Case Studies in Infectious Disease: Listeria Monocytogenes 9781136986550, 9780815341420, 0203853938, 0815341423, 1136986553

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Listeria monocytogenes

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.

Vice President: Denise Schanck Editor: Elizabeth Owen Editorial Assistant: Sarah E. Holland Senior Production Editor: Simon Hill Typesetting: Georgina Lucas Cover Design: Andy Magee Proofreader: Sally Huish Indexer: Merrall-Ross International Ltd ©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 0-203-85393-8 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

Listeria monocytogenes

A young woman was admitted to hospital with fever, headache, myalgia, and joint pains of 48 hours duration. The previous day she had attended a lunch where she had eaten ham and a soft cheese. She was 26 weeks pregnant. The admitting physician thought the patient may have listeriosis and a blood culture was taken in addition to a full blood count. Gram-positive cocci were reported on the Gram stain of the blood culture and the patient was started empirically on teicoplanin. The following day small hemolytic colonies were present on the blood agar (Figure 1) and a Gram stain revealed gram-positive rods. Further testing showed the organism was motile with tumbling motility and it was biochemically identified as Listeria monocytogenes. A diagnosis of listeriosis was made and the patient’s treatment was changed to ampicillin and gentamicin. Figure 1. Colonies of Listeria monocytogenes on blood agar.

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 Listeria monocytogenes is the cause of human disease. It is a gram-positive nonsporing motile bacillus (Figure 2). There are six species of Listeria: L. monocytogenes, L. ivanovii, L. welshimeri, L. innocua, L. seeligeri, and L. grayi. The most common cause of human disease is L. monocytogenes, although L. ivanovii can rarely cause disease. Listeria species grow on blood agar (see Figure 1) and L. monocytogenes produces a narrow zone of b-hemolysis often only seen beneath the colonies. The organism grows at 37∞C but can also grow slowly at 4∞C and this can be used as an enrichment technique when examining foodstuff. The organism shows a characteristic tumbling (end over end) movement at 25∞C, which is diagnostic. L. monocytogenes has several serotypes based on cell wall (O) and flagellar (H) antigens. The majority of disease is caused by serotypes 1/2a, 1/2b, and 4b. Several molecular subtyping techniques (multilocus enzyme electrophoresis, pulse field gel electrophoresis, and ribotyping) have been found useful in epidemiological investigations. Source of infection L. monocytogenes has been isolated from a variety of natural sources including soil, water, animals, and vegetables and is widely distributed in the animal kingdom, with over 40 species of wild and food-source animals including birds, crustaceans, and fish being colonized. The organism can

Figure 2. Scanning electron microscopic (EM) image of Listeria monocytogenes showing flagella.

2

LISTERIA MONOCYTOGENES

also be carried in the intestine of about 5% of the human population without any symptoms of disease. Infection is acquired by consumption of contaminated food (Figure 3) such as fish, salad, pate, soft cheeses, salami, ham, and coleslaw, where contamination rates as high as 70% may occur. Ingestion of Listeria probably occurs frequently and the organism can be carried in the intestine of the human population for short periods without any symptoms of disease. Interestingly, disease develops mainly in specific groups of individuals including pregnant women, neonates, and immunocompromised patients (see clinical presentation in Section 3 below).

Entry and spread within the body The organism enters the epithelial cells of the intestine using specific adhesion molecules (described in Section 2) and then enters the bloodstream. This gives rise to septicemia or meningitis as the two most common presentations. Localization of the organism in the central nervous system (CNS) is frequently seen, although it is not common in pregnant women for some unidentified reason. An alternative route of infection to the CNS may be intra-axonal spread directly from the peripheral nerves in the gastrointestinal tract. The organism can also cross the placenta to give rise to fetal disease, and subsequent abortion. Epidemiology This organism is found worldwide but most countries do not keep accurate records. In the UK there are about 25 cases per annum. In the USA there were 135 reported cases in 2005, which represents an incidence of 0.3/100 000 population and a decrease of 32% from 1996–1998 figures. In France there were 269 cases in 1999, falling to 209 in 2003.

2. What is the host response to the infection and what is the disease pathogenesis? L. monocytogenes is an intracellular pathogen and a risk factor for infection is lack of cell-mediated immunity. Listeria penetrates both nonphagocytic Figure 3. There are a variety of sources of infection with Listeria.

