism.” The Lancet. 2, 8303. 320 (8303): 860864. Rice, A. L., Sacco, L., Hyder, A., Black, R. E., 2000. Malnutrition as an underlying cause of childhood deaths associated with infectious diseases in developing countries. Bulletin of the World Health Organization. 78:1207-21. Stawicki, Stanislawp, et al., 2020. “The 2019-2020 novel coronavirus (Severe acute respiratory syndrome coronavirus 2) pandemic: A joint American college of academic international medicine-world academic council of emergency medicine multidisciplinary COVID19 working group consensus paper.” Journal of Global Infectious Diseases. 12 (2): 47-93. Von Economo, K., 1917. “Die Encephalitis lethargica.” Wiener klinische Wochenschrift (in German). Leipzig and Vienna: Franz Deuticke 1918. 30: 581-585. Weinraub, B., 1974. “Smallpox Grows in India; Worst Over, Officials Say.” The New York Times. WHO. 2004. “China’s latest SARS outbreak has been contained, but biosafety concerns remain - Update 7.” World Health Organization. Worldmeter. (2021). https://www.worldometers.info/coronavirus/country /india/. Accessed on 19.06.2021.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 9

RISE OF MICROBES AND PANDEMICS IN SHAPING HUMAN CIVILIZATION M. Hayarnnisa*, Ann Mary Jacob and S. M. Merlin Department of Zoology Government Arts and Science College, Elanthoor, Pathanamthitta, Kerala, India

ABSTRACT Until less than a few decades ago, the virus caused diseases wereout of the limelight; hence the research in this area was meager. In 2002 and consecutive years the stages changed drastically with the findings of new pathogenic viruses, including Severe Acute Respiratory Syndrome (SARS-CoV-1), Middle Eastern Respiratory Syndrome (MERS–CoV) and the recent zoonotic SARS-CoV-2, has caused alarm across the globe. SARS-CoV-2 is an airborne disease circulated by symptomatic patients and also asymptomatic individuals undergoing incubation of the disease. SARS-CoV-2 causes a “cytokine storm syndrome”, characterized by a severe and fatal uncontrolled systemic inflammatory response enhanced by the activation of interleukin 6 (IL6) and that can lead to organ failure and mortality. Risk factors include *

Corresponding Author’s Email: [email protected].

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M. Hayarnnisa, Ann Mary Jacob and S. M. Merlin old age, hypertension, diabetes, cardiovascular disease and can be categorized as a multi-organ disease. Epidemiology is crucial to the fight against any disease. The knowledge of how diseases spread, and why, has figured high in the struggle to understand, contain and respond to COVID-19. Investigations of data on infections and deaths,that model the virus’s spread, have driven policy judgments all over the globe.This review summarizes the current knowledge on the history of the pandemic in detail from plagueto COVID-19.

Keywords: SARS-CoV-2, COVID-19, Cytokine Storm syndrome, interleukin 6, pandemic

INTRODUCTION The pandemic is a type of disease that affects the human population throughout the world.A disease or illness is not known as a pandemic simply because many people are killed by it; it must also be contagious (Dodds and Walter 2019). Cancer kills several individuals, but since the disease is not viral or contagious, it is not treated as a pandemic.This chapter briefly examines ten of the major pandemics that have swept the globe at various times in the past, discussing their epidemiology and effects on human society, the sociocultural and medical responses they gave rise to. They were selected for their specific character, antibiotic resistance, mutation rates and high mortality rates.In the Holy bible Book of Revelation, Chapter 16, seven bowls of God’s wrath will be dumped on the World by angels, again some of the bowls containing plagues that are likely to be contagious in nature: according to the Biblical views, pandemic outbreaks are the bookends of human races. “So the first angel went and poured out his bowl on the earth, and harmful and painful sores came upon the people who bore the mark of the beast” (Revelation 16:2).

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PLAGUE Plague is a prehistoric epidemic that was identified in North Africa and the Middle East during Classical times. The underlying cause of the plague, an extremely deadly illness caused by infection of the gramnegative bacterium Yersinia pestis, has been studied by scientists for over a decade (Byrne 2004). The zoonotic character of the infection was among their most significant findings and that plague occurs in natural cycles comprising transmission between rodent hosts and flea vectors (Karlen 1996). The plague had changed the role of the middle class people, capital accumulation, welfare distribution and disrupted sociopolitics significantly with the shift from feudalism to centralized governments (Bell and Lewis, 2004).

“SPANISH FLU” PANDEMIC (1918–1920) The Spanish flu pandemic was the first true worldwide pandemic in the first decades of the twentieth century and the first to emerge in the sense of scientific medicine, with specialties such as infectious diseases and epidemiology researching the essence of the illness and the trajectory of the pandemic as it proceeded (Wald 2008). That is only the real global pandemic with catastrophic effects for populations around the world as of this moment. It was caused by the influenza virus strain H1N1, a strain that in the early years of the twenty-first century saw encore epidemic. Despite developments in epidemiology and public health, despite its name, the true cause of Spanish flu remains unclear both at the time and in subsequent decades. These questions are perpetuated by the conditions of the Spanish flu. It took place amid the First World War, with severe censorship in place and reasonably modern means of transport, including intercontinental travel. The lethal H1N1 strain of the influenza virus spread to every region of the globe. In addition to Europe, where large troop movements and overcrowding have led to massive dissemination,

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the outbreak has ravaged the USA, Asia, Africa and the Pacific Islands (Crawford 2018). The death rate for the Spanish flu ranged from 10% to 20%. When more than a fifth of the world’s population caught the flu at some point, the death rate was massive – well over 50 million, probably 100 million dead (Huremovic 2019). It killed more people in a year than Black Death killed in a century. This pandemic, unusually, had a lethal impact on mainly young and previously stable individuals. This is possibly due to the triggering of a cytokine storm that disrupts the immune system. August 1918, influenza had evolved into an even more virulent and life-threatening form, emerging to kill all of those who escaped it during the first wave. Spanish flu had a profound effect on our ccivilization. Many influential politicians, musicians and scientists were either infected by or succumbed to the flu (Murray and Kenneth 2006).

HIV PANDEMIC (1980) HIV/AIDS is a global pandemic cascading through decades, nations and cultures presenting new problems with every new version and with every new community it impacts. It began in the early 1980s in the United States, generating considerable public interest as HIV inevitably escalated to AIDS and finally to death. The early spread of HIV was characterized by its prevalence among the gay community and high mortality, which contributed to marked social alienation and stigma (Piot and Bernhard 2001). HIV affects about 40 million people worldwide (prevalence rate: 0.79 percent) and has killed about the same number of people since 1981.It caused around one million deaths a year worldwide (down from almost two million in 2005). Although it is a global public health phenomenon, the HIV outbreak is especially troubling in some sub-Saharan regions. In African countries and US has a disproportionate effect on the gay community and transgendered women. HIV has attracted considerable public health support, both domestically and globally as well as pharmaceuticals, as a comparatively slow pandemic (Fraser et al., 2011).

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Advances in therapy (protease inhibitors and antiretrovirals) have made HIV a chronic disease that can be monitored by medicines.It is a rare infectious illness that has been able to draw exposure to mental wellbeing.

SMALLPOX OUTBREAK IN FORMER YUGOSLAVIA (1972) Smallpox was a highly contagious disease for which Edward Jenner developed the world’s first vaccine in 1798 caused by the Variola virus.It was a highly contagious disease with prominent skin eruptions and mortality of about 30%. It may have been responsible for hundreds of millions of fatalities in the twentieth century alone.Due to global effort under Donald Henderson’s mentorship in 1967, smallpox was eradicated within a decade of global eradication (Moss 2011). The infection of smallpox in the former Yugoslavia in 1972 was far from an epidemic, let alone a pandemic,but it exemplified the challenges of a rapidly spreading, highly contagious disease in the modern world. It began with the rise of a pilgrim from the Middle East who had evolved a fever and skin eruptions (Washer 2010). Microbes that infect other animals confront host immune responses, and must subdue or elude innate and adaptive immune responses to successfully establish infection. The effect of escape mutations and antigenic variation in influenza viruses is distinguished for human and public health, as it offers to the need to produce and deliver new influenza vaccines nearly every year and it provides for global pandemics when new antigenic variants are generated that are not recognized by antibodies generated by prior vaccination or infection/antigenic variation is a common strategy in multiple other pathogens. The effect of antigenic variation on pathogen survival, replication, and transmission is established by a broad range of pathogens, including viruses, intracellular and extracellular bacteria, and intracellular and extracellular eukaryotic parasites. Furthermore, multiple molecular mechanisms bear antigenic variation, including nucleotide substitution, gene exchange, recombination to place different copies of a

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multigene family into a transcriptionally-active site, alternative transcription without recombination, and transcriptional selection by phase variation. Lastly, antigenic variation includes an antibody, CD4, and CD8 T cell recognition.

NIPAH (1999) Nipah is a viral disease that affects both humans and animals. Chronic lung diseases, encephalitis and even mortality can result. Occurrences of Nipah have been confirmed mostly in Southeast Asia (i.e., Malaysia, Singapore, India, and Bangladesh).The Nipah incident confirmed in the Kozhikode and Malappuram districts of Kerala in May 2018 was the quarter in the Nipah Virus occurrences in India in 2001 and 2007, both in West Bengal (Singh et al., 2019).

SARS (2003) Severe Acute Respiratory Syndrome (SARS) was the very first epidemic of the twenty-first century to draw widespread interest. The SARS Coronavirus (SARS-CoV) originated in China and infected less than 10,000 people, primarily in China and Hong Kong, as well as in other countries, such as 251 cases in Canada (Toronto).This epidemic was one of the first acute infections with facets of mental health studied in the process and the response, in various parts of the world and different populations, generating important evidence on the influence of infectious respiratory outbreaks on infected people, communities and cultures including mental health issues encountered by healthcare professionals (Fong 2017).

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MERS (2012) Middle East Respiratory Syndrome (MERS) is a viral respiratory condition that is new to humans. It was first recorded in Saudi Arabia in 2012 and it has since distributed to several other nations, such as the United States. Almost all of the individuals affected with MERS-CoV had serious respiratory diseases, including fever, cough, and shortness of breath.A lot of them have suffered with this disease and mortality rate was high (Dawson 2019). The transmission of airborne infectious diseases such as SARS, H1N1, and MERS not only diminishes people’s outdoor activities but also affects a nation’s economy, including direct sales. Globalization, which is distinguished by the various international movement of people and goods, has made the spread of such diseases to other nations unpredictable.

EBOLA OUTBREAK (2014–2016) Ebola virus, native to Central and West Africa, with fruit bats likely to act as a reservoir, occurred in a small village in Guinea in December 2013. Borne primarily within families, it entered Sierra Leone and Liberia, where it managed to produce significant outbreaks over the following months, with more than 28,000 cases and more than 11,000 deaths reported (Cenciarelli 2015). A relative handful of cases have been reported in Nigeria and Mali, but these infections soon suppressed the Ebola epidemic, which has been the greatest outbreak of Ebola infection to date, generated worldwide attention when atravelerfrom Liberiadied of pneumonia in Texas in September 2014, infected two nurses caring for him, and caused considerable public alarm about potential Ebola outbreaks (Oldstone 2017). This led to significant public health and military effort to address the outbreak and help contain it on site. This pathogen is an expanding threat to human populations since its distribution range is increasing quicker than anticipated. The Ebola

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outbreaks in Western Africa and the Democratic Republic of Congo have fast spread affecting huge numbers of individuals in five African countries. The disease has reached the United States and Spain. This situation represents a new hurdle to control the spread of the disease. Innovative drugs have been used to treat a few infected people with promising results.

ZIKA (2015–2016) Zika was a little established, latent virus found in rhesus monkeys in Uganda. Before 2014, the last reported human outbreak was documented in Micronesia in 2007. The virus was then reported in Brazil in 2015, following an epidemic of mild fever that triggered a flat, pinkish rashes on skin, bloodshot eyes, fever, knee pain and fatigue; symptoms similar to dengue (Cauchemez et al., 2016). It’s a mosquito-borne disease (Aedesaegypti), but it can be transmissible. Although its moderate course, which originally made it unremarkable from a public health viewpoint. Infection with Zika can lead to Guillain-Barre syndrome in adults and more unfortunately the victims are pregnant women,lactating women and children below five (Jones 1989)

CORONA VIRUS (2019) The coronavirus epidemic came to light on 31 December 2019, when China notified the World Health Organization of a cluster of cases of pneumonia of an unexplained origin in Wuhan City, Hubei Province. Consequently, the epidemic spread to more provinces in China and the rest of the world. It has now been declared as a pandemic by the WHO (Zhang et al., 2020).

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The SARS-CoV-2 virus is quickly mutating. This is a problem since these highly communicable versions of SARS-CoV-2 are now found in the U.S., U.K, South Africa, India and other countries (Allam et al., 2020). The genetic material of all viruses is encoded in either DNA or RNA; one interesting feature of RNA viruses is that they change much more rapidly than DNA viruses. Unfortunately, the coronavirus is RNA virus; though it challenges our health care system and scientific community. Nevertheless, at the time of reporting, access to vaccines that inhibit life-threatening infectious diseases continues inequitable to all infants, children and adults in the world. This is a dilemma that many individuals and companies are struggling hard to approach globally.

CONCLUSION As this chapter makes clear, incidences of pandemics in detail, the recent pandemic coronavirus is just another incident in the legacy of human civilization against microbes. This fight is going to continue forever, while mutation is a natural occurrence in the world and can cause new disease outbreaks at any time. Epidemics are flaring up with some corner or another corner across the World.Outbreaks of infection also been regional within a fraction of days, it will spread to distant edges. Therefore, now it’s the peak time to be extra vigilant. Surveillance of wildlife for high-risk pathogens, surveillance and risk reduction in people at high risk of contact with wildlife, improve biosecurity of the wildlife trade and animal markets should be followed with strict enforcement of laws.

REFERENCES Allam, Mayar, ShuangyiCai, Shambavi Ganesh, MythreyeVenkatesan, SaurabhDoodhwala, Zexing Song, Thomas Hu, Aditi Kumar, Jeremy

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Heit, and Ahmet F. Coskun .2020. “COVID-19 diagnostics, tools, and prevention.”Diagnostics 10, no. 6: 409. Bell, Clive, and Maureen Lewis. “The Economic implications of epidemics old and new.”World Economics, vol 5, no 3, 2004, pp. 137-174. Byrne, J. P. 2004. The black death. Greenwood Publishing Group. Cauchemez, Simon, Marianne Besnard, PriscilliaBompard, Timothée Dub, Prisca Guillemette-Artur, and Dominique EyrolleGuignot.2016. “Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study.”The Lancet 387, no. 10033, 2125-2132. Cenciarelli, Orlando, Stefano Pietropaoli, Andrea Malizia, MariachiaraCarestia, Fabrizio D’Amico and Alessandro Sassolini. 2015, “Ebola virus disease 2013-2014 outbreak in west Africa: an analysis of the epidemic spread and response.” International journal of microbiology. Crawford, Dorothy H .2018. Viruses: a very short introduction. Oxford University Press. Dawson, Patrick, Mamunur Rahman Malik, FaruqueParvez, and Stephen S. Morse. 2019. “What have we learned about Middle East respiratory syndrome coronavirus emergence in humans? A systematic literature review.” Vector-Borne and Zoonotic Diseases 19, no. 3: 174-192. Dodds andWalter. 2019. “Disease now and potential future pandemics.” In The World’s Worst Problems, pp. 31-44. Springer, Cham. Fong, I. W. 2017. “Emerging zoonoses.” Emerging Infectious Diseases of the 21st Century. Springer International. Fraser-Hurt, Nicole, Khangelani Zuma, Peter Njuho, FadzaiChikwava, and Emma Slaymaker. (2011). “HIV Epidemic, Response and Policy Synthesis.” Huremovic, Damir. 2019. “Brief history of pandemics (pandemics throughout history).” In Psychiatry of Pandemics, pp. 7-35. Springer, Cham.

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Jones, John Verrier, Dianne P. Mosher, Edith Jones, C. Noel Williams, Dickran Malatjalian, Roland I. Carr, and Mervat Mansour.1989. “Antibodies to cardiolipin in patients with primary biliary cirrhosis.” Canadian Journal of Gastroenterology 3, no. 3: 98-102. Karlen, A .1996. Man and microbes: disease and plagues in history and modern times. Simon and Schuster. Moss, Bernard. 2011. “Smallpox vaccines: targets of protective immunity.” Immunological reviews 239, no. 1: 8-26. Murray, Christopher JL, Alan D. Lopez, Brian Chin, Dennis Feehan, and Kenneth H. 2006.” Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918–20 pandemic: a quantitative analysis.” The Lancet 368, no. 9554 22112218. Oldstone, Michael BA, and Madeleine R. Oldstone.2017. Ebola’s Curse: 2013-2016 Outbreak in West Africa. Academic Press. Piot, Peter, Michael Bartos, Peter D. Ghys, Neff Walker, and Bernhard Schwartlander. 2001. “The global impact of HIV/AIDS.” Nature 410, no. 6831 (2001): 968-973. Singh, Raj Kumar, KuldeepDhama, Sandip Chakraborty, Ruchi Tiwari, SenthilkumarNatesan, RekhaKhandia, and Ashok Munjal. 2019. “Nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies–a comprehensive review.” Veterinary Quarterly 39, no. 26-55. Wald, Priscilla. 2008 Contagious: cultures, carriers, and the outbreak narrative. Duke University Press. Washer, Peter.2010. Emerging infectious diseases and society. Springer. Zhang, Zuqin, Wei Yao, Yan Wang, Cheng Long, and Xinmiao Fu.2020 “Wuhan and Hubei COVID-19 mortality analysis reveals the critical role of timely supply of medical resources.” Journal of Infection 81, no. 1 :147-178.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 10

COVID-19 PANDEMIC: A BOON OR BANE FOR NATURE Asha Ramachandran*, PhD Department of Botany Government College Kottayam, Kerala, India

ABSTRACT The global crisis aroused due to COVID 19 pandemic is a reminder that we all are mere players in the hands of nature, the supreme power controlling humankind for decades. The initial phase of this disease was a grace period for mother earth. Due to restricted movements of people within their respective cities, there has been a relief for the environment – no exhausts from factories, no fumes from cars, clean rivers and oceans, clear sky, and fresh air to breathe. Besides making us aware of the importance of co-existence in nature, the pandemic dramatically helped to reduce carbon emissions globally. As far as the environment is concerned, COVID 19 turned out to be a blessing in minimizing the pollution level by limiting the anthropogenic activities to an extend. This disaster came out as a stroke of luck to nature which was getting worse day by day. The environmental pollution index throughout the *

Corresponding Author’s Email: [email protected].

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Asha Ramachandran globe is declining every day in a dramatic way after the lockdown period, which indicates the world is a self-healing system that balances all the ebb and flow in its own way. On the other side, the huge medical waste and human waste accumulated to overcome the pandemic ridden period has enhanced our impact on the environment negatively. It poses a serious threat to the biosphere and the harmony of life maintained. Our oceans and landfill sites are already overwhelmed with the amount of waste we generated, and the emergence of this pandemic added up to the situation, resulting in increased demand for PPE such as masks, gloves, face shields etc., all ending up in the natural environment. The pandemic forced a shift in the nature of education and work, utilizing emerging technologies and electronic machines will impose another serious hazard as dumping e-waste in the near future. Nature is thus creating numerous challenging and adverse situations for us to be more considerate towards using its natural resources and demanding to be more innovative and judicious at these times to fight the battle against COVID 19 and emerge out as successful from such situations.

Keywords: COVID 19, pandemic, anthropogenic, biosphere

INTRODUCTION The global outbreak of Corona Virus Disease 2019 (COVID-19) has badly affected every realm of human lives and the environment. The measures that have been taken to control the spread of the virus, and the slowdown of social and economic activities all over the world, have significant effects on the environment. The COVID-19 lockdown in almost every nation in the world will hopefully prove to be an eyeopener for the public and is certainly a strong message to climate change deniers and science skeptics. While humans feel suffocated staying at home for a long time, nature is breathing more easily than in the previous years. The effective measures identified to reduce the spread of disease include wearing face masks and hand gloves, washing hands with soap, frequent use of the antiseptic solution and maintaining social distance (WHO 2020). To control the spread of the virus and reduce the increasing mortality rate, governments of most affected countries limited the movement of people. India restricted the movement of the largest number

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of people (approximately 1.3 billion) as a preventive measure of COVID19, which started on March 24, 2020 (Somani et al., 2020). Except for emergency services like medical, food, fire, police etc., all others, including the educational sector, are forced to shut down to encourage people to stay at home. All the public transport services were suspended, except emergency services, during the lockdown. Governments effectively managed the situation to control the spread of the virus by implementing strict laws and new strategies to avoid the crowding and spreading of the pandemic. The world has been witnessed the most extensive travel restrictions after World War II during this pandemic ridden time. As of April 7, 2020, World Economic Forum reported that nearly 3 billion people faced with some form of lockdown globally (WEF 2020). Overall, COVID-19 has made a huge impact globally by disrupting the socioeconomic and cultural background. Still, it directly or indirectly affected the environment to improve the quality of air and water, reduce noise and restore ecology. On the other side, the increased use of personal protective equipment (PPE) (e.g., face mask, hand gloves, gowns, goggles, face shield etc.), their haphazard disposal and generation of a huge amount of hospital waste leads to increased pollution rate, thereby creates much more environmental burden than before.

EFFECT OF COVID-19 ON THE ENVIRONMENT DURING LOCKDOWN PERIOD In many ways, the lockdown has been a boon to life on earth. It offers a chance for nature to recover herself while also providing the rivers, soil, and animals with a brief relief from the relentless assault that humans expose them to. The pandemic has helped significantly improve air quality in different cities across the world, reduces greenhouse gas emissions, lessens water pollution and noise, and reduces the pressure on tourist destinations, which may assist with the restoration of the ecological system. When noise and air pollution in cities reduce so

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suddenly and drastically, of course, the animals living in our vicinity will be more fearless to show themselves. But certain groups of animals are negatively affected because of the lockdown, which makes their lives quite difficult. The other animals in trouble during the lockdown are the street dogs and stray cattle since they have not been properly fed.

REDUCTION OF AIR POLLUTION AND GREENHOUSE GAS EMISSIONS As industries, transportation, and companies have been closed down because of the measures taken to control the virus, nearly 50% reduction of N2O and CO occurred in many major cities worldwide. NO2 is emitted from the burning of fossil fuels, 80% of which comes from motor vehicle exhaust. NO2 causes acid rain with the interaction of O2 and H2O, and several respiratory diseases for humans. The levels of NO2 reduced by almost 70% in Delhi, one of the most air-polluted cities in India (Thiessen 2020). NASA has been releasing new satellite images and data revealing the reduction in air pollution, reduction of nitrogen dioxide (NO2), and carbon dioxide (CO2), carbon monoxide (CO), particulate matter (PM 2.5) in different places across the world during the lockdown. The ozone hole is showing signs of recovery by itself. Vehicles and aviation contribute almost 72% and 11% of greenhouse gas emissions, respectively. Many countries restricted international traveller from entry and departure to contain the virus, and commercial aircraft companies canceled flights due to fewer bookings. These travel restrictions have resulted in reduced CO2 emissions. It is reported that 96% of air travel dropped globally due to the COVID-19 pandemic (Wallace 2020), which ultimately affects the environment. Less consumption of fossil fuel, decreased demand for oil, reduced global coal consumption, less energy demand etc., rejuvenated nature. It is projected that the pandemic could cut 1,600 metric tons of CO2, equivalent to above 4% of the global total in 2019 (Evans 2020).

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REDUCTION OF WATER POLLUTION In developing countries, the water pollution rate is high as domestic wastes and industrial effluents are dumped into water bodies without much treatment. During the lockdown period, the major industrial sources of pollution have shrunken or completely stopped, helped to reduce the pollution load in water bodies. There is a significant reduction in physicochemical parameters like the concentration of pH, electric conductivity, total coliform, dissolved oxygen, biological oxygen demand and chemical oxygen demand from various rivers during the lockdown in comparison to the pre-lockdown period (Arif et al. 2020). All parameters meet the national drinking water quality standards, which can be used without conventional treatment methods. Ban for tourism, public and water recreation activities made the rivers and ponds undisturbed and resulted in the reappearance of aquatic plants. Reduced industrial water consumption, construction and manufacturing solid wastes, export-import business, movement of merchant ship etc., contributes to reduce emission and marine pollution.

REDUCTION OF NOISE POLLUTION The elevated levels of sound due to various human activities are a serious issue affecting physiological health and causes issues including cardiovascular disorders, hypertension, sleep shortness and hearing loss. Moreover, anthropogenic noise pollution has adverse impacts on wildlife, negatively affecting the balance of the ecosystem. Because individuals are being told to stay at home by their governments, the level of noise in most cities has decreased significantly during the lockdown period. This has resulted in a significant reduction in economic activity, vehicle movement, and communication across the globe. According to the Central Pollution Control Board (CPCB 2020) of India, the noise level of the residential area of Delhi is reduced 55 dB (daytime) and 45 dB (night)

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to 40 dB (daytime) and 30 dB (night), respectively. The lockdown brought back the organisms to their abandoned home, and clean, calm air with the chirping of birds is the evidence of reinstating natural order.

TOURISM AND ECOSYSTEM BALANCE Tourism is one of the best profit earning businesses of many countries nowadays, and the sector has witnessed a remarkable change over the years because of connectivity networks and increased transportation facilities. The tourism industry is considered responsible for 8% of global greenhouse gas emissions (Lenzen et al. 2018). Shutting down of the industry and local restrictions due to the COVID-19 outbreak helps to minimize the number of tourists in the places of natural beauty around the world. Reduction in the energy consumption and other natural resources by the accommodation providers and dumping of wastes, like plastics impairing nature by tourists, is appreciably decreased during the period. The marine ecosystem is improved, and animals are set free to migrate and breed without any human annoyance.

EFFECT OF COVID-19 ON THE ENVIRONMENT DURING POST LOCKDOWN PERIOD 

Increase in biomedical waste generation

The major threat to public health and the environment since the outbreak of COVID-19 is the generation of medical wastes from hospitals, which is increasing at an alarming rate globally. Hospital wastes include biomedical wastes for sample collection of suspected COVID-19 patients, diagnosis, treatment of many patients, and chemicals for disinfection purposes. A sudden rise of hazardous waste and its proper management has become a challenge to the governments and local

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waste management authorities. It is reported that the SARS-CoV-2 can exist a day on cardboard and up to three days on plastic materials and stainless steel (Van-Doremalen et al. 2020). Hence, medical wastes generated (needles, syringes, bandages, masks, gloves, used tissue, discarded medicines etc.) should be managed properly to reduce further infection and environmental pollution, which is now a matter of concern globally. 

Safe use of the equipment and haphazard disposal

People are using face masks, hand gloves and other safety equipment like PPE to protect themselves from COVID-19, but their usage increases the bulk of healthcare waste generated. Most people dump this waste in open places or mix it with household garbage, which later clogs the waterways and worsens pollution. Face masks and other plastic based protective equipment are the potential sources of micro plastic fibers in the environment. Usually, polypropylene is used to make N95 masks and Tyvek for protective suits, gloves, and medical face shields, which can persist for a long time and release dioxin and toxic elements into the environment (Singh et al. 2020). Improper disposal and mixing up of household garbage and hazardous medical waste increases the risk of disease transmission among populations. 

Solid waste and recycling

Dumping of municipal waste adversely affects the climate and environment, leading to increased pollution rates. Increased demand for online shopping and home delivery results in a huge amount of household waste from shipped package materials. Due to the pandemic, waste recovery and recycling activities are postponed or halted in many countries to control viral infection, increasing the pollutants and toxic materials.

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Increased e-waste generation

The pandemic witnessed a digital revolution in the higher education system through online lectures, teleconferencing, digital open books, online examinations, and virtual environments. Also, companies have been forced to adopt new ways, shift from office working systems to work at home culture. The purchase of new technology and electronic gadgets to resume education via online mode and facilitate employees transition from office to work at home during the pandemic has sparked both data security and e-waste generation increasing day by day. 

Impact on waste

The increased volume of non-recyclable waste has led to the generation of huge quantities of organic waste; local waste problems have emerged in addition to much discussed dramatic rise in medical waste and packaging from online shopping. The huge demand for disposable medical products such as single use gloves, surgical masks and PPE has created a deluge of medical waste. As this waste is left for decay, threatening levels of methane emissions are expected to rise in the coming years. The huge amount of solid medical waste is not only an environmental issue, but it puts the life of workers employed for waste collection and disposal at serious risk. Increased use of electronic gadgets to cope with technological adaptations results in huge amounts of ewaste. It is the major source of heavy metal toxicity and contamination. 

Ecosystem at risk

The natural ecosystem and wildlife are also at risk during this pandemic time. Environmental protection workers in national parks and wildlife sanctuaries are required to stay at home during the lockdown, leaving these areas unmonitored and prone to poaching. The killing of rhino in Assam’s Kaziranga National Park, the increase in poaching of wild jaguars and pumas in Columbia and endangered species in countries

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across Asia and Africa are glaring examples of how wildlife is in threat. Deforestation in the Brazilian Amazon rose to 30% recently. The climate crisis has been ticking around, and anthropogenic activities without considering the balance of nature are putting biodiversity at higher risk. 

Other effects on the environment

The application of disinfectants in commercial and residential areas to prevent the spread of the virus may harm the beneficial species to some extend. The SARS-CoV-2 virus was detected in the COVID-19 patient’s faeces and from municipal wastewater in many countries, including Australia, India, Sweden, Netherlands, and the USA (Mallapaty 2020). It is challenging to treat this wastewater before draining them into water bodies in underdeveloped countries.

A NEW FUTURE The COVID-19 pandemic has elicited a global response to fight against the virus for sustainable living and environmental management. Some possible strategies are proposed for global environmental sustainability. 

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Sustainable industrialization policies like less energy-intensive industries, the use of cleaner fuels and technologies, and strong energy efficient systems should be introduced. Proper spacing and a hygienic environment should be maintained among a large number of workers in the same industry. Encourage the use of green and public transport, carpooling, use of the bicycle for short distance etc., helps to keep the environment pollution free. Recommend the use of renewable energy sources like solar, wind, hydro power, geothermal heat and biomass lowers the

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 

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demand for fossil fuels like coal, oil, and natural gas, which can play a significant role in reducing greenhouse gas emissions. Industrial and municipal wastewater should be treated properly before discharge into aquatic systems. Proper care should be adopted in recycling and reusing waste, especially segregation and disposal methodologies for hazardous and infectious medical waste. Ecotourism should practice eco-friendly, promoting sustainable livelihoods, cultural preservation, and biodiversity conservation. Minimum consumption of resources for a sustainable future.

During the lockdown period, pollution levels and carbon emissions decreased, but will these changes be long lasting or a boon for the environment? While the death toll has mounted from a single case in Wuhan to a global pandemic, humans have been forced indoors, even as nature seemed to reboot. We have to explore and analyze the impact of the COVID-19 pandemic on the environment and implement proposed strategies to achieve long-term benefits for global environmental sustainability.

CONCLUSION COVID-19 is a real challenge to humanity; permanent measures to contain the virus are not identified so far. The global response to the fight against the disease and the campaigns going on to make aware of people how to live and survive along with COVID-19 is relief worthy and appreciating. The pandemic affects the climate and environment directly or indirectly, and we need to initiate time-oriented efforts to reach environmental sustainability. The current global pause on commercialism and aggressive exploitation of everything on nature gives us a chance to rethink our relationship with nature. We are witnessing cleaner air; a more silent world, and it can trickle down into our health too. The real challenge now facing is renewing eco-friendly climatic approach. There

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may be a considerable decrease in public transport due to fear of contagion and reliance on individual cars, which will result in increased pollution levels. However, efforts from all sectors are welcoming– companies can reduce business travels, opt for video conferencing to achieve the same results; people can prioritize health and family bonds by choosing to stay home rather than vacationing and travelling, cultivate positive habits, cut down on food waste and luxuries. The challenges posed by COVID-19 are high, but they will soon pass. A sustainable life is expected in future so that we can revive the crushed economy and sociocultural aspects.

REFERENCES Arif, Mohammad, Kumar, Rajesh, Parveen, shagufta. 2020. “Reduction in Water Pollution in Yamuna River Due to Lockdown Under COVID-19 Pandemic” ChemRxiv. Preprint. https://doi.org/10.26434/ chemrxiv.12440525.v1. CPCB. Central Pollution Control Board. 2020. Ministry of Environment, Forest and Climate Change, Government of India. 2020. Daily River Water Quality Monitoring Data. Evans S. 2020. “Global emissions analysis: corona virus set to cause largest ever annual fall in CO2 emissions” Accessed March 5 https://www.carbonbrief.org/analysis-coronavirus-set-to-causelargest-ever-annual-fall-in-co2-emissions. Lenzen, M., Sun, Y.Y., Faturay, F., Ting, Y.P., Geschke, A. and Malik A. 2018. “The carbon footprint of global tourism” Nature Climate Change 8:522–528. Mallapaty S. 2020. “How sewage could reveal true scale of corona virus outbreak” Nature 580:176–177. Singh, N., Tang, Y. and Ogunseitan O. A. 2020. “Environmentally sustainable management of used personal protective equipment.” International Journal of Environment Science and Technology. 54:8500-8502.

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Somani, M., Srivastava, A. N., Gummadivalli, S. K. and Sharma A. 2020. “Indirect implications of COVID-19 towards sustainable environment: an investigation in Indian context.” Bioresource Technology Reports 11:100491. Thiessen T. 2020. “How clean air cities could outlast COVID-19 lockdowns” Accessed March 13 https://www.forbes.com/sites/ tamarathiessen/2020/04/10/how-clean-air-cities-could-outlast-covid19-lockdowns/#292a5e866bb5. Van-Doremalen, N., Bushmaker, T., Morris, D. H., Holbrook, M. G., Gamble, A., Williamson, B. N. and Lloyd-Smith J. O. 2020. “Aerosol and surface stability of SARSCoV-2 as compared with SARS-CoV-1” New England Journal of Medicine 16:1564–1567. Wallace. G. 2020. “Airlines and TSA Report 96% Drop in Air Travel as Pandemic Continues” Accessed February 8 https://edition.cnn. com/2020/04/09/politics/airline-passengers-decline/index.html. WHO. 2020. “Rational use of PPE for corona virus disease (COVID19)” Accessed January 14 https://apps.who.int/iris/bitstream/ handle/10665/331498/WHO-2019-nCoV-IPCPPE_use-2020.2-eng. WEF. 2020. World Economic Forum. Geneva. “High Noon during Corona virus Lockdown” Accessed February 23 https://www. weforum.org/agenda/2020/04/high-noon-lockdown-around-theworld.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 11

MENTAL HEALTH ISSUES IN COVID-19 Hridya Vijay1,* and Nitha Balan 2, PhD 1

University Associate, Curtin University, Perth, Australia 2 Department of Microbiology, Sree Ayyappa College, Eramallikkara, Alappuzha, India

ABSTRACT The new era pandemic which quivered the lives of people across the globe is COVID-19. This was epidemiologically connected to the Huanan Seafood wholesale market in the Hubei province of China and later advanced to all other parts of the world. Followed by the declaration of Covid-19 as pandemic by the WHO, several countries entered a complete lockdown. The symptoms of Covid-19 were invasive and took the lives of millions of people worldwide. Apart from the physical ailments associated with it, the disease had potential impacts in mental health of the patients and survivors which was similar to the conditions in Post-Traumatic Stress syndrome. Nevertheless, we could say that the social media had a greater influence in developing mental illness to the patients apart from the isolation and quarantine. More of a counseling and psychosocial education can help people to thrive from the mental health issues. *

Corresponding Author’s Email: [email protected].

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Keywords: COVID-19, SARS-CoV-2, WHO, mental health issues, psychosocial education

INTRODUCTION In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China, which was epidemiologically connected to the Huanan Seafood Wholesale Market. On inoculating the respiratory samples of patients into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed that to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a betacoronavirus belonging to the subgenus Sarbecovirus. In February, World Health Organization (WHO) renamed it as COrona VIrus Disease 19 pandemic [COVID-19]. The global spread and the millions of deaths caused by the COVID-19 led the WHO to declare a pandemic on 12 March 2020. As yet, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty (Ciotti et al., 2020). The patients with COVID-19 are likely to present symptoms extending from mild to severe with a significant portion of them remaining asymptomatic carriers, who have the potential to spread the disease. The most commonly reported symptoms may be fever (83%), cough (82%) and shortness of breath (31%) (D. Wang et al., 2020). In case of patients with pneumonia, chest X-ray usually shows multiple mottling and groundglass opacities (D. Wang et al., 2020; Zhu et al., 2020). There were also additional astrointestinal symptoms including vomiting, diarrhea, and abdominal pain which are described in atleast 2– 10% of the patients with COVID-19(Chen et al., 2020; D. Wang et al., 2020). In COVID-19, patients generally demonstrate a decline in their lymphocyte and eosinophils counts, lower median hemoglobin values as well as increases in WBC, neutrophil counts, and serum levels of CReactive Protein (CRP), lactate dehydrogenase (LDH), aspartate

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aminotransferase (AST), and alanine aminotransferase (ALT) (Lippi and Plebani 2020). Even though the prime target of coronavirus infection is the lung, the wide distribution of angiotensin‐converting enzyme-2 (ACE2) receptors in certain cases in organs may lead to cardiovascular, gastrointestinal, kidney, liver, central nervous system and ocular damage which has to be closely monitored (Hamming et al., 2004; Renu, Pureti, and Valsala Gopalakrishnan 2020). Often the cardiovascular system gets affected, accompanied with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events (Ciotti et al., 2020; Long et al., 2020).

MENTAL HEALTH ISSUES IN COVID-19 During any outbreak of an infectious disease, the psychological reactions of the population play a crucial role in determining both spread of the disease and the occurrence of emotional agony and social disorder during and post-outbreak. When health care prioritize testing, dropping transmission as well as the treatment for symptoms and critical patient care, psychological and psychiatric requirements should be addressed during any stage of pandemic management (Cullen et al., 2020). In a survey of 1210 respondents from 194 cities in China in January and February 2020 found that 54% of respondents rated the psychological impact of the COVID-19 outbreak as moderate or severe; 29% reported moderate to severe anxiety symptoms; and 17% reported moderate to severe depressive symptoms (Wang et al., 2020). Currently, there is an upsurge in the amount of information and concerns on global mental health, after the hit of COVID 19. It was studied there was a decline in the values of their hematocrit, calcium and phosphorus levels after 2 weeks of isolation as well as there was a significant delay in their normalization of the levels of circulating cellfree genomic DNA (ccf-gDNA) and circulating cell-free mitochondria DNA (ccf-mtDNA), (indicators of psychophysical stress in humans)

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during the hemodialysis among patients on comparison with controls, during the Korean MERS-CoV outbreak in 2015. The patients were treated with hemodialysis in an isolated environment. This data indicates that medical isolation (quarantine) during the Korean MERS outbreak has caused high level of stress in hemodialyzed patients (Kim et al., 2019). Health care providers may also develop psychiatric disorders after coping with stressful community events. As per previous studies, 27% of health care workers reported psychiatric symptoms in 2003, during the SARSCoV outbreak in Singapore (Lee et al., 2018). The rate of symptoms increased even after the isolation (home quarantine). During the COVID-19 emergency, medical workers in Wuhan were dealing with high risk of infection alongside inadequate protection against contamination, work overload, frustration, discrimination, isolation, negative emotions, deprived contact with their families and exhaustion (Kang et al., 2020). The current situation is causing mental health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear (Jones et al., 2017). These mental health issues not only affect attention, understanding and decision-making capacity of medical workers, but also could thwart the fight against COVID-19(Kang et al., 2020; Torales et al., 2020). It is studied that the pandemic-related prophylactic measures such as social distancing, isolation and quarantine, as well as the social and economic fallout can also trigger psychological mediators such as distress, worry, fear, anger, annoyance, anguish, frustration, guilt, helplessness, loneliness, and nervousness. These are the common features of typical mental health suffering that many individuals will experience during and after the pandemic (Ahorsu et al., 2020; Banerjee 2020; Cheung, Chau, and Yip 2008; Xiang et al., 2020). In extreme cases, such mental health conditions may also lead to suicidal behaviors (e.g., suicidal ideation, suicide attempts, and actual suicide). It is well ascertained that depression is the major cause of around 90% of global suicides (Mamun and Griffiths 2020). Similar situations have been reported in previous pandemics as a statistical data revealed that the suicide rate among elderly people increased in Hong Kong both during

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and after the SARS (Severe Acute Respiratory Syndrome) pandemic in 2003 (Cheung, Chau, and Yip 2008). People tend to feel anxious and insecure when the environment around them changes. Rumors grow when the cause or progression of the disease and outcomes are unclear in case of outbreaks of infectious diseases (Ren, Gao, and Chen 2020). Anxiety and fear related to infection generally lead to acts of discrimination and prejudice. This was the underlying reason for targeting and blaming people from Wuhan for the COVID‐19 outbreak by other Chinese people and being stigmatized them by the whole world, which was evident when people started to address the virus as ‘China virus’ and the use of terms such as ‘Wuhan virus’ and the ‘New Yellow Peril’ by the media (Ren, Gao, and Chen 2020). Hypervigilance, for example, can arise because of fear and anxiety and, in severe cases, result in post‐traumatic stress disorder (PTSD) and/or depression (Perrin et al., 2009). In the case of mass quarantine, experiencing social isolation and an inability to tolerate distress escalate anxiety and fear of being trapped and loss of control, and the spread of rumors (Rubin and Wessely 2020). Rumors lead to feelings of uncertainty and are extrinsically linked to issues such as panic buying and hoarding behavior (Usher, Durkin, and Bhullar 2020). Another concern for people contracting the disease in general population may be post-traumatic stress disorder (PTSD) arising from exposure to trauma. The current medical conditions of a life-threatening viral infection like COVID 19, is not considered as a potential trauma, which can lead to PTSD, but the psychopathologic attributes like depression and anxiety disorders can trigger. Certain groups of people are always vulnerable for these kinds of psychosocial effects during pandemic. In particular, people who contract the disease, those at heightened risk for it (including the elderly, people with compromised immune function, and those living or receiving care in congregate settings), and people with preexisting medical, or psychiatric problems are at higher risk for adverse psychosocial outcomes. Health care providers are also particularly vulnerable to emotional distress in the current pandemic, given their risk of exposure to the virus, concern about

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infecting and caring for their loved ones, shortages of personal protective equipment (PPE), longer work hours, and involvement in emotionally and ethically fraught resource-allocation decisions. Their numerous emotional outcomes, including stress, depression, irritability, insomnia, fear, confusion, anger, frustration, boredom, and stigma associated with quarantine, some of which persisted after the quarantine was lifted(Pfefferbaum and North 2020).

