Case Studies in Infectious Disease: Echinococcus Spp 9781136987465, 9780815341420, 0203853806, 0815341423, 1136987460

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Echinococcus spp.

Peter M. Lydyard Michael F. Cole John Holton William L. Irving Nino Porakishvili Pradhib Venkatesan Katherine N. Ward

This edition published in the Taylor & Francis e-Library, 2009. To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.

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©2010 by Garland Science, Taylor & Francis Group, LLC

This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. All rights reserved. No part of this book covered by the copyright heron may be reproduced or used in any format in any form or by any means—graphic, electronic, or mechanical, including photocopying, recording, taping, or information storage and retrieval systems—without permission of the publisher.

The publisher makes no representation, express or implied, that the drug doses in this book are correct. Readers must check up to date product information and clinical procedures with the manufacturers, current codes of conduct, and current safety regulations. ISBN 978-0-8153-4142-0 Library of Congress Cataloging-in-Publication Data Case studies in infectious disease / Peter M Lydyard ... [et al.]. p. ; cm. Includes bibliographical references. SBN 978-0-8153-4142-0 1. Communicable diseases--Case studies. I. Lydyard, Peter M. [DNLM: 1. Communicable Diseases--Case Reports. 2. Bacterial Infections--Case Reports. 3. Mycoses--Case Reports. 4. Parasitic Diseases-Case Reports. 5. Virus Diseases--Case Reports. WC 100 C337 2009] RC112.C37 2009 616.9--dc22 2009004968

Published by Garland Science, Taylor & Francis Group, LLC, an informa business 270 Madison Avenue, New York NY 10016, USA, and 2 Park Square, Milton Park, Abingdon, OX14 4RN, UK. Visit our web site at http://www.garlandscience.com ISBN 0-203-85380-6 Master e-book ISBN

Peter M. Lydyard, Emeritus Professor of Immunology, University College Medical School, London, UK and Honorary Professor of Immunology, School of Biosciences, University of Westminster, London, UK. Michael F. Cole, Professor of Microbiology & Immunology, Georgetown University School of Medicine, Washington, DC, USA. John Holton, Reader and Honorary Consultant in Clinical Microbiology, Windeyer Institute of Medical Sciences, University College London and University College London Hospital Foundation Trust, London, UK. William L. Irving, Professor and Honorary Consultant in Virology, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK. Nino Porakishvili, Senior Lecturer, School of Biosciences, University of Westminster, London, UK and Honorary Professor, Javakhishvili Tbilisi State University, Tbilisi, Georgia. Pradhib Venkatesan, Consultant in Infectious Diseases, Nottingham University Hospitals NHS Trust, Nottingham, UK. Katherine N. Ward, Consultant Virologist and Honorary Senior Lecturer, University College Medical School, London, UK and Honorary Consultant, Health Protection Agency, UK.

Preface to Case Studies in Infectious Disease The idea for this book came from a successful course in a medical school setting. Each of the forty cases has been selected by the authors as being those that cause the most morbidity and mortality worldwide. The cases themselves follow the natural history of infection from point of entry of the pathogen through pathogenesis, clinical presentation, diagnosis, and treatment. We believe that this approach provides the reader with a logical basis for understanding these diverse medically-important organisms. Following the description of a case history, the same five sets of core questions are asked to encourage the student to think about infections in a common sequence. The initial set concerns the nature of the infectious agent, how it gains access to the body, what cells are infected, and how the organism spreads; the second set asks about host defense mechanisms against the agent and how disease is caused; the third set enquires about the clinical manifestations of the infection and the complications that can occur; the fourth set is related to how the infection is diagnosed, and what is the differential diagnosis, and the final set asks how the infection is managed, and what preventative measures can be taken to avoid the infection. In order to facilitate the learning process, each case includes summary bullet points, a reference list, a further reading list and some relevant reliable websites. Some of the websites contain images that are referred to in the text. Each chapter concludes with multiple-choice questions for self-testing with the answers given in the back of the book. In the contents section, diseases are listed alphabetically under the causative agent. A separate table categorizes the pathogens as bacterial, viral, protozoal/worm/fungal and acts as a guide to the relative involvement of each body system affected. Finally, there is a comprehensive glossary to allow rapid access to microbiology and medical terms highlighted in bold in the text. All figures are available in JPEG and PowerPoint® format at www.garlandscience.com/gs_textbooks.asp We believe that this book would be an excellent textbook for any course in microbiology and in particular for medical students who need instant access to key information about specific infections. Happy learning!!