LISTERIA MONOCYTOGENES

3

and phagocytic cells, thus avoiding the host immune system. Following entry via the epithelial cells of the gastrointestinal tract Listeria enters the lamina propria where it enters dendritic cells and macrophages. Listeria adhesion protein (LAP) is an important adhesin and binds to heat-shock protein 60 expressed on cells. Additionally, Listeria has surface proteins, for example Act A and internalin (InlA,B), which are important in cellular penetration. Act A binds to heparin on the cell surface and internalin binds to E-cadherin, which induces actin re-arrangement and phagocytosis of the bacterium. Listeria is taken up into membrane-bound vesicles (phagosomes in phagocytic cells). Uptake of Listeria into endosomes by the nonphagocytic epithelial cells is via receptor-mediated endocytosis. In order to avoid phagolysosome fusion and thus killing, in professional phagocytic cells, Listeria escapes from inside the phagosome by secreting a pore-forming enzyme listeriolysin O and phospholipases that disrupt the phagosome membrane. Escape from the endosomes in nonphagocytic cells occurs in a similar way. Once in the cytoplasm the organism replicates and a protein (Act A) at one pole of the cell precipitates and polymerizes actin. This polymerized actin forms a growing scaffold that pushes the bacterium through the cytoplasm to the plasma membrane where it makes contact with the plasma membrane of an adjacent cell, is promptly ingested, and the whole process is repeated (Figure 4). The infected host cells eventually die by apoptosis or necrosis.

Figure 4. Escape of Listeria monocytogenes from the phagosome, actin polymerization, and movement into an adjacent cell. 1, uptake; 2, escape from the phagosome by listeriolysin O and phospholipases; 3, actin polymerization; 4, penetration to an adjacent cell; 5, intracytoplasmic replication.

1 phagocytosis

phagosome

2 phagosome lysis

3 formation of actin tail

5 replication in cytoplasm

4 Listeria infects neighboring cell

4

LISTERIA MONOCYTOGENES

In the CNS, Listeria will predominately penetrate microglia and to a lesser extent astrocytes and oligodendrocytes. Direct penetration into neurons is rare, although if co-cultured with macrophages Listeria can penetrate neurons following cell to cell contact. L. monocytogenes may invade the CNS by several routes: hematogenous spread and direct invasion of endothelial cells of the blood–brain barrier; circulating mononuclear cells carrying Listeria; or a direct neural route by intra-axonal spread. In some animals, Listeria may initially be taken up by tissue macrophages in the mouth and spread by cell to cell contact with distal nerve axons and thence by intra-axonal spread into the brain. The role of this route in humans is unclear. Once bacteria arrive in the brain, encephalitis is established by direct cell to cell spread. Pathologically in the brain following infection there is necrosis and focal hemorrhages with meningoencephalitis (Figure 5), microabscesses, vasculitis, and perivascular lymphocytic infiltration. L. monocytogenes is present in the necrotic parenchymal lesions and can be seen in the cytoplasm of macrophages and endothelial cells. Figure 5. Listeria monocytogenes meningoencephalitis. MRI scan showing enhancement around the left midbrain and thalamus and cerebral peduncle, indicating meningoencephalitis in a case of Listeria infection in an immunocompromised patient.

Listeria avoids both the innate and humoral immune system by its intracellular localization. However, antibodies to Listeria can be detected along with complement. These can enhance opsonization, resulting in killing of Listeria by NK (natural killer) cells, dendritic cells, and macrophages. Interferong (IFN-gg) is a key cytokine produced by NK cells, CD4+ Th1 cells, and CD8+ T cells and is important in the immune response to infection with Listeria. Escape from the phagosome in dendritic cells and interleukin (IL)10 are both important for the development of protective cytotoxic CD8 memory cells. This is presumably via enhancement of Th1 responses. Once taken up by activated macrophages many Listeria will be killed following phagolysosome fusion and subsequent oxygen-dependent and independent routes. However, bacteria localized in nonactivated macrophages and epithelial cells and those escaping from the phagosome before phagolysosome fusion can survive in granulomas produced by overactive CD4+ Th1 cells, as in tuberculosis (TB).

3. What is the typical clinical presentation and what complications can occur? L. monocytogenes affects mainly pregnant women, neonates, and immunocompromised individuals. In pregnancy the disease may present as an acute febrile flu-like illness and unlike disease in nonpregnant adults, meningitis is an uncommon presentation. Most disease occurs in the third trimester. About 25% of perinatal infections result in fetal death (leading to spontaneous abortion) and of those that survive about 70% will develop neonatal disease. Infection acquired in utero may result in granulomatosis infantiseptica, which has a high mortality and is due to widespread granulomatous abscesses in many organs. Neonatal infection presents either as an early onset bacteremia or as a late onset (1–2 weeks post partum) meningitis.

LISTERIA MONOCYTOGENES

5

In immunocompromised patients and those over 60 years of age, listeriosis presents most frequently with meningitis (60%) and bacteremia (30%). Brain abscess, abscesses in other organs or endocarditis may complicate bacteremia. Listeria infection in the CNS may present with a meningitis that is indistinguishable from other causes of meningitis or as a meningoencephalitis with altered consciousness and seizures. Large outbreaks of Listeria gastroenteritis in otherwise healthy individuals have occasionally been reported, which presents as diarrhea, fever, and myalgia. This presentation has been linked to consumption of high counts of Listeria in food. Rarely otherwise healthy individuals may develop an encephalomyelitis of the brainstem caused by Listeria, which presents with a flu-like prodrome and a few days later with an acute onset of cerebellar signs, cranial nerve palsies, and respiratory failure.