CHILDREN AND COVID-19 Recently, several studies are being carried out in the field of mental health and stability of children, especially in the case of trauma and this has become a national public health issue (Blaustein n.d.). Trauma can be explained as a series of “events that overwhelm a person’s ability to adapt to life, leading to strong negative emotions that are associated with the degree of experienced or witnessed threat to self”. As a result of the COVID-19 pandemic, all schools from the kindergarten to 12th grades are closed until the following academic year. Schools are now emphasizing on ensuring students to continue receiving academic sessions, through distance or online instruction. But this is not practical for the children who rely on schools for behavioral and mental health supports. It is very evident that the mental health of children is being viewed as secondary or unrelated to academic success (Blaustein n.d.). Presently, there do not appear to be systematized efforts by schools to offer mental health coping skills services to students who depend on them to address their trauma-related needs. In the absence of such services, the COVID-19 pandemic could be contributing to cumulative trauma for many children across this globe, which may increase the probabilities of developing mood and anxiety disorders and elevated hyperarousal symptoms (Karam et al., 2014) Once children return back to schools, the government should ensure a quick establishment of a new normal (Shapiro et al., 2006). Schools may have to consider population-based mental services in which supports are tailored to promote the overall

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psychological well-being of all students, provide supports to caretaker and school environments, and intervene in significant socioemotional and behavior problems (Doll and Cummings 2007; Phelps and Sperry 20200611).

INFLUENCE OF SOCIAL MEDIA ON COVID-19 In this generation, it is definite that in each community crisis, people tend to seek out event-related information to stay updated on what is happening around. Those people (particularly patients) who had direct contact via phone text messages and used social media for critical updates during the lockdown were exposed to more differing information and stress. Also, higher acute stress was reported by heavy social media users in a study. A report by (Purgato et al., 2018) enlightens us with the significance of making substantive official updates, by the authorities concerned, stringent periodic monitoring of social media to reduce exposure to misleading information and distress during crisis events. “Like previous epidemics and pandemics, the unpredictable consequences and uncertainty surrounding public safety, as well as misinformation about COVID-19 (particularly on social media) can often impact individuals’ mental health including depression, anxiety, and traumatic stress”(Cheung, Chau, and Yip 2008; Zandifar and Badrfam 2020).

FIRST COVID-19 SUICIDE CASE IN BANGLADESH On 25th of March 2020, a 36-year-old Bangladeshi man (Zahidul Islam, from the village of Ramchandrapur) committed suicide after returning from Dhaka because both he as well as the villagers thought that he was infected with COVID-19, just because of mere symptoms like fever, cold and weight loss. Due to the social avoidance and insults by

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others around him, he committed suicide by hanging himself from a tree in the village near his house. Unfortunately, the autopsy showed that the victim was COVID-19 negative. Prejudice was considered as the major cause of the suicide of the young man (Mamun and Griffiths 2020).

REMEDY MEASURES During and post-pandemic mental health support and follow-up is recommended to be provided even 6 months after the release from isolation particularly for those individuals with prior vulnerable mental health status. Support should include accurate information as well as appropriate supplies for the subjects, including food, clothes and accommodation, if needed (Lin et al., 2007). In the south Asian country like Bangladesh and India, common people in the village are generally less educated than those living in the cities. Therefore, elevated fears and misconceptions surrounding COVID-19 among villagers might have led to increasing levels of xenophobia, which might be the major contributing factor in committing suicides. It is also recommended for online-based mental health intervention programs which are a way of endorsing more reliable and authentic information about COVID-19 and making available possible telemedicine care. Finally, as suggested by (Banerjee 2020), the role of a psychiatrist during a pandemic such as COVID-19 should include as (i) educating individuals about the common adverse psychological consequences, (ii) encouraging health-promoting behaviors among individuals, (iii) integrating available healthcare services, (iv) facilitate problem-solving, (v) empowering patients, their families, and health-care providers, and (vi) promoting self-care among health-care providers. Practical steps to manage our mental health during these difficult times include managing media consumption and accessing information which allows us to take practical steps to protect ourselves and our loved ones accessing non‐official information can foster further, and often unnecessary, anxiety and panic. Increasingly populations are being asked to stay in our homes for personal safety and the safety of

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others. Ensuring daily exercise activities have a positive impact on our mental health. Prophylactic efforts such as screening for mental health problems, psychoeducation, and psychosocial support should focus on these and other groups at risk for adverse psychosocial outcomes. Health care providers can offer suggestions for stress management and coping (such as structuring activities and maintaining routines), link patients to social and mental health services, and counsel patients to seek professional mental health assistance when needed. Since media reports can be emotionally disturbing, contact with pandemic-related news should be monitored and limited, open discussions should be encouraged to address children’s reactions and concerns, education and training regarding psychosocial issues should be provided to health system leaders, frontline workers, first responders, and health care professionals, risk-communication efforts should anticipate the complexities of emerging issues such as prevention directives, vaccine availability and acceptability, and needed evidence-based interventions relevant to pandemics and should address a range of psychosocial concerns. Mental health professionals can help craft messages to be delivered by trusted leaders (Pfefferbaum et al., 2012).

CONCLUSION As discussed, the pandemic Covid-19 has demonstrated mental health issues in the patients and survivors. Due to the lockdown in several countries people are still separated from their dear ones. This also triggers the stress and anxiety disorders, ultimately leading to depression. Several remedy measures like that of psychosocial education, counseling and awareness are the best possible remedies which can have assured impact over these conditions. The development of vaccines against this disease can have enlightenment among people across the globe.

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Journal: EMJ 24 (1): 12–17. https://doi.org/10.1136/emj.2006.0 35089. Lippi, Giuseppe, and Mario Plebani. 2020. “The Critical Role of Laboratory Medicine during Coronavirus Disease 2019 (COVID-19) and Other Viral Outbreaks.” Clinical Chemistry and Laboratory Medicine 58 (March). https://doi.org/10.1515/cclm-2020-0240. Long, Brit, William J. Brady, Alex Koyfman, and Michael Gottlieb. 2020. “Cardiovascular Complications in COVID-19.” The American Journal of Emergency Medicine 38 (7): 1504–7. https://doi.org/ 10.1016/j.ajem. 2020.04.048. Mamun, Mohammed A., and Mark D. Griffiths. 2020. “First COVID-19 Suicide Case in Bangladesh Due to Fear of COVID-19 and Xenophobia: Possible Suicide Prevention Strategies.” Asian Journal of Psychiatry 51 (June): 102073. https://doi.org/10.1016/j.ajp.2020. 102073. Perrin, Paul C., O. Lee McCabe, George S. Everly, and Jonathan M. Links. 2009. “Preparing for an Influenza Pandemic: Mental Health Considerations.” Prehospital and Disaster Medicine 24 (3): 223–30. https://doi.org/10.1017/S1049023X00006853. Pfefferbaum, Betty, and Carol S. North. 2020. “Mental Health and the Covid-19 Pandemic.” New England Journal of Medicine 383 (6): 510–12. https://doi.org/10.1056/NEJMp2008017. Pfefferbaum, Betty, David Schonfeld, Brian W. Flynn, Ann E. Norwood, Daniel Dodgen, Rachel E. Kaul, Darrin Donato, et al., 2012. “The H1N1 Crisis: A Case Study of the Integration of Mental and Behavioral Health in Public Health Crises.” Disaster Medicine and Public Health Preparedness 6 (1): 67–71. https://doi.org/10.1001/ dmp.2012.2. Phelps, Chavez, and Linda L. Sperry. 20200611. “Children and the COVID-19 Pandemic.” Psychological Trauma: Theory, Research, Practice, and Policy 12 (S1): S73. https://doi.org/10.1037/tra0000 861. Purgato, Marianna, Chiara Gastaldon, Davide Papola, Mark van Ommeren, Corrado Barbui, and Wietse A. Tol. 2018. “Psychological

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Therapies for the Treatment of Mental Disorders in Low- and Middle-Income Countries Affected by Humanitarian Crises.” The Cochrane Database of Systematic Reviews 7 (July): CD011849. https://doi.org/10. 1002/14651858. CD011849.pub2. Ren, Shi-Yan, Rong-Ding Gao, and Ye-Lin Chen. 2020. “Fear Can Be More Harmful than the Severe Acute Respiratory Syndrome Coronavirus 2 in Controlling the Corona Virus Disease 2019 Epidemic.” World Journal of Clinical Cases 8 (February): 652–57. https://doi.org/10.12998/wjcc. v8.i4.652. Renu, Kaviyarasi, Lakshmi Pureti, and Abilash Valsala Gopalakrishnan. 2020. “Coronaviruses Pathogenesis, Comorbidities and Multi-Organ Damage – A Review.” Life Sciences 255 (May): 117839. https://doi.org/10.1016/ j.lfs.2020.117839. Rubin, G. James, and Simon Wessely. 2020. “The Psychological Effects of Quarantining a City.” BMJ 368 (January): m313. https://doi.org/ 10.1136/ bmj.m313. Shapiro, Alan, Lynn Seim, Randal C. Christensen, Abhay Dandekar, Michael K. Duffy, David M. Krol, Irwin Redlener, and Arturo Brito. 2006. “Chronicles from Out-of-State Professionals: Providing Primary Care to Underserved Children after a Disaster: A National Organization Response.” Pediatrics 117 (5 Pt 3): S412-415. https:// doi.org/10.1542 /peds.2006-0099N. Torales, Julio, Marcelo O’Higgins, João Mauricio Castaldelli-Maia, and Antonio Ventriglio. 2020. “The Outbreak of COVID-19 Coronavirus and Its Impact on Global Mental Health.” International Journal of Social Psychiatry 66 (4): 317–20. https://doi.org/10.1177/ 00207640 20915212. Usher, Kim, Joanne Durkin, and Navjot Bhullar. 2020. “The COVID‐19 Pandemic and Mental Health Impacts.” International Journal of Mental Health Nursing 29 (3): 315–18. https://doi.org/10.1111/inm. 12726. Wang, Cuiyan, Riyu Pan, Xiaoyang Wan, Yilin Tan, Linkang Xu, Cyrus S. Ho, and Roger C. Ho. 2020. “Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019

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Coronavirus Disease (COVID-19) Epidemic among the General Population in China.” International Journal of Environmental Research and Public Health 17 (5). https://doi.org/10.3390/ijerph 17051729. Wang, Dawei, Bo Hu, Chang Hu, Fangfang Zhu, Xing Liu, Jing Zhang, Binbin Wang, et al., 2020. “Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.” JAMA 323 (11): 1061–69. https:// doi.org/10.1001/jama. 2020.1585. Xiang, Yu-Tao, Yuan Yang, Wen Li, Ling Zhang, Qinge Zhang, Teris Cheung, and Chee H. Ng. 2020. “Timely Mental Health Care for the 2019 Novel Coronavirus Outbreak Is Urgently Needed.” The Lancet Psychiatry 7 (3): 228–29. https://doi.org/10.1016/S2215-0366(20) 30046-8. Zandifar, Atefeh, and Rahim Badrfam. 2020. “Iranian Mental Health during the COVID-19 Epidemic.” Asian Journal of Psychiatry 51 (March): 101990. https://doi.org/10.1016/j.ajp.2020.101990. Zhu, Na, Dingyu Zhang, Wenling Wang, Xingwang Li, Bo Yang, Jingdong Song, Xiang Zhao, et al., 2020. “A Novel Coronavirus from Patients with Pneumonia in China, 2019.” The New England Journal of Medicine 382 (8): 727–33. https://doi.org/10.1056/NEJMoa 2001 017.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 12

THE IMPACT OF COVID-19 ON YOUNGSTERS Joby Jose1 and Shaiju K. Sebastian2,*, PhD 1

Vadasseryil House, Peruvanthanam, Kodikuthy, Kerala, India 2 Department of Hospitality and Tourism Management, Marian College Kuttikkanam, Kuttikkanam, Kerala, India

ABSTRACT COVID-19 is caused by the coronavirus, and is transferable from one person to another through contact. The virus which usually affects the respiratory functions of a person, was first identified in China. The impact created by this pandemic is very severe. The COVID-19 disease and the related measures taken by the governments, like the lockdown, have created a significant impact on young people which need to be analysed and understood. The lockdown days brought about a number of changes in the normal life of the youth. The purpose of this research is to identify the impact of COVID-19 on college students in Kerala. Various studies on the subject have concluded that COVID-19 has affected the students’ family relationships, their use of the social media, their social behaviour, their skill development and academic activities. *

Corresponding Author’s Email: [email protected].

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Joby Jose and Shaiju K. Sebastian This study shows that COVID-19 led to a more positive family relationship than a negative one, although arguments and clashes of opinion in the family occurred more frequently. The use of the social media considerably increased during the pandemic. Students spent time on social media more for leisure than for academic purposes. Another important area of understanding relates to the beginning of negative behavioural changes in them. The study found that students became lazier, lethargic and sleepy during the lockdown. Their seriousness towards academic activities took a downward turn. On a positive note, it was found that COVID-19 and the lockdown made positive changes in the skill development of the youth. Cooking and gardening were two areas in which the youth improved their skills. The study concludes by asserting that COVID-19 and the lockdown made significant changes in the minds of the young people.

Keywords: COVID-19, family relationship, skill development, social media usage, academic performance, behavioural changes

INTRODUCTION The COVID-19 global pandemic and its impacts have created problems for all people in the society. People of different age groups are experiencing the after-effects in different ways. The COVID-19 crisis has a significant impact on young people, especially in the areas of education, employment, mental health, family relationships and many more (Abraham 2006). It will also affect the future generations badly, their well-being and happy living. The government has taken measures, such as lockdown, quarantine, avoidance of social meetups and so on, in order to ensure prevention of this infectious disease. These measures, however, have also created vulnerability and risks within the family. Keeping schools closed leads to distress in various families. Students feel isolated, alone and unhappy being in the confines of the home for an unbearably long time. Studies related to media usage during the pandemic have observed that there was a hike in the usage of social networking (Akhtarul et al., 2020). The number of hours’ students spent on social media has drastically increased. The academic sector was among the first

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few that faced rapid shutdown of all activities. The whole pattern of education changed into a new model. Students have concerns and problems regarding their academic life. They also exhibit various behavioural and emotional changes due to the extended lockdown situation brought about by the Coronavirus pandemic. Various studies have revealed that stress, sleepiness, anxiety, fear, etc., among students have increased (Akhtarul et al., 2020). Some positive changes, however, have also been observed regarding the skill development of the students. Many have used this time for engaging in productive activities and displaying their inherent talents. The major objectives of this study are to examine the impact of COVID-19 on family relationships among the youth, changes in their skill development, changes in their usage of social media, changes to their academic activities, and also to gain insight into their negative behaviour.

BACKGROUND OF THE STUDY The COVID-19 disease is caused by the coronavirus and is transferable from one person to another through contact. This virus usually affects the respiratory functions. The impact created by this pandemic is very severe. This virus which was unknown before was first identified in China. The COVID-19 pandemic and lockdown measures have created a significant impact on young minds; the impact of the pandemic can be fully understood only in the future. The lockdown days have effected various changes in the normal life of the youth. A study conducted by Mitra et al., (2020) explores the patterns of physical activities, sleeping behaviour and such changes seen in children between the ages of five to seventeen during the lockdown. It is seen that the sleeping behaviour of the youth has changed. They use social media late into the night, and go to sleep only at around 3:00 a.m. or 4:00 a.m. As a result, they always feel sleepy and tired. There is hardly any outdoor game or activity, and they feel completely isolated. Using the mobile

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phone and other gadgets is the solution that they find for overcoming boredom, but this will create various mental issues. In another study, Cao et al., (2020) observed that almost 0.9% of the respondents’ experience severe anxiety; 2.7% face moderate anxiety and 21.3% face mild anxiety. Their study reveals that anxiety and mental pressure among all people, especially the young minds, rise. The youth are worried and anxious about their academics and their future career. Son et al., (2020), in a similar study, reported that the results of 138 (71%) out of 195 students indicate that COVID-19 increases stress and anxiety. The study also found that depressive thoughts as well as the level of stress also rise on a daily basis. 91% of the respondents said that they were worried about their health as well as that of their family. COVID-19 has made significant changes in their sleeping pattern and also instilled disruptive thoughts in their minds. Social interaction is an important aspect of child growth. COVID-19 and its related measures like lockdown and social distancing lower the chances for social interaction. The students’ concerns about their future and their academic performance also get highly influenced. Emotional instability and over concern, fear, stress, anxiety, etc., are found to be the detrimental consequences of the lockdown measures.

MATERIAL AND METHODS The primary data for the study was collected directly from the respondents through questionnaires. For the secondary data, sources like websites, publications, magazines, mass media and textbooks were used. The sample size adopted to conduct this research was a total of 122 college students from Kerala. The method of data collection which was adopted to conduct this research was the questionnaire method using a 5point Likert scale. The various methods that were used for data analysis include ANOVA, Independent Sample T-test and Mean Scores.

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RESULT AND DISCUSSION Figure 1 shows the age group of the respondents. Here, 38% of the respondents are in the age group of 21-22; 31% belongs to the 18-19 age group; 27% are in the 20-21 age group; and 4% belongs to the age limit 23-24.

Figure 1. Age group of the respondents.

Figure 2. Gender of the respondents.

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Figure 2 shows the gender of the respondents. Here, 55% of the respondents are male and 45% female.

Figure 3. Education of the respondents.

Figure 3 exhibits the educational status of the respondents. 51% respondents are undergraduate students; 47% are postgraduates; 1% each are doing B.Ed. and Diploma. Table 1. Impact of COVID-19 on family relationships Impact on the family Positive change in the family Negative change in the family

Mean 3.89 3.00

SD 0.65 0.75

Table 1 above and Table 2 below show that COVID-19 has brought about more positive changes (M = 3.89, SD = 0.65) than negative ones (M = 3.00, SD = 0.75) in the family. Table 3 below shows the result of the independent sample t-test. As per the result, the significance values of positive change (0.14) and negative change (0.89) are the same for both male and female. For negative change, the test significance values are (0.89) respectively for both the age groups, which is above (0.05). So, we retain the null

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hypothesis. This means that there is no significant difference between male and female, or positive and negative family relationships. Table 2. Gender and family relationship Family relationship

Gender Male Female Male Female

Positive change in the family Negative change in the family

N 67 55 67 55

Mean 3.82 3.99 3.00 3.01

SD 0.69 0.59 0.76 0.74

Sig. (2-tailed) 0.14 0.14 0.89 0.89

As per the result, the significance values of positive change (0.14) and negative change (0.89) are the same for both male and female. Table 3. Education and family relationships Level of education Undergraduation Post-graduation Diploma B.Ed.

N 64 56 1 1

Mean 3.82 3.98 3.66 4.33

SD 0.67 0.63

F 0.76

S 0.514

Table 4. Impact of COVID-19 on skill development Mean 3.10

Skill development

SD 0.50

Table 4 shows the mean score of skill development of the youth during COVID-19. Here the Score is (M = 3.10, SD = 0.50). Thus, it is significant. The impact of COVID-19 brings about skill development among the students. Table 5. Gender and skill development

Skill development

Gender Male Female

N 67 55

Mean 3.07 3.15

SD 0.541 0.458

Sig. (2-tailed) 0.426 0.419

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Table 5 shows the result of the independent sample t-test. As per the test, the significance values of skill development are (0.426) for male and (0.419) for female, which is above (0.05). So, we retain the null hypothesis, which means that there is no significant difference between male and female in skill development. Table 6. Education and skill development Level of education Undergraduation Post-graduation Diploma B.Ed.

N 64 56 1 1

Mean 3.03 3.18 2.87 3.87

SD 0.52 0.46

F

Sig.

1.699

0.171

Table 6 shows the result of ANOVA. The significance value is more than 0.05 for skill development (0.171). There is no significant difference between the level of education and that of skill development. Table 7. Skills acquired during COVID-19 Skills Honed my skills in cooking and gardening Improved my technical skills like Excel, Word, Photoshop Enhanced my skills in painting, drawing, artistic work, etc. Learned basic life skills for household such as electrical, plumbing and mansion works

N 122 122 122

Mean 3.78 3.49 3.34

SD 1.04 0.88 1.03

122

3.10

0.99

From Table 7 above, it is clear that students polished their skills mainly in cooking, gardening etc. It has a mean score of 3.78. Technical skills also have a good mean score, 3.49. Table 8. Impact of COVID-19 on the usage of social media

Impact on Social Media usage

Mean 4.0410

SD 0.53

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Table 8 shows that the impact of COVID-19 made a significant change in the use of social media (M = 4.04, SD = 0.53). This proves that the Social Media usage has increased during the pandemic. Even though COVID-19 is looked down upon as a curse on humanity, it has been instrumental in making some positive impacts also from the view of the youngsters in Kerala according to the findings of the research. COVID19 has contributed to a positive relationship among family members. It has helped in developing skills like cooking and gardening, besides technical skills, among the college students. The study, however, also brought to light that COVID-19 impacted on the youngsters in such a way that there has been an unprecedented rise in the use of the social media. The academic performance of the students has gone down; the majority of them feel tired; they are inactive; and finally, the otherwise vibrant youth are stressed out more than ever.

SUGGESTIONS As has been found by the study, the youth have improved their skills in cooking, gardening and technical areas, and so their parents must motivate and support them in the further development and growth of these skills. As the study observes that their seriousness towards academics and related activities has decreased, teachers could think about changing the pattern of teaching and adopting new technology in disseminating knowledge. It will help in retaining their interest in studies. Making the youth involved in daily work and routine jobs at home may help them overcome their negative behavioural change. Both indoor and outdoor games as well as agriculture-related engagements can be assigned to the youngsters to reduce their overuse of social media and save them from addiction and withdrawal behaviour. Fostering positive vibes in the family will ensure togetherness and enhance the relationship among family members, which will help the youth to overcome all hardships and enable them to soar higher.

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CONCLUSION COVID-19 made a significant impact on the life of the youth. Changes were seen in their relationship with their family members, their skill development, social media usage, academic activities and behaviour. It is found that COVID-19 made a positive rather than a negative impact on family relationships. It led to a feeling of family togetherness and synergy, even though clashes of opinion and arguments increased. Students also used this time for skill acquisition and training. Cooking and gardening were the skills found to be most acquired ones. Technical skills were another area where students improved their skill. The study reveals that the usage of social media and the time spent on it increased. Students spent more time on the social media for leisure purposes than for academic activities. The result of the research also shows that the seriousness and interest of the youth in academic activities lessened. COVID-19 also brought about negative behavioural changes like aggressiveness in the young minds. Students became lazier, shy, tired and sleepy. Thus, the authors conclude that the COVID-19 pandemic and the related lockdown made a significant impact on college students in a number of aspects.

REFERENCES Akhtarul Islam, Md, Sutapa Dey Barna, Hasin Raihan, Md Nafiul Alam Khan, and Md Tanvir Hossain. 2020. “Depression and Anxiety among University Students during the COVID-19 Pandemic in Bangladesh: A Web-Based Cross-Sectional Survey.” PLoS ONE 15 (8 August): 1–12. https://doi.org/10.1371/journal.pone.0238162. Bhatia, Rajesh. and Abraham, Priya. 2020. “The Enigmatic COVID-19 Pandemic.” Indian Journal of Medical Research 152 (1): 1–5. https://doi.org/10.4103/ijmr.IJMR_3639_20.

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Cao, Wenjun, Ziwei Fang, Guoqiang Hou, Mei Han, Xinrong Xu, Jiaxin Dong, and Jianzhong Zheng. 2020. “The Psychological Impact of the COVID-19 Epidemic on College Students in China.” Psychiatry Research. https://doi.org/10.1016/j.psychres.2020.112934. Mitra, Raktim, Sarah A. Moore, Meredith Gillespie, Guy Faulkner, Leigh M. Vanderloo, Tala Chulak-Bozzer, Ryan E. Rhodes, Mariana Brussoni, and Mark S. Tremblay. 2020. “Healthy Movement Behaviours in Children and Youth during the COVID-19 Pandemic: Exploring the Role of the Neighbourhood Environment.” Health and Place. https://doi.org/10.1016/j.healthplace.2020.102418. Son, Changwon, Sudeep Hegde, Alec Smith, Xiaomei Wang, and Farzan Sasangohar. 2020. “Effects of COVID-19 on College Students’ Mental Health in the United States: Interview Survey Study.” Journal of Medical Internet Research. https://doi.org/10.2196/21279.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 13

THE PANDEMIC AND ITS IMPACTS WITH A SPECIAL FOCUS ON COVID-19 SITUATION IN INDIA Prem Jose Vazhacharickal1,2,*, Jiby John Mathew1 and N. K. Sajeshkumar1 1

Department of Biotechnology, Mar Augusthinose College, Ramapuram, Kerala, India 2 Rural Urban Center, Department of Agricultural Economics University of Agricultural Sciences, Bangalore, Karnataka, India

ABSTRACT Pandemics are for the most part disease outbreaks that become widespread as a result of the spread of human-to-human infection. Throughout the history of mankind, pandemics have consistently produced large-scale demographic, economic and political disruptions. There have been many significant disease outbreaks and pandemics recorded in history, including Spanish Flu, Hong Kong Flu, SARS, H7N9, Ebola, Zika and COVID-19. The COVID-19 impact on the *

Corresponding Author’s Email: [email protected].

208 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar economy has created an unprecedented situation. Almost all sectors of the economy were hit due to this pandemic situation. The main objective is to assess the impact of pandemic and COVID-19 pandemic across the globe with special emphasis on social, ecological and economical aspects. We based our study with an extensive literature search using Google Scholar and Google search engine using the search string “COVID-19* AND pandemic*”. We also included complex search strings “pandemic history” AND “pandemic impact”. Lockdown is considered to be an effective measure in slowing the spread of coronavirus around the globe. To further stop the spread of the virus, many countries are currently in some degree of lockdown. Second wave of Corona virus infection with much more spreading and lethality were reported in many countries across the globe. These countries especially United Kingdom, Germany, Netherlands and other European countries made reintroduction of strict lockdowns and other regulations to control the spread of the COVID-19 pandemic. The worldwide spread of the novel coronavirus has further led to neuropsychiatric issues such as fear, anxiety, depression, panic attacks, psycho-motor excitement, suicidal deaths and a general decrease in overall wellbeing. Because of a significant disruption of supply chains and marketing due to the lockdown, seen at an intra- and inter-state level, farmers have been stuck with a larger amount of perishables like milk, fruits and vegetables. The economic recessions have put significant financial strain on many families, which might increase unhealthy conflict, family breakdown, abuse, depression and domestic violence. The psychological impacts of the COVID-19 lockdown might be a challenge for an indefinite period, hence it is necessary to devise coping strategies, mental health interventions and create awareness using the available resources.

Keywords: COVID-19, gross domestic product, lock down, Corona Virus, pandemic, social distancing, PPE Kits

INTRODUCTION Pandemics are for the most part disease outbreaks that become widespread as a result of the spread of human-to-human infection (Lau et al., 2007; Saunders-Hastings and Krewski, 2016; Qiu et al., 2017). Throughout the history of mankind, pandemics have consistently produced large-scale demographic, economic, and political disruptions

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(Almond, 2006; Mordechai et al., 2019). There have been many significant disease outbreaks and pandemics recorded in history of mankind, including Spanish Flu (Trilla et al., 2008; Phillips, 2014), Hong Kong Flu (Joffe Lee, 2004; Fung et al., 2011), SARS (Chen et al., 2005; Peng et al., 2010), H7N9 (Gao et al., 2013; Liu et al., 2013), H1N1 (Lipsitch et al., 2011; Team, 2009), Ebola (Baize et al., 2014; Aruna et al., 2019), Zika (Petersen et al., 2016; Musso and Gubler, 2016), Nipah (Chua, 2003; Ang et al., 2018) and COVID-19 (Solomon et al., 2020; Rome and Avorn, 2020). The word “Pandemic” originates from the Greek pan meaning “all” and demos “the people”. A novel coronavirus named severe acute respiratory coronavirus 2 (SARS-CoV-2) was first identified in a seafood market in Wuhan City, Hubei Province in China, at the end of 2019 (Zhu et al., 2020). The contagious respiratory illness caused by this novel coronavirus is called coronavirus disease 2019 or, in short, COVID-19 (Wu et al., 2020). From February 2020, COVID-19 cases soared across most of Europe, the United States, Australasia, Asia and on to Africa Zhu et al., 2020; Wu et al., 2020; Solomon et al., 2020; Rome and Avorn, 2020). This pandemic has reached every corner of the planet, and similar to previous pandemics, it has caused substantial medical, economic, and social disruption leading to almost 96 million cases and more than two million deaths as on January 2021. The COVID-19 impact on the economy has created an unprecedented and uncertain situation. Almost all sectors of the economy were hit due to this pandemic situation and created huge loss to developed, developing and underdeveloped economies. Based on this background, the main objective of our study is to assess the impact of COVID-19 pandemic across the globe with special emphasis on social, ecological and economical aspects as well as its impact on agricultural sector in India with special emphasis on farmers and agricultural labourers.

210 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar

METHODOLOGY The study was carried out with an extensive literature search using Google Scholar and Google search engine using the search string “COVID-19* AND pandemic*”. The World Wide Web search also included complex search strings “pandemic history” AND “pandemic impact” AND “Indian agriculture”. In addition, contacted various known persons involved in medical, health care and allied sector across different parts of the globe via WhatsApp and social media to assess the impact of COVID-19 in their respective area. Overall, our query via World Wide Web (WWW) and mobile phone gave a general picture and holistic overview of the COVID-19 situation across the globe and its impact on Indian agriculture. We decided to restrain from any further quantitative physical survey due to the lockdown and spread of COVID-19 situation in India.

RESULT AND DISCUSSION The history of mankind is marked by a number of significant pandemics especially smallpox, cholera, plague, dengue, AIDS, influenza, SAR, West Nile disease and tuberculosis (Trilla et al., 2008; Phillips, 2014; Gao et al., 2013; Liu et al., 2013). Influenza pandemic occurred in recurring events and has unpredictable and severe consequences across the globe (Qiu et al., 2017). Influenza pandemics appear about three times every century since the 1500s with a gap of every 10-50 years. The 20th century witnessed 3 influenza pandemics especially “Spanish flu” (1918-1919), “Asian flu” (1957-1958), and “Hong Kong flu” (1968-1969). Each pandemic has a severe impact on human life as well as on economic development and growth. The influenza pandemic has killed more than 20 million people in the world and evaluated as the most dreadful epidemic recorded in human history (Qiu et al., 2017).

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Recently the world witnessed at least seven large-scale outbreaks; Hantavirus pulmonary syndrome, severe acute respiratory syndrome, H5N1 influenza, H1N1 influenza, Middle East respiratory syndrome, Ebola virus disease epidemic and COVID-19 pandemic (Gostin et al., 2016). The influenza H1N1 2009 virus (A/2009/H1N1) was the first pandemic influenza of the 21st century and affected the whole world with a mortality of more than 18,000 persons (Rewar et al., 2015). Ebola caused death of more than 11 000 people with an economic loss in the world more than USD $2 billion, estimated by World Bank (Maurice, 2016). Zika virus continues to spread in the year 2016 and threatens the health of people in 34 countries at risk (Troncoso, 2016) and decline substantially in the later years (Nikookar et al., 2020; Dhimal et al., 2018). These outbreaks make scientists and governments across the globe alert about a re-appearance of the devastation of the Spanish flu pandemic or a new unknown pandemic in the human history (Lin et al., 2016; Qiu et al., 2017).

FEATURES OF PANDEMIC The meaning and understanding of the term pandemic vary across the globe, there are some key features which are widely accepted. 



Wide geographic extension: The term pandemic usually refers to diseases that extend over large geographic area. With the emergence of pandemic influenza, pandemics were categorized as trans-regional and global (Taubenberger and Morens, 2009). During the H1N1 outbreak in 2009, around 178 countries were affected (Rewar et al., 2015; Qiu et al., 2017). Disease movement: The term pandemic implies unexpected disease movement or spread via transmission that can be traced from place to place. The typical disease movement include widespread person-to-person spread of diseases caused by respiratory viruses, such as influenza and SARS, or enteric

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organisms (Vibrio cholera), or by vectors (dengue). Influenza A (H1N1), restressed, widespread transmission in both hemispheres between April and September 2009. Due to special climatic conditions that exist in both hemispheres, this is early in the influenza season in the temperate southern hemisphere but out of season in the northern hemisphere (Barrelet et al., 2013). This out-of-season transmission is an important characterization of influenza pandemic (Qiu et al., 2017). Novelty: The term pandemic usually describes diseases that are new or associated with novel variants of existing organisms; antigenic shifts (influenza viruses), and historical epidemics of diseases (plague). Novelty can be considered as relative concept, and there have been 7 cholera pandemics during the past 200 years, caused by mutant variants of the same organism (Morens et al., 2009). In the 21th century, SARS, avian influenza and COVID-19 are three newly emerged infections with pandemic potential that have arisen from Asia (Qiu et al., 2017). Severity: The term pandemic has been usually applied to severe or fatal diseases (the Black Death, HIV/AIDS and SARS). “Global pandemics with high mortality and morbidity occur when a virulent new viral strain emerges, against which the human population has no immunity” (Rewar et al., 2015). Severity of a pandemic is usually estimated by the case fatality ratio (Donaldson et al., 2009). “In contrast with Ebola, most cases die within 10 days of their initial infection, with a mortality rate of 50–90%”. The H7N9 outbreak has caused more than 600 human infections, with 30% mortality rate (Su and He, 2015; Qiu et al., 2017). In the year 2021 January end the COVID-19 death tolls rise to 2.35 million around the globe (Worldometers, 2021). High attack rates and explosiveness: Pandemics are characterised by high rates of attack and explosive nature of spreading (Influenza H1N1 or Ebola). If the transmission is non-explosive in nature, even if it is widespread, this is not classified as a pandemic. In the case of West Nile, the virus spread to the

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Middle East and Russia, and the Western Hemisphere in 1999. Since the transmission was slow and the attack rate was low, so it is not considered as a pandemic. Diseases with low rates of transmission or low rates of symptomatic disease are very rarely classified as pandemics, although they have a wide spreading capacity. Acute Haemorrhagic Conjunctivitis (AHC) in 1981, and cyclic global recurrences of scabies also have been called pandemic when they exhibit explosive or with wide and recurrent geographic spread (Donaldson et al., 2009). Right from the initial outbreak of the COVID-19, epidemiologists and public health experts undoubtedly recommended quarantining and isolation of the positive cases as one of the most effective preventive strategies. Minimal population immunity: Pandemics can be better understood in partly immune populations, with limiting microbial infection and transmission, population immunity/heard immunity can be a powerful anti-pandemic force (Taubenberger and Morens, 2009). Pandemics are characterised by lack of population immunity, so a large part of the population get easily infected (Kaudhry and Fangriya, 2015). In the case of H7N9 with a new variant of the influenza virus, the population had no immunity, so the disease spread worldwide in a short time (Wildoner, 2016; Qiu et al., 2017) which is also true in the case of COVID-19 pandemic. Infectiousness and contagiousness: The term pandemic has less commonly been used to describe presumably non-infectious diseases, such as obesity, or risk behaviours, such as cigarette smoking which are not transmissible. Pandemic diseases are infectious and can be transmitted from one person to another person. This transmission can be direct (person to person) or indirect (person to vector to person) (Morens et al., 2009). The SARS virus was transmitted from person to person by persons in close quarters, while H7N9 was often spread through contact with living poultry (Su and He, 2015). The impact of avian-

214 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar influenza strain to human health lies in its potential to mutate into a strain capable of sustained person-to-person transmission (Qiu et al., 2017). The possible mode of corona virus transmission includes contact, droplet, airborne and fomite (Li et al., 2020).

PANDEMIC IMPACT Infectious disease outbreaks can easily cross national and international borders due to advances in transportation facilities and globalization. These outbreaks threaten economic and regional stability, as already witnessed by the HIV, H1N1, H5N1, and SARS epidemics and pandemics (Verikios et al., 2015). Beyond the debilitating, sometimes fatal, consequences for those directly affected, pandemics have a range of negative social, economic and political consequences (Davies, 2013). As an example, “The impact of pandemic influenza ie. H1N1 in 2009 was not just on mortality, but also on health-care systems, animal health, agriculture, education, transport, tourism and the financial sector. In short, a pandemic event threatens all aspects of the economic and social fabric” (Drake, 2012). The SARS (2003) and the Ebola pandemics (2013 and 2015) totally disrupted the economies and social order in China and West African countries. Ebola and other pandemics have reduced the life spam of families and communities. The Ebola and COVID-19 pandemics have disrupted essential services such as education, transport, and tourism, undermined the West African economies and across the globe (Nabarro and Wannous, 2016; Li et al., 2020). COVID-19 has been declared a pandemic by the World Health Organisation (WHO) as confirmed cases approach 200000 patients and exceed 8000 deaths across over 160 countries (Poudel and Subedi, 2020; Spinelli and Pellino, 2020).

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Health Effects Pandemics affected millions of people globally, causing wide-spread serious illness in a large population leading to thousands of deaths. In 14th century, the ‘Black Death’ plague is considered as the dreadful disease in Europe and elimated half the population of Europe (Ross et al., 2014). In the 20th century, the three major pandemic: 1) Spanish flu (1919-1920), caused 20-40 million deaths (Taubenberger and Morens, 2009); 2) Asian flu (1957-1958), caused around 2 million deaths; 3) Hong Kong flu (1968-1969) which caused 1 million deaths (MacKellar, 2007; Wildoner, 2016). Infectious disease disasters, including pandemics and emerging infectious disease outbreaks, account for a quarter to a third of global mortality (Verikios et al., 2015). In the case of developing countries, pandemics and infectious diseases have the potential to kill, and the likelihood of deaths range from 5 to 10 percent (Kern, 2016). In 2003, during the outbreak of SARS there were more than 8000 infected cases, with over 700 deaths (almost 9%) worldwide in just 6 months (Wong and Leung, 2007). Influenza is considered as one of the most serious pandemics which can result in considerable morbidity and mortality. Influenza pandemics are characterised by a high incidence and fatality rate, rapid and wide-spread transmission nature. The influenza pandemics have killed significant numbers of people worldwide in the year 2016, with an estimated 8,870–18,300 deaths in 2009– 2010 (Prager, 2016). In May 2009 a new H1N1 virus capable of human-to-human transmission emerged from Mexico (Verikios et al., 2015). According to WHO, 182,166 laboratories confirmed cases of influenza A/H1N1, with 1799 deaths reported in 178 countries up to August 13, 2009 (Rewar et al., 2015). The US Centers for Disease Control and Prevention (CDC) estimates that the peak H1N1 season (April 2009 to April 2010) in the United States which resulted in 43–89 million cases, 195–403 thousand hospitalizations, and 8,870–18,300 deaths (Bhandari et al., 2013). Over the past several years, the threat and anxiety towards pandemics has greatly increased. The H5N1 has repeatedly managed to infect humans in several Asian and European countries (Kaudhry and Fangriya,

216 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar 2015). With 387 confirmed cases of human H5N1 infection across 15 countries since from late 2003 to late 2008, including 245 deaths, the H5N1 could easily become another major pandemic (Enemark, 2009). The occurence of the zoonotic influenza A (H7N9) virus in China, also created concerns about the potential for a pandemic to arise from an avian influenza strain. The H7N9 viruses has caused more than 600 human infections, with nearly 30% mortality (Su and He, 2015), and could be considered to have pandemic potential (Tanner et al., 2015). Other major threats in recent times have been pandemics of Dengue, Ebola and COVID-19. The incidence of the severe and fatal form of the Dengue has increased dramatically in developing countries especially in Latin America (2015–2016 dengue epidemics) with first case recorded in Brazil in May 2015 and caused more than 1.5 million cases up to December 2015 with the involvement of 34 countries by March 2016 (Troncoso, 2016). The Ebola outbreak in West Africa was an unprecedented public health emergency crisis of global concern. WHO reported that there were 28,581 Ebola Virus Disease (EVD) confirmed in October 2015, with 11,299 deaths in West African countries especially Liberia, Guinea and Sierra Leone. The estimated case fatality proportion was 40% (Nabarro and Wannous, 2016) with more than 11,000 people died across nine countries due ot the Ebola zoonotic ‘spill over’ (Ross et al., 2015).