The authors March, 2009

Table of Contents The glossary for Case Studies in Infectious Disease can be found at http://www.garlandscience.com/textbooks/0815341423.asp Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 Case 11 Case 12 Case 13 Case 14 Case 15 Case 16 Case 17 Case 18 Case 19 Case 20 Case 21 Case 22 Case 23 Case 24 Case 25 Case 26 Case 27 Case 28 Case 29 Case 30 Case 31 Case 32 Case 33 Case 34 Case 35 Case 36 Case 37 Case 38 Case 39 Case 40

Aspergillus fumigatus Borellia burgdorferi and related species Campylobacter jejuni Chlamydia trachomatis Clostridium difficile Coxiella burnetti Coxsackie B virus Echinococcus spp. Epstein-Barr virus Escherichia coli Giardia lamblia Helicobacter pylori Hepatitis B virus Herpes simplex virus 1 Herpes simplex virus 2 Histoplasma capsulatum Human immunodeficiency virus Influenza virus Leishmania spp. Leptospira spp. Listeria monocytogenes Mycobacterium leprae Mycobacterium tuberculosis Neisseria gonorrhoeae Neisseria meningitidis Norovirus Parvovirus Plasmodium spp. Respiratory syncytial virus Rickettsia spp. Salmonella typhi Schistosoma spp. Staphylococcus aureus Streptococcus mitis Streptococcus pneumoniae Streptococcus pyogenes Toxoplasma gondii Trypanosoma spp. Varicella-zoster virus Wuchereia bancrofti

Guide to the relative involvement of each body system affected by the infectious organisms described in this book: the organisms are categorized into bacteria, viruses, and protozoa/fungi/worms

Organism

Resp

MS

GI

H/B

GU

CNS

CV

Skin

Syst

1+

1+

L/H

Bacteria Borrelia burgdorferi

4+

Campylobacter jejuni

4+

Chlamydia trachomatis

2+ 2+

Clostridium difficile

4+

4+

Coxiella burnetti

4+

Escherichia coli

4+

4+

Helicobacter pylori

4+

4+

4+

4+

4+

Listeria monocytogenes

2+

4+

Mycobacterium leprae

4+ 4+

4+

2+ 4+

Neisseria meningitidis

2+ 4+

Rickettsia spp.

4+ 4+

Salmonella typhi

4+

4+ 1+

1+

2+

1+ 1+

4+

Streptococcus pyogenes

4+ 4+

Streptococcus mitis Streptococcus pneumoniae

2+

2+

Neisseria gonorrhoeae

Staphylococcus aureus

4+

4+

Leptospira spp.

Mycobacterium tuberculosis

2+

4+

1+

4+

3+

4+

4+ 3+

Viruses Coxsackie B virus

1+

1+

4+

1+

Epstein-Barr virus Hepatitis B virus

4+

2+

4+

4+

Herpes simplex virus 1

2+

4+

4+

Herpes simplex virus 2

4+

2+

4+

2+

Human immunodeficiency virus

Influenza virus

2+

4+

1+

Norovirus

1+

4+

Parvovirus

2+

Respiratory syncytial virus

4+

Varicella-zoster virus

2+

3+

4+ 2+

4+

2+

Protozoa/Fungi/Worms Aspergillus fumigatus

4+

Echinococcus spp.

2+

Giardia lamblia Histoplasma capsulatum

1+ 4+ 4+

3+

1+

Leishmania spp.

4+

4+ 4+

4+

4+ 4+

Toxoplasma gondii Trypanosoma spp.

4+ 4+

Plasmodium spp. Schistosoma spp.

2+

2+ 4+

Wuchereria bancrofti

4+

4+ 4+ 4+

The rating system (+4 the strongest, +1 the weakest) indicates the greater to lesser involvement of the body system. KEY: Resp = Respiratory: MS = Musculoskeletal: GI = Gastrointestinal H/B = Hepatobiliary: GU = Genitourinary: CNS = Central Nervous System Skin = Dermatological: Syst = Systemic: L/H = Lymphatic-Hematological

Echinococcus spp.

A 28-year-old Kurdish refugee complained of upper abdominal pain for 4 months. He had recently noticed some pain on the right side of his chest. He had not noticed any fever and his weight was stable. His doctor requested a chest X-ray. This showed a mass lesion in the right lung. He was referred to the Thoracic Surgical Department at the local hospital. A CT scan of his chest and abdomen was requested. This demonstrated a cystic structure in his liver, with another cyst in his chest (Figure 1). The surgeons excised the lung lesion. The histopathologists reported that it was a hydatid cyst. The patient was referred to the Infectious Diseases Department. A serological test was positive for Echinococcus. He was given treatment with albendazole and his remaining cyst was monitored serially on scans.

Figure 1. Pulmonary hydatid cysts. Chest X-ray showing hydatid cysts (opaque areas at center right and center left) in a patient’s lungs. The cysts are caused by the parasitic tapeworm Echinococcus sp. Humans are not a natural host for the parasite, but may become infected from ingesting eggs shed in the feces of an infected dog or other canids. Cysts may be formed in the liver, lungs or any other

organ in the body. Large pulmonary cysts may cause symptoms, including shortness of breath, chest discomfort and sometimes wheeze. Treatment involves giving antiparasitic drugs and careful surgical resection when possible.

1. What is the causative agent, how does it enter the body and how does it spread a) within the body and b) from person to person? Causative agent Echinococcus species are tapeworms, also known as cestodes. Adults are only 3–8.5 mm in length. Two species are responsible for the majority of human infections. Echinococcus granulosus arises from dogs and other canids and has been described worldwide. It causes cystic echinococcosis. Echinococcus multilocularis arises from arctic or red foxes and is restricted to the Northern Hemisphere. It causes alveolar echinococcosis. Infection with the latter seems to be spreading as red fox populations have been growing. Adult tapeworms live in the intestines of the dog or wild canid hosts. They attach to the mucosa with suckers and hooks. There are different parts to the structure of the tapeworm, and these are shown in Figure 2. The adult tapeworms lay eggs, which pass out in the feces and contaminate the soil.

2

sucker

ECHINOCOCCUS SPP.

uterus with eggs

Echinococcus granulosus

Figure 2. An adult tapeworm of Echinococcus granulosus.

These may be swallowed by an intermediate host such as sheep for E. granulosus and small mammals for E. multilocularis.

Entry and spread within the body Humans are infected if they accidentally swallow eggs. The eggs have a tough shell that breaks down and releases a larval form called the oncosphere. The oncosphere burrows into the intestinal wall and then spreads to other parts of the body along blood vessels or lymphatics. The liver is the commonest site of infection as most of the intestinal drainage of blood is along the portal vein to the liver. However, infection could arise anywhere in the body. When the oncosphere lodges in an organ it develops into a vesicle. This progressively grows into a cyst. The cyst wall includes an inner germinal layer. From this buds a stage called protoscolex within brood capsules. Around the germinal layer is an acellular, laminated layer. For E. granulosus this cyst is unilocular and known as a hydatid cyst. For E. multilocularis the cyst is multilocular, or referred to as alveolar. Occasionally cysts can rupture giving rise to secondary, ‘daughter’ cysts. The structure of a hydatid cyst due to E. granulosus is shown in Figure 3.

inflammatory cells germinal layer fibrosis acellular layer

Figure 3. Histopathology of the structure of a hydatid cyst. Round protoscoleces are seen on the right. They arise from a thin germinal layer, which is surrounded by an acellular layer; the host inflammatory cells can be seen to the left of this.

Person to person spread Humans do not spread Echinococcus spp. from person to person. Humans are an end host, with occasional exceptions. Intermediate hosts Animals such as sheep or cattle may ingest E. granulosus eggs shed in dog feces. They can act as intermediate hosts. When sheep or cattle are killed, dogs may eat their meat or offal. When the dogs swallow cysts within infected tissues the protoscoleces are released. They attach to the dogs’ intestinal mucosa to mature into the adult tapeworms. Thus the life cycle is completed (Figure 4). Dogs are the definitive hosts. This life cycle for E. granulosus occurs on farms but for E. multilocularis there is a rural, or sylvatic, life cycle with small mammals serving as the intermediate host and arctic or red foxes as the definitive host. Epidemiology Given the life cycle, hydatid disease is most common where dogs and animals such as sheep and cattle mix. In the United Kingdom hydatid disease has been mainly found in sheep farming areas such as North Wales. Worldwide the Turkana district of Kenya has one of the highest incidences of human cystic echinococcosis. Dogs are a key part of Turkana communities that herd cattle. The Turkana do not always bury their dead. Dogs may then scavenge human remains and continue the life cycle.