Economics Impacts Influenza pandemic posed a serious threat not only to the entire population, but also to the world economy. The pandemic impact can result in economic loss which leads to instability of the world economy through direct costs, long term burden, and indirect costs. The direct costs of dealing and counter defencing with the disease outbreak can be very high. The Ebola outbreak has seriously created economic instability throughout West Africa. The Ebola outbreak in Sierra Leone in 2015 cost USD 6 billion in direct costs (hospitals, staff, medication), and the direct

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costs alone accounts to 3 years of funding for WHO (Gostin and Friedman, 2015). It has been calculated that there was an economic loss of USD 1.6 billion for the three countries compared with the economic growth in the previous year 2014 (Kern, 2016). According to the Global Health Risk Framework for the Future (GHRF) Commission, every year on average infectious disease outbreaks cost globally about USD 60 billion in direct costs (Maurice, 2016). One of the severe long-term burdens is from the loss of earnings of those who have died. Prager et al. (2016) have estimated that economic losses from a pandemic influenza in the USA would be USD 90 - 220 billion, and of that, 80% would come from the value of expected future lifetime earnings of those who would die. MacKellar (2007) estimated that the economic cost of an influenza pandemic range from USD 374 billion for a mild pandemic to USD 7.3 trillion for a severe pandemic. The mathematical models indicate that a future influenza pandemic could have total costs USD 71-166 (Rebmann, 2010). “Recent years have seen at least six large-scale outbreaks-hantavirus pulmonary syndrome, severe acute respiratory syndrome, H5N1 influenza, H1N1 influenza, Middle East respiratory syndrome, and Ebola virus disease, which cost the world more than $2 billion, according to World Bank calculations” (Maurice, 2016). Indirect costs are also very heavy and include everything that contributes to a decline in GDP. The example of SARS, especially its impacts on the region affected the 2003 annual GDP of China decreased by 1% and the GDP of Southeast Asia also declined by 0.5% (MacKellar, 2007). Lee and McKibbin (2004) estimated income loss ranges from USD 12.3-28.4 billion for East and Southeast Asia in the SARS outbreak in 2003 (Fan and Pernia, 2003). The effect of pandemic in various sectors of economy varies and some sectors of economy may be more heavily affected than others. For instance, Prager et al. (2016) estimate that the air transport industry would suffer a loss of almost 20% or USD 7.9 billion, if US residents cut down on travel. Pandemics create both immediate and long-term effects that can damage the economy of a nation for many years in future (Prager et al., 2016). The psychological

218 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar and economic impact of ineffective screening at airports were substantially directly affecting airport business in the 2003 SARS outbreak (Chung, 2015).

Social Impacts The social impacts of pandemics were severe, include travel was strictly limited, and schools closing, markets and sporting were closed. Maintaining social distancing, frequent washing of hands with sanitizers and wearing of N-95 masks were adopted for the prevention of COVID19 pandemic. All these are a likely reality should a pandemic with true potential for high morbidity and mortality emerge. Population mobility and transportation is also a key factor in pandemic crisis. Movement was difficult and the travel including visiting families, carrying goods to markets were restricted by military check points. The closure of airports and cancellation of flights affected many people’s travel, livelihood, and family life. With the rapid development in worldwide aviation over the last two decades, the risk of global pandemics has escalated with increased passenger traffic. With modern and efficient air travel, SARS, which originated from southern China was rapidly transmitted to more than 30 countries in early 2003 (Wong and Leung, 2007). Closing the airports harmed the economy of the affected regions. School closure is often considered the first non-pharmaceutical intervention for implementation in a pandemic, as students potentially dangerous in spreading the virus. Timely school closure and cancellation of public gatherings was significantly associated with reduced mortality related to influenza epidemics during the 1918 influenza epidemic in the United States (Chen et al., 2011). More than 1,300 public, charter, and private schools in 240 communities across the United States closed during the spring wave of the 2009 pA(H1N1) pandemic (Navarro et al., 2016). School closure also raises a range of ethical and social issues, particularly since families from underprivileged backgrounds are likely to

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be disproportionately affected by the intervention (Cauchemez et al., 2009). Closing markets has been tried for some outbreaks, especially for zoonotic diseases. Closure of wholesale and retail live poultry markets was associated with cessation of zoonotic outbreaks of H5N1 and H7N9 (Peiris et al., 2016). This caused disruption of food supply in the cities and people cannot find necessary food and living things because markets and shops were closed. This also caused a long-lasting change in people’s diet. After the occurrence of avian influenza, the consumption of poultry products fell by more than 80% on average in the market of Jilin province in China (Zhang and Liu, 2016), and affected the income of many farm workers. After COVID-19 pandemic outbreak in China, the Wuhan market was completely closed which is the suspected source of pandemic origin. The public games including sporting were cancelled because public gatherings may accelerate the pandemic spread. Enforced dose contact at work and household crowding were related to a higher incidence of selfreported influenza-like illness in the 2009 H1N1 pandemic (Kumar et al., 2012). “In some areas, fear produced panic among people leads bustling neighbourhoods during Ebola crisis in West Africa (Folayan and Brown, 2015). The disease may leave long-term physiological and psychological effects on people, which affect their ability to earn a living. In Brazil, Zika virus leaves a generation of children born with neurological disorders that may impose severe lifelong limitations (Ribeiro and Kitron, 2016). Trade-off between the social costs of interventions and the cost of uncontrolled spread of the virus were involved in the decisions to mitigate influenza outbreaks in Ebola outbreak (Prieto and Das, 2016).

Security Impacts A security threat associated influenza pandemic is not a recent phenomenon. Global security is threatened by from pandemics, in terms of lives and economic stability (Maurice, 2016). Pandemics are no longer

220 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar simply a dimension of public health and clinical medicine, but are a social issue, a development issue, and a global security issue (CastilloChavez et al., 2015). Pandemics cause devastation to human lives and livelihoods like wars leading to financial crises. Pandemic prevention and response should focus on both national and global security; not just as a matter of health (Kern, 2016). Bioterrorism including biological weapons and bioterrorist attacks, are often come from the ‘naturally occurring’ emerging and re-emerging infectious disease outbreaks. Many of the pandemics have been suspected to have human interference as a part of biological weapons manufacturing to suppress the economic growth of enemies including the SARS and COVID-19 pandemic. Military readiness of the impact of influenza epidemics and pandemics have been paid close attention by Governments since at least 1782 (Hirsch, 1883; Parsons, 1891), while the influenza pandemic of 1918 was erroneously named the ‘Spanish Flu’ because of fears over signalling military weakness. A ‘war disease’ reputation was also attracted by influenza in the aftermath of the 1918 Spanish Flu pandemic (Francis et al., 1947). Arriving as it did at the end of the First World War, the pandemic irrevocably linked those two catastrophes. It demonstrated that virulent influenza may be more devastating to human life than war itself (Beveridge, 1977; Potter 1991). The key trading routes of regions has already proven to be a hot spot for novel infectious diseases SARS, Dengue Haemorrhagic Fever, severe complications from enterovirus and influenza strains such as H5N1 and H7N9, has multiple states in political transition, civil unrest, dormant and active armed conflicts, and has a number of states recovering from armed conflict (Davies, 2013). Police brutally attacking the public for breaching curfews appeared in news media during the Ebola virus disease outbreak. Invoking arguments of global health security might further encourage this kind of violent response (Gostin and Friedman, 2015; Horton & Das, 2015).

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COVID-19 PANDEMIC As of February 11, 2021, 107,856,100 cases and 2,364, 900 deaths from 2019 novel coronavirus disease (COVID-19 caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) were recorded worldwide (Worldometers, 2021; Figure 1, 2, 3, 4 and 5). The novel coronavirus started in mainland China, with a geographical emphasis at Wuhan and had widely spread over globe (Sardar et al., 2020; Gupta et al., 2020).

Figure 1. Total Coronavirus cases (linear scale) in India from Feb 15, 2020, to Feb 09, 2021. Adapted from Worldometers, 2021.

Figure 2. Daily new Coronavirus cases (cases per day) in India from Feb 15, 2020, to Feb 09, 2021. Adapted from Worldometers, 2021.

222 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar

Figure 3. Active Coronavirus cases (number of infected people) in India from Feb 15, 2020, to Feb 09, 2021. Adapted from Worldometers, 2021.

Figure 4. Total Coronavirus death cases (linear scale) in India from Feb 15, 2020, to Feb 09, 2021. Adapted from Worldometers, 2021.

Figure 5. Newly infected cases vs newly recovered coronavirus cases (number of newly infected vs number of recovered and discharged patients each day) in India from Feb 15, 2020, to Feb 09, 2021. Adapted from Worldometers, 2021.

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Impact of COVID-19 Lockdown Lockdown is considered to be an effective measure in slowing the spread of coronavirus around the globe (Barkur et al., 2020; Flaxman et al., 2020). To further stop the spread of the virus, many countries are currently in some degree of lockdown. Until then, extreme social distancing is the only intervention available to keep healthy individuals spaced from each other. Even in the best-case scenario, coronavirus vaccine development is likely to take 12-18 months. While the preventive vaccine and treatment option are yet to be developed, the worldwide spread of the novel coronavirus has further led to neuropsychiatric issues such as fear, anxiety, depression, panic attacks, psycho-motor excitement, suicidal deaths and a general decrease in overall wellbeing (Brooks et al., 2020; Xiang et al., 2020). Similarly, patients who are infected with COVID-19 are at a greater risk of developing mental health problems, as they are facing stigma and discrimination from their own family members. Similar situations were faced by the general public as well as many medical practitioners during previous outbreaks such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Ebola (Jeong et al., 2016; Leary et al., 2018; Rogers et al., 2020; Rubin and Wessely, 2020; Wing and Leung, 2012). Until now, there is a paucity of information on the socioeconomic and psychological aspects of the various communities in the face of COVID-19, which is critical for formulating policies and interventions to curb the pandemic.

Background of COVID-19 Pandemic in India The 2019 pandemic novel coronavirus was first confirmed in India on January 30, 2020 in the state of Kerala (Sardar et al., 2020). A total of 10,871,600 confirmed cases and 155,750 deaths in the country have been reported as of February 11, 2021 (Worldometers, 2021; Figure 2, 3, 4, 5, 6). The Indian government introduced social distancing and safety

224 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar awareness as a precaution to avoid the spread of the disease. Indian government implemented a 14-hour voluntary public curfew on 22 March 2020 (Sardar et al., 2020; Gupta et al., 2020). On 24 March 2020, Prime Minister Narendra Modi ordered a nationwide lockdown for 21 days (lockdown 1.0) as a preventive measure against COVID-19 pandemic in India (Chaurasiya et al., 2020; Ray et al., 2020; Paital et al., 2020; The Hindu Net Desk, 2020). This brought India to a complete standstill and restricted the movement of 1.3 billion population in India. It was ordered after a 14-hour voluntary public curfew, followed by enforcement of a series of regulations in the country's COVID-19 affected regions. The lockdown was implemented when the number of confirmed positive corona cases in India reached around 500 (Mahajan, 2020; Chaurasiya et al., 2020; Ray et al., 2020). On 14 April 2020, with the number of coronavirus infected cases crossing 10,000 in India, Prime Minister Narendra Modi extended the nationwide lockdown until 3rd May 2020 (lockdown 2.0). Even before Modi’s speech, seven states have extended the restrictions till April 30th (The Hindu Net Desk, 2020). On 1st May, the Government of India extended the nationwide lockdown by two weeks until 17th May (lockdown 3.0). On 17th May, the Government of India extended the nationwide lockdown until 31st May (lockdown 4.0) with some relaxations. The Government has divided the entire nation into three zones viz., green, red and orange with relaxations applied accordingly (The Hindu Net Desk, 2020). On 30th May, it was announced that, the ongoing lockdown would be further extended till 30th June in containment zones, with services resuming in a phased manner starting from 8th June and it was termed as "Unlock 1.0”. The lockdown was announced in phased manner and the details are given below. Phase-I: Phase-II: Phase-III: Phase-IV: Phase-V:

25th March to 14th April 2020 (21 days) 15th April to 3rd May 2020 (19 days) 4th May to 17th May 2020 (14 days) 18th May to 31st May 2020 (14 days) 1st June to 31st June 2020 (Unlock 1.0)

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Phase-VI: 1st July to 31st July 2020 (Unlock 2.0) Phase-VII: 1st August to 31st August 2020 (Unlock 3.0) Phase-VIII: 1st September to 30th September 2020 (Unlock 4.0) Phase-IX: 1st October to 31st October 2020 (Unlock 5.0) Phase-X: 1st November to 30th November 2020 (Unlock 6.0) Phase-XI: 1st December to 31st December 2020 (Unlock 7.0) Phase-XII: 1st January to 31st January 2021 (Unlock 8.0) Phase-XIII: 1st February to 28th February 2021 (Unlock 9.0) Though the lockdown was essential to curb the spread of COVID-19 in India, it adversely affected the population especially the agriculture labours, whose livelihood has been devastated by these lockdown restrictions (Larue, 2020; Heuser et al., 2020). Farmers and farm workers across several states said work has come to a standstill on the fields. While the government had announced an economic package in the month of March, the relief has focused mainly on the land-owning farmers. For the landless labourers, there has been no income over these lockdown periods, forcing many to adopt drastic measures like reducing their food intake to cope with the income loss. In the lockdown 3.0, the Government once again announced a huge special economic package of Rs. 20 lakh crores (10% of the country’s GDP) to boost up all the activities and focussed mainly the agriculture and allied sectors in the country. According to the Socio-Economic and Caste Census of 2011, it was estimated that 51% of India’s rural population is landless (Biswas, 2019; Alkire and Seth, 2013). The impact of the lockdown imposed for several weeks create a big financial problem and poses the question of survival among them. India’s agricultural sector depends on migrant labourers for several operations. Now, an estimated 50 million migrant labourers (of India’s 140 million) are expected to have returned to their native places from cities following the nationwide lockdown on March 24. The present COVID-19 lockdown scenario has a deep impact on many seasonal crops especially wheat grown as a rabi crop, which will affect both supply-side as well as demand-side management.

226 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar Due to the complete lockdown and panic situation arising due to the COVID-19 pandemic situation, majority of the migrant labourers returned to the home states. Reverse migration due to COVID-19 provides an opportunity for hinterland administration to engage and accommodate the returned labourers in gainful employment and the sole short-term option is to leverage the potential of agriculture. They could be successfully employed in labour-intensive sectors like livestock, fisheries and food processing which may also create labour surplus and reduced wages. This labour help maintain the production level, resulting in increased share of labour in the agricultural sector.

COVID-19 and Farming in India The impact of the lockdown for several weeks created a big financial problem and poses the question of survival among them. While the government had announced two times economic package during COVID19 lockdown, the relief has focused agriculture and allied sectors mainly on the land owning farmers, labours, market reforms, dairy as well as fishery sectors were also given due importance in the special economic package that will boost up the agricultural and allied sectors activities in the country.

Lockdown and Impacts on Agriculture Production In Karnataka, non-availability of labour has hurt operations in many parts. In the case of paddy fields in Raichur, Bellari, Koppal and Gangavathi were ready for harvesting but farmers were facing labour issues. The increasing use of mechanical harvesters has helped in the present circumstances, though their inter-state movement has been severely curtailed. Besides the main crops such as ragi and maize, farmers cultivated green gram, black gram and sesame, especially in Mysuru, Chamarajanagar, Mandya and Hassan districts, during this

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season. But there is concern whether farmers will take up cultivation of these crops given the situation. If sowing is delayed, it will hurt the yield and overall productivity of the crops. In case of fruits, muskmelon in Tumakuru and watermelons and muskmelons in Kolar and Shivamogga districts, farmers faced problems in harvesting due to lack of specialised and skilled labourers required for harvest, those labours come from outside the state. Farmers who have grown vegetables like tomatoes in Chitradurga, Tumkur, Kolar and Mandya, cabbage in Belagavi, chillies in Kodagu are also not able to market their produce. However, Plantation crops like Coffee (largest coffee producing state in the country), the lockdown has hit processing, nursery activities, transport and irrigation even though the plucking of beans is over in most places and also pepper estate work has halted. Radically hit as they tend to be more dependent on migrant labour. Flower growers have destroyed their flowers following lack of demand during lockdown. Brightly coloured roses, chrysanthemums, lilies, marigold and other flowers that might normally have been destined for marriage decoration and temples – are being destroyed by growers in a unprecedented manner. Hence, a compensation of Rs. 25,000 per hectare limited to a maximum extent of one hectare for the crop loss was provided by the state government (special package to growers). Farmers who have grown vegetables and fruits were not able to market their produce and incurred losses. For compensation, the government announced relief package to the fruits and vegetable growers. Consequently, the shortage of migrant labour has resulted in a sharp increase in daily wages for harvesting of crops in local fields. In many areas, the rise is as high as 50 per cent, making it un-remunerative for producers. Since, prices have collapsed due to either lack of market access due to no transportation and closure of borders. This is in contrast to areas where migrant labourers have returned home from urban areas and this has led to a sharp decline in agricultural wages. Karnataka activated MGNREGA with revised wage of ₹202 a day (The Hindu Net Desk, 2020), which helped the labours.

228 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar In Tamil Nadu, 65-year-old N. Subramaniam (Vattakudi village in Vedaranyam) not had any work for at least a month now. A landless labourer, Subramaniam and his family of seven survive on farm work, supplemented with work under the MGNREGA. The law, passed in 2005, guarantees 100 days of manual labour employment in a year to every rural household that demands it (Chopra, 2014). By looking into these situations in the country, the Government has announced special package to MGNREGA that, Increase (Rs. 20) in wage to Rs. 202 a day from Rs. 182 to benefit 13.62 crore families. The paddy harvest in most of Tamil Nadu is over and the work primarily depends on harvesting of crops such as a banana and other fruits, vegetables like tomatoes and spinach, and given the summer season, mangoes (Jha et al., 2015). But no farmer has called them in for work in the last three weeks (lockdown 1.0) despite the government assuring them that agricultural activities are exempted from the lockdown restrictions. According to Subramaniam, post-paddy harvest time is actually a good time for labourers. “other crops are labour intensive and usually, we make more money during April-May season,” he said. This is because machines are used to harvest paddy across large swathes, the smaller crops like vegetables and fruits require more labour hands. The Tamil Nadu government on 24th March announced that, ration card holders would get Rs. 1000 as relief for the COVID-19 situation plus free rice, dal and oil for the month of April. Subramaniam said that money was exhausted in matter of days. “We have nothing now. We have cut down on food, eating half of the rice we used to and that too mainly with thovayal” (paste made with either vegetables or plant stems). In Andhra Pradesh, especially major chilli cultivation belts, farm labourers harvesting has come to a halt in most parts. Most of the labourers employed in these chilli farms are migrant from neighbouring districts and North Indian states such as Bihar and Uttar Pradesh. When the lockdown was announced suddenly on March 24, many labourers who had camped near the chilli fields were trapped with nowhere to go.

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The contradicting announcements in the first few days of the lockdown led to chaos and panic among migrant labours. Mr. Mathew who runs contract pineapple business in Vazakulam, Kerala told that, majority of his migrant workers fled to their native places in North Eastern states of India due to some mysterious message and hoax news related to COVID-19 before the official lockdown. This may be due to the fact that the first COVID-19 confirmed cases were reported in Kerala on 30th January. When the government eventually said agricultural activities were exempted on March 29, farming and other agriculture related activities had already come to a standstill. Most of the farmers and labours did not go to field for any agricultural activities due to the fear that the police might stop them for violating the lockdown restrictions. Most of the pineapple production was transported to North Indian states, due to lockdown, the producer cannot find buyers from other states and had to sell locally at lesser price. “I also faced problems in harvesting the pineapple due to the labour shortage” said Mr. Mathew. The restrictions on movement apart, the labourer said farmers were worried about selling their crop after harvesting. Small farmers would rather harvest the crop themselves than paying wages, given the situation. Madhya Pradesh’s Tikamgarh district is part of the drought-prone Bundelkhand region. The young members of most rural families will migrate to Delhi and the surrounding urban areas to work in industrial and construction jobs, while the older members stay and work in small farms. When the lockdown began, most of the urban labourers decided to return home in village thinking that they are safe and will have food. Most of them covered part of the 500-700-km journey on foot, the rest by hitching rides on trucks. Most of them were stopped by the police or met with some accident or health issues and were unable to reach their destinations. Large farmers were literally not much affected and used harvester machines since hiring labour during the lockdown was impracticable which made the farm workers without any regular income. “There is no work in the fields. There is no work outside,” one farm worker said. “Everyone is sitting at home.”

230 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar The implications of labour and credit shortages are not limited to the crop sector but also on the dairy farming and livestock sector. The limited availability of credit, labour and machinery are hindering the integrated harvest management. The residue of rabi crops, especially from wheat, is widely used for feeding the cattle which serves as an additional source of income for farmers as well as a rich source for cattle feed. The current scenario may lead to a decline in the availability of cattle feed and also in absolute income of the farmers. The price of feed may also increase. The implication of this development may lead to a rise in the price of milk and related products. The milk distribution systems were also affected as the farmers were unable to sell their milk due to shut down of the milk collection booth or agencies, which leads to local selling as well as value added products especially ghee, curd, cheese production. The report said that, Demand of Milk reduced by 20-25%, to combat, 560 Lakh litre per day (LLPD) procured by cooperatives against daily sale of 360 LLPD.

Lockdown and Impacts on Trade and Tourism Being one of the largest nations in South Asia, China, United States and United Arab Emirates are the major trading countries for India. As a precautionary measure to avoid COVID-19 spread in India, the Government of India closed the major borders to China, Nepal, Pakistan and Bangladesh including the domestic and international flight. This completely halted the trade with the neighbouring as well as nonneighbouring countries. This closure limited the availability of raw materials which as usually imported. The same scenario also happened for the export products which has to find local and domestic markets. The lockdown created a situation of panic-buying and hoarding of goods especially in the urban areas of India. Thousands of Indians, who want to return to India got stuck in various regions especially middle east, Europe and America due to country wide lock down on 24 March and

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International flight ban. This include migrant laborers, students and Indian citizens living abroad. As a measure to reduce and protect against spreading coronavirus infection World Health Organization (WHO) encourage the people to wash hand with soap and water or an alcohol based and proper usage of face masks. This ignited panic-buying and hoarding of these goods, leading to the shortage in majority of cities in India. Due to the COVID19 outbreak, the hardest hit sector of the economy is tourism. The World Travel and Tourism Council research reported that Indian’s tourism sector was responsible to generate 13681billion of INR in revenue (6.8% of total economy) and supported more than 8% of total employment in 2019 (World Travel and Tourism Council, 2020). Postponing of the tourists travel plans and suspension of all the Indian visas including the on-arrival visa along with the countrywide lockdown, has led to the loss of jobs to many thousands. India, being receiving the highest remittance in the world (79 billion USD) followed by China and Mexico at 67 billion and 36 billion respectively. These remittances constituted 2.9% of India’s GDP and remittances formed the country's foreign exchange money of roughly around 22% to 23%. The decline in remittance can limit the families from getting out of poverty, paying off unscrupulous loans, and investment in education, health and land.

Lockdown and Impacts on Education The action of the government of India to close all educational institutions, postponing of all state and national level examinations and prohibiting the gathering of more than 5 people together led to an outflux of many thousands of people from various metropolitan cites and states across India. This reverse migration also caused the spreading of virus and caused unemployment and food insecurity in rural areas across India. Another factor for the sudden reverse migration is the perception of the village environment as pure and unlikely to get corona virus infection (Cuello-Garcia et al., 2020). The drastic increase in new infection rates,

232 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar lesser tests, increased media reporting and death tolls have increased public anxiety. The absence of clear messages and the desire for facts have heightened fear among the public and propelled them to seek information from less reliable portals (Rubin and Wessely, 2020). The current pandemic has imposed multiple restrictions on research as laboratories have been closed, and scientists and researchers have been working from home, limiting recruitment in studies. According to the World Bank (2020), the COVID-19 pandemic has caused more than 1.6 billion children and youth in 161 countries to be out of school, which is close to 80% of the world’s enrolled students. Parents have experienced increased pressure to work from home, to keep their work running as well as to take care of schooling children at home at the same time, while caregiver resources including grandparents and the wider family have been restricted (Fegert et al., 2020). With the unprecedented lockdown, most parents have worries about their children’s education and future as their school education has been halted until further notice. The Government of India has decided to introduce a digital education system to continue the teaching learning process, and this has further burdened parents with the load of school fees and online internet fees. It is further stressful for parents with a low income who have to struggle for daily wages and do not have proper internet access, as it compromises the learning needs of their children.

Lockdown and Impacts on Media Sectors The infodemics, misinformation and inaccurate conception are spreading quicker from fake and unauthorized news portal websites, contributing to myths and rumours in the society. Myths related to alcohol, adding hot peppers, ginger and garlic to food, and exposing oneself to temperatures higher than 25° or to cold weather and snow to kill the coronavirus are misleading people. Therefore, there is a need to be thoughtful and conscious when communicating on social media and other communication platforms (UNICEF, 2020a). Authorized health

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organizations and the government should provide timely information through reliable portal platforms and ban unauthorized websites to avoid misleading the public. A large number of people have assumed the lockdown as vacation time and are pressurizing others to engage in forceful academic or jobrelated activities. During the lockdown, several social networking media messages, instead of promoting, are actually compromising the mental health of individuals in the society. People have their individual coping strategies and not all can perceive the pandemic lockdown as an opportunity to learn. Several messages are demanding people to come out with new skills during the lockdown, which has further aggravated the psychological pressure and mental stress (Oldekop et al., 2020).

Lockdown and Impacts on Health This pandemic crisis has significantly transformed the working environment, resulting in high-pressure work, and unfavourable and demanding interactions among health workers. Frontline health workers, including doctors, nurses, certified caregivers, lab technologists and pharmacists, with inadequate supplies of PPE, have been giving their best professional services to protect human lives. While trying to balance life as a healthcare professional and as a member of a family, dealing with highly infectious clients has led to guilt about potentially exposing their families to infection (Ramaci et al., 2020). Contracting COVID-19 has increased stigma and social discrimination among people. Some house owners have been reported to evict nurses, doctors and other medical professionals from their rental apartments fearing the spread of the novel coronavirus in their neighbourhood. Cured patients upon returning home are socially avoided and discriminated against, leading to decrease in moral support. Stigma can negatively affect clients searching for medical care at a time when they are at their most vulnerable stage. Stigma and social discrimination can lead to hiding of symptoms and avoid seeking of medical care,

234 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar making it tremendously difficult for health care professionals and the government to control the disease. This stigmatization can discourage people from adopting healthy behaviours and can dramatically increase the suffering of people, leading to fatigue, stress and other mental distress. Hence, by understanding the disease, building trust, showing empathy to those affected, and adopting effective practical measures, people can help to save their dear ones (UNICEF, 2020b). The COVID-19 pandemic has brought serious psychological impact among health workers, students and the general public around the globe. Globally, a notable increase in suicide rates occurs after natural disasters such as floods, hurricanes and pandemic (Goldmann and Galea, 2014; Khetrapal et al., 2020). The pandemic-related restraints, such as spatial distancing, isolation and home quarantine, are impacting on economic sustainability and wellbeing, which may induce psychological issues such as sadness, worry, fear, anger, annoyance, frustration, guilt, helplessness, loneliness and nervousness (Bhuiyan et al., 2020; Mukhtar, 2020).

Lockdown and Impacts on Vulnerable People According to the United Nations 2018–2019, 6.7% of the population lived below the poverty line of earning $1.25 per day. The link between poverty and communicable disease is well-evident (Alsan et al., 2011; Bhutta et al., 2014). COVID-19 is no exception and has triggered increasing unemployment, loan defaults and major economic losses around the globe (Kantamneni, 2020). The economic downturn caused by COVID-19 can increase the economic instability, health inequalities and social disparities in India, which can have a huge impact on the poverty levels. While the lockdown has affected traders, especially people with small shops and those with limited sources of income, the poor, marginalized people and daily wagers are more vulnerable. Research has shown that a pandemic like COVID-19 can result in increased mental burden to marginalized or low income people via socioeconomic

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disadvantage such as job insecurity, housing instability, discrimination and food insecurity (Goldmann & Galea, 2014). There have been many significant pandemics recorded in human history, and the pandemic related crises have caused enormous negative impact on health, economies, and even national security in the world. However, the term “pandemic” has a long history, it is still not defined by many medical texts, and the conception is still changing. But there are some key features of a pandemic, including wide geographic extension, disease movement, novelty, severity, high attack rates and explosiveness, minimal population immunity, infectiousness and contagiousness, which help us to understand what pandemics are. The negative impacts of pandemic are serious. Pandemics have infected millions of people, causing wide-spread serious illness in a large population and thousands of deaths. It represents a serious threat not only to the population of the world, but also to its economy. The impact of economic loss can result in instability of the economy, which is through direct costs, long term burden, and indirect costs. The social impacts of pandemics were severe, travel was strictly limited, and schools were closed, markets and sporting were closed. All these are a likely reality should a pandemic with true potential for high morbidity and mortality emerge. A security threat of pandemic influenza as is not a recent phenomenon. Global security is threatened by pandemics, in terms of lives and economic stability. An effective and efficient emergency response can reduce avoidable mortality and morbidity and reduce the types of economic and social impacts. How to have an effective and efficient emergency management will be a critical task of governments to deal effectively with disease outbreak and a pandemic now and in future. The lockdown curfews, self-isolation, social distancing and quarantine have affected the overall physical, mental, spiritual and social wellbeing of the Indians. With the beginning of lockdown, the government decided to shut down all cinema halls, gyms, health clubs and museums, as well as banned the gathering of people for cultural, social or religious activities, including temples, monasteries, churches and mosques. In the case of death, the pandemic has disrupted the normal

236 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar bereavement processes of families. Although these measures are taken for the protection of people from COVID-19 pandemic, it has created fear, anxiety and uncertainty among the Indians.

CONCLUSION Pandemics are for the most part disease outbreaks that become widespread as a result of the spread of human-to-human infection. Throughout the history of mankind, pandemics have consistently produced large-scale demographic, economic, and political disruptions. The economic recessions have put significant financial pressure on many families, which might increase unhealthy conflict, family breakdown, abuse, depression and domestic violence. The psychological impacts of the COVID-19 lockdown might be a challenge for an indefinite period, hence it is necessary to emphasize and address coping strategies, mental health interventions and awareness using the available resources. India needs to be prepared for re-emergence or the second wave of COVID-19 pandemic. The long-term battle with corona virus may help people to win against battle by developing high efficient vaccines and medicines as India is the global leader in vaccine production with a capacity of 3.6 billion doses of vaccine per day.

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238 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar Evans JAS. The attitude of the secular historians of the age of Justinian towards the classical past. Traditio. 1976;32:164–165. doi: 10.1017/ S0362152900005572 Fears JR. The plague under Marcus Aurelius and the decline and fall of the Roman empire. Infect Dis Clin N Am. 2004;18(1):65–77. doi: 10.1016/S0891-5520(03)00089-8. Flecknoe D, Charles Wakefield B, Simmons A. Plagues & wars: the ‘Spanish flu’ pandemic as a lesson from history. Med Confl Surviv. 2018;34(2):61–68. doi: 10.1080/13623699.2018.1472892. Hajar R. The air of history (part II) medicine in the Middle Ages. Heart Views. 2012;13(4):158–162. doi: 10.4103/1995-705X.105744. Halliday S. Death and miasma in Victorian London: an obstinate belief. BMJ. 2001;323:1469. doi: 10.1136/bmj.323.7327.1469. Horgan J. Justinian’s Plague (541–542 CE). Ancient history encyclopedia; 2014 Dec 26. Retrieved from https://www.ancient.eu/ article/782/ Ilic M, Ilic I. The last major outbreak of smallpox (Yugoslavia, 1972): the importance of historical reminders. Travel Med Infect Dis. 2017;17:69–70. doi: 10.1016/j.tmaid.2017.05.010. Kalra S, Kelkar D, Galwankar SC, Papadimos TJ, Stawicki SP, Arquilla B, Hoey BA, Sharpe RP, Sabol D, Jahre JA. The emergence of ebola as a global health security threat: from ‘lessons learned’ to coordinated multilateral containment efforts. J Global Infect Dis. 2014;6(4):164–177. doi: 10.4103/0974-777X.145247. Kindhauser MK, Allen T, Frank V, Santhanaa RS, Dye C. Zika: the origin and spread of a mosquito-borne virus. Bull World Health Organ. 2016; 10.2471/BLT.16.171082. Langmuir AD, Worthen TD, Solomon J, Ray CG, Petersen E. The Thucydides syndrome: a new hypothesis for the cause of the plague of Athens. N Engl J Med. 1985;313:1027–1030. doi: 10.1056/NEJM 198510173131618. Littman RJ. The plague of Athens: epidemiology and paleopathology. Mt Sinai J Med. 2009;76(5):456–467. doi: 10.1002/msj.20137.

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240 P. Jose Vazhacharickal, J. John Mathew and N. K. Sajeshkumar Scheidel W. The great leveler: violence and the history of inequality from the stone age to the twenty-first century. Chapter 10: the black death. Princeton: Princeton University Press; 2017. pp. 291–313. Sehdev PS. The origin of quarantine. Clin Infect Dis. 2002;35(9):1071– 1072. doi: 10.1086/344062. Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis. 1998;178(1):53–60. doi: 10.1086/ 515616. Smith RD. Responding to global infectious disease outbreaks: lessons from SARS on the role of risk perception, communication and management. Soc Sci Med. 2006;63(12):3113–3123. doi: 10.1016/ j.socscimed.2006.08.004. Tarantola D. DA Henderson, Smallpox Eradicator. Am J Public Health. 2016;106(11):1895. doi: 10.2105/AJPH.2016.303477. The Editors of Encyclopaedia Britannica. Black death, Encyclopædia Britannica; 2018 Sept 4. https://www.britannica.com/event/BlackDeath. The Noble Qur’an Surah 7, v. 133. Thucydides, history of the Peloponnesian War, Book 2, Chapter VII. p. 89–100., trans. Crawley R. Digireads.com Publishing; 2017 Sept. ISBN-10: 1420956418. Today’s HIV/AIDS epidemic factsheet. https://www.cdc.gov/nchhstp/ newsroom/docs/factsheets/todaysepidemic-508.pdf. Centers for Disease Control and Prevention. U.S. Government. Accessed Oct 2018. Trifonov V, Khiabanian H, Rabadan R. Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. N Engl J Med. 361(2):115–9. 10.1056/NEJMp0904572. PMID 19474 418. Wang H, Wolock TM, Carter A, Nguyen G, Kyu H, Gakidou E, Hay SI, Mills EJ, Trickey A. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the global

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burden of disease study 2015. Lancet HIV. 2016;3(8):e361–e387. doi: 10.1016/s2352-3018(16)30087-x. Whitford F. Expressionist portraits. Abbeville Press; 1987. p. 46. ISBN 0-89659-780-6. World Health Organization (WHO). Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. http://www.who.int/csr/sars/country/table2004_04_21/en/. Yapijakis C. Hippocrates of Kos, the father of clinical medicine, and Asclepiades of Bithynia, the father of molecular medicine. Review. In Vivo. 2009;23(4):507–514.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 14

THE PANDEMIC AIDS Tharakupeedikayil Abdul Majeed Sajeena* Department of Biosciences, MES College Marampally, Aluva, India

ABSTRACT Acquired Immunodeficiency Syndrome (AIDS) is one of the major pandemic diseases. The etiological agent is Human Immunodeficiency Virus (HIV). HIV is a member of the subgroup Lentivirus of the family Retroviridae. It is a highly mutable virus exhibiting frequent antigenic variation and cell tropism. The genome of the virus has structural genes, nonstructural genes and regulatory genes. The two important strains of HIV have been recognized based on molecular and antigenic differences. They are HIV-1 and HIV-2. AIDS is primarily a sexually transmitted disease. T helper cells are primarily infected resulting in immunosuppression. When the virus enters the blood or tissue of a person, it come into contact with CD4 cells. The virus binds to the CD4 receptor of the T helper cell by its receptor, the envelope glycoprotein gp120 resulting in cell fusion. AIDS patients cannot respond to new antigens. The CD4:CD8 ratio (2:1) get reversed. Activity of monocytes, macrophages, natural killer cells and cytotoxic T lymphocytes (CTLs) *

Corresponding Author’s Email: [email protected].

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Tharakupeedikayil Abdul Majeed Sajeena are affected thereby diminishing the cell mediated immune response. Polyclonal activation of B cells results in production of many useless antibodies to irrelevant antigens leading to a condition called hypergammaglobulinaemia. Accumulation of immune complexes can initiate Type III hypersensitivity. Thus, both cell mediated and humoral immunity are suppressed. The HIV virus exhibits a longer incubation period of up to 10 years. The natural evolution of this syndrome includes many stages leading finally to the end stage, AIDS. Patients are more prone to malignancies and many opportunistic infections. Kaposi’s sarcoma is seen in male homosexuals. Recurrent pneumonia is another diagnostic feature of AIDS. The specific tests for HIV detection include demonstration of virus, viral antigens, antibodies and isolation of virus. Antibody detection is the simplest and most widely used technique for HIV diagnosis. ELISA is the most widely employed screening test. The confirmatory test for AIDS is western blotting. No specific vaccines are available. General measures such as health education, source identification and elimination of high-risk activities can be undertaken for prevention of AIDS.

Keywords: AIDS, T helper cell, HIV, CD4, CD8

INTRODUCTION The greatest challenge to public health in modern times is the emergence and spread of the pandemic AIDS. The first indication of this syndrome appeared in 1981 in USA among young adults who were homosexuals (Weiss et al., 2004). Among them an unexplained outbreak of Pneumocystis pneumonia and Kaposi’s sarcoma were observed. Both diseases are markers of collapsed immune system. In 1983, Luc Montagnier and colleagues from the Pasteur Institute, Paris isolated a retrovirus from a West African patient with persistent generalized lymphadenopathy. They named it as Lymphadenopathy Associated Virus (LAV) (Barre-Sinoussi et al., 1983). Other similar isolates were reported from AIDS cases under different names. The International Committee on Virus Nomenclature decided the name Human Immunodeficiency Virus (HIV) for all these virus isolates. Epidemiologic and phylogenetic analysis implies that HIV was introduced into the human population

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around 1920 to 1940. HIV-1 evolved from non-human primate immunodeficiency viruses from Central African chimpanzees and HIV-2 from West African sooty mangabeys (Gao et al., 1999; Mushahwar, 2007).

HUMAN IMMUNODEFICIENCY VIRUS (HIV) The causative agent of AIDS is Human Immunodeficiency Virus. The two human immunodeficiency viruses, HIV-1 and HIV-2, are members of the family Retroviridae and the subgroup Lentivirus. Retroviruses have been found in various vertebrate species, associated with a wide variety of diseases, in both animals and humans. The HIV-1 and HIV-2 originated from the Simian Immunodeficiency Viruses (SIVs) of primates. They had a zoonotic origin but now direct spread occurs from human to human. Retroviruses have been found associated with malignancies, autoimmune diseases, immunodeficiency syndromes, aplastic and haemolytic anaemia, diseases of bone and joints and disorders of the nervous system (Weiss et al., 2004).

HIV Structure HIV is a spherical enveloped virus with a size of 90-120nm. The outer shell or the envelope of the virus is covered with glycoprotein spikes gp120 and gp41. These spikes allow the virus to lock onto the CD4 receptor of CD4 T helper cells and enter the cell (Protein Data Bank, 2014). Inside the envelope is a matrix. The nucleocapsid is a coneshaped structure located in the centre of the virion. The two enzymes essential for HIV replication, the reverse transcriptase and integrase are located in the capsid. The genome is diploid with two identical single strands of positive sense RNA (Protein Data Bank, 2014).

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Viral Genes and Antigens The viral genome has structural genes as well as non-structural genes and regulatory genes. The gene products act as antigens. They can be employed in diagnosis and prognosis of infection. The structural genes are gag, pol and env. The gag gene is expressed as precursor protein p55 and determines the viral core and shell. The synthesis of envelope glycoprotein gp 160 is determined by the env. The gp 160 is cleaved to form the gp 120 (surface spikes) and gp 41 (Trans membrane anchoring protein). The gp120 is the major envelope antigen and antibodies are seen in blood till the final stage of the infection. The pol gene is coding for the polymerase enzyme reverse transcriptase, protease and endonuclease. The non-structural and regulatory genes are tat, nef, rev, vif, vpu & vpx, vpr and LTR (Gallo et al., 1988). The tat gene enhances the expression of all viral genes. The viral replication is down regulated by nef genes. The expression of structural proteins is enhanced by rev genes (Mushahwar IK 2007). The infectivity of the virus is influenced by vif gene. The maturation and the release of the progeny virion is enhanced by vpu and vpx. vpr stimulates the promoter region of the virus. (King Steven R, 1994). LTR sequences seen on either end contain sequences giving various signals (King, 1994).

Antigenic Variation and Diversity HIV is a highly mutable virus with frequent antigenic variation, cell tropism and cytopathology. Two types of HIV are recognized based on antigenic and molecular differences- Type 1 and Type 2. The original isolates of HIV and the related strains belong to HIV type 1. Antigenic differences seen in HIV strains is important in serodiagnosis (Faria et al., 2014). Based on their cellular tropism HIV-1 strains are subdivided into three main groups (Naif et al., 1998). They are referred to as macrophage-tropic with a non-syncytium-inducing phenotype or T-cell line tropic with a syncytium-inducing phenotype or dual tropic HIV-1

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strains. (Naif et al., 1999). HIV-1 strains are classified into ten subtypes designated A to J based on sequence analysis of the gag and env genes. Sub type A is the most prevalent worldwide. Subtype C is the most prevalent type in India (Robertson, et al. 1995).

Pathogenesis The principal host cell is CD4 T lymphocytes. Virus enters the blood or tissues of a person and comes into contact with T helper cell. It can spread through sexual contact or blood, from mother to child during pregnancy, during childbirth or through breast-feeding. The envelope glycoprotein gp 120 of the virus binds to the CD4 receptor of T helper cell. Cell fusion is brought about by the transmembrane gp41. The participation of a core receptor molecule is required for cell fusion and virus entry. This is followed by genome uncoating and internalization in to the cell. Reverse transcription results in the synthesis of double stranded DNA. It is integrated in the host cell genome with the help of enzyme integrase. The damage of CD4+T lymphocyte is the primary pathogenic mechanism of HIV. The T4:T8 ratio is reversed (Wahren et al., 1987). The major damage is to cell mediated immunity. As T helper cell activity is essential for the optimal function of B cells, humoral immunity is also affected. Polyclonal activation of B cell resulting in hypergammaglobulinaemia is an important feature of HIV. Due to lack of secretion of activating factors Monocyte macrophage function is affected. Elevated levels of immune complexes, diminished delayed hypersensitivity, reduced antibody response to new antigens etc. are some immunological abnormalities associated with HIV infection (Laurence, 1984).