2. What is the host response to the infection and what is the disease pathogenesis? Potentially the host may mount a response to the oncospheres, after they have entered the intestine, or against the cysts, which become surrounded by the acellular, laminated layer. There may also be a host response to fluid that leaks from a ruptured cyst.

ECHINOCOCCUS SPP.

6 scolex attaches to intestine

definitive host dogs and other canidae

3

4

4

1 adult in small intestine

4 2

5 protoscolex from cyst

4

ingestion of cysts (in organs) i

3 4

ingestion of eggs (in feces)

2 embryonated egg in feces

d

4 hydatid cysts in liver, lungs, etc.

infective stage d diagnostic stage i

intermediate hosts sheep, goats, swine 3 oncosphere hatches: penetrates intestinal wall

Little is known of the host response to the oncospheres. A single or small number of oncospheres may not pose a sufficient antigenic stimulus to trigger an adaptive immune response. The innate immune response, utilizing phagocytic cells or complement, may attack them after invasion of the intestinal mucosa. Once a hydatid cyst has developed an antibody response occurs that is initially IgM followed by an IgG and IgE response. If these antibodies also recognize the oncospheres they could play a part in preventing further ingested oncospheres from causing additional infection. An inflammatory response occurs around the maturing cyst. This is triggered by complement activation. There is an infiltration of macrophages and lymphocytes and these include both CD4+ and CD8+ T lymphocytes. Both Th1- and Th2-type cytokines are found, such as interferon (IFN)-gg, interleukin (IL)-4, and interleukin-10. Eventually a hostderived, fibrous layer forms around the cyst. Complement activation and inflammation subside as the acellular layer accumulates. It is thought that there is local immunomodulation with impaired macrophage responses, impaired dendritic cell differentiation, and T-regulatory cells. Cystderived antigens, including an antigen B, affect the maturation and function of dendritic cells, such that when they present antigen to lymphocytes the immune response skews to a Th2 pattern. The latter is characterized by IL-4 production and increased IgG and IgE levels.

Figure 4. Life cycle of Echinococcus granulosus. Adult worms living in the dog intestine shed eggs in dog feces. These contaminate the environment and may be ingested by intermediate hosts such as sheep. In the intestine oncospheres hatch from the eggs and penetrate the intestinal wall. The oncosphere spreads to other organs and eventually matures into a cyst. Within the cyst protoscolices develop. When a cyst is ingested by a dog the protoscolices are released, attach to the intestinal mucosa as a scolex, and mature into adult worms.

4

ECHINOCOCCUS SPP.

Pathogenesis Large cysts cause pressure and may cause pain or dysfunction of the organ affected. If a hydatid cyst ruptures its proteinaceous contents leak, with a sudden, large antigenic stimulus. This can cause an anaphylactic reaction if IgE antibodies trigger the activation of mast cells and the systemic release of histamine and other mediators (type 1 hypersensitivity).

3. What is the typical clinical presentation and what complications can occur? Hydatid cysts grow gradually. They may not cause any physical problems and may remain asymptomatic. Just over half of infected individuals are asymptomatic. When the cyst is large pressure effects may cause pain or dysfunction of the organ affected. If a cyst ruptures, daughter cysts may cause additional problems and cystic fluid can trigger life-threatening anaphylaxis. Hydatid cysts may be found in any part of the body but about 90% occur in the liver or lung or both. Large cysts in the liver can cause upper abdominal pain. The pain may localize more to the right side of the abdomen, as the right lobe of the liver is most frequently affected. The liver can enlarge and become palpable. The cyst may become secondarily infected with bacteria. If the cyst presses on the biliary tree obstructive jaundice can develop. Rupture into the biliary tree may lead to daughter cysts in the common bile duct. Again these can cause an obstructive jaundice. In the lung large cysts may cause pain. This may be felt as a central chest ache. When cysts abut the chest wall they cause localized pain at these sites. Very large cysts may compromise breathing and make individuals short of breath. Hydatid disease due to E. granulosus has a case fatality rate of about 2%. Infection due to E. multilocularis has a higher mortality rate. It can cause any of the clinical features associated with hydatid disease, but can have a progressive course with growing cysts that enlarge the liver and compromise its function. If cysts rupture an abrupt antigenic challenge may trigger anaphylaxis. A classical anaphylactic reaction comprises swelling of lips, tongue, vocal chords, and bronchial airway mucosa; urticarial reactions in the skin; and a fall in blood pressure. Eosinophilia may be observed if there is cyst leakage but is not uniformly present with intact cysts.

4. How is the disease diagnosed and what is the differential diagnosis? The case history illustrates that sometimes the diagnosis is made after surgical removal of a lesion and histopathological examination. However, it is preferable to make a diagnosis before surgery as accidental incision of a cyst and leakage of its contents may trigger anaphylaxis. Either ultrasound of the liver or a CT scan of thorax or abdomen may reveal a cystic structure. Some features are highly suggestive of a hydatid cyst. There is a thick cyst wall. Septa may be seen within the cyst. If the germinal layer detaches from the cyst wall the inner septa may float in the fluid like a ‘water lily.’ Mature, degenerating cysts may become calcified.

ECHINOCOCCUS SPP.

Serological tests are available for Echinococcus antibodies. Methods used include enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination assays, and latex agglutination assays. The antigens used in assays are derived from hydatid cyst fluid. There may be cross-reactions with other tapeworm infections affecting specificity. Sensitivity may be as low as 50% for infection in the lung, but more than 80% for liver.

Differential diagnosis The differential diagnosis is from other causes of cystic structures. The range of possibilities is larger for the lung (see Ryu and Swensen, 2003) than for the liver. In the liver benign cysts with thin walls can occur. Liver tumors may have the same shape, but are more solid structures. Serological tests will also help to eliminate other pathologies.

5. How is the disease managed and prevented? Management Treatment by surgery and chemotherapy may not be required for small asymptomatic cysts. Surgical removal may be required for troublesome cysts if technically feasible. Prior treatment with albendazole has been shown to benefit the management of liver hydatid cysts (see Gil-Grande et al., 1993). Albendazole given continuously for 1–3 months reduces cyst viability and can lead to shrinkage, making surgery safer. For small, troublesome cysts albendazole treatment alone may be sufficient. Combination treatment with praziquantel may be more effective. Another approach to the management of some cases of cystic echinococcosis has been aspiration of accessible cysts with a needle and injection of an agent such as 95% ethanol to kill the protoscoleces inside the cyst. The ethanol is then aspirated back after 20 minutes. Microscopy of the aspirate shows free protoscoleces, which are sometimes referred to as ‘hydatid sand.’ This method is referred to as PAIR, which stands for Puncture, Aspiration, Injection, Reaspiration. The key risk is anaphylaxis if cyst fluid leaks out. Experienced units report success with PAIR but its place in management requires further investigation.

Prevention Humans need to maintain high standards of hand washing to avoid swallowing eggs. Prevention of Echinococcus infection requires breaking the natural life cycle. Dogs have been treated with arecoline or praziquantel. Praziquantel baiting has been used to treat red foxes. On farms dogs are kept away from offal. Vaccines have been trialed in sheep and dogs. A recombinant DNA vaccine containing the gene for an oncosphere antigen, and designated EG95, has shown >90% protective efficacy in sheep. Despite efforts, Echinococcus infection continues to be a problem in many countries.

5

6

ECHINOCOCCUS SPP.

SUMMARY 1. What is the causative agent, how does it enter the body and how does it spread a) within the body and b) from person to person?

●

Hydatid cysts due to E. granulosus are mostly found in the liver or lung or both. The cysts of E. multilocularis are primarily found in the liver.

●

The causative agent is Echinococcus granulosus or Echinococcus multilocularis. These are tapeworms, or cestodes.

●

Large hydatid cysts in the liver can cause pain, may obstruct the flow of bile, and may rupture into the biliary tree.

●

Adult Echinococcus tapeworms live in the intestine of dogs or foxes and shed eggs in the feces. Dogs and foxes are the definitive hosts.

●

Disease due to E. multilocularis can be steadily progressive.

●

●

The eggs are accidentally swallowed by other species. Once swallowed oncospheres emerge from the eggs, penetrate the intestinal wall, and spread to other parts of the body where they form cysts.

Cyst rupture and leakage of proteinaceous contents can trigger an anaphylactic reaction.

●

●

4. How is the disease diagnosed and what is the differential diagnosis?

Dogs are infected when they eat meat or offal containing cysts. This happens for instance on farms, where they might eat offal from sheep or cattle.

●

Diagnosis is based on imaging such as ultrasound or CT scan. Typical radiological features may be present to diagnose hydatid disease.

●

Additional tests include serology.

Species such as sheep or cows are therefore referred to as intermediate hosts. Humans are usually an end host.