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Clinical Features of HIV Infection A wide spectrum of clinical features can be seen in HIV infection. The following stages are there in the natural evolution of HIV infection: 

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Acute HIV infection: About 50% of infected persons experience headache, lymphadenopathy, low grade fever, malaise. On the onset of illness, the antibody test for HIV is usually negative and becomes positive during the course of infection. So this is also called ‘seroconversion illness’ (Cascade Collaboration, 2001). Asymptomatic or latent infection: This is a symptomless phase HIV infection which may not cause any other symptoms for several years. About 5-10% of the infected can escape the clinical AIDS even up to 15 years or more. They show HIV antibodies in blood and are infectious during this period. Such patients are called ‘long term survivors.’ There is no microbiological latency as the virus multiplication goes on. The virus will still be active, infects new cells and makes copies of itself. HIV can still be passed on during this stage. If untreated, HIV infection can cause severe damage to the immune system (Weiss et al., 2004). Persistent generalized lymphadenopathy: This stage is characterized by enlargement of lymph nodes. Lymph nodes enlarges at least 1cm in diameter and last for three months. This may progress to AIDS or ARC. AIDS related complex (ARC): Include patients with severe immunodeficiency and suffer from minor opportunistic infections such as oral candidiasis, herpes zoster, tuberculosis, salmonellosis etc. The symptoms are fatigue, fever, persistent diarrhea and marked weight loss. Other complications are generalized lymphadenopathy and splenomegaly. Many of the ARC patients progress to AIDS in a few months (Weiss et al., 2004).

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AIDS: This is the end stage of disease. The immune defence mechanism breaks down irreversibly. The patient is subjected to progressive opportunistic infections and malignancies. Clinical severity varies with the type of infection. Recurrent pneumonia is an indicative of AIDS. Oral thrush. gingivitis, dysphagia, chronic colitis etc. are some gastrointestinal problems seen in AIDS. The opportunistic infections of CNS are toxoplasmosis, cryptococcosis, CMV, herpes, tuberculosis, aspergillosis, candidiasis and lymphoma. HIV can cross the blood-brain barrier causing encephalopathy leading to loss of higher functions, progressing to dementia. Malignancy seen in male homosexuals is Kaposi’s sarcoma. Lymphomas are also seen as both Hodgkin and non-Hodgkin types. The common cutaneous lesions are folliculitis, impetigo, candidiasis, seborrhic dermatitis and molluscum contagiosum. Virus transmission occurs from mother to fetus in the first trimester of pregnanacy. Perinatal infection is more common. Chronic diarrhea, lymphadenopathy, tuberculosis and opportunistic bacterial infections are seen in pediatric AIDS (Hopewell et al., 1986).

Epidemiology The molecular studies show that the progenitor of HIV Type 1transferred to humans from chimpanzees living in equatorial West Africa. HIV Type 2 entered the human population from Sooty Mangabey monkey. It is primarily a sexually transmitted disease and is mainly transmitted among male homosexuals with large number of sexual partners. In developing countries heterosexual transmission is mainly seen. Best method for reducing the sexual transmission is health education. The second method of transmission is through blood and blood products. This can be reduced by screening of blood donors before transfusion. Contaminated needles can transmit infection among drug addicts. Another mode of transmission is from mother to baby during or

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after birth. HIV present in breast milk is rarely transmitted to babies (Nduati et al., 2000).

Laboratory Diagnosis HIV assays can be divided into two categories: screening assays and confirmatory assays. The detection of HIV infection can be done by testing the presence of HIV-specific antibodies (Gürtler L. A, 1996). Direct diagnosis of HIV infection is also possible by the demonstration of infectious virus, using cell culture technique, or the identification of p24 antigen (viral antigen) or viral nucleic acid through Nucleic Acid Testing (NAT). The quantitative detection of virus has become very important. The concentration of viral RNA in plasma, (“viral load”), has become an indispensable tool for guiding the antiretroviral therapy (Berger et al., 2001) Different algorithms are currently used depending on the purposes of the test. A highly sensitive algorithm is used for the detection of anti-HIV antibodies during screening of blood samples for donations and for epidemiological studies. A positive result in a highly sensitive screening test must be followed for diagnosis. A further investigation using a confirmatory test, to confirm the positive results obtained must be done. Screening EIA: A variety of manual and automated test methods are available today. Automated systems are often used for performing screening assay, as large numbers of samples can be tested. It is safe and economical. The first-generation EIA assays employed “whole virus antigen.” An “indirect” approach is used to detect the antibodies to HIV antigens. Viral lysate is bound to solid phase, in the wells of a microtitre plate. An antigen-antibody binding will occur on addition of serum sample that contains antibodies directed against HIV antigens. All unbound constituents of the serum are removed by a washing step, including all antibodies. The bound antibodies are detected by the addition of a conjugate (second antibody). An enzyme molecule is added in the next step. The unbound conjugate is removed by washing. A

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substrate is added and the product produced by the action of enzyme generates color and is read at the spectrophotometer. The intensity (optical density) of the color developed is proportional to the antibody concentration in the serum sample. Positive and negative control specimens must be included for comparing the results. The firstgeneration EIA were sensitive enough. One drawback was that it proved less effective regarding their specificity (Fanales-Belasio et al., 2010). The second-generation EIA appeared in 1987. It employed the same indirect format as the first-generation assays. The difference was that instead of the full viral lysate, the HIV recombinant antigens and peptides were employed in solid phase. This increased the specificity and sensitivity of the test. This also reduced the window period (FanalesBelasio et al., 2010) enabling the detection of antibodies as early as 33-35 days after infection. The third generation EIA were designed on a new format in 1994. Recombinant HIV-1 and HIV-2 proteins and/or peptides, bound on the solid phase is employed to react with the serum sample. This ensured higher sensitivity and specificity. It reveals all potential classes of anti-HIV antibodies (IgG, IgM and IgA). This tests drastically reduced the “window period” to about 22 days after infection (Brust et al., 2000). Fourth-generation assays have been introduced to reveal the presence of both the antibodies and the p24 major antigen of. This has permitted to further reduce the window period. In the near future, it can be expected that the fourth-generation EIA will replace the third generation assays due to their importance in the screening of low and high-risk populations (Brust et al., 2000).

Confirmatory Test The most commonly used confirmatory tests are Western Blotting (WB) and Line Immune Assays (LIA). The western blotting is a confirmatory assay and is only carried out if the sample is found reactive during screening. The commercially available western blots include both HIV-1 and HIV-2 antigens. The HIV denatured proteins are blotted on

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strips of a nitrocellulose membrane and incubated with patient serum (Morb Mortal Wkly Rep, 1991). If the serum contains specific antibodies against the various viral proteins, they will bind to the corresponding protein. An enzyme-labelled secondary antibody and a suitable substrate can be used to reveal this reaction. The presence of HIV proteins can be revealed by a colorimetric reaction. The antibodies can be recognized as “bands” on the strip. The result may be positive, negative or intermediate. The criteria for the interpretation of HIV Western blot may differ. The Centers for Disease Control will consider a positive WB only if at least any two of p24, gp41, and gp120/160 proteins are present (Tebourski, 2004), whereas according to WHO recommendations, a WB may be judged positive only if two Env bands are found (Tebourski, 2004). Western blotting assay is very expensive. Assays similar to WB, based on recombinant proteins and/or synthetic peptides capable of detecting antibodies to specific HIV-1 and/or HIV-2 proteins, generically called LIA have been developed. Examples include the INNOLIA, RIBA assays, and Pepti-Lav. These assays produce fewer indeterminate results when compared to WB, but are expensive as WB.

Rapid Tests A number of rapid HIV tests are available. They are also referred to as Rapid/Simple (R/S) test devices. All these tests are following one of four immunodiagnostic principles such as particle agglutination, immunodot, immuno filtration and immune chromatography (Giles, 1999). In most cases, whole blood or capillary blood from a fingertip can be used. The problems of both sensitivity and specificity can arise in HIV rapid testing (Ekwueme et al., 2003).

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HIV Antigen Diagnosis The diagnosis of HIV infection can be done through the detection of the virus components. The commercial tests that can identify HIV nucleic acid, either RNA or proviral DNA, is Nucleic Acid Tests (NAT). NAT is based on Polymerase Chain Reaction (PCR), branched DNA (b-DNA), Nucleic Acid Sequence-Based Amplification (NASBA), Ligase Chain Reaction (LCR), or real-time PCR. NAT can be used for the diagnosis of HIV infection in special situations, like in suspected acute infection, with undetectable antibodies and in newborns of HIV-infected mother with maternal antibodies. The risk of acquiring HIV through blood transfusion is found to be reduced by approximately 50% using NAT (Pillonel, 2005). HIV-1 DNA PCR assays, represent the gold standard for diagnosing HIV in infants and children younger than 18 months. Assays for the detection of recent HIV infections: Detection of recent HIV infections is an important tool for the evaluation of the current pattern of HIV transmission in a community. New methods have been developed to discriminate recent and chronic infection (Kothe et al., 2003). The methods are grouped under the term of STARHS (Serological Testing Algorithm for Recent HIV Seroconversion). A number of antibody-based assays- “detuned” assay, BED-capture enzyme immuno assay, IDE-V3 immunoassay,have been developed, which permit to discriminate recent from chronic infections (Parekh et al., 2002).

Treatment Early diagnosis of AIDS and treatment of opportunistic infections is very useful. General management of the patient is very important. A number of effective drugs such as nucleoside analogues and protease inhibitors have been used as monotherapy or in various combinations. Adverse side effects and high cost are two limitations of these drugs and restrict their use in poor countries.

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Prophylaxis The general measures for prevention of AIDS are health education, identification of sources and avoiding high risk activities. There is no specific vaccine due to high mutability, antigenic diversity and long latency. Several possible strategies such as immunization with modified whole virus, viral sub units, synthetic epitopes etc. have been adopted for vaccine production.

CONCLUSION The world has learned from the HIV epidemic that new highly contagious viruses can arise at any time. If the epidemiology implies it is an infectious disease, the country must be prepared to face a lethal illness. The outbreak has also shown us that the country’s blood supply, which is generated from humans, is extremely vulnerable to infection. The blood supply of every country is a vital, one-of-a-kind, life-giving resource. The donation of whole blood and other blood products saves the lives of many people. Several federal agencies are assisting in the response to this public health emergency. The National Blood Policy has entrusted the protection of the nation'’ blood supply to the Public Health Service, which includes the CDC, FDA, and NIH. The greater likelihood of recurring threats to the blood supply has prompted this Committee to rethink methods, policies, and resources in order to ensure that our society’s supply of safe blood and blood products is preserved.

REFERENCES Andersson S, Asjö B, Jenum PA, Manner I, Njölstad G, Ragnhildstveit E, Skaug K, Söderquist B, von Sydow M. (2004). Relevance of a

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combined HIV antigen/antibody assay to detect early HIV infections in low prevalence population: case reports. Clin Lab; 50:409-13 Berger A, Preiser W, Doerr HW. (2001). The role of viral load determination for the management of human immunodeficiency virus, hepatitis B virus and hepatitis C virus infection. J Clin Virol; 20:23-30. Brust S, Duttmann H, Feldner J, Gürtler L, Thorstensson R, Simon F. (2000). Shortening of the diagnostic window with a new combined HIV p24 antigen and anti-HIV-1/2/O screening test. J Virol Methods; 90:153-65. Cascade Collaboration. (2001). The relationships between HIV test interval, demographic factors and HIV disease progression. Epidemiol Infect; 127: 91–100. Centers for Disease Control (CDC). (1991). Interpretive criteria used to report western blot results for HIV-1-antibody testing-United States. MMWR Morb Mortal Wkly Rep; 40:692-5. Ekwueme DU, Pinkerton SD, Holtgrave DR, Branson BM. (2003). Cost comparison of three HIV counseling and testing technologies. Am J Prev Med; 25:112- 21. Fanales-Belasio E, Raimondo M, Suligoi B, Buttò S. (2010). HIV virology and pathogenetic mechanisms of infection: a brief overview. Ann Ist Super Sanità; 46(1):5-14. Faria NR, Rambant A, Suchard MA, Baele G, Bedford T, Ward MJ, Tatem AJ, Sousa JD, Arinaminpathy N, Pépin J, Posada D, Peeters M, Pybus OG, Lemey P. (2014). HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations. Science. 346:56–61. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M, Shaw GM, Sharp PM, Hahn BH. (1999). Origin of HIV-1 in the chimpanzee Pan troglodytes. Nature. 397:436–441. Giles RE., Perry KR., Parry JV. (1999). Simple/rapid test devices for anti-HIV screening: do they come up to the mark? J Med Virol; 59: 104-9.

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Gürtler L. (1996). Difficulties and strategies of HIV diagnosis. Lancet; 348:176-9. Hopewell, PC. and Luce, JM. (1986). Pulmonary manifestations of the acquired immunodeficiency syndrome. Clin Immunol. Aller. 6:489519. King Steven R. (1994). “HIV: Virology and Mechanisms of disease.” Annals of Emergency Medicine. 24 (3): 443–449. Kothe D, Byers RH, Caudill SP, Satten GA, Janssen RS, Hannon WH, Mei JV. (2003). Performance characteristics of a new less sensitive HIV-1 enzyme immunoassay for use in estimating HIV seroincidence. J Acquir Immune Defic Syndr; 33:625-34. Mushahwar IK. (2007). “Human Immunodeficiency Viruses: Molecular Virology, pathogenesis, diagnosis and treatment.” Perspectives in Medical Virology. 13: 75–87. Naif HM, Li S, Alali M, et al. (1998). CCR5 expression correlates with susceptibility of maturing monocytes to human immunodeficiency virus type 1 infection. J Virol 72:830-6. Naif HM, Li S, Alali M, et al. (1999). Definition of the stage of host cell genetic restriction of replication of human immunodeficiency virus type 1 in monocytes and monocytederived macrophages by using twins. J Virol. 73:4866-81 Nduati, R., John, G., Ngacha DA, et al. (2000). Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomised clinical trial. JAMA. 283:1167–1174. Parekh B, Kennedy MS, Dobbs T. (2002). Quantitative detection of increasing HIV type 1 antibodies after seroconversion: a simple assay for detecting recent HIV infection and estimating incidence. AIDS Res Hum Retrov; 18:295-30.7. Pillonel J, Laperche S, Etablissement Francais du Sang. (2005). Trends in risk of transfusion-transmitted viral infections (HIV, HCV, HBV) in France between 1992 and 2003 and impact of nucleic acid testing (NAT). Euro Surveillance 10: 5-8. Protein Data Bank. (2014). HIV Envelope Glycoprotein (accessed 7 November 2018).

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Protein Data Bank. (2014). HIV Capsid (accessed 7 November 2018). Robertson, DL., Hahn, BH., Sharp, PM. (1995). Recombination in AIDS viruses. Journal of Molecular Evolution 40: 249–259. Tebourski F, Slim A, Elgaaied A. (2004). Tebourski F, Slim A, Elgaaied A. 2004. The significance of combining World Health Organization and Center for Disease Control criteria to resolve indeterminate human immunodeficiency virus type-1 Western blot results. Diagn Microbiol Infect Dis; 48:59-61. Wahren, B., Morfeldt-Månsson, L., Biberfeld, G., Moberg, L., Sönnerborg, A., Ljungman, P., Werner, A., Kurth, R., Gallo, R., Bolognesi, D. (1987). Characteristics of the specific cell-mediated immune response in human immunodeficiency virus infection. J Virol 61: 2017–2023. Weber, B. (2006). Screening of HIV infection: role of molecular and immunological assays. Expert Rev Mol Diagn; 6:399- 411. Weiss RA, Dalgleish AG, Loveday C, Pillay D. (2004). Human Immunodeficiency Viruses. In: Zuckerman AJ, Banatvala JE, Pattison JR, Griffiths PD, Schoub BD (eds). Principles and Practice of Clinical Virology. 5th ed. Chichester: John Wiley & Sons Ltd, pp 721-57.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 15

THE PLAGUE PANDEMIC Thushara Balakrishnan* Department of Microbiology, Vydehi Institute of Medical Sciences and Research Center, Bangalore, India

ABSTRACT Throughout human history, there have been several pandemics such as plague, smallpox and tuberculosis. The deadliest pandemic in recorded history was the Black Death [the plague], which killed an estimated 75- 200 million people in the 14th century. There have been three great pandemics of plague recorded in 541, 1347 and 1894 CE, each time causing devastating mortality of people and animals across nations and continents. The causative agent of plague is Yersinia pestis, a gram-negative, facultatively anaerobic, non-spore forming coccobacillus in the family Enterobacteriaceae. Plague is a zoonosis for which urban and sylvatic rodents are the most important enzootic reservoirs. Human plague occurred in North and South America, Asia and Africa. Infections are transmitted from rodents to humans via the bite of an infected flea, Xenopsylla cheopis. The other routes of *

Corresponding Author’s Email: [email protected]; Thushara Balakrishnan, Research Scholar.

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Thushara Balakrishnan infection include contact with body fluids of infected animals, inhalation of respiratory droplets from animals or humans with pneumonic plague. The three clinical forms of plague are the bubonic, septicemic and pneumonic plague. Bubonic plague is the most common form characterized by high fever, chills, headache, associated with one (or more) very painful lymph node, usually inguinal (bubo), at the site of a flea bite. The mortality rate in untreated patients is approximately 50% because of septicaemia. Septicemic plague is the rarest and most serious of the three plague varieties and cause disseminated intravascular coagulation and is almost fatal when untreated. Death of tissue (gangrene) causes the blackening of extremities, mostly fingers, toes, and nose. Pneumonic plague is a severe lung infection following an initial bubonic or septicemic plague infection. It is transmitted by inhalation of airborne droplets from another person or animal infected with pneumonic plague. The most apparent symptom of pneumonic plague is coughing, often with haemoptysis, headache, weakness, and rapidly developing pneumonia with shortness of breath, chest pain, with bloody or watery sputum. Pneumonia progresses for two to four days and may cause respiratory failure and shock. Patients will die without early treatment. The CDC has classified Yersinia pestis as a category A biologic agent for potential bioterrorism. Bacteremia and septicemia frequently developing in the infection process often leads to secondary infection of other organs including lungs, spleen, and central nervous system. Plague is diagnosed by demonstrating Yersinia pestis in blood or body fluids such as lymph node aspirate, sputum, or cerebrospinal fluid. Serology showing a four-fold rise in antibody titers for F1 antigen is also diagnostic. Aminoglycosides, Fluoroquinolones and Doxycycline are the antibiotics of choice. Standard infection control practices, including handwashing, is highly recommended for preventing the infection. Post-exposure prophylaxis with antibiotics should be given for individuals with close contact with an infectious case or who had a potential respiratory exposure. Currently, there is no licensed vaccine. A live vaccine containing encapsulated Yersinia pseudotuberculosis strain V674pF1 is found to be effective against pneumonic plague in mice.

Keywords: black death, pandemic, bioterrorist weapon, plague

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INTRODUCTION Plague is an infectious zoonotic disease caused by the bacteria, Yersinia pestis, usually found in small mammals and their fleas. It is one of the ten internationally quarantinable diseases and is often fatal without prompt and appropriate antibiotic treatment. (Schriefer and Petersen 2011, 627-638). Human beings get infected by the bite of infected fleas, or through direct contact with infected materials or by inhalation. The pneumonic form of plague is very contagious and can trigger severe fatal epidemics through person-person contact via droplets in the air. Plague, also called the ‘Black death,’ was responsible for widespread pandemics with high mortality and killed more than 50 million people in Europe during the fourteenth Century (WHO, 2017). The ancient disease continues to cause periodic outbreaks in some parts of the world and remains endemic in some regions. Currently, plague is mostly endemic in 3 countries: Democratic Republic of Congo, Madagascar, and Peru. Today, plague can be easily treated with antibiotics. If diagnosed early, and the use of standard precautions and public health measures like quarantine had helped prevent the transmission of infection (WHO, 2017). However, plague today is still an important and potentially serious threat to humans and animals. Additionally, as it could be used as a biowarfare agent for world bioterrorism, understanding its pathogenesis, routes of transmission, clinical syndromes, epidemiology, treatment options and prophylactic measures is important for medical students, teachers, researchers, and medical practitioners.

GREAT WORLD PANDEMICS Though numerous epidemics of plague have been reported throughout history, the pandemics of the 6th, 14th and 20th centuries had the greatest impact on human society, resulting in great mortalities and for the social, economic and cultural consequences that resulted. The three great world pandemics of plague recorded in 541, 1347, and 1894

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centuries had different geographic origins and paths of spread, each time killing millions of people and animals across nations and continents leading to economic and social devastation of the society.

Justinian Plague of 541-544 The first great pandemic of plague recorded in history was the Justinian Plague of 541 CE, named after Justinian I, the Roman emperor of the Byzantine Empire at the time. The epidemic originated in Ethiopia in Africa and spread to Pelusium in Egypt in 540. It then spread west to Alexandria and east to Gaza, Jerusalem, and Antioch. It was then carried on sea routes through ships to both sides of the Mediterranean, arriving in Constantinople (now Istanbul) in the autumn of 541. The pandemic killed over a third of the city’s population in the spring of 542. Over the next three years, plague spread through Italy, southern France, the Rhine valley, and Iberia. It then spread north to Denmark and west to Ireland, then further to Africa, the Middle East, and Asia Minor. Nearly 100 million people were killed in the epidemics that occurred in Asia, Africa, and Europe between the years 542 and 546. The pandemic contributed to the demise of Justinian’s reign, permanently damaged the economic and social fabric of the society and marked the end of Roman rule, followed by an eight-year famine (Rosen 2007, 2-8) (Morony 2007, 59-86). Over the next 200 years, major outbreaks of plague occurred throughout Constantinople, Iraq, Egypt, Syria, Mesopotamia, Ireland, and England. Intermittent cycles of plague continued in Europe till the middle of the 8th century, and thereafter it went into hibernation until re-emerging as a major epidemic in the 14th century (Frith 2012, 11-16).

The ‘Black Death’ of Europe in 1347 to 1352 The Black Death of 1347 was the second great plague pandemic over the 14th to 18th centuries. The second pandemic originated in the

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Himalayan region of Central Asia in the mid-1300s. It then spread westward through overland trade routes and reached Sicily in 1347. It further spread to Italy, Greece, and France through sea routes and later throughout Europe by land route (Schriefer and Petersen 2011, 627-638). The plague epidemic present in the East in 1346 was brought to the Crimea from Asia Minor by the Tartar armies of Khan Janibeg in 1347, who had laid siege to the town of Kaffa (now Feodosiya in Ukraine), a Genoese trading town on the shores of the Black Sea. When the siege of the Tartars was unsuccessful, they catapulted plague infected dead bodies over the walls of Kaffa in revenge. In panic, the Genoese traders fled the city carrying the illness with them to Constantinople and across the Mediterranean to Messina, Sicily, where the great pandemic of Europe started. By 1348 plague reached Marseille, Paris and Germany, then Spain, England and Norway in 1349, and eastern Europe in 1350. The Tartars left Kaffa, carrying the plague away with them spreading it further to Russia and India. The second pandemic also caused great social and economic disruption leading to the wiping out of whole families and abandoning of villages. It also affected the food and trading industry and did not leave people of any social order. The Black Death killed a quarter of the European population and another 25 million in Asia and Africa from 1347 to 1350. Half of the population from major cities like Florence, Venice and Paris succumbed to the plague. A second major epidemic occurred in 1361, killed 10 to 20% of Europe’s population. Before the third pandemic, small epidemics of plague continued throughout the world. A major outbreak of pneumonic plague occurred in Europe and England, killed a fifth of London’s population alone between 1665 and1666. The great fire of London in 1666, which might have disturbed the normal habitat of the rodent population, is believed to contribute to the end of the pandemic (Frith 2012, 11-16).

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The Third Pandemic of 1894 In 1855, plague re-emerged from its wild rodent reservoir in the remote Chinese province of Yunnan and advanced along the tin and opium routes and reached the provincial capital of Kunming in 1866, the Gulf of Tonkin in 1867, the Kwangtung province port of Pakhoi (now Peihai) in 1882 and reached Canton in 1894 and then spread to Hong Kong. It reached Bombay by 1896 through sea routes and by 1900, plague reached on majority of seaports on every continent, through infected rats travelling the international trade routes on the new steamships (Gregg, 1985). It was during this pandemic, Alexander Yersin discovered the bacillus in Hong Kong. Plague reached Australia in 1900, which led to 12 major outbreaks between 1900 to 1925, killing 535 people, mostly from Sydney (Curson, 1985). The third pandemic killed over 15 million people until 1959, the majority of which were in India. Several outbreaks of plague occurred in China and Tanzania in 1983, Zaire in 1992, and India, Mozambique, and Zimbabwe in 1994 (Perry and Jacqueline1997, 35-66).

PLAGUE: A BIOTERRORIST AGENT The U.S Centers for Disease Control and Prevention (CDC) has classified plague into Category A potential biologic threats. Category A agents are considered as the highest priority pathogens. The other agents of this group include anthrax, botulism, smallpox, tularemia and viruses causing hemorrhagic fevers. The wide availability of the organism, its potential for mass production and aerosolization, along with its highly contagious nature and the high mortality rate, has made it to be used as a biologic weapon for centuries. The aerosolized plague bacilli used as bioweapon can remain viable for up to one hour and can be dispersed for distances up to 10 km, and can cause primary pneumonic plague (main clinical manifestation of plague due to exposure to biowarfare of plague) in those who are inhaling the bacilli. The contagious nature of the disease

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and person-person transmission via respiratory aerosol can lead to secondary cases of primary pneumonic plague in addition to causing infection in those inhaling the aerosol. In 1995, a microbiologist in Ohio was arrested for obtaining Yersinia pestis in the mail from the American Type Culture Collection, using a credit card and a false letterhead. The U.S Congress reacted to this incident by passing a law in 1997 that anyone who intends to send or receive any of the 42 different agents used as bioweapons should first register with the CDC. (Lane and Fauci 2013, 71-85). The Mongolian Tartars, in the 14th century, propelled plagueinfected bodies into the walls of the Crimean city of Kaffa (now, Feodosiya, Ukraine), leading to the defeat of the city, initiating the second wave of the Black Death in Europe (Sandrock, 2016, 699-712). Many countries, including the United States, the former Soviet Union and Japan, had developed this agent as a bioweapon during and after World War II (Borio 2005, 3601-3605). Though it didnot work out, the Venetian intelligence services had planned to attack Ottoman soldiers with a liquid made from the spleens and lymph nodes of plague victims in the seventeenth century, during the Venetia-Ottoman War (Lane and Fauci 2018, 1-22). The Imperial Japanese army unit 731 used plague as a bioweapon against the Chinese army during World War II (Higuita and Drevets 2021, 636-637). The Japanese warplanes dropped plaguecontaminated rice and fleas into Chuhsien, China, leading to an outbreak of pneumonic plague on October 27, 1940. According to World Health Organization, only 50 kg of Y. pestis released in aerosolized form over a major city is sufficient to develop the deadly pneumonic plague subtype causing widespread devastation and death (Glatter and Finkelman 2021, 176-181).

Etiology It was Alexandre Yersin (1863-1943), a French physician who described and cultured the causative organism of plague and identified it under the microscope in June 1894, in Hong Kong, during a deadly

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epidemic of plague (Butler 2014, 202-209). The name of the organism underwent several changes from Bacterium pestis (until 1900) to Bacillus pestis (after1900) to Pasteurella pestis (in 1923), finally acquiring the current designation as Yersinia pestis (in 1970) as a posthumous honor to the discoverer of the pathogen (Zietz and Dunkelberg 2004, 165-178). In 1897, Masanori Ogata, suspected the role of fleas in the transmission of plague, and he successfully infected a mouse with a suspension of infected ground fleas (Barbieri et al. 2020, 1-44). Though Yersin was the first person to observe some connection between rat mortality and human epidemics of plague, he did not suspect fleas as vectors. It was PaulLouis Simond, a French naval doctor and successor of Yersin (18581947) in 1898, discovered that the bacteria are transmitted to human beings from rodents by fleabites through several experiments carried out in Karachi, then in India. Adding to his findings, he also observed bacilli in the gut of fleas that had fed on infected rodents (Butler 2014, 202209). He demonstrated that the oriental rat flea was the vector for the bacillus and the sources of the bacillus were the sewer rats (Frith 2012, 11-16). Ricardo Jorge, in 1927 also reported that wild rodents serve as a plague reservoir (Riedel 2005, 116-124).

Morphology Y. pestis is a non-motile, non-sporing, non-acid fast, gram-negative coccobacillus in the family Enterobacteriaceae. It exhibits bipolar or safety pin staining with Wright, Giemsa or Wayson stains (Lane and Fauci, 2013, 71-85). The organism is covered by a slime layer, which is more visible in infected tissues than in cultures (Schriefer and Petersen 2011, 627-638).

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Culture It is an aerobe and facultative anaerobe. Grows within a temperature range14-37-degree Celsius, the optimum temperature for growth is 27 degree celsius. The bacteria grow on nutrient agar producing small transparent colonies, which later becomes opaque on continued incubation. Flocculent growth occurs at the bottom and sides of the tube in nutrient broth. In fluid culture, bacilli tend to form chains. On blood agar, non-hemolytic, dark brown colonies are produced due to absorption of hemin pigment. Colourless colonies are formed on MacConkey agar due to non-lactose fermentation. Colonies on MacConkey agar disappear after 2-3 days because of autolysis. Characteristic stalactite growth (growth hangs from surface to the depth of the broth) is observed on ghee broth (broth with ghee floating on top). Pleomorphic forms, commonly seen in older cultures and on media containing 3% NaCl helps in identification (Thomas 2007, 206-212) (Coghlan 2012, 479-482).

Identification Tests Oxidase test is positive; Catalase is negative. Ferments glucose, mannan and maltose with only acid, no gas; does not ferments lactose, rhamnose and sucrose. MR test is positive, VP is negative. Does not liquefy gelatin, forms indole, utilizes citrate or hydrolyses urea (Thomas 2007, 206-212).

Biotypes of Yersinia pestis Based on glycerol fermentation and nitrate reduction, three biotypes of plague bacilli have been described, causing human infections. They are: Antiqua: ferments glycerol and reduces nitrate; is found to be responsible for the Justinian plague in 6th Century Medievalis: ferments

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glycerol but negative for nitrate reduction; is responsible for the Black death in 14th Century. Orientalis: does not ferment glycerol, but reduces nitrate. It is the predominant biotype today originated in Southern China in 1890, spreading along the shipping routes. Primary foci are in India, Myanmar and China. It is the causative agent of the 1894 pandemic and wild plague in western USA, South America, South Africa (Butler 2014, 202-209). However, a paleo microbiological analysis by Drancourt et al. in 2004 indicated that all three pandemics were most likely caused by the Orientalis biovar (Drancourt et al. 2004, 1585-1592). A fourth biovar Microtus (also known as pestoides) is identified, which is pathogenic to the rodent genus Microtes (Voles), mice and other small rodents, but not to large mammals including humans (Schriefer and Petersen 2011, 627-638). Table 1. Biochemical identification of Yersinia pestis biovars Y. pestis biovar

Characteristic reactions Glycerol Nitrate Antiqua + + Medievalis + Orientalis + Microtus + (Schriefer and Petersen 2011, 627-638).

Arabinose + + + -

Epidemiology Plague is primarily a disease of rodents. The infection is maintained in nature by natural enzootic cycles between wild rodent populations and their flea ectoparasites. (Schriefer and Petersen 2011, 627-638). Plague can be transmitted by any of the following routes; a) mainly due to bite of infected fleas by rodent vectors; b) rarely through clothing or grain; c) through ingesting contaminated animals; d) physical contact with infected victims or contact with body fluids from infected animals; e) direct inhalation of infectious respiratory droplets from animals, particularly cats or humans with pneumonic plague; f) bioterrorist attack

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with zaerosolized plague bacilli as bioweapon (Yang 2018, 1-6) (Butler 2013, 788-793) (Glatter and Finkelman 2021, 176-181). Epidemics often occur when rat population that live near the human population get infected by wild rodents. Epizootics causing high mortality in commensal rodent population forces the flea to bite an alternative host, including humans, thus causing human plague (Schriefer and Petersen 2011, 627-638). In order to maintain the infection in the local rodent hosts; the flea must be able to ingest the plague organism with its blood meal; it must have a long-life span to allow the multiplication of the bacilli; it should be able to transfer the sufficient number of pathogens to initiate infection, and finally they must be present in large numbers to infect the rodents. The fleas acquire infection by feeding on infected rodents. The bacilli multiply in the flea gut, block the proventriculus and eventually block the passage of blood into the stomach. The interval between the ingestion of infected blood and blocking in the proventriculus is known as the extrinsic incubation period. When such a blocked flea bites another rodent, blood cannot continue to enter its stomach and instead remains in the oesophagus. When the flea stops sucking, the oesophagus recoils and the accumulated blood, mixed with the bacteria, is regurgitated into the bite wound, transmitting the infection. Wound bite contaminated with the faeces of infected fleas can also transmit the infection. (Bramanti et al. 2016, 1-26). When the infected rodent dies, the flea leaves the carcass searching for a new host and may bite human beings in the absence of another rat. Two natural cycles of plague exist- 1) urban or domestic plague, occurring in the rodent population, living in proximity with human beings and 2) wild or sylvatic plague occurring in wild rodents, independent of human beings (Corbel, 2007, 343-346), (Thomas 2007, 206-212). The earliest plague epidemic reported was in China in 224 BC. An estimated 500,000 individuals fled their homes in fear of plague outbreak in India in 1994 (Lane and Fauci, 2018, 1-22). 38,359 human cases with 2845 deaths were reported from 25 countries between 1989 and 2003. 80% of these cases were reported from Africa, 15% from Asia and the remainder from the Americas (Schriefer and Petersen 2011, 627-638). 1006 cases were

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reported from the United States between 1900 and 2012, with 80% of the cases being bubonic plague. Between 1960 and 2006, 447 plague cases were reported from the United States, of these, the majority (80%) cases were reported from New Mexico, Arizona, and Colorado and 10% from California. Recent outbreaks of plague reported to WHO occurred in the Democratic Republic of Congo (2005, 2006), China (2009) and Peru (2010) (Higuita and Drevets 2021, 636-637). Between 2004 and 2009, plague was endemic in Madagascar, accounting for 30% of all human cases worldwide. There were 3248 plague cases reported globally during the period 2010-2015, including 584 deaths, with the majority (75%) being in Madagascar (WHO, 2017). In the first decade of the twenty-first century, 21,725 cases of plague were reported to the World Health Organization (WHO), and 90% of these cases were from Africa. The overall fatality rate was 7.4% (Lane and Fauci 2018, 1-22). Plague started declining recently, and in 2018, only five countries reported cases of plague (Higuita and Drevets 2021, 636-637).

Vectors Most human infection is caused by the bite of an infected rodent flea, Xenopsylla cheopis, the Oriental rat flea. Other flea species (ground squirrel flea,), such as Oropsylla montanus, the primary vector for human plague in the United States, also can transmit plague. Other flea species transmitting infections are X. astia, Ceratophyllus fasciatus (Thomas 2007, 206-212). Research with human body lice (Pediculus humanus) in a rabbit model of plague showed that lice also could transmit infection (Vallès et al. 2020, 1-22). Epidemics of plague generally occurs in cool, humid seasons, which supports the multiplication of fleas in large numbers. Plague infections are generally interrupted in hot, dry weather, which is unfavourable for the flea to thrive. (Thomas 2007, 206-212). The human flea, Pulex irritans was responsible for the recent plague outbreak in Madagascar (Bramanti et al. 2016, 1-26).

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Reservoir The enzootic species vary according to the geographical region of origin. It is black rats and shrews in Madagascar, great gerbils in Kazakhstan, jirds in Algeria, marmots in China, ground squirrels, deer mice, and voles in the United States, gerbils (Tatera indica), sewer rats (Rattus norvegicus, R. rattus) and bandicoot in India. Other animals, such as rabbits, field mice, squirrels, camels, cats, and dogs that are infected through flea bites or ingestion of infected rodents helps in the maintenance of infection in the more stable reservoir species. The ability of Y. pestis to survive and multiply in the soil of abandoned rodent burrows for a prolonged period can infect new burrowing rodents, thereby maintaining the infection during inter-epidemic periods and subsequently leading to the re-emergence of plague outbreaks. (Thomas 2007, 206-212) (Butler, 2013, 788-793).

Antigens Yersinia pestis is antigenically complex, and immunoprecipitation techniques and biochemical analysis characterize approximately 20 antigens. Plague bacilli are antigenically homogeneous, and serotypes do not exist. Yersinia pestis harbours three virulence plasmids— (1) pFra that encodes the anti-phagocytic capsular protein fraction 1 (F1) and the murine toxin, which is a phospholipase, expressed only at temperatures below that of mammalian systems enables the bacteria to survive in the harsh environment of flea gut during blood meal digestion (2) pYV that encodes V antigen and Yersinia outer proteins (Yops), which inhibits phagocytosis and intracellular killing of the bacillus and reduce inflammation (3) pPla that makes a plasminogen activator that allows bacteria to spread in tissues by dissolving fibrin clots. (Butler, 2013, 788793).

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Other Possible Virulence Determinants Include Pesticin 1, Bacteriocins, Coagulase and fibrinolysin, ability to synthesize purines, plague toxins etc. Two plague toxins are identified. One is an endotoxin, a heat stable somatic antigen comprising of Lipopolysaccharide, similar to the endotoxins of other gram-negative bacteria is believed to be responsible for the terminal toxaemia of plague (Corbel 2007, 343-346). Another toxin is a heat labile protein with both properties of exotoxin and endotoxin, which can be toxoided (Thomas, 2007, 206-212). Pathogenic Yersinia species contain a siderophore, called Yersiniabactin (Ybt), which can scavenge iron from the host. The Ybt genes are located in a 102-kb chromosomal region termed the pgm (pigmentation) locus. An additional operon within the pgm region known as hms locus encode hemin storage proteins, which enable biofilm formation and proventricular blockage required for efficient transmission of Yersinia pestis from vector flea to mammals (Schriefer and Petersen 2011, 627-638). A type III secretion systems consisting of a membrane spanning complex, present in Y. pestis allows the bacteria to inject protein directly into the cytoplasm of host cells (Caroll and Hobden 2016, 275-276).

Pathogenesis and Clinical Features Plague is a severe febrile illness characterized by acute onset of headache, myalgia, malaise, chills, prostration, and gastrointestinal symptoms and is fatal, if left untreated. (Schriefer and Petersen 2011, 627-638). After the intradermal inoculation of plague bacilli by the fleas, the bacilli are engulfed by the macrophages and polymorphonuclear cells. But bacilli resist intracellular phagocytosis and multiply in large numbers to reach the lymphatics, where a hemorrhagic inflammation ensues, leading to necrosis of the enlarged lymph node. The ensuing bacteremia disseminate the organism in all organs, leading to the development of necrotic lesions in all organs (Caroll and Hobden 2016, 275-276). In

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human beings, plague occurs in three main forms: bubonic, pneumonic and septicemic.

Bubonic Plague Most of the plague seen in the world today is bubonic plague and is the result of a bite by a plague infected flea. The incubation period is 2-5 days. The lymph nodes draining the site of entry of the bacillus become infected and massive multiplication of bacilli lead to erythematous, painful swelling, called bubo, (bubo; derived from Greek word ‘bubon,’ meaning ‘groin”) at the inguinal, axillary/ cervical regions. Sometimes, infection remains localized at the site of flea bite with minor constitutional symptoms, known as pestis minor (Corbel 2007, 343-346). High fever, headache, malaise, chills, nausea, vomiting, diarrhea, tachycardia, hypotension, lethargy, and restlessness are the commonest manifestations (Higuita and Drevets 2021, 636-637). Bacteremia and septicemia frequently develop and lead to secondary infections of other organs including lungs, spleen, and central nervous system. (Higuita and Drevets 2021, 636-637) Complications: bronchopneumonia, septicemia or meningitis, shock, disseminated intravascular coagulation, purpuric skin lesions, acral cyanosis and gangrene. (Higuita and Drevets 2021, 636-637) Case fatality in untreated cases exceeds 50%. (Corbel 2007, 343-346). Pneumonic Plague Primary pneumonic plague is the main clinical manifestation occurring after a bioterrorist attack with aerosolized Y. pestis spread over a wide area that is densely populated (Lane and Fauci 2013, 71-85). It is acquired as a primary infection by inhalation of droplets with Y. pestis from other pneumonic cases (human or animal) / aerosols generated from cultures or infected tissues (Corbel 2007, 343-346) or rarely as a secondary complication of bubonic or septicemic plague (Schriefer and Petersen 2011, 627-638). Patients develop fever, cough with hemoptysis, dyspnea and gastrointestinal symptoms 1-6 days following exposure, which progresses into fulminating pneumonia and respiratory failure.

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(Higuita and Drevets 2021, 636-637) Clinical features of pneumonia will be accompanied by pulmonary infiltrates, cavitations, alveolar hemorrhage and consolidation on chest x-ray and are not pathognomic for Y. pestis. The mortality rate is 100% in the absence of antibiotics and 50% even among treated cases. (Schriefer and Petersen 2011, 627-638). Death usually occurs within 2-6 days (Lane and Fauci 2013, 71-85).

Septicemic Plague Septicemic plague occurs when the organism is directly introduced into the bloodstream by the infected flea, without localizing in the regional lymph node (Lane and Fauci 2013, 71-85) or when the bacterium is directly introduced into the bloodstream via a cut or wound (Schriefer and Petersen 2011, 627-638), or as a complication of bubonic or pneumonic plague (Corbel 2007, 343-346). It is the rarest and most serious of all three plague varieties and cause disseminated intravascular coagulation and is almost fatal when untreated. Death of tissue (gangrene) causes the blackening of extremities, (black death) mostly fingers, toes, and nose. (Glatter and Finkelman 2021, 176-181).

Diagnosis Plague should be suspected when a person complains about the abrupt onset of fever, lymphadenopathy or sepsis and there is any history of flea bite or exposure to an infected animal or person, or patient is from an endemic area. (Higuita and Drevets 2021, 636-637). Diagnosis of plague should be conducted in both humans and rodents to prevent the epidemic from spread.

Lab Diagnosis in the Rat Specimen- dead rat. The carcass should be handled carefully as it might contain infected fleas. After pouring kerosene on the carcass to remove any fleas, the carcass is dipped in 3% Lysol to destroy ectoparasites.

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Autopsy Postmortem examination shows marked local inflammatory condition at the site of inoculation with necrosis and oedema. The spleen will be enlarged and congested, showing greyish-white patches in the tissue. Peri glandular inflammation and oedema, most frequent in the cervical lymph node, shows the tendency of the flea to attack the rat’s neck region. Other findings include pleural effusion, liver congested and mottled, and congestion and haemorrhage under the skin and in internal organs (Coghlan 2012, 479-482). Microscopic Demonstration Smears are made from material aspirated from the buboes. Pleomorphic gram-negative coccobacilli exhibiting bipolar staining with Giemsa, Wright’s and Wayson stains is tentative for diagnosis of bubonic plague. (Ditchburn and Hodgkins 2019, 65-70). Culture Samples like skin, liver spleen, pleural effusion, bubo material, heart blood, bone marrow etc., are inoculated onto nutrient agar, blood agar, MacConkey agar etc. and looked for characteristic colony morphology. Animal Inoculation As microscopy and culture may not be successful from badly putrefied carcasses, animal inoculation into a guinea pig and white mice can be done by rubbing the putrefied tissue on the shaven abdomen to recover the bacilli. Serological Tests Thermoprecipitation test: Filtrate from infected tissue containing Y. pestis is mixed with antisera against Y. pestis in a test tube, a precipitate is formed within five minutes at the junction of the filtrate and antiserum.

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Passive Hemagglutination Test If serum from infected rats containing antibodies to Y. pestis is mixed with sheep RBCs coated with F1 antigen of Y. pestis, hemagglutination will occur (Thomas 2007, 206-212). Lab diagnosis in humans:     

Specimens – depend upon the type of plague. Bubonic plague-material from local skin lesions and infected buboes Pneumonic plague – expectorated sputum Septicemic plague – blood Blood – blood culture is intermittently positive in all forms of plague

Direct Demonstration Demonstration of gram-negative coccobacilli with bipolar staining observed with smears stained by gram stain and methylene blue is presumptive for Y. pestis. Smears made from bubo show considerable pleomorphism. (Thomas 2007, 206-212) (Coghlan, 2012, 479-482). Culture Cultures made from bubo material, blood and sputum are inoculated onto Nutrient agar, Blood agar, MacConkey agar, ghee broth etc. and examined for characteristic growth. Demonstration of F1 capsular antigen of Y. pestis by immunospecific staining helps in confirming the identity of the isolated bacilli as Y. pestis. Sputum can be inoculated onto a simple selective medium of Kniseley et al. (1964), consisting of azole Blood agar enriched with glucose and calcium to obtain pure growth (Kniseley et al. 1964, 491-496). Biochemical reactions and stained smears from pure growth help in further identification. (Coghlan 2012, 479-482). Animal Inoculation If smears and cultures are negative, specimens can be inoculated onto guinea pigs and white mice, subcutaneously, or through nasal mucosa or

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through shaved skin. Local inflammation occurs at the site of inoculation followed by the death of the animal within 2-5 days. After the autopsy, bacilli are recovered from the samples by culture or smears. (Thomas 2007, 206-212).

Serology A four-fold rise in titre of two serum samples collected at an interval of 3 weeks or a single titre of more than 1:28 is suggestive of infection. Field testing of a rapid test using monoclonal antibodies has been developed to detect Y. pestis F1 antigen in bubo aspirates and sputum. (Higuita and Drevets 2021, 636-637). IgG and IgM ELISA tests and a rapid dipstick assay using the F1 antigen are also introduced recently. ELISA for F1 antigen in serum and bubo aspirates exhibited 100% sensitivity and 99% specificity (Schriefer and Petersen 2011, 627-638) (Higuita and Drevets 2021, 636-637) (Shepherd et al. 1984, 771-773). A rapid and more cost-effective diagnostic tool is the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, which can identify distinctive protein profiles for each bacterial species and the three biotypes of Y. pestis. Its advantages include lack of requirement for expensive antibodies and PCR reagents, speed, and automated ease of use. (Butler, 2013, 788-793). Molecular Methods PCR with primers based on F1 gene sequences is a rapid and sensitive method for presumptive diagnosis. (Thomas 2007, 206-212). Another novel technique is a PCR/electrospray ionization-mass spectrometry to detect DNA specific of Y. pestis to screen environmental and clinical samples for suspected bioterrorism pathogens (Butler, 2013, 788-793).

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Antibiotic Treatment Human death can be prevented by the early recognition of symptoms and treatment with antibiotics during the first two days of illness (or within 18 hours of onset), without waiting for the confirmation of the diagnosis. Antibiotics cannot prevent death if bacteremia exceeds a certain threshold level (Corbel 2007, 343-346). The aminoglycosides (gentamicin and streptomycin), the fluoroquinolones (ciprofloxacin, moxifloxacin, and levofloxacin) and doxycycline are the first, second and third-line classes of antibiotics. Streptomycin (15mg/kg up to 1g) intramuscularly (IM) every 12 hours and gentamicin (5-7mg/kg/day intravenously (IV)/IM in one or two doses daily) are used in severe infection. Fluoroquinolone’s dosages include Ciprofloxacin 400mg IV/ 500mg orally every 12 hours; levofloxacin 500-750 mg IV/orally daily; and moxifloxacin 400mg IV /orally daily. For doxycycline, initially, a 200mg loading dose is given, followed by 100mgIV /orally every 12 hours (Higuita and Drevets 2021, 636-637). Chloramphenicol and sulphonamides can be used in certain circumstances but are not effective for pneumonic plague. IV Chloramphenicol is recommended for patients with meningitis symptoms. Large doses of tetracyclines within 48 hours of onset is indicated for uncomplicated bubonic plague and should be continued for ten days. Though invitro penicillin sensitivity is observed, it is not effective for treatment. Antibiotic therapy should be continued for a total of 10-14 days. As some strains carrying antibiotic resistance genes are reported, combined therapy is advisable until the sensitivity of the strain is known (Higuita and Drevets 2021, 636-637) (Coghlan 2012, 479-482) (Corbel 2007, 343-346). An isolate of Y. pestis obtained from a 1995 plague case in Madagascar was found to be multi-drug resistant to Streptomycins, Sulphonamides, Tetracyclines and Chloramphenicol (Ditchburn and Hodgkins 2019, 65-70).

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Prophylactic Measures As infections with plague can cause severe outcomes resulting in high mortality, timely diagnosis and appropriate treatment are essential for survival and reduction of complications. Bubonic plague can evolve into pneumonic plague, if not identified early and left untreated. Hence, (WHO, 2020) has recommended the following response measures for all forms of plague: 







 



Appropriate collection of samples (e.g., pus from buboes, blood, or sputum) and identification of Y. pestis bacilli in the samples by different laboratory techniques Prompt treatment of identified cases with appropriate antibiotics such as aminoglycosides, fluoroquinolones, chloramphenicol, tetracyclines, sulfonamides etc. Protection of health care workers using standard precautions, including the use of personal protective equipment and chemoprophylaxis with antibiotics such as doxycycline (for 7day duration or as long as they are exposed to the infected patients). Confirmed or suspected patients with pneumonic plague should be isolated under respiratory droplet precautions for at least 48 hours after appropriate antibiotics are initiated and provided with disposable surgical masks to prevent transmission of infection by aerosols. Close contacts of pneumonic plague should be identified, informed, and monitored and given 7-day chemoprophylaxis. Optimal infection control measures should be observed during funeral and burial ceremonies. The crowding of people should be discouraged during these ceremonies. A vigilant health care workforce should be deployed to manage plague outbreaks effectively. They should be able: to diagnose infected cases quickly, identify risk factors, conduct surveillance

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In addition to this, general prophylactic measures like the destruction of rodent population by application of rat poison and flea population by application of insecticide to rat infested areas should be encouraged. Construction of rat proof houses and buildings and fumigation of ships and aircraft to prevent the rats from gaining access is also highly recommended to prevent the spread of plague. (Thomas 2007, 206-212).

Vaccines Worldwide, live attenuated and formalin-killed Y. pestis vaccines are available for human use. They can confer some protection against bubonic, but not the pneumonic plague. The vaccines are of little use during human plague outbreaks, as a minimum of one month or more is required to develop a protective immune response. The vaccine is indicated for persons who are exposed to Y. pestis, such as laboratory technicians in plague reference and research laboratories. The killed vaccine used in India is a whole culture antigen prepared at the Haffkins Institute, Mumbai. The vaccine is given subcutaneously, two doses at an interval of 1-3 months, followed by a third six months later. Protection by this vaccine does not last for more than six months. Live vaccines produced from avirulent strains in some countries are causing severe reactions. As none of the vaccines confers long term immunity, revaccination is necessary at six months intervals (Thomas, 2007, 206212). A live attenuated vaccine was developed in 1931 by Georges Girard and Jean Robic from the non-pigmented strain of the plague bacillus in Madagascar called EV. Similar live attenuated vaccines of the EV series, including EV76, EV NIIEG and Tjiwide, were administered to millions of people in Madagascar, Indonesia, Vietnam, and the Soviet Union. A single dose of EV NIIEG live vaccine was able to induce immune

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responses that lasted one year against bubonic and, to some extent, pneumonic plague. The vaccine was pathogenic in nonhuman primates and reactogenic in humans. When administered intranasally and intravenously, the vaccine retained virulence. The lack of transparent protection, lack of availability of safety data from previous large-scale human immunization, and the lack of genetic stability of the vaccine strain due to many passages has prevented the EV series of vaccines from gaining worldwide acceptance, especially in the US and Europe (Sun and Singh 2019, 1-9) (Butler 2014, 202-209). Recombinant vaccines based on recombinant subunits of the F1 capsule and the V outer membrane of Y. pestis elicited antibodies against both F1 and V and found to be protective against plague pneumonia when transferred passively to mice before inhalational challenge with virulent Y. pestis. Two recombinant vaccines were developed- One containing a defined amount of the subunits, designated rF1 and rV, and the other, a fusion protein, designated rF1- rV. Both the vaccines were safe and immunogenic after phase 1, and phase 2 human clinical trials and no serious vaccine-related adverse events were reported (Butler, 2013, 788-793). A live oral vaccine developed from encapsulated Yersinia pseudotuberculosis strain V674pF1, is found to be effective against pneumonic plague in mice (Higuita and Drevets 2021, 636-637). According to the recent WHO Plague Vaccine Workshop in 2018, there exists at least 17 plague vaccine candidates in the pipeline, including subunit (F1/V-based with adjuvant), bacterial vector-based (e.g., OMV-delivered, Salmonella expressed), viral vector-based (e.g., Ad5-based, Chad-based), E. coli T4 bacteriophage-based, and live attenuated (e.g., Y. pseudotuberculosis-based or Y. pestis-based) vaccines expressing one or several primary antigens of Y. pestis (e.g., F1 capsular protein antigen, LcrV antigen, YscF antigen, and/or pesticin coagulase), which have been tested in different animal models. Two of these candidates have completed a Phase 2 clinical trial and are moving toward FDA licensure, and several candidates had plans to enter clinical trials in 2019. (W.H.O Workshop 2018, 1-12).

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CONCLUSION As plague is still endemic in many parts of the world, plague endemic countries should take necessary steps to ensure that it does not cross their borders through the air or sea routes to other non-infected countries. The emergence of drug resistant strains of Y. pestis should also be given adequate attention, as drug resistant strains can lead to the reemergence of plague. The public should be properly educated about the appropriate preventive measures to be undertaken in case of any notifiable disease outbreak. A standardized antibiotic regimen should be developed considering the drug resistant strains in mind. Effective, cheaper, and safer vaccines should be made available, particularly in endemic countries, to curb this epidemic.

REFERENCES Barbieri, R., M. Signoli, D. Chevé, C. Costedoat, S. Tzortzis, G. Aboudharam, D. Raoult, and M. Drancourt. 2020 “Yersinia pestis: the natural history of plague.” Clinical Microbiology Reviews 34, no. 1.1-44. Borio, L. L. 2005. “Plague as an agent of bioterrorism.” Mandell, Douglas and Bennett’s Principles and Practice of Medicine. Pennsylvania: Elsevier Churchill Livingstone: 3601-3605. Bramanti, Barbara, Nils Chr Stenseth, Lars Walløe, and Xu Lei. 2016 “Plague: A disease which changed the path of human civilization.” In Yersinia pestis: retrospective and perspective, Springer, Dordrecht. 1-26. Butler, Thomas. 2013. “Plague gives surprises in the first decade of the 21st century in the United States and worldwide.” The American journal of tropical medicine and hygiene 89, no. 4: 788-793. Butler, Thomas. 2014 “Plague history: Yersin’s discovery of the causative bacterium in 1894 enabled, in the subsequent century,

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scientific progress in understanding the disease and the development of treatments and vaccines.” Clinical Microbiology and Infection 20, no. 3 (2014): 202-209. Caroll, Karen C., and Hobden, Jeffery A. 2016. Yersinia and Pasteurella. Javetz, Melnick and Adelberg’s Medical Microbiology. 27th edn. McGraw Hill education. 275-276. Coghlan, Joyce D.2 012 Ch-28 Yersinia, Pasteurella, Francisella. Mackie and Mc Cartney. Practical Medical Microbiology. 14th edn Churchill, Livingstone An imprint of Elsevier edited by J G Collee, A G Fraser, B P Marmion, A Simmons. 479-482. Corbel M J. 2007. Chapter 35. Yersinia, Pasteurella and Francisella In Medical Microbiology 17th edn. Editors- David Greenwood, Richard Slack, John Peutherer, Mike Barer. Churchill Livingstone, Elsevier. 343-346. Curson, Peter. 1985. Times of crisis: epidemics in Sydney 1788-1900. Sydney University Press, 1985. cross ref. Ditchburn, Jae-Llane, and Ryan Hodgkins. 2019. “Yersinia pestis, a problem of the past and a re-emerging threat.” Biosafety and Health 1, no. 2: 65-70. Drancourt, Michel, Véronique Roux, Lam Tran-Hung La Vu Dang, Dominique Castex, Viviane Chenal-Francisque, Hiroyuki Ogata, Pierre-Edouard Fournier, Eric Crubézy, and Didier Raoult. 2004. “Genotyping, Orientalis-like Yersinia pestis, and plague pandemics.” Emerging infectious diseases 10, no. 9: 1585-1592. Frith, John. 2012. “The history of plague–Part 1. The three great pandemics.” Journal of Military and Veterans’ Health 20, no. 2: 1116. Glatter, Kathryn A., and Finkelman, Paul. 2020. “History of the Plague: An Ancient Pandemic for the Age of COVID-19.” The American Journal of Medicine 134, no 2. 176-181. Gregg, Charles T. 1985. Plague: An Ancient Disease in the Twentieth Century. Revised edition. Albuquerque. University of New Mexico Press. cross ref.

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Higuita, Nelson Ivan Agudelo., and Drevets, Douglas A. 2021 Chapter: “Plague.” Conn’s current therapy. 1st edn Elsevier. 636-637. Knisely, Ralph F., Lois M. Swaney, and Harold Friedlander. 1964 “Selective media for the isolation of Pasteurella pestis.” Journal of bacteriology 88, no. 2 (1964): 491-496. Lane, H. Clifford., and Fauci, Anthony S. 2018. Chapter S2. “Microbial Terrorism.” Harrison’s principles of Internal medicine. 20th edn Mc Graw Hill Education. 1-22. Lane, H. Clifford., and Fauci, Anthony S. 2013. Chapter 7. “Microbial Terrorism.” Harrison’s Infectious diseases. Dennis L. Kasper. Anthony S. Fauci (Editors) Mc Graw Hill Education. 71-85. Morony, Michael G. 2007. “‘For whom does the writer write? ‘The first bubonic plague pandemic according to Syriac sources.” Plague and the End of Antiquity. Cambridge university press. 59-86. Perry, Robert D., and Jacqueline D. Fetherston. 1997. “Yersinia pestis-etiologic agent of plague.” Clinical microbiology reviews 10, no. 1: 35-66. Philip A Thomas. 2007 Chapter 10. “Gram negative bacteria.” In Clinical Microbiology. 206-212. Orient Long man private limited, 160 Annasalai, Chennai. Riedel, Stefan. 2005. “Plague: from natural disease to bioterrorism.” In Baylor University Medical centre Proceedings 18, no. 2, pp. 116124. Taylor & Francis. Rosen, William. Justinian’s Flea: The First Great Plague and the End of the Roman Empire. New York: Viking Penguin, 2007. Sandrock, Christian. 2016. “Bioterrorism.” Murray and Nadel’s Text Book of respiratory medicine. 6th edn. Elsevier. 40,699-712.e2. Schriefer., Martin E and Petersen, Jeannnine M. 2011. “Yersinia.” In Manual of Clinical Microbiology Volume 1.10th Edn. Editors: James Versalovic, Karen C Caroll, Guido Funke, James H Jorgensen, Marie Louise Landry, David W Warnock 2011. ASM Press, American Society for Microbiology 1752 N, St. NW, Washington Dc 200362904 USA. 627-638.

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Shepherd, A. J., P. A. Leman, D. E. Hummitzsch, and R. Swanepoel. 1984. “A comparison of serological techniques for plague surveillance.” Transactions of the Royal Society of Tropical Medicine and Hygiene 78, no. 6: 771-773. Sun, Wei., and Singh, Amit K. 2019. “Plague vaccine: recent progress and prospects.” npj Vaccines 4, no. 1: 1-9. Vallès, Xavier, Nils Chr Stenseth, Christian Demeure, Peter Horby, Paul S. Mead, Oswaldo Cabanillas, Mahery Ratsitorahina et al. 2020. “Human plague: An old scourge that needs new answers.” PLoS neglected tropical diseases 14, no. 8: 1-22. e0008251. World Health Organisation. Workshop. 2018 Efficacy trials of Plague vaccines: endpoints, trial design, site selection. April 23, 2018 INSERM, Paris, France. 1-12. World Health Organization. 2017. Plague fact sheets, 31 oct 2017. World Health Organization. 2020. Disease outbreak news. Emergencies, preparedness response. Plague Democratic Republic of the Congo. 23 July 2020. Yang, Ruifu. 2018. “Plague: recognition, treatment, and prevention.” Journal of clinical microbiology 56, no. 1.1-6. Zietz, Björn P., and Hartmut Dunkelberg. 2004. “The history of the plague and the research on the causative agent Yersinia pestis.” International journal of hygiene and environmental health 207, no. 2 (2004): 165-178.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 16

FUTURE PANDEMICS: AGENTS, POTENTIAL AND IMPACTS Sunaina Valappay Cheenatukandy* Independent Researcher, Ernakulam, Kerala, India

ABSTRACT The ongoing COVID-19 pandemic has changed the dimensions of human life. This new novel coronavirus has taken the world through a plethora of challenges affecting the health, economy, social and global security. As of 25 May 2021, with the death of 34,72,068 people and 167,011,807 affected, it’s high time to focus on measures to save future generations. The covid vaccination drive has started and the WHO approved vaccines are Oxford–AstraZeneca, Pfizer-BioNTech, Sinopharm-BBIBP, Moderna, and Johnson & Johnson. Dated 23 May 2021, a total of 1,489,727,128 vaccine doses have been administered worldwide. WHO Director-General Tedros Adhanom Ghebreyesus has put forward the concept of an integrated One Health approach to public health, animal health and the environment, during the opening of the 27thTripartite Annual Executive Committee Meeting World Organization for Animal Health (OIE) to prevent future pandemics (17 *

Corresponding Author Email: [email protected].

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Sunaina Valappay Cheenatukandy February 2021). Four international organizations - the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (OIE), the United Nations Environment Programme (UNEP) and the World Health Organization (WHO) will operate under One Health approach to identify the links between the health of people, animals, and the environment. This will contribute to safeguard the human race. He also warned about the possibility of the next pandemic threat – Disease X and other zoonotic diseases which could arise anytime. According to the WHO chief, the COVID-19 pandemic demonstrated “intimate” linkages between the health of humans, animals and ecosystems, as zoonotic diseases spread between animals and people. For combatting the next pandemic, the World Health Organisation (WHO) prepared a global strategy for a pandemic response, the research and development (R&D) Blueprint. This R&D Blueprint has a list of identified priority diseases and a roadmap response plan for each of them. The diseases which pose a significant public health risk because of their potential to cause pandemics, as well as the lack of sufficient countermeasures against these (diseases), includes Crimean-Congo hemorrhagic fever (CCHF), MERS, SARS, Ebola, Nipah and several other dangerous infectious diseases. In this chapter, we will discuss some priority diseases which could arise as a future pandemic.

Keywords: future pandemics, disease -X, Ebola virus, Marburg virus, MERS, SARS-CoV, SARS-CoV-2

INTRODUCTION A pandemic is a widespread epidemic infectious disease affecting people on a worldwide scale. A new virus strain or subtype that easily transmits between humans can cause a pandemic. Due to the close relationship between humans and animals, many potential future killer pathogens could trigger the next emerging disease. There have been many fatal pandemics in our history and few are listed here. Prehistoric epidemic: Circa 3000 B.C (an epidemic that wiped out a prehistoric village in China 5000 years ago), Plague of Athens: 430 B.C. (an epidemic that ravaged the people of Athens and lasted for five years), Antonine Plague: A.D. 165-180 (killed over 5 million people in the

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Roman empire), Plague of Cyprian: A.D. 250-271 (estimated to have killed 5,000 people a day in Rome alone), Plague of Justinian: A.D. 541542 (The Byzantine Empire was ravaged by this bubonic plague), The Black Death: 1346-1353 (wiped out over half of Europe’s population by strain of the bacterium Yersinia pestis), Cocoliztli epidemic: 1545-1548 (viral hemorrhagic fever that killed 15 million inhabitants of Mexico and Central America caused by Salmonella paratyphi C), American Plagues: 16th century, Great Plague of London: 1665-1666 (The Black Death’s last major outbreak in Great Britain), Great Plague of Marseille: 17201723, Russian plague: 1770-1772, Flu pandemic: 1889-1890, American polio epidemic: 1916, Spanish Flu: 1918-1920,Asian Flu: 1957-1958, AIDS pandemic and epidemic: 1981-present day, H1N1 Swine Flu pandemic: 2009-2010, West African Ebola epidemic: 2014-2016, Zika Virus epidemic: 2015-present day and COVID-19 (SARS-CoV-2), the current pandemic (Jarus, 2020).

CRIMEAN-CONGO HEAMORRHAGIC FEVER VIRUS (CCHFV) Crimean-Congo hemorrhagic fever (CCHF) is a severe viral hemorrhagic fever, with a fatality rate of 10–40% in humans. It is a tickborne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV), which is a member of the Nairovirus genus (family Bunyaviridae). It was first reported in Crimean (1944) as an endemic among the agricultural workers. Its geographical distribution is in Eastern Europe, particularly in the former Soviet Union, throughout the Mediterranean, in north-western China, central Asia, southern Europe, Africa, the Middle East, and the Indian subcontinent (As of 11 March 2021, listed on CDC). Hyalomma ticks are the principal source of human infection (Whitehouse 2004, 145). The virus is transmitted to humans through infected tick bites, squashed ticks, or direct contact with viraemic animals or humans.

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Tick species identified as infected with the virus include Argasreflexus, Hyalommaanatolicum, Hyalommadetritum, Hyalomma, marginatum marginatum and Rhipicephalus sanguineus. The virus may spread from endemic to nonendemic areas via migrating birds and livestock transfer. Like other tick-borne zoonotic agents, CCHFV generally circulates in nature unnoticed. If a zoonotic animal becomes infected by the bite of infected tick, the virus remains in their bloodstream for about one week after infection. This allows the tickanimal-tick cycle to continue when another tick bites. (Aslam et al., 2015, 15-20). CCHFV has been isolated from numerous domestic and wild vertebrates, including cattle, goats, sheep, hares, hedgehogs, a Mastomys spp. mouse and even domestic dogs. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S) (Shayan et al., 2015,180).

Symptoms The incubation period varies with the source of infection. It is usually 1 to 3 days, with a maximum of 9 days in case of infection by a tick bite and 5-6 days with a maximum of 13 days if through infected blood or tissue. High fever, muscle pain, dizziness, abnormal sensitivity to light, mental disturbances, abdominal pain and vomiting are the major symptoms. Apart from this, some may develop tachycardia (fast heart rate), lymphadenopathy (enlarged lymph nodes), and a petechial rash (a rash caused by bleeding into the skin) on internal mucosal surfaces. The petechiae may give way to larger rashes called ecchymoses, and other hemorrhagic phenomena. Liver hepatitis, kidney failure, shock, and sometimes acute respiratory distress syndrome are also observed. People usually begin to recover 9–10 days after the appearance first of symptoms. Two weeks after the onset of illness 30% of the patients may succumb. (Dr. Ergönül O 2006, 203–214).

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Diagnosis CCHF virus infection can be diagnosed by several different laboratory tests: Enzyme-linked immunosorbent assay (ELISA), antigen detection, serum neutralization, reverse transcriptase-polymerase chain reaction (RT-PCR) assay and virus isolation by cell culture. (Hawman, 2018).

Prevention and Treatment The antiviral drug ribavirin has been used in the treatment of human disease. No vaccine has been approved so far for the treatment of CCHF. Awareness of the risk factors and educating people about the measures they can take to reduce exposure to the virus can be done as prophylaxis. This includes reducing the tick-to-human transmission, animal-to-human transmission and the risk of human-to-human transmission in the community (Shayan et al., 2015, 180-189).

EBOLA Ebola virus disease (EVD) or Ebola hemorrhagic fever (EHF) is caused by a group of viruses within the genus Ebolavirus. Ebola virus was first discovered in 1976, in two simultaneous outbreaks: one in Nzara (a town in South Sudan) and the other in Yambuku (the Democratic Republic of the Congo). This virus belongs to the family of Filoviridae which includes three genera: Cuevavirus, Marburgvirus, and Ebolavirus (Kadanali and Gul Karagoz 2015,81). Out of several viruses in the genus, only four (Ebola, Sudan, Taï Forest, and Bundibugyo viruses) are known to cause disease in people. Disease in nonhuman primates and pigs is thought to be caused by the Reston virus. EBOV, species Zaire ebolavirus, is responsible for the largest number of outbreaks and is more fatal. The case fatality rate of the Ebola disease

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virus is around 50%. The most commonly affected are humans and nonhuman primates (such as fruit bats, monkeys, gorillas, chimpanzees and porcupines). The virus spreads to people initially through direct contact with the blood, body fluids, secretions, organs and tissues of the infected animals. It then spreads rapidly to other people through direct contact with the body fluids of a person who is sick with or has died from EVD. This can occur when a person touches these infected body fluids (or objects that are contaminated with them), and the virus enters the body through broken skin or mucous membranes in the eyes, nose, or mouth. It can also be transmitted through sexual contact with someone who is affected with EVD, and also after recovery from EVD. The virus can remain in certain body fluids, like semen even after being recovered from the disease. During an Ebola outbreak, the rate of transmission is very high in healthcare settings (such as clinics or hospitals). The incubation period is between two and 21 days, usually between four and ten days. (Kourtis et al., 2015, 893-897). Fruit bats of Pteropodidae family, such as Hypsignathus monstrous, Epomopsfranqueti, and Myonycteristorquata are thought to be the natural host of the Ebola virus. Ebolaviruses contain single-stranded, non-infectious RNA genome. Ebola virions are 80 nanometers (nm) in width and maybe as long as 14,000 nm. (Hasan et al., 2019, 189).

Signs and Symptoms The onset of the disease is sudden, with a severe fever, weakness, decreased appetite, muscular pain, joint pain, headache, and sore throat. This is accompanied by nausea, vomiting, diarrhea, abdominal pain, and sometimes hiccups. Severe vomiting and diarrhea results in acute dehydration. This is followed by shortness of breath and chest pain, along with swelling, headaches, and confusion. A maculopapular rash on the skin with a flat red area covered with a small bump is observed in few cases (Heinz, 2010). Internal and external bleeding is manifested in infected person, five to seven days after the first symptoms. Patients may

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show signs like vomiting blood, coughing up blood, or blood in the stool. Bleeding into the whites of the eyes may also occur, though heavy bleeding is uncommon. Few patients recover seven to 14 days after the first symptoms. Low blood pressure from fluid loss and blood loss due to hemorrhage is the main reason for the loss of life usually six to sixteen days from the first clinical manifestation. Cases are reported with people ending up in coma near the end of life (Prof. Malvy et al., 2019, 936948). Clinically it is difficult to distinguish EVD from other infectious diseases such as malaria, typhoid fever and meningitis. Many diagnostic methods are used to detect Ebola Virus like antibody-capture enzymelinked immunosorbent assay (ELISA), antigen-capture detection tests, serum neutralization test, reverse transcriptase polymerase chain reaction (RT-PCR) assay, electron microscopy, virus isolation by cell culture. Current WHO recommended tests include: Automated or semi-automated nucleic acid tests (NAT) for routine diagnostic management. Rapid antigen detection tests for use in remote settings where NATs are not readily available. These tests are recommended for screening purposes as part of surveillance activities, however reactive tests should be confirmed with NATs. Currently two treatments are available for the treatment of Ebola virus, approved by the U.S. Food and Drug Administration (FDA) to treat EVD caused by the Ebola virus.

Prevention and Treatment The first drug approved in October 2020, Inmazebexternal icon, is a combination of three monoclonal antibodies. The second drug, Ebangaexternal icon, is a single monoclonal antibody and was approved in December 2020. These particular monoclonal antibodies bind to a portion of the Ebola virus’s surface called the glycoprotein, which prevents the virus from entering a person’s cells. A vaccine, called rVSVZEBOV is experimentally used and studied in a trial involving 11 841 people. It is proved highly protective against EVD in a major trial in Guinea in 2015.The rVSV-ZEBOV vaccine was used in the 2018-2019

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Ebola outbreak in DRC. (as per CDC). As per CDC, on 7 February 2021, the Minister of Health of the Democratic Republic of the Congo announced an outbreak of Ebola Virus Disease (EVD) after the laboratory confirmation of one case in North Kivu Province. The case was an adult female living in Biena Health Zone. As of 8 February 2021, a total of 117 contacts has been identified and are under follow up. Investigations and response activities are ongoing.

MARBURG Marburg virus disease is an extremely dangerous disease that causes Marburg virus disease in humans and nonhuman primates. Marburg virus (MARV) is a member of the Marburgvirus genus that contains two different viruses: MARV and Ravn virus (RAVV). The viral genome contains non-infectious, linear non-segmented, single-stranded RNA genomes of negative polarity that possess inverse-complementary 3’ and 5’ termini, do not possess a 5’ cap, are not polyadenylated, and are not covalently linked to a protein. Marburg virus genomes are approximately 19 kbp long and contain seven genes in the order 3’-UTR-NP-VP35VP40-GP-VP30-VP24-L-5’-UTR.This hemorrhagic fever is similar to Ebola viral disease, but with a fatality ratio of up to 88%. It is in the same family as the virus that causes Ebola virus disease. (Olejnik et al., 2019). The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen (requiring biosafety level 4-equivalent containment). In the United States, the NIH/National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centre for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group. It was first identified in an outbreak in Marburg and Frankfurt in Germany, and in Belgrade, Serbia, in 1967. The outbreak was associated with laboratory work using African green monkeys (Cercopithecus aethiops) imported from Uganda. The name Marburg virus is derived from Marburg (the city in Hesse, Germany, where the

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virus was first discovered). Later outbreaks and sporadic cases have been reported in Angola, the Democratic Republic of the Congo, Kenya, South Africa (in a person with recent travel history to Zimbabwe) and Uganda. In 2008, two independent cases were reported in travellers who visited a cave inhabited by Rousettus bat colonies in Uganda. Marburg virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. The transmission of the virus is from fruit bats (reservoir host- the African fruit bat, Rousettus aegyptiacus) and it can be transmitted between people via body fluids, through unprotected sex and broken skin. The incubation period is between 2 to 21 days after infection.

Symptoms The symptoms are similar to that of Ebola virus disease with bleeding (haemorrhage) from multiple areas, blood clot, breakdown of liver function, headache, muscle pain, flushing of the skin, and circulatory shock. After an incubation period of 2–21-day, flu-like symptoms (fever, chills, malaise and myalgia) is noted. Other clinical manifestations are multi-system involvement, including systemic (prostration, lethargy), gastrointestinal (anorexia, nausea, vomiting, abdominal pain, diarrhea), respiratory (chest pain, shortness of breath, cough), vascular (conjunctival injection, postural hypotension, edema) and neurologic (headache, confusion, seizure, coma). Hemorrhagic manifestations may develop during the peak of the illness which include petechiae, ecchymoses, uncontrolled bleeding from venepuncture sites, epistaxis and other mucosal hemorrhages, and post-mortem evidence of visceral hemorrhagic effusions. Death has been reported between 8 and 9 days after onset, usually preceded by severe blood loss and shock (Dennis Bente et al., 2009, 12-17).

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Prevention and Treatment Prevention and control measures recommended are preventing the transmission of the virus from bat to humans, contain community transfer, outbreak containment methods and strict attention to good hygienic practices among health workers treating the disease. Ebola virus infection is slightly more virulent than Marburg viral infection. Diagnosis is also like that of Ebola including culture, RT-PCR, serology, and immunohistochemistry, depending on the time course of the infection. Diagnostic samples include blood, other body fluids and tissue obtained at autopsy. Studies are ongoing for actual treatment of the virus. Marburg vaccines (cAd3, MVA-BN-Filo and MARV DNA) are in Phase I clinical trials and one (MVA-BN-Filo) is scheduled for a Phase 2/3 clinical trial. Multiple Marburg candidate platforms (rVSV, VLP, Adenovirus, DNA) have demonstrated protection in NHPs. Potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. Early professional treatment of symptoms like dehydration considerably increases survival chances. (Kortepetera et al., 2020,233242). Major Marburg out breaks-Uganda (2014, 2012,2005), Netherland and the United states of America (2008), Agola (2005), Democratic Republic, South Africa (1975), Yugoslavia and Germany (1967). As per WHO, recent outbreaks of MRV are found mostly in Uganda (2017, 2012, 2008).

VIRAL INFECTIONS BY CORONA VIRUS Coronaviruses belong to the Coronaviridae family in the Nidovirales order, which contains a single-stranded RNA as a nucleic material. Though it was thought to infect only animals, in human Severe acute respiratory syndrome (SARS) outbreak was caused by SARS-CoV, 2002 in Guangdong, China. A decade later The Middle East respiratory syndrome (MERS-CoV) caused an endemic in Middle Eastern countries. In 2019, a new coronavirus was identified as the cause of a disease

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outbreak that originated in Wuhan, China. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and belongs to the member of the β group of coronaviruses. (Shereen et al., 2020,92) The disease it causes is called coronavirus disease 2019 (COVID-19). In March 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic. New coronaviruses that cause severe illness in humans are:

MERS Middle East respiratory syndrome (MERS) is caused by a virus in the family of Coronaviridae and has a large RNA viral genome of approximately 26-33 kb. The infectious agent is Middle East respiratory syndrome-related corona virus (MERS-CoV). Since its discovery in 2012 (Saudi Arabia), MERS have been reported in 28 countries across the world. Among the cases of MERS-CoV, most of them are reported in the Middle East and North Africa region, Europe, East Asia and the United States. Out of this 80% of the cases are reported in Saudi Arabia (Ramadan and Houssam Shaib, 2019,35).

Symptoms Although MERS is thought to be originated from bats, human infections are from camels (Dromedary camels) and so also called Camel flu. The incubation period is between 5 days to 2 weeks. These viral respiratory infections are sporadic and cause localized outbreaks. The clinical symptom of MERS-CoV infection ranges from no symptoms (asymptomatic) or mild respiratory symptoms to severe acute respiratory distress syndrome, multiorgan failure and death. The symptoms include feverishness, chills, rigors, sore throat, non-productive cough, and dyspnea. Other symptoms of respiratory tract infections, including rhinorrhea, sputum production, wheezing, chest pain, myalgia, headache,

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and malaise, may also be present. The disease is more problematic for people with a pre-existing medical condition that weakenes their immune systems. (Chan et al., 2015). Varying manifestations like pneumonia, gastrointestinal symptoms, including diarrhea, vomiting are also found. Severe illness can result in respiratory failure that requires mechanical ventilation and support in an intensive care unit. Around 35% mortality had been reported by WHO. Human to human transmission is comparatively low. Specific drug treatment or vaccine is not available for MERS and infection prevention and control measures to have to be followed. MERS-CoV continues to be endemic with low-level public health threats, which has a pandemic potential if the virus is mutated.

Prevention and Treatment Effective MERS therapeutics are still in the early stages of research and evaluation. Several broad-spectrum antiviral agents including nitazoxanide, viral methyltransferase inhibition and nucleotide prodrugs have shown in vitro activity against MERS-CoV. Early results for novel MERS-specific therapeutics that inhibit viral replication or have specific neutralizing activity are promising. Three types of vaccines on the trial run are the dromedary camel vaccine to prevent zoonotic transmission, a human vaccine for long-term protection of persons at high exposure risk and a human vaccine for reactive use in outbreak settings (Cirino et al., 2019).

SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS (SARS-COV) This virus SARS is a disease caused by an infection with a different coronavirus SARS-CoV. It is a family member of the genus Betacoronavirus and subgenus Sarbecovirus. It causes severe acute

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respiratory syndrome (SARS), which can lead to a life-threatening form of pneumonia. This enveloped positive-sense single-stranded RNA virus is of almost 30 kb in genomic size. The SARS-related coronavirus was one of the several viruses identified by the World Health Organization (WHO) in 2016 as a likely cause of a future epidemic. The prediction came true as the SARS coronavirus targets the epithelial cells of the respiratory tract, resulting in diffuse alveolar damage and potentially dangerous. SARS was first reported in Asia (February 2003). According to the World Health Organization (WHO), a total of 8,098 people worldwide became sick with SARS during the 2003 outbreak andout of these, 774 died. Though it spread to many countries, we could contain it and no reported cases are available after 2004. Bats serve as the main host reservoir species for the SARS-related coronaviruses like SARSCoV-1 and SARS-CoV-2. After the isolation of SARS-CoV, SARSCoV-like viruses were found in palm civets and a raccoon dog from wildanimal markets in the Guangdong Province of China.

Symptoms Several organs/cell types may be infected during the illness. The virus mostly affects different organ/cell types including mucosal cells of the intestines, tubular epithelial cells of the kidneys, neurons of the brain, and several types of immune cells. Evidence is there that certain organs may suffer from indirect injury. In general, clinical manifestation begins after 2 -7 days after infection and includes high fever (temperature greater than 100.4°F [> 38.0 °C]), chills, headache, and overall feeling of discomfort, and body aches. Patients develop a dry cough during this period and some have mild respiratory symptoms at the outset. Most patients develop pneumonia. Clinical deterioration, often accompanied by watery diarrhea, commonly occurs 1 week after the onset of illness. As SARS progresses, it can lead to failure of the lungs, liver, or heart. Older adult populations are severely affected during outbreaks and mortality rates are higher in the age group above 65. (Cheng et al., 2007,660-662).

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Prevention and Control No vaccines are available for the treatment of SARS, although supportive measures are beneficial. Prevention and control consist of strict isolation of infected individuals, containment measures to arrest the infection and good hygiene measures to be followed (as per CDC).

SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS (SARS-COV-2) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly known as coronavirus or COVID-19 is declared a global pandemic on March 11, 2020. It was first reported in Wuhan, China in December 2019. Around the world, there are now 100 COVID-19 vaccine candidates undergoing clinical trials and 184 candidates in preclinical development. There are four categories of vaccines in clinical trials: Whole virus, protein subunit, viral vector and nucleic acid (DNA and RNA). WHO approved vaccines are Oxford–AstraZeneca, PfizerBioNTech, Sinopharm-BBIBP, Moderna, and Johnson & Johnson.The Oxford–AstraZeneca COVID-19 vaccine, sold under the brand names Vaxzevria and Covishield, is a viral vector vaccine, the Pfizer–BioNTech COVID-19 vaccine, also known as Comirnaty, is an mRNA vaccine, the Sputnik V COVID-19 vaccine is a viral vector vaccine, Sinopharm BBIBP-CorV COVID-19 vaccine is an inactivated virus vaccine, the Moderna COVID-19 vaccine is an RNA vaccine, the Johnson & Johnson COVID-19 vaccine is a viral vector vaccine, Covaxin is an inactivated virus vaccine. In India, the vaccines approved are Covaxin and Covishield. Covaxin is an inactivated vaccine, made up of killed coronaviruses, making it safe to be injected into the body. It is produced by Bharat Biotech. Covishield, the Oxford-AstraZeneca vaccine is being manufactured locally by the Serum Institute of India, the world’s largest vaccine manufacturer. The vaccine is made from a weakened version of a

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common cold virus (known as an adenovirus) from chimpanzees. It has been modified to look more like coronavirus - although it can’t cause illness.