●

Cross-reactions with other tapeworm infections affect the specificity of serology. Sensitivity ranges from 50 to 80%.

●

The differential diagnosis is from other causes of cystic lesions.

2. What is the host response to the infection and what is the disease pathogenesis? ●

●

Little is known about the host response to the oncospheres when they penetrate the intestinal wall. Once the oncospheres develop into cysts in tissues there is a surrounding inflammatory response triggered by complement activation, involving macrophages and then a CD4+ and CD8+ T-lymphocyte response.

●

Eventually an acellular and fibrous layer develops around the cyst with down-regulation of the immune and inflammatory response.

●

The pathogenesis of disease depends on the size of cysts. Large cysts can pose a physical problem in the infected organ.

●

If cysts rupture and leak an IgE-mediated response can be triggered.

3. What is the typical clinical presentation and what complications can occur? ●

Small cysts may remain asymptomatic.

5. How is the disease managed and prevented? ●

Uncomplicated, asymptomatic cysts may be left alone.

●

Symptomatic cysts may be treated with albendazole to reduce cyst viability.

●

Surgical resection may then be performed if necessary and if feasible.

●

Some experienced centers also undertake a procedure called PAIR, which involves percutaneous puncture of cysts, aspiration of contents, injection of etanol, and then reaspiration.

●

Prevention requires breaking the life cycle by treating dogs and preventing the consumption of offal by dogs. To avoid accidental infection humans must maintain high standards of hand hygiene.

ECHINOCOCCUS SPP.

7

FURTHER READING Gottstein B, Reichen J. Echinococcosis/hydatidosis. In: Cook GC, Zumla A, editors. Manson’s Tropical Diseases, 21st edition. Saunders/Elsevier, London/Philadelphia, 2003: 1561–1582.

REFERENCES Craig PS, McManus DP, Lightowlers MW, et al. Prevention and control of cystic echinococcosis. Lancet Infect Dis, 2007, 7: 385–394. Gil-Grande LA, Rodriguez-Caabeiro F, Prieto JG, et al. Randomised controlled trial of efficacy of albendazole in intraabdominal hydatid disease. Lancet, 1993, 342: 1269–1272.

McManus DP, Zhang W, Li J, Bartley PB. Echinococcosis. Lancet, 2003, 362: 1295–1304. Ryu JH, Swensen SJ. Cystic and cavitary lung diseases: focal and diffuse. Mayo Clin Proc, 2003, 78: 744–752.

WEB SITES Centers for Disease Control and Prevention (CDC), 2008, United States Public Health Agency: www.cdc.gov/

World Health Organization, Initiative for Vaccine Research, Copyright WHO 2008: www.who.int

Centre for Infections, Health Protection Agency, HPA Copyright, 2008: www.hpa.org.uk

MULTIPLE CHOICE QUESTIONS The questions should be answered either by selecting True (T) or False (F) for each answer statement, or by selecting the answer statements which best answer the question. Answers can be found in the back of the book.

C. Cysts usually develop from the oncosphere in the intestinal wall. D. Humans spread infection when they pass eggs in their feces.

1. Which of the following are true about Echinococcus?

E. For E. granulosus dogs continue the life cycle when they eat sheep or cattle offal.

A. Echinococcus is a cestode tapeworm. B. Echinococcus granulosus is restricted in its geographical distribution to the Northern Hemisphere. C. Adult worms live in the intestine of humans, sheep or cattle. D. The life cycle for Echinococcus granulosus involves dogs. E. Echinococcus multilocularis does not cause human infections. 2. Which of the following are true about the life cycle of Echinococcus infection? A. Humans are infected by swallowing eggs. B. The larval form that arises from the eggs is called an oncosphere.

3. Which of the following are true about the epidemiology of Echinococcus infection? A. Infection is principally an urban disease. B. The high incidence of infection observed in the Turkana district of Kenya is due to local fox populations. C. Infection due to E. multilocularis can occur in arctic regions. D. Red fox populations are diminishing with a corresponding decline in E. multilocularis. E. E. granulosus infection is disappearing worldwide.

8

ECHINOCOCCUS SPP.

MULTIPLE CHOICE QUESTIONS (continued) 4. Which of the following components are included in the host response to Echinococcus?