HANTA VIRUS Hantaviruses (genus Orthohantavirus, family Hantaviridae, order Bunyavirales) are enveloped, negative-sense, single-stranded, tripartite RNA viruses that are emerging zoonotic pathogens. Hantavirus infection can cause hantavirus disease in humans. Natural reservoir hosts are rodents, bats, moles, and shrews. It has a worldwide distribution and is responsible for greater than 150,000 cases of disease per year. The virus is responsible for two major diseases: Haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) or hantavirus cardiopulmonary syndrome (HCPS). Old World hantaviruses, including the prototypic hantavirus Hantaan virus (HTNV), Puumala virus (PUUV), and Dobrava virus (DOBV), were found predominantly in Europe and Asia, cause HFRS. Seoul virus (SEOV), an HFRS-causing hantavirus carried by the Norway rat (Rattus norvegicus) has a widespread distribution coinciding with transportation of this rodent reservoir worldwide. New World hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV), found mostly in the Americas, and Choclo virus (CHOV) found in Central America, causing HPS with a case fatality rate of up to 40%. Hantavirus transmission to humans occurs when a person inhales aerosols or dust particles of orthohantaviruscontaminated rodent urine, feces, or saliva. Forestry and farming practices in an area with a large rodent population make the people involved in it prone to these diseases. Orthohantavirus-induced diseases pose a public health threat worldwide owing to significant morbidity and mortality rates. (Won-Keun Kim et al., 2021).

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Symptoms Human hantavirus infections are predominantly found in rural areas (forests, fields, farms, etc.), where rodents hosting the virus might be found. Humans do not belong to the natural host range of hantaviruses. Infected individuals may experience headaches, dizziness, chills, fever and myalgia. They may also experience gastrointestinal (GI) symptoms including nausea, vomiting, abdominal pains, and diarrhea, followed by sudden onset of respiratory distress and hypotension. Other symptoms usually include shortness of breath, rapid breathing (tachypnea), rapid heartbeat (tachycardia), and sometimes joint pain (arthralgia), back and/or chest pain, and/or sweating. Clinical manifestations usually occur from two to four weeks after initial exposure, though symptoms may appear as early as one week to as late as eight weeks following exposure. The case fatality rate can reach up to 50% (T. Avšič-Županc et al., 2019).

Treatment Laboratory diagnosis of hantavirus infection done by serologic tests and reverse transcriptase-polymerase chain reaction (RT-PCR). Enzymelinked immunosorbent assay (ELISA) and Western and strip immunoblot assays (serological tests) also used. Growth of the virus is technically difficult and requires a biosafety level 3 laboratory. There is no specific approved therapy is available for either HFRS or HCPS as per U.S. Food and Drug Administration. The treatment is primarily supportive and is recommended that patients with HCPS and severe HFRS should be moved to an intensive care unit for close monitoring and care. Care should be taken to maintain the patient’s fluid (hydration) and electrolyte (e.g., sodium, potassium, chloride) levels, maintenance of correct oxygen, blood pressure levels, amount of diuresis and kidney function to avoid dangerous overhydration (for patients that are anuric and with leaky capillaries). Ribavirin has been used in the treatment of HFRS in China and clinical studies on Chinese HFRS patients suggest that ribavirin

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therapy can significantly reduce the mortality rate if given in the first 5 days after onset of symptoms. (Yuill, 2020).

ADENO VIRUS Adenoviridae is a family of double-stranded non-enveloped, linear DNA viruses of 34–36 kbp length DNA. Adenovirus was first isolated from human adenoid tissues in 1953 by Rowe and his colleagues. Human adenoviruses (HAdVs) are classified in the family Adenoviridae, genus Mastadenovirus, which contains seven known species, from A to G. Currently, there are 88 different HAdV types known and new adenovirus types continue to emerge (Dhingra et al., 2019). The adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Transmission of adenovirus can occur by aerosol droplets, faecal-oral transmission, and contaminated fomites. Adenovirus causes persistent infections in both immunocompetent and immunocompromised individuals (LaRosa, 2015). Adenovirus remains a significant threat to public health. The interaction between humans and their closest living relatives creates an inherent risk of pathogen transfer, which is an important concern for both, public health and wildlife conservation.

Symptoms Upper respiratory tract infections (URI) pneumonia and diarrhea are the deadliest in infants. Patients have symptoms like common cold or flulike symptoms, sore throat, acute bronchitis (inflammation of the airways of the lungs, sometimes called a “chest cold”), pneumonia (infection of the lungs), pink eye (conjunctivitis), acute gastroenteritis (inflammation of the stomach or intestines causing diarrhea, vomiting, nausea and stomach pain). There are several techniques for the detection of adenovirus. Cell culture with confirmatory immunofluorescence assay

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(CC-IFA) allows for visualization of adenovirus proteins or antibodies through binding to a fluorescent dye. PCR, laboratory antigen tests, immunochromatography, and enzyme immunoassays may also be used. (Abelson et al., 2019).

Prevention and Treatment Currently, there is no adenovirus vaccine available to the public. Vaccine for adenovirus types 4 and 7 is used only in military personnel who may be at higher risk for infection from these two adenovirus types. This vaccine contains live viruses that can be shed in the stool and potentially cause disease in other people if transmitted. As the safety and effectiveness of this vaccine has not been studied in the general population or people with weakened immune systems, it is not approved for use outside of the military. Methods to prevent adenovirus infections involve frequent hand washing for more than 20 seconds, avoiding touching the eyes, face, and nose with unwashed hands, and avoiding close contact with people with symptomatic adenovirus infection. Infected individuals are advised to cough or sneeze into the arm or elbow instead of the hand, avoid sharing cups and eating utensils, and refrain from kissing others. Outbreaks of conjunctivitis caused by adenovirus can be prevented by the chlorination of swimming pools. Despite their role as pathogens, some HAdVs and simian adenoviruses (SAdVs) have been used or proposed as tools in vaccine delivery, gene therapy, and cancer studies. Due to the unique ability to infect a broad range of cell types, adenovirus-based vectors can be used to transduce and deliver transgenes to different cell types including both replicating and quiescent cell populations. This is a breakthrough in gene therapy and puts adenoviral vectors on top of viral vectors for gene delivery. The newly emerging infectious diseases, such as SARS, Ebola, and Zika, and the continuing threat of bioterrorism have increased the requirement of novel vaccine platforms which can be designed and produced on a large scale within a

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short period. Adenoviral vectors, due to their versatility, a broad range of tissue tropism, well characterised genome, ease of construction, the adeptness to rapid mass production, and induction of robust transgenespecific humoral and cellular immune responses, have proven to be valuable in the development of vaccines for emerging viral infectious diseases. The adenoviruses are potentially used for vaccine production on large scale for HIV, malaria, Ebola virus, and Zika viruses. Adenoviral vector to deliver a DNA molecule that encodes the SARS-CoV-2 spike (S) protein used in vaccine production from Oxford University/ AstraZeneca (the UK), Cansino Biologics (China), Sputnik V (Russia) and Janssen Pharmaceuticals/Johnson & Johnson (the Netherlands and USA).

DISEASE X Disease X is a hypothetical name that was cited by the World Health Organization (WHO) in February 2020 as priority disease that could cause a future epidemic. It would be a new disease with an epidemic or pandemic potential caused by an unknown pathogen. Disease X is a concern for mankind as there is a possibility of jumping of zoonotic viruses to our world from the wild. Director of the US National Institute of Allergy and Infectious Diseases Anthony Fauci stated that the concept of Disease X would encourage WHO projects to focus their research efforts on entire classes of viruses (e.g., flaviviruses), instead of just individual strains (e.g., zika virus) so that WHO could take timely actions against unforeseen strains. We have around 1.6 million unknown viruses deep down in the forest which has the immense capacity to strike us hard as a pandemic. The COVID-19, caused by the SARS-CoV-2 virus strain has met the requirements to be the first Disease X according to the WHO experts. Disease X could be any pathogen including viruses, bacteria, fungi, parasites, or prions. Out of the 400 emerging infectious diseases, there are fewer likely chances for bacteria (including rickettsia), viral or prion pathogens, protozoa, fungi, and helminths to be the next Disease X.

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The most devastating recent emerging diseases like HIV, influenza H1N1 and H5H1, severe acute respiratory syndrome coronavirus, Lassa virus, Ebola virus, and Middle East respiratory syndrome coronavirus which are RNA viruses pose as a potential threat due to their ability to replicate in numerous hosts. The high mutuality rate of RNA viruses owing to its error-prone reverse transcription results in highly virulent strains capable of catastrophic outbreaks. Moreover, human activities near wildlife, the creation of animal source foods with little monitoring of employees and a poorly understood supply chain, insect and tick vectors, extreme population density, and constrained surveillance and laboratory capacity could lead to a new pandemic (Simpson et al., 2020).

CONCLUSION The way to deal with a pandemic is to make sure it never happens in the first place. Through greater conservation efforts and ending the over exploitation of Earth’s resources, we can prevent future pandemics. This could be achieved with a good surveillance system. A strong, wellfunded health system for eco-epidemiological studies to identify virus reservoirs and sample to sequence the virus, surveillance of unusual events, bringing together local communities and agents in the field to detect the first spillover cases and act quickly to avoid an epidemic, supported by immunization programs and robust early warning systems that alert us to new diseases, are all factors which could help us to be prepared for the next pandemic. Together with the localized and rapid control, this surveillance needs to be deployed before diseases become epidemic or pandemic. Deeper human encroachment into the undisturbed forest, deforestation, hunting for bushmeat, or shopping at wild animal and fish market can lead to virus spread as humans become exposed themselves to animals and the diseases they carry. To put an end to the potential future emerging zoonotic pandemic long-term surveillance needs to be done. This includes establishing an international council specializing in pandemic prevention; taking a one-health approach to

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pandemic preparedness; considering health impacts in development projects; implementing taxes on meat consumption and other high-risk activities; listing high disease-risk species (such as bats and primates) as illegal in the wildlife trade. To prevent future pandemics Tripartite consisting of WHO, OIE, and the Food and Agriculture Organization (FAO) with the UN Environment Programming has put forward the One Health approach for outbreak alert and response.

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Jarus, Owens. (2020). “All about history: 20 of the worst epidemics and pandemics in history.” Live Science. Accessed May 24,2021. Kadanali, Ayten and Gul Karagoz. (2015). “An overview of Ebola virus disease.” Northern Clinics of Istanbul 2 (1): 81–86. doi: 10.14744/ nci.2015.97269 PMCID: PMC5175058, PMID: 28058346.Accessed May 13,2021. Kelly-Cirino, Cassandra, Laura T Mazzola, Arlene Chua, Christopher J Oxenford, Maria D Van Kerkhove. (2019). “An updated roadmap for MERS-CoV research and product development: focus on diagnostics.” BJM global health. doi: 10.1136/bmjgh-2018-001105. Accessed May 22,2021. Khanal, Subrat, Pranita Ghimire, and Amit S. Dhamoon. (2018). “The Repertoire of Adenovirus in Human Disease.” Biomedicines. 6 (1)30. doi:10.3390/biomedicines6010030, PMCID: PMC5874687PMID: 29 518985. Accessed May 22, 2021. Kim,Won-Keun, Seungchan Cho, Seung-Ho Lee, Jin Sun, Geum-Young Lee, Kyungmin Park,Daesang Lee, Seong Tae Jeong and Jin-Won Songl. (2021). “Genomic Epidemiology and Active Surveillance to Investigate Outbreaks of Hantaviruses.” Frontiers in Cellular and Infectious Microbiology. https://doi.org/10.3389/fcimb.2020.532388. Accessed May 22, 2021. Kortepetera, Mark G, Kerry Dierbergb, Erica S. Shenoyc, Theodore J. Cieslaka. (2020). “Marburg virus disease: A summary for clinicians.” International Journal of infectious diseases. Volume 99. 99:233242.https://doi.org /10.1016/j.ijid.2020.07.042. Accessed May 22, 2021. Kourtis, Athena P, Kristie Appelgren, Michelle S. Chevalier, and Anita McElroy. (2015). “Ebola virus disease.” HSS Public access. 34 (8): 893–897.doi: 10.1097/INF.0000000000000707.Accessed May 24, 2021. Malvy Denis, Anita K McElroy, Hilde de Clerck, Prof Stephan Günther, Johan van Griensven. (2019). “Ebola virus disease.” The Lancet. Seminar| Volume 393, ISSUE 10174, 936-948.DOI: https://doi.org/ 10.1016/S0140-6736 (18)33132-5. Accessed May 13, 2021.

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Olenek, Judith, Elke Mühlberger, and Adam J. Hume. (2019). “Recent advances in Marburgvirus research.” F1000 research doi: 10.12688/f1000research.17573.1, PMCID: PMC6530603, PMID: 31131088.Accessed May 13, 2021. Ramadan, Nour and Houssam Shaib. (2019). “Middle East respiratory syndrome coronavirus (MERS-CoV): A review.” Germs. 9 (1):35– 42. doi: 10.18683/germs.2019.1155, PMCID: PMC6446491, PMID: 31119115.Accessed May 22, 2021. Rosa, G. La, S. Della Libera, S. Petricca, M. Iaconelli, D. Donia, P. Saccucci,F. Cenko, G. Xhelilaj and M. Divizia. (2015). “Genetic Diversity of Human Adenovirus in Children with Acute Gastroenteritis.” Hindwai. Biomed Research international. Article ID 142912. https://doi.org/ 10.1155/2015/142912. Accessed May 24, 2021. Shayan, Sara, Mohammad Bokaean, Mona Ranjvar Shahrivar, Sadegh Chinikar. (2015). “Crimean-Congo Hemorrhagic Fever.” Oxford Academic. Laboratory Medicine, Volume 46, Issue 3, 1 August 2015, 180–189. Accessed 13 May 2021. https://doi.org/ 10.1309/ LMN1P2FRZ 7BKZSCO. Shereen, Muhammad Adnan, Suliman Khan, Abeer Kazmi, Nadia Bashir, and Rabeea Siddiquea. (2020). “COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses.” Journal of Advanced Research 24: 91–98. doi: 10.1016/j.jare.2020.03.005, PMCID: PMC7113610, PMID: 32257431. Accessed May 22, 2021. Simpson Shmona, Michael C Kaufmann, Vitaly Glozman, Ajoy Chakrabarti. (2020). “Disease X: accelerating the development of medical countermeasures for the next pandemic.” The Lancet infectious diseases. Volume 20, Issue 5, E108-E115. DOI: https:// doi.org/10.1016/S1473-3099(20)30123-7. Accessed May 22, 2021. Singh, Shakthi, Rakesh Kumar and Babita Agrawal. (2018). “Adenoviral Vector-Based Vaccines and Gene Therapies: Current Status and Future Prospects.” IntechOpen. DOI:10.5772/intechopen.79697. Accessed May 24, 2021.

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Whitehouse, Chris. A. (2004). “Crimean-Congo hemorrhagic fever.” Antiviral Research 64 (3):145-60. doi: 10.1016/j.antiviral.2004.08. 001.Accessed May 13, 2021. Yuill, Thomas M. 2020 “Hantavirus Infection.” MSD Manuel professional version. Accessed May 22, 2021.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 17

SARS-COV-2 AND DIABETICS Sweety Gopinath* Azeezia Medical College Hospital, Meeyannoor, Kerala, India

ABSTRACT Coronavirus disease-19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus. SARS-CoV-2 infection can cause mild to moderate respiratory illness. Millions of people have already been infected and so many have died around the world due to this pandemic. Serious infections may develop in people with underlying diseases and those who are older. The pandemic is a serious challenge for diabetic patients. People with diabetes (both type 1 and 2) can have impaired immune systems, which increases the risk of complications and mortality.

Keywords: COVID-19, RNA viruses, diabetes, DPP-4, ACE-2, metabolic disease

*

Corresponding Author’s Email: [email protected].

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INTRODUCTION Coronaviruses are a family of viruses that pose severe health threats to humans as well as animals. Three zoonotic coronaviruses have been identified during the last two decades. They are Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Swine Acute Diarrhea Syndrome (SADS). SARS and MERS emerged in 2003 and 2012, which can cause several outbreaks and caused a worldwide pandemic that took thousands of human lives, while SADS affected the swine industry in 2017. They have common characteristics like they are all highly pathogenic to humans or livestock, their agents originated from bats, and two of them originated in China (Fan et al., 2019). Generally, coronaviruses develop widespread respiratory disease, gastrointestinal and central nervous system diseases in humans and animals. Some viruses can easily adapt to new hosts and environments through mutation and recombination, hence they alter host range and tissue tropism. Single-stranded viruses mutate faster than double-stranded viruses. (Fan et al., 2019). Hence, health threats from coronaviruses are constant and long-term. A new coronavirus was identified in 2019, which is known as Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2). It causes coronavirus disease in 2019 (COVID-19). The World Health Organization declared the COVID-19 outbreak as a pandemic by March 2020. Coronaviruses are a group of positive-sense single-stranded RNA viruses with an envelope of about 80-120 nm. It is the second largest of all RNA virus genomes which cause diseases in mammals and birds. The severity of illness and symptoms of COVID-19 can range from mild to severe. Some people can have no symptoms (asymptomatic), some may have mild symptoms, while some others may experience worsened symptoms such as pneumonia, shortness of breath, etc. Mild illnesses in humans include cases like the common cold (which can also be caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. The common signs of a person

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infected with the coronavirus include respiratory syndrome, kidney failure, and even death. The 2019 new coronavirus or “2019-n CoV” was discovered because of Wuhan viral pneumonia cases in 2019 and was named by the World Health Organization on January 12, 2020, confirming that it can cause colds and the MERS and more serious diseases such as SARS (Fan et al., 2019).

STRUCTURE OF CORONAVIRUS Coronavirus belongs to the family of Coronaviridae and order Nidovirales (Cascella et al., 2021). They are classified into four different genera: Alphacoronavirus, Betacoronaviruses, which infects mammals, and Gammacoronavirus, which infects avians, and Delta coronavirus which can infect both avians and mammals. SARS-CoV, MERS-CoV comes under the genera of beta coronaviruses (Li 2016). Coronaviruses are large, spherical, enveloped particle-containing positive-sense singlestranded RNA associated with a nucleoprotein within a capsid comprised of matrix protein. Their genome ranges from 27 to 32 kb and is the largest among all the RNA viruses. The envelope bears club-shaped glycoprotein projections, which gave its name. Some coronaviruses possess a hemagglutinin-esterase protein (HE) (De Haan et al., 1998). The spike protein contains three segments: a large ectodomain which has S1 and S2 subunit for receptor binding and membrane fusion respectively, a transmembrane anchor, and a short intracellular tail (Li 2016).

COMMON FEATURES OF CORONAVIRUSES INCLUDE 

A highly conserved genomic organization with a large replicase gene preceding structural and accessory genes,

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Expression of many non-structural genes by ribosomal frameshifting, Several unique of unusual enzymatic activities encoded within the large replicase-transcriptase polyprotein, and Expression of downstream genes by synthesis of 3’-nested subgenomic mRNAs.

The typical organization of the genome is 5’-leader-UTR-replicase-S (Spike)-E (Envelope)-M (Membrane)-N (Nucleocapsid)-3’-UTR-poly (A) tail. They possess accessory genes that encode accessory protein and have importance in viral pathogenesis, not in replication (Baranov et al., 2005).

VIRAL ENTRY AND PATHOPHYSIOLOGY Receptor recognition is the first step involved in any viral infection. (Ni et al., 2020) Viruses usually enter into host cells by attaching to the cell surface receptor and they eventually enter the viral genome into host cells. For the entry of Coronaviruses into host cells, they first bind to a cell surface receptor for viral attachment, enter the endosomes, and then fusion of viral and host membranes takes place. SARS- CoV-2 has sequence similarity with bat-originated viruses, SARS-CoV and MERSCoV. Angiotensin-converting enzyme-2 or ACE-2 is the cellular receptor for the SARS-CoV-2. This receptor can be found in different locations, like the upper respiratory system, kidney tubular epithelium, alveolar epithelial cells in the lungs, the heart, endothelial cells, enterocytes, and the pancreas. Viral replication starts once they reach the cytosol, where it replicates and forms mature virions. Mature virions start spreading. The SARS-CoV-2 infection affects the immune cells and thereby releases a high amount of inflammatory cytokines, which is known as the cytokine storm. It can cause multiorgan damage (York n.d. 2021). A mature virus contains spike protein on its surface as trimers having S1 head and S2 as stalk. The S1 subunit has two domains, one at C-

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terminal (S1-CTDs) and the other one at N-terminal (S1-NTDs), and both domains having the function of receptor-binding domains(RBDs). Coronavirus S1-NTDs can recognize either sugar receptors or protein receptors (Li 2016). During the membrane fusion process, these domain undergoes proteolytic activation and conformational changes. (Shang et al., 2020).

WHY ARE DIABETIC PATIENTS MORE PRONE TO COVID-19? Diabetic patients are more susceptible to hospitalization and mortality resulting from viral, bacterial, and fungal infections than those without diabetes. Diabetes mellitus (DM) is a common chronic metabolic disease and is often identified as an independent risk factor for developing respiratory tract infections (Klekotka, Mizgała, and Król 2015). Diabetic patients appear to develop more serious diseases and to require mechanical health care support systems than other COVID-19 infected individuals. Hypertension, obesity, cardiovascular disease, hyperglycemia are some of the comorbidities associated with patients who had COVID-19 with diabetes. Among these, hypertension is the most common comorbidity. This is because people with diabetes possess less immune function. In the case of respiratory illness, these categories of people are more prone to lower respiratory infection (Unnikrishnan, 2020).

DPP-4 RECEPTOR Dipeptidyl peptidase-4 (DPP-4) is a type ΙΙ transmembrane glycoprotein bound aminopeptidase, which is ubiquitously in many tissues and was first isolated 1970s. DPP-4 is multifunctional, which plays an important role in glucose and insulin metabolism. In the case of

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immune regulation, they activate T cells and upregulate CD-86 expression. Through catalytic and non-catalytic mechanisms DPP-4 can increase inflammation in type 2 diabetes. (Iacobellis 2020). SARS-CoV-2 can infect different tissues and their constituent cells. (Bassendine et al., 2020). The virus binds to the host cell by the surface receptor ACE-2, but the latest studies show that like MERS–Co-V, these viruses use coreceptors – DPP-4/CD26 receptor. DPP-4/CD26 receptor is expressed widely on epithelia and endothelia of the systemic vasculature, kidney, lung, small intestine, and heart. Their distribution in the respiratory tract of humans allows the viral entry into the airway tract and this would lead to cytokine storm and cause fatal COVID-19 pneumonia (Solerte et al., 2020). DPP4 is a link between diabetes and the severity of COVID-19. COVID-19 infection can severely affect vascular integrity, so preserving the integrity of the vascular system is of utmost importance.DPP inhibitors (DPPi) are usually used to control the severity of COVID-19 infection in diabetic patients. Gliptins (DPPi) are antidiabetic drugs that inhibit DPP4 enzymatic activity thereby controls glucose homeostasis. DPP4 degrades and inactivates incretin hormones GLP-1 and GIP. (Valencia et al., 2020).

THE ROLE OF ANGIOTENSIN-CONVERTING ENZYME-2 (ACE-2) RECEPTOR ACE-2 is a type-1 integral membrane glycoprotein (Tipnis et al., 2000) that acts as an entry receptor for SARS-CoV-2, the virus responsible for coronavirus disease 19 (COVID-19) which is widely expressed by bronchial mucosal epithelial cells, and its expression can also be found in epithelial cells of lungs, blood vessels, kidney, intestine. (Yang et al., 2020). ACE-2 functions as a carboxypeptidase and its major substrate are Ang-ΙΙ. To a lower extent, ACE-2 can degrade other angiotensins which include Ang-Ι, Angiotensin1-7, Angiotensin1-9

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(Tikellis and Thomas 2012). ACE-2/Ang(1-7) system protects lungs from acute respiratory distress syndrome (ARDS) by providing antioxidant and anti-inflammatory role.ACE-2 protective against lethal avian influenza A H5N1 infection(Zou et al., 2014). Patients with DM show reduced ACE2 expression possibly due to glycosylation, which is a sign of severe lung injury and ARDS with COVID-19 (Wu et al., 2020). Increased infectivity and virulence of SARS-CoV-2 can be seen in diabetic patients. (Zhou et al., 2021). Studies show that patients with diabetes are considered a high-risk group because the receptor expression can be increased if the diabetic patients are prescribed ACE inhibitors (Seewoodhary and Oozageer 2020). The use of drugs such as ACE inhibitors(ACEi) and angiotensin-receptor blockers (ARBs) in diabetic patients markedly increased the expression of ACE-2. The ACE-2 stimulating drugs would facilitate the entry of SARS-CoV-2 into the host cell and this might result in more severe and fatal diseases (Pal and Bhansali 2020). ACE-2 is altered in patients with chronic diseases, such as diabetes, due to metabolic alterations, therefore increasing the chance of infection and severity of the disease in these patients (Finucane and Davenport 2020). After the viral infection, the cells undergo necrosis or apoptosis, processes in which the activation of pro-inflammatory chi or cytokines, which are responsible for triggering inflammatory responses, and for the accumulation of defense cells at the site, occur. People with chronic hyperglycemia have a deregulated expression of ACE2, which leaves the cells more vulnerable to inflammatory effects, since, in addition to the regulation of systemic arterial hypertension (SAH), this enzyme has protective effects, especially about inflammation (Cheng, Wang, and Wang 2020) (Codo et al., 2020). The deregulated ACE-2 expression in pancreatic cells causes disturbance in function and affects the production of hormones responsible for the regulation of glucose in our body. This may prevent the assembly of a coordinated and appropriate physiological response to the combat of the invading agent. The high glucose level in monocyte induces viral replication and pro-inflammatory cytokines are

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increased, which usually act only on the death of lung cells (Coperchini et al., 2020). The cytokine storm is followed by the immune system attacking the body due to an uncontrolled and widespread inflammatory response, which can cause multiple organ failure and in the most severe cases of SARS-CoV-2 infection, death. Several complications are associated with Covid-19 infected diabetes patients. Studies show that people with diabetes have poor metabolic control when infected with COVID-19, this may lead to reduced viral clearance. Obesity is also a common risk factor. Coronaviruses can worsen the underlying conditions of diabetes patients like hypertension, coronary artery disease, and chronic kidney disease, which is the actual reason for the high mortality rate. Due to the increased production of furin (a membrane-bound protease, helps in viral entry) in diabetes patients, there occurs increased viral replication and infection (Gupta, Hussain, and Misra 2020).

COVID-19 IMPACT ON DIABETES The viral infection can induce glucose dysregulation in people who already have diabetes or they can cause new-onset diabetes in those who do not have diabetic history. Studies show that SARS-CoV-2 infection increases the blood glucose level in diabetic patients and became difficult to control. The COVID-19 impact on diabetic patients includes: Glucose dysregulation, Acute responses to pneumonia, Enhanced stress state, Disease‐related gastrointestinal symptoms, Isolation‐related irregular lifestyles, Metabolic disturbance associated with infection, Impact of covid‐19 on obesity, decreased ATP production, change happens in body weight, elevated glycolytic rate and several other immunological changes. Increased stress state and instability in mood can worsen the infection (Zhou et al., 2021). The severity of SARS-CoV-2 disease progression and death determining factors includes severe hypoxia, thrombocytopenia, old age, and hyperglycemia. Hyperglycemia is one of the characteristics of

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diabetes caused by insufficient insulin production by the pancreas, may lead to serious complications if left untreated, and can develop kidney failure, limb amputations, blindness, and cardiovascular diseases. Therefore, diabetic patients should maintain glucose blood levels. The immune response, which is important for fighting against SARS CoV-2 disease gets impaired if one with diabetes has poor blood glucose control. (Ni et al., 2020).

CONCLUSION Diabetic patients are vulnerable to many diseases. Once they got infected with COVID-19 they are at high risk of developing several other serious or fatal diseases. So, glycemic control is very important. Boosting the immunity by doing exercise and having a proper diet will help to avoid the worsening of the infectious condition. DPP4 vaccine could be useful to control glucose homeostasis, this needs to be well-studied. Since this subject is new, information regarding these topics and areas are limited and unclear. There can be too many unknown factors that worsen the infection in diabetic patients which is yet to be discovered.

REFERENCES Baranov, Pavel V., Clark M. Henderson, Christine B. Anderson, Raymond F. Gesteland, John F. Atkins, and Michael T. Howard. (2005). “Programmed Ribosomal Frameshifting in Decoding the SARS-CoV Genome.” Virology 332, no. 2 (February 20, 2005): 498– 510. https://doi.org/10.1016/j.virol.2004.11.038. Bassendine, Margaret F., Simon H. Bridge, Geoffrey W. McCaughan, and Mark D. Gorrell. (2020) “COVID-19 and Comorbidities: A Role for Dipeptidyl Peptidase 4 (DPP4) in Disease Severity?” Journal of

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Diabetes 12, no. 9: 649–58. https://doi.org/10.1111/1753-0407. 13052. Cheng, Hao, Yan Wang, and Gui-Qiang Wang. (2020). “OrganProtective Effect of Angiotensin-Converting Enzyme 2 and Its Effect on the Prognosis of COVID-19.” Journal of Medical Virology 92, no. 7: 726–30. https://doi.org/10.1002/jmv.25785. Codo, Ana Campos, Gustavo Gastão Davanzo, Lauar de Brito Monteiro, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, João Victor Virgilio-da-Silva, Juliana Silveira Prodonoff, et al., (2020) “Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.” Cell Metabolism 32, no. 3 (September 1: 437-446.e5. https://doi.org/ 10.1016/j.cmet.2020. 07.007. Coperchini, Francesca, Luca Chiovato, Laura Croce, Flavia Magri, and Mario Rotondi. (2020). “The Cytokine Storm in COVID-19: An Overview of the Involvement of the Chemokine/ChemokineReceptor System.” Cytokine & Growth Factor Reviews, 53 (June 1: 25–32. https://doi.org/10.1016/j.cytogfr.2020.05.003. De Haan, Cornelis AM, Lili Kuo, Paul S. Masters, Harry Vennema, and Peter JM Rottier. (1998) “Coronavirus Particle Assembly: Primary Structure Requirements of the Membrane Protein.” Journal of Virology 72, no. 8: 6838–50. Fan, Yi, Kai Zhao, Zheng-Li Shi, and Peng Zhou. (2019). “Bat Coronaviruses in China.” Viruses 11, no. 3:210. Finucane, Francis M., and Colin Davenport. (2020). “Coronavirus and Obesity: Could Insulin Resistance Mediate the Severity of Covid-19 Infection?” Frontiers in Public Health 8 https://doi.org/10.3389/ fpubh.2020.00184. Gupta, Ritesh, Akhtar Hussain, and Anoop Misra. 2020) “Diabetes and COVID-19: Evidence, Current Status, and Unanswered Research Questions.” European Journal of Clinical Nutrition 74, no. 6 (June: 864–70. https://doi.org/10.1038/s41430-020-0652-1.

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Iacobellis, Gianluca. (2020) “COVID-19 and Diabetes: Can DPP4 Inhibition Play a Role?” Diabetes Research and Clinical Practice 162 (April: 108125. https://doi.org/10.1016/j.diabres.2020.108125. Klekotka, Renata Barbara, Elżbieta Mizgała, and Wojciech Król. (2015) “The Etiology of Lower Respiratory Tract Infections in People with Diabetes.” Advances in Respiratory Medicine 83, no. 5: 401–8. https://doi.org/ 10.5603/PiAP.2015.0065. Li, Fang. 2016) “Structure, Function, and Evolution of Coronavirus Spike Proteins.” Annual Review of Virology 3, no. 1 (September 29: 237– 61. https://doi.org/10.1146/annurev-virology-110615-042301. Ni, Wentao, Xiuwen Yang, Deqing Yang, Jing Bao, Ran Li, Yongjiu Xiao, Chang Hou, et al., 2020) “Role of Angiotensin-Converting Enzyme 2 (ACE2) in COVID-19.” Critical Care 24, no. 1 (December: 1–10. https://doi.org/10.1186/s13054-020-03120-0. Pal, Rimesh, and Anil Bhansali. (2020) “COVID-19, Diabetes Mellitus and ACE2: The Conundrum.” Diabetes Research and Clinical Practice 162 (April): 108132. https://doi.org/10.1016/j.diabres. 2020.108132. Seewoodhary, Jason, and Ravi Oozageer. (2020) “Coronavirus and Diabetes: An Update.” Practical Diabetes 37, no. 2: 41–42. https://doi.org/10. 1002/pdi.2260. Shang, Jian, Gang Ye, Ke Shi, Yushun Wan, Chuming Luo, Hideki Aihara, Qibin Geng, Ashley Auerbach, and Fang Li. (2020) “Structural Basis of Receptor Recognition by SARS-CoV-2.” Nature 581, no. 7807 (May): 221–24. https://doi.org/10.1038/s41586-0202179-y. Solerte, Sebastiano Bruno, Antonio Di Sabatino, Massimo Galli, and Paolo Fiorina. (2020) “Dipeptidyl Peptidase-4 (DPP4) Inhibition in COVID-19.” Acta Diabetologica, June 6, 1–5. https://doi.org/10. 1007/s00592-020-01539-z. Tikellis, Chris, and M. C. Thomas. (2012) “Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease.” International Journal of Peptides (March 20): 1–8. https://doi.org/10.1155/2012/256294.

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Tipnis, Sarah R., Nigel M. Hooper, Ralph Hyde, Eric Karran, Gary Christie, and Anthony J. Turner. (2000) “A Human Homolog of Angiotensin-Converting Enzyme: Cloning and Functional Expression as a Captopril-Insensitive Carboxy Peptidase*.” Journal of Biological Chemistry 275, no. 43 (October 27): 33238–43. https://doi.org/10.1074/jbc.M002615200. Unnikrishnan. “Diabetes and Coronavirus Disease-2019 (COVID-19).” Accessed April 5, 2021. https://www.journalofdiabetology.org/ article. asp?issn=2078-7685;year=2020;volume=11;issue= 2;spage= 52;epage= 56;aulast=Unnikrishnan#ref21. Valencia, Inés, Concepción Peiró, Óscar Lorenzo, Carlos F. SánchezFerrer, Jürgen Eckel, and Tania Romacho. (2020). “DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?” Frontiers in Pharmacology 11. https://doi.org/ 10.3389/fphar. 2020.01161. Wu, Chaomin, Xiaoyan Chen, Yanping Cai, Jia’an Xia, Xing Zhou, Sha Xu, Hanping Huang, et al., (2020). “Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.” JAMA Internal Medicine 180, no. 7 (July 1): 934–43. https://doi.org/ 10.1001/jamainternmed .2020.0994. Yang, Yongshi, Fujun Peng, Runsheng Wang, Kai Guan, Taijiao Jiang, Guogang Xu, Jinlyu Sun, and Christopher Chang. (2020). “The Deadly Coronaviruses: The 2003 SARS Pandemic and the 2020 Novel Coronavirus Epidemic in China.” Journal of Autoimmunity 109 (May 1): 102434. https://doi.org/10.1016/j.jaut.2020.102434. York, Kimberly E. Ng, Joshua P. Rickard. (2021). “The Effect of COVID19 on Patients With Diabetes.” Accessed April 5, 2021. https://www. uspharmacist.com/article/the-effect-of-covid19-on-patients-withdiabetes. Zhou, Yue, Jingwei Chi, Wenshan Lv, and Yangang Wang. (2021). “Obesity and Diabetes as High-Risk Factors for Severe Coronavirus Disease 2019 (Covid-19).” Diabetes/Metabolism Research and Reviews 37, no. 2: e3377. https://doi.org/10.1002/dmrr.3377.

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Zou, Zhen, Yiwu Yan, Yuelong Shu, Rongbao Gao, Yang Sun, Xiao Li, Xiangwu Ju, et al., (2014) “Angiotensin-Converting Enzyme 2 Protects from Lethal Avian Influenza A H5N1 Infections.” Nature Communications 5, no. 1 (May 6): 3594. https://doi.org/10.1038/ ncomms4594.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 18

PANDEMICS AND ETHNOMEDICINE Tojo Jose1,* and Sebastian Antony2 1

Centre for Research and Evaluation, Bharathiar University, Coimbatore, Tamil Nadu, India 2 Department of Botany, St. Berchmans College, Changanacherry, Kottayam, Kerala, India

ABSTRACT The term “Pandemic” is generally taken to refer to a widespread epidemic of transmissible disease throughout the whole of a country or one or more continents at the same time. Key features of pandemics are wide geographic extension, disease movement, high attack rates and explosiveness, minimal population immunity, novelty, infectiousness, contagiousness, and severity. The appearance and spread of pandemics occurred regularly throughout history. Major pandemics and epidemics that struck the human race rigorously were plague, cholera, flu, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).The world is currently affecting the new deadly disease, Coronavirus disease 2019 (COVID-19) pandemic, which is caused by SARS- Cov-2 Virus. This pathogenic virus spread all over

*

Corresponding Author’s Email: [email protected].

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Tojo Jose and Sebastian Antony the world. As it is a virus, it can extend easily and cause severe illness to humans. Several improved tactics have been taken in scientific and medicinal concern; we must consider the medicinal values of plantbased medicines to prevent many pandemic diseases.

Keywords: pandemics, MERS-CoV, SARS-CoV, COVID-19, epidemic, communicable diseases, ethnomedicine

INTRODUCTION The term “Pandemic” is derived from Greek, ‘pan’ meaning “all” and demos “the people.” The term is generally taken to refer to a widespread epidemic of transmissible disease throughout the whole of a country or one or more continents at the same time (Honigsbaum, 2009). The globally accepted definition of a pandemic as in the Dictionary of Epidemiology: “an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people” (Harris, 2000). Pandemics have numerous common constituents (Morens et al., 2009) like:     

Wide geographic extension – they are widely spatially distributed or are global Disease spread via a transmission that can be traced from location to location High attack rates and explosiveness, i.e., multiple cases appear within a short period Minimal population immunity Novelty, they are new and/ or associated with novel variants of existing organisms

The appearance and spread of communicable diseases with a pandemic nature occurred regularly throughout history. Major pandemics and epidemics such as plague, cholera, flu, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory

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syndrome coronavirus (MERS-CoV) have already distressed humanity. COVID-19, caused by SARS-CoV-2, is presently affecting the whole world. Table 1. A timeline of pandemics Sl. No.

Pandemics

Causative Agent

Years

1

Antonine plague (smallpox/measles)

Smallpox virus/ Measles virus

AD 165-180

2

Plague of Justinian

3 4

Black death Smallpox

Variola virus

5

1-6 Cholera pandemics

Vibrio cholerae (Bacteria)

6 7 8 9

Yersinia pestis (Bacteria) Influenza A/H2N5 (Virus) Influenza A/H1N1 (Virus) Influenza A/H2N2 (Virus)

11

Third Plague Russian flu Spanish flu Asian flu Seventh Cholera pandemic Hong Kong flu

12

HIV/AIDS

10

13 14 15 16 17

SARS (Severe Acute Respiratory Syndrome) Swine flu Ebola Virus Disease (EVD) MERS (Middle East Respiratory Syndrome) COVID-19

Yersinia pestis (Bacteria)

AD 541-543

Influenza A/H3N3 (Virus) Human Immunodeficiency Virus (HIV) (Virus)

AD 1347-1351 AD 1520 AD 1817-1824 AD 1827-1835 AD 1839-1856 AD 1863-1875 AD 1881-1886 AD 1889-1923 AD 1865-onwards AD 1889-1890 AD 1918-1919 AD 1957-1959 AD 1961onwards AD 1968-1970 AD 1981onwards

SARS-CoV (Virus)

AD 2002-2003

Influenza A/H1N1 (Virus)

AD 2009-2010

Ebola Virus

AD 2014-2016

Vibrio cholerae (Bacteria)

MERS CoV (Virus) SARS- Cov-2 (Virus)

AD 2015onwards AD 2019onwards

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Despite medical and public health advances, the menace of pandemics has been gradually increasing since the latter half of the twentieth century. The main cause is the processes of globalization and global change of which travel and tourism (Burkle, 2006; Hall, 2020; Allen et al., 2017).

ETHNOMEDICINE IN PANDEMICS For several centuries people have used plants for curing ailments. Plant products – as parts of foods or botanical potions and powders – have been used with varying success to cure and prevent diseases throughout history. Written records about medicinal plants date back at least 5000 years to the Sumerians (Swerdlow, 2000). The treatment based on indigenous medicinal practices is prominent in non-industrialized societies. Towards the end of the twentieth century, many cultures were dominated by plant-based treatment modalities. Many of the treatment methods and medicinal formulations have been used for a long while itself. The use of indigenous information in treating a diverse array of ailments is increasing. Plants are not only used to treat diverse ailments but also to keep and increase physical, mental, and spiritual health (Akinyemi et al., 2018). Pandemics are a part of human life. In history, the human population has been struck by various pandemics and sometimes even 20-30% of the population had been wiped out. Various treatment modalities have been executed to control and for the treatment of the pandemics. Plants and plant based medicinal formulations are often used in different periods for controlling diseases. The table projects the various pandemics, their causative organism and plants used for their treatment.

Pandemics Black Plague Dengue fever Smallpox Chikungunya Malaria Jaundice

Polio

Ebola Spanish flu

Sl. No. 1 2 3 4 5

6

7

8

9

H1N1 Influenza A virus

Ebola virus (EBOV)

Poliovirus

Causative Organism Yersinia pestis Dengue virus (DENV) Variola major, Variola minor Chikungunya virus (CHIKV) Plasmodium falciparum, P. vivax, P. ovale and P. malariae Hepatitis B virus

Asclepias tuberosa, Gelsemium sempervirens, Actea racemosa, Atropa belladonna, Eupatorium perfoliatum, Ferula assa-foetida

Plant used Allium sativum Azadirachta indica Sarracenia purpurea Andrographis paniculata Sida rhombifolia, Momordica charantia, Ricinus communis, Annona muricata Azadirachta indica, Moringa oleffera, Ocimum sanctum, Phyllanthus embilica, Trichopus zeylanicus, Verbena officinalis, Wedelia calendulacea, Withania somnifera Crysophyllum albidum, Spondias mombin, Zephyranthes candida, Khaya senegalensis, Lippia multiflora, Sida acuta, Uvaria chamae, Poga oleosa, Tetrapleura teraptera, Senna siamea, Thoningia sanguinea Nicotiana benthamiana

Table 2. Major plant-based treatments for various pandemics

Budzianowski, 2015 Lee et al., 2009 Abascal & Yarnell, 2006

Ogbole et al., 2013

References Khaytin, 2019 Parida et al., 2002 Arndt et al., 2012 Jain et al., 2020 Willcox & Bodeker 2004 Thyagarajan et al., 1988

Pandemics Swine flu

Yellow fever Zika fever

Cholera

Severe Acute Respiratory Syndrome (SARS)

Tuberculosis

Sl. No. 10

11 12

13

14

15

Mycobacterium tuberculosis

SARS-associated coronavirus (SARS-CoV)

Vibrio cholerae serogroup O1 or O139

Flavivirus Zika virus (ZIKV)

Causative Organism H1N1 virus

Ocimum basilicum, Acacia farnesiana, Artemisia ludoviciana Andrographis paniculata, Tinospora cordifolia, Chrysopogon zizanoides, Cyperus rotundus, Santalum album, Mollugo cerviana, Trichosanthes cucumerina, Piper nigrum, Zingiber officinale. Haemanthus albiflos, Clausena anisata and Artemisia afra

Plant used Ocimum sanctum, Ocimum basilicum, Zingiber officinale, Alium sativum, Phyllanthus emblica, Aloe vera, Tinospora cordifolia, Glycyrrhiza glabra, Andrographis paniculata, Withania somnifera, Curcuma longa, Azadirachta indica, Aegle marmelos, Trachyspermum ammi, Mentha piperita, Terminalia chebula, Camellia sinensi Enantia chlorantha Doratoxylon apetalum

Table 2. (Continued)

Lawal, et al. 2014

Fasola et al., 2011 Haddad et al., 2019 Sánchez, et al. 2010 Lakshmi et al., 2020

References Shah, & Krishnamurthy, 2013

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COVID-19 COVID-19 is caused by severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). In the 21st century, the human population has been rigorously affected by the pandemic covid-19 virus. Coronaviruses are nonsegmented, enveloped viruses with single-stranded RNA (ssRNA) ranging between 26 to 32 kb in length. Electron microscopy (EM) of negative-stained SARS-CoV-2 particles exposed their spherical shape, with the diameter ranging from 60–140 nm and an outer surface with distinctive 9 to 12-nm–long spikes (Zhu et al., 2020). Coronaviruses use an RNA-dependent RNA polymerase (RdRp) complex to replicate their genome and transcription of their genes (Snijder et al., 2016).This pandemic has a wide range of repercussions in all aspects of human life. Although the vaccine has been proved effective to control the disease, diverse indigenous and plant-based treatment modalities have been practised at various parts of the world. In Africa, indigenous treatment methods have been practised to control the spread of COVID 19. The plant Artemisia annua is used for the treatment (WHO, 2020). The medicinal formulations embedded on plants namely Glycyrrhizae uralensis, Artemisia annua, Lindera aggregate, Agastache rugosa, Astragalus membranaceus, Pyrrosia lingua, Ecklonia cava, Gymnema sylvestre, Polygonum multiflorum, Houttuynia cordata, Lycoris radiata, Mollugo cerviana, Tinospora cordifolia, Saposhnikoviae divaricate and Cassia alata have a wide range of therapeutic applications (Adhikari, B. et al., 2021). Nepal is famous for its folk medicine and many traditional treatment methods. The plant species Zingiber officinale is used effectively against the treatment of covid -19 (Khadka, D. et al., 2020). The plants Pyrrosia lingua, Lycoris radiate and Artemisia annua are effectively used against severe respiratory ailments and is used in treatment modalities of covid-19 (Li et al., 2005).

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ADVANTAGES OF PLANT-BASED FORMULATIONS IN PANDEMICS Plant based medicines have become a popular form of healthcare worldwide. Herbal formulations have been the most effective treatment for various infectious diseases. Herbal medicines are of a broader therapeutic index. They are also inexpensive and easily available. They also have better reception from the patients (Sarojini et al., 2020). Herbal medicines are considered natural and safer and less or no side effects (Ahmad and Sharma, 2020). Many research outcomes record the use plant based medicinal formulations for dealing with ailments ranging from common influenza to cancer. Since herbal formulations are rich in antioxidants, they can control the growth of cancerous tissue and reduce the risk of cardiovascular ailments. Many of the medicinal plants used in herbal formulations for the treatment of pandemics improve the overall immunity of the body. The fibre content can reduce the cholesterol level in the blood and stabilize the blood sugar. Being easily accessible, affordable and having promising results, herbal remedies become common exclusively among marginalized populations.

CONCLUSION An epidemic that has a global sphere of expansion is called a pandemic. The sphere of influence crosses countries and even continents, and the sphere of infection is intense and cataclysmic. At regular intervals, the world has been struck by pandemics and sometimes wiped out even 20 – 30% of the human population. Some of the major pandemics that have catastrophic outcomes in the human race were Plague, Cholera, Asian flu (H2N2), Spanish flu (H1N1), Severe Acute Respiratory Syndrome (SARS), Swine flu (H1N1), Hong Kong flu (H3N3) and Middle East Respiratory Syndrome (MERS). The Spanish flu has eradicated 100 million of the human population during its

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catastrophic outbreak. The present generation is under the tragic ramifications of the COVID-19 pandemic. Pandemics have their repercussions in all facets of human life. It has its disastrous corollaries in the social relationships, healthcare, economy and even the mental state of the people. A considerable fraction of the human race, exclusively the economically marginalized portions, is at a stage of tumbling into extreme poverty owing to the COVID-19 pandemic. Hence, it is a need of the hour to mould measures to control and reduce the spread of pandemics and cast treatment modalities with minimal side effects and easy access to the common man. For a long time in history, the human population is in a deep association with indigenous treatment methods. Treatment methods engrained on plant-based formulations have been used for a long time to control and treat pandemics. In this track, ethnomedicine is of paramount importance. As the term indicates, ethnomedicine is linked to indigenous populations. In ethnomedicine, there is an incorporation of indigenously practised treatment approaches in dealing with ailments. The treatment modalities solely embedded in plant rooted medicinal formulations is the core of ethnomedicine. Many of the indigenous populations harbour unique treatment experiences for various ailments. When we trace back to the treatment methods engulfed for different pandemics at different periods, the records point out that medicinal formulations purely entrenched in plant extracts gained from different indigenous settlements were used to treat and control the spread of pandemics. Research has revealed that treatment modalities ingrained in herbal formulations aided the treatment of epidemics/pandemics like Spanish flu, Swine flu, Ebola, Cholera, Severe Acute Respiratory Syndrome (SARS), Smallpox, Tuberculosis etc. A hand full of herbal remedies has been practised globally for the treatment and control of the COVID-19 pandemic. Some plants used in the medicinal formulations are Glycyrrhizae uralensis, Artemisia annua, Lindera aggregate, Agastache rugosa, Astragalus membranaceus, Pyrrosia lingua, Ecklonia cava, Gymnema sylvestre, Polygonum multiflorum and many more. The information gathered by this study is a footing stone for new research in the field of drug innovations for COVID-19.

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REFERENCES Abascal, K., and Yarnell, E. 2006. Herbal treatments for pandemic influenza: learning from the eclectics’ experience. Alternative & Complementary Therapies, 12(5), 214-221. Adhikari, B., Marasini, B. P., Rayamajhee, B., Bhattarai, B. R., Lamichhane, G., Khadayat, K., Adhikari, A., Khannal, S. & Parajuli, N. 2021. Potential roles of medicinal plants for the treatment of viral diseases focusing on COVID‐19: A review. Phytotherapy Research. 35(3):1298-1312. Ahmad, Aminu Saleh, and Ruchi Sharma. 2020. “Comparitive Analysis of Herbal and Allopathic Treatment systems.” European Journal of Molecular & Clinical Medicine, no. 7 :2869-2876. Akinyemi, O., Oyewole, S. O., & Jimoh, K. A. 2018. Medicinal plants and sustainable human health: a review. Horticulture International Journal, 2(4), 194-195. Alagu Lakshmi, S., Shafreen, R. M. B., Priya, A., & Shunmugiah, K. P. 2020. Ethnomedicines of Indian origin for combating COVID-19 infection by hampering the viral replication: using structure-based drug discovery approach. Journal of Biomolecular Structure and Dynamics, 1-16. Allen, T., Murray, K. A., Zambrana-Torrelio, C., Morse, S. S., Rondinini, C., Di Marco, M., Breit, N., Olival, K. J., & Daszak, P. 2017. Global hotspots and correlates of emerging zoonotic diseases. Nature Communications, 8(1), 1124. https://doi.org/10.1038/s41467-01700923-8. Arndt, W., Mitnik, C., Denzler, K. L., White, S., Waters, R., Jacobs, B. L., et al., 2012. In vitro characterization of a nineteenth-century therapy for smallpox. PloS One 7, e32610. doi: 10.1371/journal.pone. 0032610. Budzianowski, J. 2015. Tobacco against Ebola virus disease. Przeglad lekarski, 72(10), 567- 571.

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Burkle, F. M. Jr, 2006. Globalization and disasters: Issues of public health, state capacity and political action. Journal of International Affairs, 59(2), 231–265. Fasola, T. R., Adeyemo, F. A., Adeniji, J. A., & Okonko, I. O. 2011. Antiviral Potentials of Enantia chlorantha Extracts on Yellow Fever Virus. Nature and Science. 9 (9). 99-105. Haddad, J. G., Koishi, A. C., Gaudry, A., Nunes Duarte dos Santos, C., Viranaicken, W., Desprès, P., & El Kalamouni, C. 2019. Doratoxylon apetalum, an indigenous medicinal plant from Mascarene Islands, is a potent inhibitor of Zika and dengue virus infection in human cells. International journal of molecular sciences, 20(10), 2382. Hall, C. M. 2020. Biological invasion, biosecurity, tourism, and globalization. In D. Timothy (Ed.), Handbook of globalization and tourism (pp.114-125). Edward Elgar. Honigsbaum, M. 2009. Historical keyword Pandemic. The Lancet, 373. Jain J., Kumar A., Narayanan V., Ramaswamy R S., Sathiyarajeswaran P., Devi MS., Kannan M., Sunil S. 2020. Antiviral activity of ethanolic extract of Nilavembu Kudineer against dengue and chikungunya virus through in vitro evaluation. J. Ayurveda Integr. Med. 11, no. 3: 329-335. Khadka, D., Dhamala, M. K., Li, F., Aryal, P. C., Magar, P. R., Bhatta, S., & Cui, D. 2020. The Use of Medicinal Plant to Prevent COVID19 in Nepal. Khaytin. 2019. ArcGIS StoryMaps. Herbal Medicine in the Black Plague. https://storymaps.arcgis.com/stories/4a9ae6b9dcc1460b8e9 7775b285592e9. Lawal, I. O., Grierson, D. S., & Afolayan, A. J. 2014. Phytotherapeutic information on plants used for the treatment of tuberculosis in Eastern Cape Province, South Africa. Evidence-Based Complementary and Alternative Medicine.1-11. Lee, C. L., Chiang, L. C., Cheng, L. H., Liaw, C. C., Abd El-Razek, M. H., Chang, F. R., & Wu, Y. C. 2009. Influenza A (H1N1) antiviral and cytotoxic agents from Ferula assa-foetida. Journal of natural products, 72(9), 1568-1572.

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Li, S. Y., Chen, C., Zhang, H. Q., Guo, H. Y., Wang, H., Wang, L., ... & Tan, X. 2005. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral research, 67(1), 18-23. Lin, L. T., Hsu, W. C., & Lin, C. C. 2014. Antiviral natural products and herbal medicines. Journal of traditional and complementary medicine, 4(1), 24-35. Morens, D. M., Folkers, G. K., & Fauci, A. S. 2009. What is a pandemic? The Journal of Infectious Diseases, 200(7), 1018–1021. https://doi. org/10.1086/644537. Ogbole, O. O., Adeniji, J. A., Ajaiyeoba, E. O., & Adu, D. F. 2013. Antipolio virus activity of medicinal plants selected from the Nigerian ethno-medicine. Academic Journals, 12(24), 3878-3883. Parida M. M. 2002. Inhibitory potential of neem (Azadirachta indica Juss.) leaves on dengue virus type-2 replication. J. Ethnopharmacol. 79:273–278. Sánchez, E., García, S., & Heredia, N. 2010. Extracts of edible and medicinal plants damage membranes of Vibrio cholerae. Applied and Environmental Microbiology, 76(20), 6888-6894. Sarojini K, Lakshminarayanan A., Smiline G. 2020. Herbal formulation: Review of efficacy, safety, and regulations. IJRPS, 11 (SPL3), 15061510. Shah, A., & Krishnamurthy, R. (2013). Swine flu and its herbal remedies. Int. J. Eng. Sci., 2(5), 68-78. Snijder E J, Decroly E, Ziebuhr J. The Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing. Adv. Virus Res. 2016; 96: 59–126. https://doi.org/10.1016/bs.aivir.2016.08.008 PMID: 277126 28. Swerdlow, J. 2000. Nature’s Medicine. Plants That Heal, National Geographic Society. Thyagarajan, S. P., Jayaram, S., Gopalakrishnan, V., Hari, R., Jeyakumar, P., & Sripathi, M. S. 2002. Herbal medicines for liver diseases in India. Journal of Gastroenterology and Hepatology, 17, S370-S376.

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Willcox, M. L., & Bodeker, G. 2004. Traditional herbal medicines for malaria. BMJ, 329(7475), 1156-1159. Zhu N, Zhang D, Wang W, Li X, Yang B, et al., A Novel Coronavirus from Patients with Pneumonia in China. 2019. N Engl. J. Med. 2020; 382: 727–733. https://doi.org/10.1056/NEJMoa2001017PMID:3197 8945.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 19

IDENTIFICATION OF ACTIVE PLANT CONSTITUENTS TO INHIBIT SARS-COV-2 BY MOLECULAR DOCKING STUDIES: A COMPREHENSIVE REVIEW M. Deepak1,2*, C. T. Sulaiman1, Indira Balachandran1 and Subhash Chandran K. Parameswaran3 1

Centre for Medicinal Plants Research, Kottakkal Arya Vaidya Sala, Kerala, India 2 Research and Development Centre, Bharathiar University, Tamil Nadu, India 3 Kerala University for Fisheries and Ocean Studies, Kerala, India

ABSTRACT The present world is witnessing a pandemic disease caused by a new strain of corona virus called COVID-19.The new strain of corona virus has got a worldwide attention and affected directly or indirectly *

Corresponding Author’s Email: [email protected].

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M. Deepak, C. T. Sulaiman, Indira Balachandran et al. almost whole of the world population. It is a serious respiratory viral disease by SARS-CoV-2 appeared as a pandemic at the end of 2019 in China.Though several preventive vaccines to lessen the cases of serious hospitalizations have already been developed, a specific drug against COVID-19 is still under research. This emerging health crisis calls for the urgent development of specific therapeutics to fight against COVID-19 to reduce the burden of this pandemic. Medicinal plants are getting more recognition in the present scenario due to the non availability of synthetic medicines. We have identified certain important active compounds from selected medicinal plants, used in Ayurveda with proven anti viral properties, like Holostemma-adakodien, Barleria strigosa and Canscora perfoliata as a part of our research on screening active constituents. In the present paper anti-viral activity of certain identified compounds from the selected plants by molecular docking method against COVID-19 was collected. The identified compounds such as 7-hydroxy-6-methoxycoumarin (scopoletin), 3,4-dihydroxycinnamic acid (caffeic acid), 3,3',4',5,7pentahydroxyflavone (quercetin), (2S,3R)-2-(3,4-dihydroxyphenyl) chroman-3,5,7-triol (catechin), 3-caffeoylquinic acid (chlorogenic acid), mangiferin and palmatine were selected for the present study. The identified compounds were found very effective in inhibiting the new corona virus as per the studies conducted. This comprehensive review will hopefully pave a way for development of phytoconstituent based antiviral therapeutic agent for treatment or prevention of COVID-19.

Keywords: Holostemma ada-kodien, Barleria strigosa, Canscora perfoliata, COVID-19, molecular docking method

INTRODUCTION The present world is witnessing a pandemic disease caused by a new strain of corona virus called COVID-19. The new strain of corona virus has got worldwide attention and affected directly or indirectly almost whole of the world population. Currently there is no specific drug against COVID-19 except vaccines. It is a serious respiratory disease due to SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona virus) and was primarily reported in China during the last months of 2019 later it was emerged as a pandemic worldwide. By the July 2020, covid has affected more than 200 territories, infecting more than 13 million

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individuals (Du et al., 2020). COVID-19 has marked the history with third life-threatening corona virus epidemic into the human population during 21stcentury (Guo et al., 2020). Chinese scientists released the sequenced SARS-CoV-2 genome for the identification and development of potential drug candidates against COVID-19 by computational methods and other therapeutic techniques (Lu et al., 2020). As the adverse effect of the pandemic in world economy and health is such tragic that therapeutics against the causative organism and related viral infestations is in high demand. Herbal based drug discovery is the main area majority are focusing since plenty of reliable traditional medicines are available against the severe symptomatic conditions of the disease. This present study aimed to review the anti-viral efficacy of natural bioactive compounds isolated from certain medicinal plants using in Ayurveda against COVID-19 via molecular docking and molecular the dynamics simulation.

PARTICULARITIES OF THE VIRUS The SARS-CoV-2 is a β-coronavirus, enveloped and positive senseRNA virus, with ~30 kb genome. SARS-CoV-2 genome possesses a complex organization encoding various structural as well as nonstructural proteins (Nsps). Majority part of viral genome (replicase ORF1ab encompassing Nsps) is translated into two overlapping polyproteins known as pp1a and pp1ab. These polypeptides also codes for ~306 amino acid long main protease (Mpro) which digests polypeptides at various conserved sites yielding 16 functional viral Nsps possessing multiple enzymatic activities especially in viral replication. One of such enigmatic protein, Nsp15, is an endoribonuclease known to be indispensable for protein interference during innate immune response. Due to functional importance of Mproand Nsp15 in viral replication and survival, both could be potential therapeutic drug targets to combat COVID-19. In addition to Nsps, SARS-CoV-2 genome also consists of structural protein encoding genes including S (spike) gene, E gene (viral

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envelop protein), and N (nucleo-capsid protein) gene. Viral spike proteins possess strong affinity with the human ACE2 (angiotensin-converting enzyme 2) receptor by which virus fuses with target membrane to gain entry into human cells (Adem et al., 2020).

REMEDIES FROM PLANT SOURCES This emerging health crisis calls for the urgent development of specific therapeutic agents against COVID-19 to potentially reduce the burden caused. Medicinal plants were getting more recognition in the present scenario because of the non availability of synthetic medicines. We have identified certain important active compounds from selected medicinal plants used in Ayurveda as a part of our research on screening active constituents.In the present paper anti-viral activity of the identified compounds by docking method was against COVID-19 was collected. The selected plants were Holostemma-ada-kodien, Barleria strigosa and Canscora perfoliata. The compounds identified from H. ada-kodien were Urs-12-en-3β-ol, 3β-Hydroxy-20(29)-lupene, 22,23-Dihydrostigmasterol, Lup-20(29)-ene-3β,28-diol, 3β-Hydroxy-12-ursen-28-ic acid, 7-Hydroxy6-methoxycoumarin, 3,4-Dihydroxycinnamic acid. Among these compounds 7-Hydroxy-6-methoxycoumarin (scopoletin) and 3,4Dihydroxycinnamic acid (caffeic acid) were selected. The compounds identified from B. strigosa were Lup-20(29)-en-3β-ol, 22,23dihydrostigmasterol, Lup-20(29)-ene-3β,28-diol, 3-β-hydroxyolean-12en-28-oic acid, 3,3',4',5,7-pentahydroxyflavone, (2S,3R)-2-(3,4dihydroxyphenyl)chroman-3,5,7-triol, 3-caffeoylquinic acid. 3,3',4',5,7Pentahydroxyflavone (quercetin), (2S,3R)-2-(3,4-dihydroxyphenyl) chroman-3,5,7-triol (catechin) and 3-caffeoylquinic acid (chlorogenic acid) were selected for the study. The compounds like mangiferin, plamatine and caffeic acid was identified from C. perfoliata and mangiferin and plamatine were selected for the present study.

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Caffeic Acid Previous reports have established the worth of polyphenols as lead compounds for drug discovery against various viral diseases (DosSantos et al., 2018). Recent studies were reported that polyphenol compounds have potential to combat with COVID-19 also (Ademetal., 2020). Caffeic acid is one among the abundant plant-based hydroxy cinnamic acid possessing 2 phenolic hydroxyl moieties. In a study caffeic acid and its derivatives were screened for the identification of novel anti-COVID-19 compounds against various SARS-CoV-2 drug targets including COVID19 Mpro(6LU7), SARS-CoV-2 S2 subunit (6LXT), Nsp15 endoribonuclease (6VWW), SARS-CoV-2 spike ectodomain open state structure (6VYB), and SARS-CoV-2 spike closed state glycoprotein structure (6VXX). And the study lead to in silico-based identification of caffeic acid as potent modulators of COVID-19 Mpro, Nsp15, coronavirus fusion protein, spike open state and closed state structure respectively (Adem et al., 2020). In another study caffeic acid and its derivatives were tested against the HSPA5 substrate-binding domain β (SBDβ), which reported to be the recognition site for the SARS-CoV-2 spike. The results showed high to a moderate binding affinity for caffeic acid to the HSPA5 SBDβ. Based on its binding affinity, it may interfere with SARS-CoV-2 attachment (Elfiky 2020). It was found that compound can bind to the substrate-binding pocket of SARS-CoV-2 Mpro with efficacy and binding energies equivalent to an already claimed N3 protease inhibitor. Similar to N3 inhibitor, caffeic acid derivative was interacting with the highly conserved residues of the proteases of corona viruses. The findings will provide valuable data for exploration and development of caffeic acid-derivatives as lead structures, novel therapeutic and prophylaxis agents against COVID-19 in the near future (Kumar 2020).

Scopoletin Coumarins are a main class of natural compounds and potential drug candidates owing to its properties of stability, solubility, and low toxicity.

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Scopoletin is a hydroxy coumarin. There are numerous evidences showing its inhibitory role against infection of various viruses such as Influenza. The mechanisms involve either inhibition of proteins essential for viral entry, replication and infection or regulation of cellular pathways.

Quercetin Flavonoids were active natural compounds with various important pharmaceutical activities. Flavonols are one of the important classes of compounds in flavonoids. Quercetin is an important flavonol. Many natural flavonoids were tested in silico for their pharmacokinetic properties and were validated as having druglike nature. Quercetin, interact on the spike proteins’ key RBD and may inhibit spread to receptors limiting viral spread. It displayed strong interactions on SARSCoV-2 proteins such as Mpro at Glu290 and Asp289, as well as on receptor binding domain of the viral spike based on the computational analysis. Hence, Quercetin can consider as an exceptional candidate for further studies (Vijayakumar et al., 2020). Another study suggested that quercetin as the most recommended compound found in medicinal plants that may act as potential inhibitors of COVID-19 Mpro. However, further research is necessary to investigate the potential uses of the medicinal plants containing these compounds (Khaerunnisa et al., 2020). A previous study investigated flavonoids for their in silico potential to bind with the active catalytic site of the main protease (3CLpro) of SARSCoV and SARS-CoV-2. And quercetin was included in the top 10 flavonoids identified. Group sequential and adaptive clinical trials should be rapidly initiated though compassionate use to establish synergistic efficacy for one of more these flavonoids used in combination with antivirals. The flavonoids are available as supplements, and could be consumed in moderation to maintain prophylactic protection from SARSCoV-2 (Peterson 2020).

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Catechin A study through computational approaches reported that catechin which have dual binding affinity, i.e., both the molecule binds to viral Sprotein and as well as ACE2. Catechin binds with S-protein and ACE2 with binding energy of -10.5 Kcal/mol and -8.9 Kcal/mol, respectively. Catechin binds with S-protein near the RBD site and causes fluctuation in the amino acids present in the RBD and it’s near proximity. In conclusion, the computational study predicts the possibility of catechins, for therapeutic/preventive intervention (Jena et al., 2021). Another study identified that pharmacokinetic profile of catechin is relatively better than all control ligands with the lowest toxicity. Molecular docking results also showed that catechin and their derivatives have a stronger affinity than control ligands. This research proved that catechin has antiviral potential through inhibition of Mpro protein and Spike glycoprotein COVID-19 virus (Frengki et al., 2021).

Chlorogenic Acid In a study chlorogenic acid was tested against the HSPA5 substratebinding domain β (SBDβ), which reported to be the recognition site for the SARS-CoV-2 spike. The results show high to a moderate binding affinity for chlorogenic acid, to the HSPA5 SBDβ (Elfiky 2020). Through the protein docking between S-protein and ACE2, it is found that Glu329/Gln325 and Gln42/Asp38 in ACE2 play an important role in the binding process of the chlorogenic acid. The results of molecular docking virtual calculation showed that chlorogenic acid could stably combine with Gln325 and Gln42/Asp38 in ACE2, respectively, which hindered the combination between S protein and ACE2. It can conclude that chlorogenic acid can be used as potential inhibitors of COVID-19 for further research and development (Yu et al., 2020).

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Palmatine A study investigated the potential activity of palmatine against Mpro. The SwissDock server was used to perform docking between validated targets Mpro with ligand palmatine. The significant ΔG value -8.281919 kcal·mol-1 indicates reliable docking interaction. Comparative docking among suggests palmatine interacts efficiently with Mpro. Thus, by this attempt it was identified asa potent inhibitor, as there is no promising and specific antiviral drug or vaccine available for the prevention and treatment of COVID-19 disease (Jadhav 2020).

Mangiferin Mangiferin is a xanthone glycoside with diverse pharmacological activities.It showed many antiviral activities in previous studies. A previous docking study exhibited that mangiferin, has significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells (Chauhan and Kalra 2020). Another study proposed that mangiferin has a better binding affinity to Mpro of COVID-19 than the famous antiviral drugs like hydroxyquinone, flavipiravir and ramdesivir (Vimal et al., 2020).

CONCLUSION The present review included the antiviral activity of selected active compounds against SARS-CoV-2, identified from certain medicinal plants using in Ayurveda. This comprehensive review will hopefully pave a way for development of phytoconstituent based antiviral therapeutic agent for treatment or prevention of COVID-19. Further studies are recommended to evaluate the antiviral effects of these

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phytochemicals against SARS-CoV-2 by in vitro and in vivo models to formulate a new drug competitor.

REFERENCES Adem, Ş., Eyupoglu, V., Sarfraz, I., Rasul, A., Zahoor, A. F., Ali, M., Abdalla, M., Ibrahim, I. M., Elfiky, A. A. 2020. Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19. Phytomediciene. doi:https://doi.org/10.1016/j.phymed. 2020.153310. Chauhan, A., Kalra, S. 2020. Identification of potent COVID-19 main protease (MPRO) inhibitors from flavonoids. Preprint. doi: 10.21203/rs.3.rs-34497/v1. Du, R.H., Liang, L.R., Yang, C.Q., Wang, W., Cao, T.Z., Li, M., Guo, G.Y., Du, J., Zheng, C.L., Zhu, Q., Hu, M., Li, X.Y., Peng, P., Shi, H.Z. 2020. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. European Respiratory Journal. 55, 5. doi:10.1183/13993003.005242020. Elfiky, A. 2020. Natural products may interfere with SARS-CoV-2 attachment to the host cell. doi: 10.21203/rs.3.rs-22458/v1. Frengki, F., Deddi, P. Putra, Fatma Sri Wahyuni, Daan Khambri, Henni Vanda, Vivi Sofi. 2020. Antiviral of catechins and their derivatives to inhibit sars-cov-2 receptors of mpro proteinand spike glycoprotein in covid-19 through the in silico approach. Jurnal Kedokteran Hewan 14, 3, 59-65. doi: https://doi.org/10.21157/j.ked.hewan.v14i3.16652. Guo, Y.R., Cao, Q.D., Hong, Z.S., Tan, Y.Y., Chen, S.D., Jin, H.J., Tan, K.S., Wang, D.Y., Yan, Y. 2020. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Military Medicine Research. 7, 11.doi:10.1186/s40779-020-00240-0.

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Jadhav, V. A., Sujata Ingle, Ahmed, R. 2020. Inhibitory activity of palmatine on main protease complex (mpro) of sars-cov-2. Preprint. doi: 10.21203/rs.3.rs-38145/v1. Jena, A. B., Namrata Kanungo, Vinayak Nayak, G.B.N. Chainy, Jagneshwar Dandapat. 2021. Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention, Preprint. doi: 10.21203/rs.3.rs-22057/v1. Khaerunnisa, S., Hendra Kurniawan, Rizki Awaluddin, Suhartati Suhartati, Soetjipto Soetjipto. 2020. Potential Inhibitor of COVID-19 Main Protease (Mpro) from Several Medicinal Plant Compounds by Molecular Docking Study. Preprint. doi:10.20944/preprints202003. 0226.v1. Kumar, V., Jaspreet Kaur Dhanjal, Sunil C. Kaul, Renu Wadhwa & Durai Sundar. 2020. Withanone and caffeic acid phenethyl ester are predicted to interact with main protease (Mpro) of SARS-CoV-2 and inhibit its activity. Journal of Biomolecular Structure and Dynamics. doi: 10.1080/07391102.2020.1772108. Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., Chen, J., Meng, Y., Wang, J., Lin, Y., Yuan, J., Xie, Z., Ma, J., Liu, W.J., Wang, D., Xu, W., Holmes, E.C., Gao, G.F., Wu, G., Chen, W., Shi, W., Tan, W. 2020. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 395, 565574.doi: https://doi.org/10.1016/S0140-6736(20)30251-8. Peterson, L. E. 2020. COVID-19 and Flavonoids: In Silico Molecular Dynamics Docking to the Active Catalytic Site of SARS-CoV and SARS-CoV-2 Main Protease. Preprint May. doi: 10.13140/RG.2.2. 22294.50246. Vijayakumar, B. G., Deepthi Ramesh, Annu Joji, Jayadharini Jayachandra prakasan, Tharanikkarasu Kannan. 2020. In silico pharmacokinetic and molecular docking studies of natural flavonoids and synthetic indole chalcones against essential proteins of SARS-

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CoV-2. European Journal of Pharmacology 886, 173448. doi: 10.1016/j.ejphar.2020. 173448. Vimal K. Maurya, Swatantra Kumar, Anil K. Prasad, Madan L. B. Bhatt, Shailendra K. Saxena. 2020. Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor. Virus Disease 31, 2, 179-193. doi: http://scihub.tw/10.1007/s13337-020-00598-8. Yu, J. W., Lu Wang, Li-dao Bao. 2020. Exploring the active compounds of traditional Mongolian medicine in intervention of novel coronavirus (COVID-19) based on molecular docking method. Journal of Functional Foods 71, 104016. doi: https://doi.org/ 10.1016/j.jff.2020.104016.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 20

PANDEMICS IN EUROPEAN LITERATURE: A REVIEW Temina Cyriac Department of English, Alphonsa College Pala, Kerala, India

ABSTRACT Mystery has always been an energy booster for literature. It has dealt with death, love, suffering, ecstasy and all of the deepest feelings in life. It can go deeper than the historical reflections of life. As life is the subject matter of literature it includes the pandemics that affected human race from its beginning. Literature invites a reader to reflect on the fear humans feel towards pandemics and death, but it also consoles the human race about the afterlife of pandemics. The aim of literary texts on pandemics is to convey the message to humanity that every person born into this world has a natural right to sustain, preserve and defend, as said in The Decameron. Pandemic literature also helps in building a platform to share the common humanist concerns and provides unity for humanity. It sometimes allows the human mind to avert from the meaninglessness of life and provides a hope that life can still go on even if half or more of the world population has been 

Corresponding Author’s Email: [email protected].

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Temina Cyriac eradicated. Pandemic literature reminds us that if there is no meaning of life outside the quarantine zone, we should create our own invented stories to create meaning. The unpredictability of origin, cause of illness and arbitrariness of the path of death makes us realise that bacteria is more powerful than a nuclear weapon. Stories of pandemic are a way of telling the entire human race about its fragile nature. Every human being holds a path to the kingdom of wellness as well as kingdom of illness. The paper explores how different works produced in impacts of pandemics in different times helps people to understand the absurdity of life as well as to seek ways to heal themselves.

Keywords: literature, pandemics, survival, hope, society

INTRODUCTION Pandemics have always been a subject for literature. Art reflects the culture. Literature is the story of human life enhanced with imagination and the desire to be fulfilled. Human conditions always intertwine with pandemics. Pandemics thus have been always a subject for literature. When a pandemic strikes the world, it brings a threat to human existence. The fear about life and civilization can modify human behaviour. This aspect of the human experience is best shown through literature. No historical or medical narrative tries to pen down the emotions and fears of human beings about pandemics. Fiction can recount the human experience along with the social implication in a vivid manner. Pandemic fiction holds up a mirror of our deepest fears about diseases and death. It helps in exploring the dimensions of the fears associated with diseases. Pandemic fiction can be apocalyptic as well as historiographic in nature. Pandemics both in fiction and real life help the world to understand the fragility of social and cultural boundaries. These fictions make us think or restructure the way humans see the world. The state of being in a disease deconstructs the homocentric world. Pandemic fiction has been a favourite area for European literature. From its beginning till now there are fictions about pandemics and its effect on humanity.

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PANDEMIC FICTIONS A pandemic that has appeared several times in European literature is the plague. Boccaccio’s Decameron tells the tale of recreation of a city from a terrific pandemic known as the Bubonic plague. “Boccaccio’s The Decameron (1353) presents pictorial tropes of Black Death in the 14th century: parents refused to nurse “their own children.” (Abdal 2) The cause of the plague according to Boccaccio is divine punishment or celestial influence. It also gives account of the social distancing and personal hygiene carried out in the city. The officials removed waste and banned people who are infected from entering the city. Through the work, Boccaccio paints all types of people during the time of pandemics. Some people obey the law and keep their distance from everyone, taking conservative measures such as self-isolation, eating and drinking moderately, and shutting out outsiders. Some others without any regard to the law roam around freely, satisfying their needs of food and fun. There was another group of people who excluded contact with the infected, but they wandered freely. Through all these paintings of the society Boccaccio tries to lament on moral degradation and the human suffering. Decameron is considered as the finest example of mediaeval plague literature. It is even now cited by physicians and scholars for its depiction of the disease. He begins the novel with “in the year, then our lord, 1348, there happened at Florence, the finest city in all Italy, a most terrible plague” (Boccaccio 5). From there onwards, many novels and literary works came with the theme of pandemics. In Chaucer’s Canterbury Tales, “Pardoner's Tale” gives an account of the plague; the Black Death. A man is instantly murdered by a man called Death who has killed thousands already. Here, the word death becomes a synonym with pandemic. The 15th and 16th centuries saw many books on pandemics in European literature. Some of them are Cronaca Modenense in the early sixteenth century by Thommasino de Bianchi who was an Italian chronicler. It was a first-hand account of the disease we now call influenza. His account of the disease, its origin and effects gave us an understanding of the history of influenza in 16th

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century Europe. Bianchi, who documented the 1510 pandemic, gave insights into how they looked upon it. Annalia Francisi Muralti, Jean Bouchet, Les Annales, Daquitaine are examples of writers related to pandemics in the 15th and 16th centuries. A Journal of the Plague Year is a book by Daniel Defoe published in 1722. It is the account of one’s experience in the year 1665 which was struck by plague in London which is known as the Great Plague of London. He describes the pains on streets and houses. The Last Man is an apocalyptic dystopian science fiction novel by Mary Shelley which describes about a new pandemic of a mysterious disease which ultimately results in the destruction of humanity. Mary Shelley’s novel The Last Man was published in 1826 and it describes 21st century Earth. The Scarlet Plague by Jack London was a fine example of post-apocalyptic fiction in modern European literature. The motif of plague in the novel reflects the fear of humans towards the diseases and death. When plague spreads in the world, immense fright was in the minds of people. The personification of the plague intensifies the effect of people who are plagued by death. The pandemic breaks the class barriers in London, but it also ruined the civilization. The novel gives the message that human brotherhood enables society to survive. “All a man could win in the conflict between plague and life” says Camus “was knowledge and memories” (Lombardi). The Plague is a novel by Albert Camus that was published in 1947. It tells the story of a plague sweeping the French Algerian city of Oran. Camus used the Cholera epidemic which killed a large proportion of people in France. This book is considered an existentialist classic. The citizens of the city of Oran are affected by plague and they are under quarantine. According to Camus, human beings are mortal lives under absurd death sentences. For him, what gives meaning to life is to fight death and suffering. So, the anti-pandemic efforts seem of little difference, but this novel portrays the value of optimism in times of hopelessness. Fighting against an epidemic is rebelling against death. So, the fight against pandemics becomes more meaningful. When the plague strikes the city of Oran, people started to search for the reason for the calamity. They dove into

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their past to find the cause of the disease but they understood that only hope can outlive the situation. Doctor Juvenile Urbino of the novel Love in the Time of Cholera is a character who is devoted to science and tries to eradicate Cholera from the world. In the novel, the condition of the epidemic is clearly shown. “After the first two weeks of the Cholera epidemic the cemetery was overflowing and there was no room left in the churches. Despite the fact that they had dispatched the decayed remains of many nameless Civic heroes to the communal ossuary.” (Garcia). Edgar Allan Poe's short story “The Masque of The Red Death” published in 1842 is a story about a prince who tries to avoid a deathly plague known as the Red Death by hiding in his abbey. The disease Red Death is open to much interpretation. Some critics address it as tuberculosis where some others see it as Cholera, because Poe witnessed an epidemic of Cholera in Baltimore in 1831. Some suggest that it can be the Bubonic plague emphasizing the Red Death and the black room at the climax. Pale Horse Pale Rider by Katherine Anne porter 1939 is about the pale rider Death who takes away an entire era. The story revolves around Miranda and others during the influenza epidemic of 1918. The story is set in Denver, Colorado. The title has a biblical reference from Revelation 6:1-8. “The four horsemen of the apocalypse are Conqueror on a white horse, War on a red horse, Famine on a black horse, and Death on a pale horse.” Station Eleven by Emily Saint John Mandel portrays the Great Lakes region before and after a pandemic strikes it. The pandemic is the Georgia flu which has killed most of the population. As the Georgian flu wreaks all through the country, the whole population evacuates. But, the work gives an ultimate hope focusing on the way art endures. The Andromeda Strain 1969 by Michelle Christian tells the story of the efforts of a team of scientist investigating the outbreak of deadly extra-terrestrial microorganism in Arizona. The deadly microorganism that came through a satellite kills people by instantaneous blood clotting. The microbe contains chemical elements but lacks DNA, RNA, proteins

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and amino acids. Scientists have given the name Andromeda for the microorganism. The story revolves around efforts to destroy Andromeda. The Stand by Stephen King centres on a pandemic that kills almost the entire world. The strain of influenza is manmade as a biological weapon in the US and it is estimated to be 99.4 percent fatal. It breaks out of the laboratory and kills almost the entire world population. The few people who have survived establish a new social system and confront each other. Journals of the Plague Years by Norman Spinard tells the story of a quickly mutating sexually transmitted viral disease which cannot be cured by vaccines. The sexual activity eventually leads to death in the story. Beauty Salon by Mario Bellatin speaks about a pandemic that affects only men. The owner of a beauty salon has transformed her business into the terminal where she takes only men who are close to death. The truly frightening thing about the story is that it lacks any kind of hope from or within the narrator, who has no solution about his faith and given that one of his rules for the terminal is that no talk about God is allowed. It is not a novel of despair but one of bleak vastness. The Years of Rice and Salt by Kim Stanley Robinson explores how different the world would have been if the Black Death plague had killed ninety-nine percent of the European population instead of one-third. It traces history and social movements. An alternate history of the world is depicted through the work. In The Betrothed, an enormously popular work about the outbreak of the bubonic plague in 1630 that killed roughly half of the population of Milan, Verona, and Venice, the Italian writer, Alessandro Manzoni, describes the people of Milan’s anger at the official response to the plague. Despite all the medical evidence, the authorities in Milan ignored the threat posed by the disease and even refused to cancel a local prince’s birthday celebration. Manzoni shows how the plague spread rapidly because the restrictions were insufficient, the enforcement was lax, and the local people did not bother to heed them. Manzoni shares with us how the general public, medical doctors and even the Tribunal of Health in Milan chose to either ignore or made light of the threat that the plague

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posed. According to Manzoni, A few Italian doctors who had warned of the impending disaster in the form of plague were met with derision or apathy. Most of the physicians joined with the people in laughing at the unhappy presages and threatening opinions of the smaller number of their brethren. He reports on how the corrupt government health officials at Milan’s Tribunal of Health chose to actively conceal evidence of the number of cases of the plague by blaming the numbers on other grounds. The medical reports were falsified and concealed by the health officers who were charged with inspecting the dead bodies. Manzoni wrote that wild conspiracy theories were doing the rounds as the scale of infection became impossible to control. The local people of Milan started blaming foreign soldiers, then witches, or shadowy poisoners. The strength of The Betrothed lies in educating us about the psychological stages in a pandemic beginning with denial and scapegoating, to displacement and, finally, belated recognition of the risks and the panic driven reactions of the public to the pandemic. The Book of M by Ben Shepherd is a novel on a plague that sweeps around the continent. It gives its victims some powers but takes away their memories. A Beginning at the End by Mike Chen gives a hopeful story of post COVID life that leads into the normal world. After a global pandemic that has taken countless lives, some survivors start their life with fragile nature. Post COVID life is well portrayed through the novel. The End of October by Lawrence Wright paints doctor Henry Parson's mental state when he finds himself at the centre of an outbreak of a deadly epidemic. The Great Believers by Rebecca Makkai is an emotional poignant story that features the effect of AIDS epidemic on some actors whose past, present and future are mixed together. The Rationing by Charles Wheelan crafts a political satire through telling the story of a pandemic striking the US, where the political elite tries to control the media and the illness. Years of Wonder by Geraldine Brooks portrays Anna Fritz who lives in self-Quarantine to keep the plague away. The year in the title is 1666 and the novel gives a rich historical background of the period. The Transmigration of Bodies by Yuri Herrera sets on two families that were

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in a town during the aftereffects of a deadly plague. Nip the Buds, Shoot the Kids by Japanese author, Kenzaburo Oe deals with a story of adolescent boys who are sent to a village afflicted by plague. The atmosphere is so terrifying as the whole village is covered by piles of rotting animal corpses. The boys strive with their fate. Survivor by Octavia E. Butler posturizes a group of human colonists fleeing a plague on Earth. The protagonist’s ability to interact with various cultures becomes the key to their survival.