8. Which of the following should be considered in the differential diagnosis of Echinococcus infection?

A. A Th2-type response has been clearly established against the invading oncospheres.

A. Benign cysts of the liver.

B. Complement activation occurs as the oncosphere matures into cysts.

C. Liver tumors.

C. Both CD4+ and CD8+ T lymphocytes are found around the cysts.

E. Amebic liver abscess.

D. An inflammatory response occurs that continues unabated around the cysts. E. Anaphylactic reactions occur in response to cysts that rupture and leak. 5. Which of the following statements are true about hydatid cysts? A. Cysts are always symptomatic. B. The spleen is the commonest location for cysts. C. Cysts are usually limited in size and do not enlarge to make organs palpable. D. More than one cyst can develop. E. Cysts can cause pain. 6. What are the recognized complications of infection? A. Rupture of cysts leading to secondary daughter cysts. B. Secondary infection with bacteria.

B. Developmental cysts in the lung. D. Cirrhosis of the liver.

9. Which of the following are relevant for the treatment of Echinococcus infection? A. Surgical resection is always indicated. B. Antiparasitic drug treatment before surgery is beneficial. C. For drug treatment albendazole is always combined with praziquantel. D. Drug treatment is used for 10 days. E. Cysts can also be killed by the injection of 95% ethanol. 10. Which of the following are true for the control of Echinococcus infection? A. It is helped by regular drug treatment of dogs to clear infection. B. It requires the avoidance of feeding farm dogs with offal.

C. Obstructive jaundice when the biliary tree is compressed by a cyst.

C. It requires the routine use of vaccination in animals.

D. Increased blood pressure during an anaphylactic reaction to cyst rupture.

E. It is helped by good hand hygiene measures in farm workers.

E. Death from progressive infection. 7. What is the diagnosis of Echinococcus infection based on? A. A very specific serological test. B. A highly sensitive serological test. C. Recognition of characteristic cyst features on ultrasound or CT scanning. D. The presence of eosinophilia in the blood. E. A diagnostic aspiration of cysts to look for protoscoleces.

D. It is helped by vaccination of humans.

Answers to Multiple Choice Questions 1. Which of the following are true about Echinococcus? A. Echinococcus is a cestode tapeworm. TRUE. B. Echinococcus granulosus is restricted in its geographical distribution to the Northern Hemisphere. FALSE: it is Echinococcus multilocularis that is restricted to the Northern Hemisphere. C. Adult worms live in the intestine of humans, sheep or cattle. FALSE: adult worms live in the intestine of dogs. D. The life cycle for Echinococcus granulosus involves dogs. TRUE. E. Echinococcus multilocularis does not cause human infections. FALSE. 2. Which of the following are true about the life cycle of Echinococcus infection? A. Humans are infected by swallowing eggs. TRUE. B. The larval form that arises from the eggs is called an oncosphere. TRUE. C. Cysts usually develop from the oncosphere in the intestinal wall. FALSE: this is not the usual site for cyst development. Instead they are more commonly found in the liver and/or lung. D. Humans spread infection when they pass eggs in their feces. FALSE: with rare exceptions humans are an end host. As adults do not live in the human intestine no eggs are produced to shed in human feces. E. For E. granulosus dogs continue the life cycle when they eat sheep or cattle offal. TRUE. 3. Which of the following are true about the epidemiology of Echinococcus infection? A. Infection is principally an urban disease. FALSE: infection is usually rural and associated with farms or nomadic herding communities. B. The high incidence of infection observed in the Turkana district of Kenya is due to local fox populations. FALSE: it is due to the close relationship of the Turkana people with their domesticated dogs. C. Infection due to E. multilocularis can occur in arctic regions. TRUE: this can be spread by the arctic fox. D. Red fox populations are diminishing with a corresponding decline in E. multilocularis. FALSE: conversely red fox populations are increasing, with an increase in E. multilocularis infection in some areas.

E. E. granulosus infection is disappearing worldwide. FALSE: there is no sign that this infection has come under control. 4. Which of the following components are included in the host response to Echinococcus? A. A Th2-type response has been clearly established against the invading oncospheres. FALSE: very little is actually known about the host response to the oncospheres when they first penetrate the intestinal mucosa. B. Complement activation occurs as the oncosphere matures into cysts. TRUE. C. Both CD4+ and CD8+ T lymphocytes are found around the cysts. TRUE. D. An inflammatory response occurs that continues unabated around the cysts. FALSE: the inflammatory response abates once the acellular layer is established. In fact immunomodulatory processes come into operation. E. Anaphylactic reactions occur in response to cysts that rupture and leak. TRUE. 5. Which of the following statements are true about hydatid cysts? A. Cysts are always symptomatic. FALSE: small cysts, in noncritical positions may cause no symptoms. B. The spleen is the commonest location for cysts. FALSE: 90% of cysts occur in the liver and/or the lung, with the preponderance being in the liver. C. Cysts are usually limited in size and do not enlarge to make organs palpable. FALSE: cysts may grow so large that the liver becomes palpable. D. More than one cyst can develop. TRUE. E. Cysts can cause pain. TRUE: depending on size and position. 6. What are the recognized complications of infection? A. Rupture of cysts leading to secondary daughter cysts. TRUE. B. Secondary infection with bacteria. TRUE. C. Obstructive jaundice when the biliary tree is compressed by a cyst. TRUE. D. Increased blood pressure during an anaphylactic reaction to cyst rupture. FALSE: in fact in anaphylaxis blood pressure falls, and

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ECHINOCOCCUS SPP.

this may be associated with an urticarial rash and swelling of mucous membranes of the lips, tongue, vocal chords, and bronchial mucosa. E. Death from progressive infection. TRUE: this is particularly the case for E. multilocularis. 7. What is the diagnosis of Echinococcus infection based on? A. A very specific serological test. FALSE: the test is actually not very specific and is used as supportive evidence once a cyst is visualized. B. A highly sensitive serological test. FALSE: the test is not highly sensitive, with reports ranging from 50% for lung cysts and 80% for liver cysts. C. Recognition of characteristic cyst features on ultrasound or CT scanning. TRUE. D. The presence of eosinophilia in the blood. FALSE: eosinophilia is not the rule for Echinococcus infection, but may be seen when cysts leak. B. A diagnostic aspiration of cysts to look for protoscoleces. FALSE: aspiration is used more in the context of treatment in the procedure called PAIR, rather than in diagnosis. There is a risk of anaphylaxis if the cyst is ruptured by puncture. 8. Which of the following should be considered in the differential diagnosis of Echinococcus infection? A. Benign cysts of the liver. TRUE: although these will not have a thick, fibrous capsule. B. Developmental cysts in the lung. TRUE: these can have various radiological appearances. C. Liver tumors. TRUE: but once detailed radiology is obtained tumors will be shown to be solid structures. D. Cirrhosis of the liver. FALSE: this can cause liver enlargement through macronodular cirrhosis, but once detailed radiology is obtained there is no cystic change. E. Amebic liver abscess. TRUE: although like a benign cyst this will not have a thick, fibrous capsule and radiologists will report the lack of defined structures within.

9. Which of the following are relevant for the treatment of Echinococcus infection? A. Surgical resection is always indicated. FALSE: sometimes surgery is technically not feasible and for very small, asymptomatic cysts may be unnecessary. B. Antiparasitic drug treatment before surgery is beneficial. TRUE: this reduces cyst viability and makes surgery safer. C. For drug treatment albendazole is always combined with praziquantel. FALSE: at the moment there is insufficient evidence to say this must be done for all cases. D. Drug treatment is used for 10 days. FALSE: treatment is continued for months, often 3 months. E. Cysts can also be killed by the injection of 95% ethanol. TRUE: As part of the procedure called PAIR used in specialist units. 10.Which of the following are true for the control of Echinococcus infection? A. It is helped by regular drug treatment of dogs to clear infection. TRUE: dogs have been treated with arecoline or praziquantel. B. It requires the avoidance of feeding farm dogs with offal. TRUE: this helps to break the life cycle. C. It requires the routine use of vaccination in animals. TRUE: at the moment vaccination has been trialed but is not routine. D. It is helped by vaccination of humans. TRUE: to date vaccination has not become practice for humans. E. It is helped by good hand hygiene measures in farm workers. TRUE.

Figure Acknowledgements Figure 1. Reprint permission kindly granted by Science Photo Library. Additional photographic credit given as Zephyr and Science Photo Library (M170/384). Figure 2. This figure is the creation of the case study author, Dr. Prith Venkatesan, and was produced specifically for this publication. Figure 3. Reprint permission kindly given by the Centers for Disease Control & Prevention, Atlanta, Georgia. Image is found in the

Public Health Image Library #910. Additional photographic credit is given to Dr. Peter Schantz who took the photo in 1975. Figure 4. Reprint permission kindly given by the Centers for Disease Control & Prevention, Atlanta, Georgia. Image is found in the Laboratory Identification of Parasites of Public Health Concern.