PANDEMIC NON-FICTIONS Literature is not only about the imagination and creation. It can give historical or scientific accounts of an event. Many authors have tried to give an omnipotent narration on pandemics that affected the world. It shows the intensity in which each time a pandemic has struck the world. The subtitle of The Great Mortality by John Kelley, “An Intimate History of the Black Death, the Most Devastating Plague of All Time,” shows the intensity of the bubonic plague and the scale of death that swept much of the known world in the 1300s. Across Asia and Europe, some 75 million people were killed by the Black Death. By going beyond the statistics and finding stories of specific places and people, he makes this staggering subject all too relatable. The Fate of Rome by Kyle Harper shows how an epidemic has played a major role in bringing down the largest ancient civilization of Rome. Rome’s decline and fall were not caused solely by sickness; indeed, the causes have been and will be debated ad nauseam across the centuries. While even this huge civilization would eventually have fractured, it was inarguably weakened over the years by a deadly strain of malaria, and Rome saw its influence beyond being a regional power ravaged by the Justinian Plague of 451 through 542 CE. The subtitle of the book, The Great Influenza by John M. Barry is “The Story of the Deadliest Pandemic in History” which conflicts with the earlier claim that the Black Death is ranked first as the deadliest

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pandemic. The wrenching scenes of suffering and the courage of those fighting the sickness are portrayed well. Barry brings in his book what many historians leave out. He brings guidance on how to deal with outbreaks of the future, which is for those in authority to be completely open and honest with their populations about the scope and danger, so that society as a whole can respond properly. The plague nicknamed the Spanish Flu, spread during World War I. Believed to have originated in Kansas, the Spanish Flu moved with the soldiers as they travelled from America to Europe, and resulted in the deaths of about 100 million people. It gives us a frank narrative of how the scientists’ efforts of finding a vaccine were often thwarted by politicians or media. If you ever wondered how people dealt with a pandemic years before the internet and fast-paced news, this is the book for you. Not only does The Great Influenza talk about this deadly disease, but it also provides future generations with ways to deal with a global catastrophe. Richard Preston’s The Hot Zone talks about the Ebola virus which is a savage killer. It is a haemorrhagic disease that causes chills, fever, pain, and, finally, blood loss that is often fatal. For years, it was scarcely understood. The Hot Zone is no less a gripping, terrifying book than it was when first published, but now we know that even Ebola, once an almost unstoppable killer, can be contained and defeated if caught fast enough. That may give at least a bit of solace to the reader still unsure of what will come from the current coronavirus pandemic. Flu: The Story of the Great Influenza Pandemic of 1918 And the Search for the Virus that Caused it by Gina Kolata portrays one of the deadliest pandemics the world has ever seen, the Great Flu or the Spanish Flu which infected about one-third of the world’s population at the time. Killing nearly forty million people overnight, this disease orphaned thousands of children, erased entire towns, and no place was deemed safe. Not only does Gina Kolata give us a detailed overview of this deadly disease, but she also breaks down the science behind the probability of such a massive pandemic occurring again, and what can be done if such a situation does take place. This book is highly relatable right now.

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The American Plague: The Untold Story of Yellow Fever, the Epidemic that Shaped our History by Molly Caldwell Crosby describes yellow fever which caused a major disruption in American society. It began with a headache, progressed to people vomiting up black blood and ended with them dead. It caused the death of about 2000 people in New York alone, while thousands were forced to relocate in Memphis with the ones who remained getting infected. The fever’s effect was so severe, it led to the American capital being shifted from Philadelphia to Washington. Three doctors were sent to Cuba from America in order to study the disease, and their revelations caused massive ripples in the medical industry. Evocative and terrifying, this book details one of the most horrendous epidemics in world history and gives us a grave warning about the future. China Syndrome: The True Story of the 21st Century’s First Great Epidemic by Karl Taro Greenfeld talks about the SARS virus that broke out in China in January 2003 and spread at an unprecedented rate. At the time, Karl Greenfeld was working as an editor with Time Asia in Hong Kong, and soon got involved in the story of an outbreak that would put China at the centre of a global catastrophe. Soon after, hospitals proved inefficient in providing adequate healthcare services to those infected, researchers and the WHO desperately tried to come up with a solution, while the Chinese government kept trying to keep the news hidden. China Syndrome serves as a warning to the world against keeping people ignorant, and the deadly consequences we have to face as a result. Silent Travelers: Germs, Genes, and the “Immigrant Menace” by Alan M. Kraut gives the immigrants’ situation at the time of pandemics. During and after an epidemic, people often blame immigrants for supposedly bringing the disease with them. This state of mind is reflected in anecdotes throughout history, e.g., when the Irish were blamed for the cholera epidemic, or when the Chinese in San Francisco were held responsible for the bubonic plague. But what people often forget is the effect these prejudices have had in shaping health and immigration policies across the world. Using research, government sources and even

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letters from patients, Alan Kraut brings us a book to show how we keep dealing with the same problems, generation after generation. The Ghost Map: The Story of London’s Most Terrifying Epidemic and How it Changed Science, Cities, and The Modern World by Steven Johnson points to August 1854, when Londoners suddenly took ill, showing symptoms of diarrhoea and wracking thirst, among others. It spread fast, consuming over 50,000 lives in England and Wales. At the centre of the story, though, is one scientist who showed the world that this deadly sickness – cholera – was water-borne, not air-borne, as per popular consensus. Even though this brought down the collective ire of the medical fraternity on him, it also led to the ultimate defeat of the disease. An incisive report on the epidemic of London is given through The Ghost Map. It is the summer of 1854, and London is just emerging as one of the first modern cities in the world. But lacking the infrastructuregarbage removal, clean water, sewers-necessary to support its rapidly expanding population, the city has become the perfect breeding ground for a terrifying disease no one knows how to cure. As the cholera outbreak takes hold, a physician and a local curate are spurred to actionand ultimately solve the most pressing medical riddle of their time. Stacking the Coffins by Ida Milne traces social history of the 1918-19 influenza pandemic’s effects on Ireland where normal patterns of life were disturbed by war and the growing separatist movement. The influenza seemed to disrupt every aspect of Irish life – culture, economics, politics, medicine and family life. Polio, an American Story by David Oshinsky tells the gripping story of the polio terror and of the intense effort to find a cure.

CONCLUSION At the time of pandemics, literature offers important insights into how people have dealt with trauma in the past and how to make sense out of a world beyond our control. Literature gives more intimate views of epidemics as it gives not only the historical account, but also the

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emotional account. The changes that happened in the world due to pandemics of the past have shaped the world in the present form. This realisation we get from literature helps us to cope with the difficult days. Literature shows us not only the statistics but how an individual has been affected by a pandemic. When COVID-19 struck the world, there was an increase in popularity of literary works that dealt with pandemics. Literature always responds to pandemics, celebrates the inquiring range of human responses and the feelings against diseases and death. The only thing that changes in literature about pandemics is time. The emotions, feelings, ethical and critical issues, events and patterns repeat themselves in pandemic literature. “History repeats itself, with none growing wiser with experience. Only literature continues to fight for a more equitable world, where healthcare is a right not a privilege and transparency in governance is a justified expectation not a pipe dream.”(Walia) Literature teaches about deadly manifestations on humanity and through the stories it will help us to live through the crisis and ultimately build hope for a better future.

REFERENCES Abdel-Fattah M. Adel, Mashhoor Abdu Al-Moghales and Suhail Ahmad (2020). “Narratives of Epidemics: Topsy-turvy Conditions of Humans and Quest for Existence.” Rupkatha Journal on Interdisciplinary Studies in Humanities (ISSN 0975-2935): 2. Accessed February 15, 2021. Book of Revelation. 6:8. The Bible. (1989). New Revised Standard Version. National Council of Church. Print. Garcia, Marquez G. (2003). Love in the Time of Cholera. Vintage International. Print. Lombardi, Esther. (2019). “Memorable Quotes from The Plague by Camus.” www.ThoughtCo.com. Accessed February 15, 2021.

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Mark, Musa., and Peter Bondanella.trans. (1982). The Decameron. Boccaccio. Mentor Books. Print. doi: https://dx.doi.org/10.21659/ rupkatha.v12n5.rioc1s28n1. Walia, Shelley. (2020). “Chronicles of death foretold: What literature tells us about pandemics.” The Hindu, June 13. Accessed February 12, 2021. https://www.thehindu.com/books/chronicles-of-deathforetold-what-literature-tells-us-aboutpandemics/article31810961.ece.

In: Pandemics and Global Health ISBN: 978-1-68507-228-5 Editors: N. Balan and M. Thomas © 2022 Nova Science Publishers, Inc.

Chapter 21

IMPACT OF COVID-19 AND LOCKDOWN ON INDIA’S FOREIGN TRADE Jinu Joseph* Department of Economics Devamatha College, Kuravilangad, Kerala, India

ABSTRACT The Indian economy has faced unprecedented shock due to the COVID-19 outbreak. The different stages of countrywide lockdown create a significant interruption in the demand and supply chain of the economy. The first case of the coronavirus was reported in the Wuhan city of China in December 2019. After the spread of this virus, many countries have shut down their airports and seaports. They have banned export and import activities. Also, China is the main supplier of raw materials to almost all countries, which adversely affects the manufacturing activities across the world due to lockdowns. China has been the highest foreign trade with India. It is considered as the major market for many Indian products like gems and jewellery, seafood, petrochemicals etc. The outbreak of coronavirus has adversely impacted Corresponding Author’s address: Email: [email protected]; Jinu Joseph, Assistant Professor, Department of Economics.

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Jinu Joseph exports of these items to China. The trade impact of the COVID-19 pandemics for the Indian economy is estimated to be around 348 million dollars. This paper gives an overview of the COVID-19 situation in India and its impact on India’s foreign trade.

Keywords: COVID-19, foreign trade, India, lockdown

INTRODUCTION The global economy has been struck hard by the continuing COVID19 pandemic driven crisis. The whole planet is passing through great uncertainty. It has turned out to be a game-changing catastrophe for the entire world. It is a humanitarian crisis as well as a social and economic crisis. It has had a wide-range and global impact on the entire corporate environment. After the Great Depression of the 1930s, the entire world has faced the most horrible recession. Currently, it is struggling with the global pandemic of COVID-19, which has had a detrimental effect on the world’s financial and economic activity in all sectors. The abrupt fall in economic activities because of the lockdown is unforeseen in the entire history of the Indian economy. The well-known economist J.M Keynes has suggested the idea of the trade cycle after the Great Depression. The four stages of the trade cycle are used to evaluate the real GDP and growth rate. The International Monetary Fund (IMF) has projected India’s GDP growth rate as 1.9 per cent, which is the worst growth rate of India after the New Economic Policy of 1991. In India, the blow on real sectors of the economy is not as good as that witnessed during the 2008 crisis. The country currently faces numerous challenges such as health crises, financial crises, and a fall in commodity prices. Most of the companies that highly depend upon international trade will suffer much pressure due to this pandemic. The whole production is turned down and expecting a severe economic recession in the global economy. This global pandemic has hit the Indian economy, which questioned the target to create an economy of $5 Trillion with 7 per cent of GDP growth by 2024.

Impact of COVID-19 and Lockdown on India’s Foreign Trade 369 According to the World Bank’s most recent appraisal, India is projected to grow 1.5 - 2.8 per cent. According to the IMF, it has expected a GDP growth of 1.9 per cent in the year 2020 and to realize the purpose of $5 Trillion economy, and is estimated to grow up at 9 per cent each year for five years. India’s growth trajectory since 2011 is illustrated in figure 1.

Figure 1. India’s Growth Trajectory Since 2011.

MATERIALS AND METHODS The present study is mainly descriptive. It is primarily based on secondary sources of data, which is collected from published and unpublished reports, various records, and the contributions of several organizations and institutions. Specifically, the secondary data sources include the data from World Trade Organisation (WTO), World Health Organisation (WHO), United Nations Conference on Trade and Development (UNCTAD), International Monetary Fund (IMF), World Bank report, Centre for Monitoring Indian Economy (CMIE) database, ITC Trade map, journals, books and websites.

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RESULTS AND DISCUSSION China, being the epicenter of the coronavirus outbreak, led the trade and business sectors to a global slowdown. As per United Nations Conference on Trade and Development (UNCTAD) estimates, it causes a decline of 2 per cent in China’s exports of intermediate inputs in 2020, which will ultimately lead to a US$ 50 billion drop in exports across global value chains. According to World Trade Organisation (WTO), world trade is anticipated to reduce by between 13 per cent and 32 per cent in 2020 because of the COVID-19 epidemic that has highly disturbed the usual economic activities. The share of India’s export to the world’s export is around 3.5 per cent, and its share of import to the world’s import is almost 3.1 per cent in 2019. The trade balance of the country has exposed a trade deficit of US$ 9.8 billion in March 2020. China is the uppermost foreign trade with India. It is considered as the major market for many Indian products, especially seafood, gems and jewellery, petrochemicals and so on. Therefore, the exports of these goods to China had been adversely impacted due to the outbreak of COVID-19. For instance, the fisheries sector alone is estimated a loss of over Rs. 1300 crore because of the fall in exports. India exports 36 per cent of its diamonds to China. The annulment of four main trade events in the country from February to April is expected to cause an estimated loss of Rs. 8000 to 10000 crores in terms of the business opportunities for Jaipur alone. Similarly, India exports 34 per cent of its petrochemicals to China. Due to exports restrictions of petrochemical products to China, the prices of these products are expected to decline. The Centre for Monitoring Indian Economy (CMIE) database shows China has been the major source of India’s imports since 2004. It had a share of 13.7 per cent of India’s total imports during 2018-19. So, any major disturbance in the Chinese economy can upset these imports and, consequently, the production and supply of various consumer goods in India. Taking China’s share in total imports to India, the total electronic imports of India are estimated for 45 per cent of China. Around two-fifths of organic chemicals and one-third of machinery that India purchases

Impact of COVID-19 and Lockdown on India’s Foreign Trade 371 from the world come from China. For fertilizers and automotive parts, China’s share in India’s total imports is over 25 per cent. About 65 to 70 per cent of active pharmaceutical products and almost 90 per cent of mobile phones arrived in India from China. As per United Nations Conference on Trade and Development (UNCTAD), India’s overall trade impact due to COVID-19 outbreak is estimated to be around US$348 million. UNCTAD ranked India 10th among the top 20 most affected economies because of the coronavirus pandemic and manufacturing slowdown in China. While in the view of the Asian Development Bank (ADB), the COVID-19 outbreak could cost the economy of India between US$387 million and US$29.9 billion in case of personal consumption losses. The overall trade impact of India due to this epidemic is estimated to be the most on the chemicals sector at 129 million dollars, textiles and apparel at 64 million dollars, the automotive sector at 34 million dollars, metals and metal products at 27 million dollars, wood products and furniture at 15 million dollars, leather products at 13 million dollars and electrical machinery at 12 million dollars. Table 1. India’s top import sources Country China USA UAE Saudi Arabia Iraq Switzerland Indonesia Singapore

Share in India’s Total Imports (%) 14.20 7.20 6.40 5.60 4.50 3.70 3.30 3.10

Source: ITC Trade map.

China is the leading import destination of India, with imports accounted for US$ 68.1 billion in 2019, estimating a share of 14.2 per cent in the total imports of India from the world. India mainly exports 7500 articles to 190 countries and import almost 6000 articles from 140

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countries. India shares its trade surplus with the USA, UAE, and Bangladesh. India has a trade deficit with China, Saudi Arabia, and Switzerland.

Figure 2. Composition of India’s Imports from China (2019).

The imports of India from China are composed of capital goods (52.2 per cent), consumer goods (14.4 per cent), intermediate goods (32.2 per cent), and raw materials (1.1 per cent). The disturbance in the supply chains of India and China might influence the intermediate commodities in India’s production processes in the short run. However, it will be the interruption in the import of major capital goods, which could generate the supply chain disruptions in the Indian market because the machinery replacements and the new technology are disrupted in the economy, thereby upsetting the productivity of the country in the long run. China is also considered India’s third largest export destination globally, with a share of 5.3 per cent of India’s total exports. The impact of COVID-19 on India’s exports is depicted in Table 2. The highest exposure of coronavirus and lockdown on leading sectors relates to commodities that create about 18 per cent of India’s exports basket: the textiles and clothing, and transportation sectors. The moderate exposure can be seen for India’s top 3 exports, such as fuels,

Impact of COVID-19 and Lockdown on India’s Foreign Trade 373 chemicals, stone, and glass, which comprise more than 40 per cent of India’s total exports. The sectors that are less reliant on export markets like vegetables, plastic or rubber, animals, food products, etc., face the lowest risks of exposure in the international trade. Table 2. Potential impact of COVID-19 on trade Potential Impact

Sectors

High

Textiles and Clothing Transportation Fuels Chemicals Stone and Glass Mach and Electricals Metals Minerals Vegetable Plastic or Rubber Animals Food Products Miscellaneous Hides and Skins Footwear Wood

Moderate

Low

India’s Exports (USD Billion) 37.0 24.3 48.6 44.6 43.1 32.2 26.6 3.9 18.0 11.0 10.6 6.8 6.4 3.3 3.1 2.7

Exports Product Share (%) 11.5 7.6 15.1 13.8 13.4 10.0 8.3 1.2 5.6 3.4 3.3 2.1 2.0 1.0 1.0 0.8

Source: World Bank WITS, 2019; Moody’s Analytics.

CONCLUSION Thus, India’s total export and import have been stagnated due to the COVID-19 lockdown. The central, as well as the state governments, have to face many social, economic, political and some other issues after the COVID-19 epidemic and lockdown. The ordinary people are not aware of the effects of the stagnation of India’s export and import. The fundamental needs that are not satisfied by the government will turn down the capabilities and enthusiasm of Indians willful in the global

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arena. Hence, the Government of India should consider the exports and imports of the country are the crucial sectors to survive the requirements of the society. The Government policymakers have to implement a significant targeted fiscal and monetary stimulus in the economy and cuts policy rates to normalize the entire economic situation in the country.

REFERENCES DebdasRakshit&Ananya Paul, 2020. “Impact of COVID-19 on Sectors of Indian Economy and Business Survival Strategies.” International Journal of Engineering and Management Research, 10 (3): 51-55. IMF (2020), Policy responses to Covid-19, International Monetary Fund, Washington DC. https://www.imf.org/en/Topics/imf-and-covid19/ Policy-Responses-to-COVID-19#I (Accessed Date: 10.11.2020). Impact of Covid-19 on the Indian Economy, http://ficci.in/spdocument/ 23195/Impact-of-COVID-19-on-Indian-Economy-FICCI-2003.pdf (Accessed Date: 5.11.2020). Implications of COVID-19 on India’s Economy and Trade, https://www. tradeeconomics.com/iec_publication/implications-of-covid-19-onindias-economy-and-trade/ (Accessed Date: 5.11.2020). Mohammed Meharoof et al., 2020. “Indian Seafood Trade and COVID19: Anticipated Impacts and Economics.” Food and Scientific Reports. 1 (8): 54 – 58. Paul Dhinakaran&Kesavan, 2020. “Exports and Imports Stagnation in India During COVID-19 – A Review” GIS Business, 15 (4): 1158 – 1177. Pranjul Srivastava, “Potential Impact of Novel COVID-19 on Indian Economy.” International Journal of Advanced Research, 8(05): 711-716, 2020. Shruti Agrawal et al.Effect Of COVID-19 On the Indian Economy and Supply Chain. Https://Www.Researchgate.Net/Publication/ 341266 520 (Accessed Date: 12.10.2020).

Impact of COVID-19 and Lockdown on India’s Foreign Trade 375 Sonkhaskar, 2020. “Impact Of COVID-19 On Indian Economy.” International Journal of Advanced Science and Technology, 29 (12): 432-439. Sunil Kumar et al., 2020. “Impact of Coronavirus (COVID-19) On Indian Economy.” Agriculture & Food, 2 (4): 301-302. ThangajesuSathish et al., 2020. “COVID-19 and its impact on India” International Journal of Creative Research Thoughts (IJCRT), 8 (5): 2020-2052. Udhaya Kumar et al., 2020. “The Rise and Impact of COVID-19 in India” Frontiers in Medicine, 7: 1-7. UN Report., (2020). Coronavirus COVID-19 wipes $50 billion off global exports in February alone, as IMF pledges support for vulnerable nations. United Nations. https://news.un.org/en/story/2020/03/ 1058601 (Accessed Date: 5.11.2020). UNCTAD Report, (2020). Coronavirus outbreak has cost global value chains $50 billion in exports. United Nations Conference on Trade and Development, https://unctad.org/en/pages/newsdetails.aspx? OriginalVersionID=2297(Accessed Date: 5.11.2020). WHO. Novel Corona virus – China. (2020). https://www. who.int/csr/ don/12-January-2020-novel-coronavirus-china/en/ (Accessed Date: 5.11.2020).

ABOUT THE EDITORS Dr. Nitha Balan Assistant Professor Department of Microbiology Sree Ayyappa College Eramallikkara, Chengannur, Kerala, India Nitha Balan, MSc., PhD is the Head of the Department, Biochemistry & Industrial Microbiology at Sree Ayyappa College, Eramallikkara, Kerala, India. She has more than 12 years of teaching experience. She has also worked in other institutes of repute like Centre for Medicinal Plants Research, AVS, Kottakkal, Kerala and Amala Cancer Research Centre, Thrissur, Kerala. She has published more than 35 scientific papers in National and International Journals. She wrote 7 book chapters and edited 3 books. She has presented more than 30 research papers at National and International Conferences in various Colleges and Universities. She is the Editorial Board member and Reviewer of several peer reviewed Journals.

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Dr. Manuel Thomas Research Consultant UniBiosys Biotech Research Labs, Sahaan Arcade Near CUSAT Metro station, University Road, South Kalamassery, Kochi, Kerala, India Manuel Thomas MSc., PhD is Research Consultant, Unibiosys Biotech Research Labs, Cochin, Kerala, India. He has more than 15 years of research experience in medical Mycology and Microbiology. He has more than 30 research publications as international and national journal articles. He has published more than 10 books in his credit. He has more than 25 conference papers at various national and international conferences. He is professionally affiliated to Society for Indian Human and Animal Mycology (SIHAM), Research India Foundation (RIF) and Social Initiative for Global Nurturing (SIGN). He is editorial Board member and Reviewer of several international journals.

INDEX A

B

academic performance, 196, 198, 203 accredited social health activists (ASHA), 23, 27 adenovirus, 91, 107, 110, 296, 301, 303, 304, 307, 308, 309, 310 AIDS, 95, 134, 141, 160, 167, 210, 212, 240, 243, 244, 245, 248, 249, 253, 254, 256, 257, 289, 329, 359 AIDS related complex (ARC), 248 angiotensin-converting enzyme-2 (ACE-2), 313, 316, 318, 319 anthropogenic, 169, 170, 173, 177 antibody, 89, 99, 102, 103, 123, 162, 247, 248, 250, 252, 253, 255, 260, 293 antigen, 89, 113, 120, 246, 250, 251, 255, 260, 271, 272, 276, 277, 280, 281, 291, 293, 304 antigenic variation, 82, 161 antioxidant(s), 319, 334 antonine plague, 130, 140, 239, 288, 329 Artemisia annua, 333, 335 Athenian plague, 129 Ayurveda, 337, 342, 343, 344, 348, 351

Barleria strigosa, 342, 344 behavioural change(s), 203 biodiversity, 7, 8, 177, 178 biological weapons, 220 biosphere, 170 Black Death, 131, 132, 133, 138, 140, 141, 160, 166, 212, 215, 237, 240, 259, 260, 261, 262, 263, 265, 268, 274, 289, 329, 355, 358, 360 bubonic plague, 129, 132, 270, 273, 275, 278, 284, 289, 358, 360, 362 Bubonic plague, 129, 132, 260, 270, 273, 275, 276, 278, 279, 284, 289, 355, 357, 358, 360, 362

C caffeic acid, 342, 344, 345, 349, 350 Canscora perfoliata, 342, 344 Canterbury Tales, 355 catechin, 342, 344, 347, 350 CD26, 318 CD4, 162, 243, 244, 245, 247

380

Index

CD8, 162, 243, 244 cell surface receptor, 316 chemokine(s), 319, 322 Chikungunya, 45, 149, 155, 331 childhood vaccine(s), 74, 103 chlorogenic acid, 342, 344, 347 cholera, 14, 45, 127, 143, 147, 210, 212, 327, 328, 329, 332, 334, 356, 357, 362, 363, 364 communicable disease(s), 121, 153, 234, 328 coronavirus, 13, 14, 16, 27, 28, 29, 32, 34, 35, 42, 43, 49, 52, 55, 63, 64, 65, 66, 67, 68, 69, 70, 71, 90, 91, 95, 97, 106, 116, 117, 135, 152, 156, 162, 164, 165, 166, 179, 180, 182, 183, 190, 191, 192, 193, 194, 195, 197, 208, 209, 214, 221, 222, 223, 231, 232, 233, 236, 287, 296, 297, 298, 300, 306, 308, 310, 313, 314, 315, 316, 317, 318, 320, 322, 323, 324, 327, 328, 332, 333, 338, 339, 341, 342, 343, 345, 349, 350, 351, 361, 367, 370, 371, 372, 375 coumarin(s), 345 Covaxin, 25, 28, 90, 91, 94, 107, 109, 300 COVID-19 pandemic, ix, 28, 43, 46, 53, 69, 105, 143, 172, 177, 178, 186, 197, 204, 208, 209, 211, 213, 214, 218, 219, 220, 224, 226, 232, 234, 236, 287, 335, 368 COVID-19 vaccine, 25, 28, 74, 92, 96, 97, 100, 108, 109, 112, 117, 118, 300 Covishield vaccine, 110 Crimean-Congo hemorrhagic fever (CCHF), 288, 289, 291, 308, 310, 311 crises, 6, 22, 24, 220, 235, 368 cytokine storm, 157, 160, 316, 318, 320 cytokine storm syndrome, 157, 158 cytokines, 316, 319

D dengue haemorrhagic fever (DHF), 149, 156, 220 diabetes, 83, 120, 123, 158, 313, 317, 318, 319, 320, 321, 322, 323, 324 diabetes mellitus, 317 diabetic patients, 313, 318, 319, 320, 321 diaspora, 31, 32, 33, 47, 48, 49, 52, 54 dipeptidyl peptidase-4 (DPP-4), 313, 317 diphtheria, tetanus, and acellular pertussis (DTaP), 100, 102, 122 disability-adjusted life years (DALY), 122 Disease X, 288, 305, 310

E Ebola virus disease (EVD), 2, 8, 136, 163, 166, 211, 216, 217, 220, 288, 291, 293, 294, 295, 296, 305, 306, 308, 309, 329, 331, 336, 361 emerging infectious disease (EID), 2, 6, 8, 9, 82, 99, 155, 166, 167, 215, 220, 283, 304, 305 empowerment, 23 encephalitis, 15, 73, 78, 79, 87, 97, 98, 143, 151, 153, 154, 155, 156, 162 endemic disease(s), 3, 98 epidemic disease(s), 4, 143 epidemic(s), 2, 3, 4, 6, 7, 8, 9, 11, 12, 14, 15, 19, 28, 36, 43, 44, 45, 65, 66, 68, 69, 71, 73, 75, 79, 82, 99, 119, 130, 133, 137, 140, 141, 143, 144, 145, 146, 147, 148, 149, 152, 153, 154, 155, 159, 161, 162, 163, 164, 165, 166, 187, 190, 193, 194, 205, 210, 211, 212, 214, 216, 218, 220, 237, 239, 240, 254, 255, 261, 262, 263, 266, 269, 270, 271, 274, 282, 283, 288, 299, 305, 306, 309, 324, 327, 328, 334, 343, 356, 357, 359, 360, 362, 363, 364, 370, 371, 373

Index epidemiology, 8, 95, 97, 99, 105, 115, 120, 139, 154, 158, 159, 167, 238, 249, 254, 255, 261, 268, 309, 328, 350 ethnomedicine, 327, 328, 330, 335 European literature, 354, 355, 356 expanded program on immunization (EPI), 121 exposure, 18, 85, 137, 145, 146, 161, 185, 187, 236, 260, 264, 273, 274, 291, 298, 302, 372

F family relationship(s), 195, 196, 200, 201, 204 FDA, 80, 90, 91, 108, 116, 117, 254, 281, 293 flavonoid(s), 346, 349, 350 folk medicine, 333 foreign trade, 367, 370 fossil fuel, 172, 178 frequent antigenic variation, 243, 246 future pandemic(s), 55, 57, 144, 166, 287, 288, 306

G global health, ix, 1, 2, 6, 217 global health security, 1, 7, 9, 139, 220, 238 globalization, 51, 163, 214, 330, 337 Great Depression, 368 greenhouse gas emissions, 171, 172, 174, 178 gross domestic product (GDP), 208, 217, 225, 231, 368

H hantaviruses, 2, 217, 301, 302, 309

381

health education, 244, 249, 254 hepatitis, 74, 75, 76,78, 86, 87, 94, 95, 97, 115, 121, 123, 150, 153, 154, 255, 290, 331 herbal formulation(s), 334, 335, 338 history, ix, 2, 6, 14, 31, 35, 46, 49, 66, 75, 77, 79, 105, 121, 127, 128, 130, 135, 137, 138, 139, 140, 141, 143, 144, 152, 158, 166, 167, 207, 208, 210, 211, 235, 236, 237, 238, 239, 240, 259, 261, 262, 274, 282, 283, 285, 288, 295, 309, 320, 327, 328, 330, 335, 343, 355, 358, 360, 362, 363, 364, 368 HIV/AIDS, 45, 75, 86, 95, 120, 122, 134, 137, 138, 140, 141, 160, 166, 167, 210, 212, 214, 236, 237, 239, 240, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 289, 305, 306, 329, 359 Holostemma ada-kodien, 342 home culture, 176 homeostasis, 318, 321 homes, 14, 47, 188, 269 homosexuals, 244, 249 hope, 85, 107, 353, 354, 357, 358, 364 Human Influenza A (H5N1), 2, 154, 211, 214, 215, 217, 219, 220, 319, 325 hyperglycemia, 317, 319, 320 hypertension, 120, 123, 158, 173, 317, 319, 320

I immunization, 73, 74, 75, 76, 83, 84, 90, 93, 101, 105, 106, 118, 119, 120, 121, 122, 123, 124, 126, 254, 281, 306 Indian agriculture, 210 indigenous, 109, 144, 330, 333, 335, 337 infection mortality rate, 120 infectious disease(s), ix, 2, 4, 6, 8, 9, 11, 35, 73, 77, 85, 87, 88, 93, 95, 108, 119,

382

Index

122, 123, 141, 144, 152, 154, 156, 159, 163, 165, 183, 185, 196, 213, 214, 215, 217, 220, 240, 254, 284, 288, 293, 305, 308, 309, 310, 313, 334 influenza, 6, 9, 36, 67, 74, 75, 78, 81, 82, 86, 87, 95, 96, 99, 100, 101, 103, 113, 133, 136, 137, 138, 140, 141, 143, 145, 150, 155, 159, 161, 167, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 235, 236, 237, 240, 306, 325, 329, 331, 334, 337, 346, 355, 357, 358, 360, 361, 363 influenza vaccine, 75, 78, 82, 96, 100, 103, 161 influenza virus, 2, 6, 67, 74, 78, 81, 82, 87, 95, 100, 101, 133, 145, 150, 154, 156, 159, 161, 192, 210, 212, 213, 215, 216, 325, 329, 331, 337, 346, 360, 361 integrated one health approach, 287 interleukin 6, 157, 158 international monetary fund (IMF), 368, 369, 374, 375 isolation, 16, 18, 22, 24, 131, 134, 181, 182, 183, 184, 185, 188, 191, 213, 234, 235, 244, 284, 291, 293, 299, 300, 320, 355

J Justinian plague, 130, 140, 239, 262, 267, 360

K Kerala, 1, 11, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 31, 48, 49, 52, 53, 54, 55, 57, 65, 66, 68, 69, 73, 119, 143, 149, 151, 156, 157, 162, 169, 195, 198, 203, 207, 223, 229, 287, 313, 327, 341, 353, 367 Kudumbashree, 21, 23, 27

L literature, 57, 94, 95, 166, 208, 210, 353, 354, 355, 356, 360, 363, 365 lockdown, 17, 18, 19, 23, 26, 27, 33, 35, 36, 43, 46, 47, 49, 50, 52, 64, 65, 69, 170, 171, 172, 173, 174, 176, 178, 179, 180, 181, 187, 189, 191, 195, 196, 197, 198, 204, 208, 210, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 367, 368, 372, 373

M malaria, 14, 75, 120, 122, 151, 293, 305, 331, 339, 360 mangiferin, 342, 344, 348 Marburg virus disease, 288, 294, 307, 309 measles, mumps and rubella (MMR), 122 meningitis, 75, 76, 87, 97, 121, 149, 273, 278, 293 meningococcal meningitis, 149 mental health, 162, 181, 183, 184, 186, 187, 188, 189, 196, 208, 223, 233, 236 mental health issues, 162, 181, 184, 189 MERS outbreak, 184 MERS-CoV, 163, 184, 191, 296, 297, 298, 309, 310, 315, 316, 328, 329 metabolic disease, 313, 317 Middle East respiratory syndrome (MERS), 2, 6, 157, 163, 166, 184, 191, 211, 217, 223, 288, 296, 297, 298, 306, 308, 309, 310, 314, 315, 316, 318, 327, 328, 329, 314, 334 migration, 33, 35, 44, 45, 46, 47, 49, 51, 52, 54, 55, 56, 67, 69, 99, 145, 226, 231 modern vaccine(s), 74, 87, 88 Moderna vaccine, 113, 116 molecular docking, 342, 343, 347, 350, 351 molecular docking method, 342, 351 mRNA vaccine, 90, 107, 300

Index mRNA(s), 74, 87, 88, 90, 91, 95, 101, 107, 112, 113, 300, 316

N negative behavioural changes, 196, 204 Nipah virus, 15, 45, 151, 156, 162, 167

O opportunistic infection(s), 244, 248, 249, 253 oriental rat flea, 132, 266, 270

P palmatine, 342, 348, 350 pandemic fiction, 354 Pandemic Influenza A (H1N1), 2, 6, 81, 82, 133, 135, 138, 139, 141, 150, 155, 159, 163, 192, 209, 211, 212, 214, 215, 217, 218, 219, 237, 239, 240, 289, 306, 329, 331, 332, 334, 337 Pfizer, 78, 84, 90, 91, 107, 111, 112, 287, 300 plague, 12, 45, 127, 128, 129, 130, 131, 132, 138, 139, 140, 143, 147, 148, 153, 154, 155, 159, 210, 212, 215, 237, 238, 239, 259, 260, 261, 262, 263, 264, 265, 267, 268, 269, 270, 271, 272, 273, 274, 276, 278, 279, 280, 281, 282, 283, 284, 285, 288, 327, 328, 329, 331, 334, 337, 355, 356, 357, 358, 359, 360, 361, 362, 364 plague vaccine(s), 281, 285 plamatine, 344 plant based treatment(s), 330, 331, 333 pneumococcal vaccine(s), 83, 84, 102, 121 polio, 75, 86, 93, 121, 122, 148, 155, 289, 331, 338, 363

383

pollution, 46, 169, 171, 172, 173, 175, 177, 178, 179 polyphenol(s), 345 polyprotein(s), 316, 343 post-traumatic stress disorder (PTSD), 185, 191 PPE kit(s), 208 pre-vaccine peak, 122 psychological reaction(s), 183 psychosocial education, 181, 189 public health, ix, 1, 2, 3, 5, 6, 7, 13, 18, 53, 64, 66, 69, 73, 74, 75, 77, 80, 83, 84, 85, 93, 96, 98, 100, 102, 103, 105, 108, 114, 116, 119, 121, 122, 124, 125, 133, 134, 141, 143, 144, 153, 154, 159, 160, 161, 163, 164, 174, 186, 192, 194, 213, 216, 220, 240, 244, 254, 261, 287, 298, 301, 303, 308, 322, 330, 337

Q quarantine, 15, 17, 18, 20, 22, 23, 24, 28, 35, 53, 64, 132, 135, 140, 181, 184, 185, 186, 196, 234, 235, 240, 261, 354, 356, 359 quercetin, 342, 344, 346

R remittance(s), 33, 44, 47, 63, 67, 231 respiratory ailment(s), 333 respiratory illness, 209, 313, 317 reverse transcriptase-polymerase chain reaction (RT-PCR), 19, 24, 291, 293, 296, 302 RNA viruses, 107, 165, 301, 306, 313, 314, 315 RNA-dependent RNA polymerase (RdRp), 333

384

Index S

scopoletin, 342, 344, 345, 346 septicemic plague, 260, 273, 274, 276 severe acute respiratory syndrome (SARS), 2, 6, 12, 13, 34, 45, 65, 70, 71, 90, 91, 107, 110, 112, 113, 114, 115, 116, 117, 127, 135, 141, 153, 156, 157, 158, 162, 163, 165, 175, 177, 180, 182, 184, 185, 190, 191, 193, 207, 209, 211, 212, 213, 214, 215, 217, 218, 220, 221, 223, 240, 241, 288, 289, 296, 298, 299, 300, 304, 305, 308, 313, 314, 315, 316, 318, 319, 320, 321, 322, 323, 324, 327, 328, 329, 332, 333, 334, 338, 341, 342, 343, 345, 346, 347, 348, 349, 350, 351, 362 severe acute respiratory syndrome corona virus (SARS-Cov), SARS-CoV-2, 13, 34, 65, 71, 90, 91, 107, 110, 112, 113, 116, 117, 153, 157, 158, 165, 175, 177, 182, 209, 221, 288, 289, 297, 298, 299, 300, 305, 313, 316, 318, 319, 320, 322, 323, 329, 333, 341, 342, 343, 345, 346, 347, 348, 349, 350, 351 single-stranded RNA (ssRNA), 82, 294, 296, 299, 314, 315, 333 skill development, 195, 196, 197, 201, 202, 204 smallpox, 12, 14, 45, 75, 93, 119, 121, 130, 135, 139, 141, 143, 148, 156, 161, 167, 210, 238, 240, 259, 264, 329, 331, 335, 336 social avoidance, 187 social distancing, 18, 19, 20, 34, 184, 198, 208, 218, 223, 235, 355 social media, 20, 74, 92, 181, 187, 195, 196, 197, 202, 203, 204, 210, 232 social media usage, 204 society, 3, 11, 19, 26, 105, 130, 158, 167, 196, 232, 233, 254, 261, 262, 284, 285, 308, 338, 354, 355, 356, 361, 362, 374

Spanish flu, 81, 133, 135, 139, 159, 210, 211, 215, 238, 329, 331, 334 Sputnik, 90, 111, 117, 300, 305 survival, 123, 138, 161, 225, 226, 237, 279, 296, 343, 354, 360, 374 swine flu, 6, 45, 135, 136, 139, 143, 150, 239, 289, 329, 332, 334, 338 sylvatic plague, 269 symptom(s), 13, 15, 17, 18, 19, 24, 35, 129, 131, 132, 136, 151, 152, 164, 181, 182, 183, 184, 186, 187, 233, 248, 260, 272, 273, 278, 290, 292, 295, 296, 297, 299, 302, 303, 314, 320, 363

T T helper cell(s), 243, 244, 245, 247 technological advancement, 32, 56 transmission, 2, 3, 5, 9, 13, 17, 24, 29, 33, 35, 45, 64, 67, 69, 74, 77, 86, 92, 144, 146, 147, 149, 150, 152, 159, 161, 163, 175, 183, 211, 212, 213, 215, 249, 253, 256, 261, 265, 266, 272, 279, 291, 292, 295, 296, 298, 301, 303, 310, 328, 349

U UN mission for emergency Ebola response (UNMEER), 6, 8 United Nations Conference on Trade and Development (UNCTAD), 369, 370, 371, 375 urban or domestic plague, 269

V vaccinations, 93, 102, 120, 124 vaccine(s), 12, 25, 26, 28, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,

Index 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 137, 148, 161, 165, 167, 189, 223, 236, 244, 254, 260, 280, 281, 282, 283, 285, 287, 291, 293, 296, 298, 300, 304, 310, 321, 333, 342, 348, 358, 361 viral infection, 34, 82, 151, 175, 185, 256, 296, 316, 319, 320 viral pneumonia, 34, 315 virtual vector, 32

W World Health Organization (WHO), 1, 3, 5, 6, 8, 9, 13, 15, 29, 32, 33, 34, 35, 36, 43, 56, 62, 70, 71, 74, 75, 76, 80, 85, 86, 90, 104, 105, 106, 108, 112, 116, 118, 119, 120, 121, 126, 135, 141, 148, 151, 156, 164, 170, 180, 181, 182, 214, 215, 216, 217, 231, 241, 252, 257, 261, 265, 270, 279, 281, 285, 288, 293, 294, 296,

385 297, 298, 299, 300, 305, 307, 314, 333, 362, 369, 375

X Xenopsylla cheopis, 132, 259, 270

Y Yersinia pestis, 128, 130, 132, 138, 159, 237, 259, 260, 261, 265, 266, 268, 271, 272, 282, 283, 284, 285, 289, 329, 331

Z Zika, 12, 79, 87, 101, 136, 139, 164, 166, 207, 209, 211, 219, 238, 289, 304, 332, 337 Zingiber officinale, 332, 333