4. How is this disease diagnosed and what is the differential diagnosis? Diagnosis of listeriosis is confirmed by isolation of L. monocytogenes from a normally sterile site such as the blood or the cerebrospinal fluid (CSF). Mis-identification of Listeria can occur as they may appear like diphtheroids or gram-positive cocci in specimens. Listeria grows well on routine diagnostic media and on blood agar L. monocytogenes (as well as L. seeligeri and L. ivanovii) are beta-hemolytic. L. monocytogenes and L. seeligeri have a narrow zone of beta-hemolysis whereas L. ivanovii has a wide double zone of hemolysis. A number of selective media exist for the isolation of Listeria from food/feces (Table 1). A number of chromogenic media have also been developed to differentiate L. monocytogenes from other Listeria spp. and other bacteria (Figure 6). Serology is not useful for diagnosis of acute cases, although listeriolysin O antibodies have been used to identify patients with noninvasive illness.

Figure 6. BBL CHROMagar showing the characteristic blue-green color of L. monocytogenes surrounded by a white opaque halo.

Table 1. Selective media for the isolation of Listeria from food/feces Selective medium

Constituents

Listeria selective agar

Tryptose, glucose, sodium chloride, thiamine, acriflavine, nalidixic acid

Oxford Listeria agar

Peptone, corn starch, sodium chloride, esculin, lithium chloride, ferric ammonium citrate

Al-Zoreky Sadine Listeria agar

Acriflavine, ceftazidime, moxalactam

Listeria PALCAM agar

Peptone, starch, sodium chloride, D-mannitol, ammonium ferric citrate, esculin, glucose, lithium chloride, polymyxin, ceftazidime, phenol red

LPM agar

Casein, peptone, beef extract, sodium chloride, lithium chloride, glycine, phenylethanol, moxalactam

HiChrome Listeria agar

Meat extract, yeast extract, peptone, rhamnose, sodium chloride, lithium chloride, chromogenic mixture

Listeria selective supplement I

Acriflavine, cyclohexamide, nalidixic acid

Listeria selective supplement II

Acriflavine, cyclohexamide, colistin, cefotetan, fosfomycin

6

LISTERIA MONOCYTOGENES

Differential diagnosis As Listeria infection presents as a pyrexia of unknown origin (PUO), a bacteremia or a meningitis, any of the microorganisms causing these conditions must be considered in the differential diagnosis. There should be a high index of suspicion for Listeria infection if PUO, bacteremia or meningitis occur in the at-risk groups. In particular the other main causes of neonatal bacteremia and meningitis (group B Streptococcus and E. coli) should be considered.

5. How is the disease managed and prevented? Management Disease caused by Listeria is usually treated with a combination of ampicillin and gentamicin. Co-trimoxazole can be used in patients who are hypersensitive to b-lactams or in place of gentamicin. In patients who are pregnant and who cannot take folic acid inhibitors, a glycopeptide can be used in place of ampicillin. Bacteremia is usually treated for 2 weeks and meningitis for 3 weeks, although because of the affinity of Listeria for the CNS one can argue that bacteremia should also be treated for 3 weeks. Brain abscess or endocarditis should be treated for 6 weeks.

Prevention At-risk individuals (pregnancy, neonates, immunocompromised) should avoid food in which Listeria can grow to high cell numbers (e.g. pate and deli meats, soft cheese, raw seafood, salad, and coleslaw) and correct foodhandling precautions will reduce the chance of infection. There are no vaccines for Listeria as yet.

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? ●

There are several species of Listeria but L. monocytogenes is responsible for the majority of disease.

●

L. monocytogenes is a motile nonspore-forming gram-positive rod.

●

L. monocytogenes can grow at 4∞C and shows characteristic tumbling motility at 25∞C.

●

L. monocytogenes produces a narrow zone of betahemolysis on blood agar.

●

Listeria spp. are ubiquitous in animals and the environment and therefore found globally.

●

Infection is usually acquired from consumption of contaminated food.

●

Neonatal infection can be acquired transplacentally.

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

Listeria is an intracellular pathogen avoiding the host immune system.

●

Listeria penetrates both phagocytic and nonphagocytic cells.

●

Listeria escapes from the phagosome with the aid of listeriolysin O.

●

Listeria precipitates actin when in the cytoplasm and penetrates adjacent cells.

●

Listeria infection is limited by CD8 cytotoxic T cells.

LISTERIA MONOCYTOGENES

isolation of the organism from sterile sites such as blood or CSF on routine blood agar.

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

L. monocytogenes typically infects pregnant women, neonates, and immunocompromised individuals.

●

Several selective media exist for the isolation of Listeria from food or feces.

●

Disease in pregnant women presents as a flu-like illness but can cause spontaneous abortion and granulomatosis infantiseptica.

●

Serology is not helpful in diagnosis of acute illness.

●

●

In neonates early post-partum disease presents as a bacteremia and late onset disease as a meningitis.

Any of the many causes of bacteremia, endocarditis, and meningitis can mimic the presentation of listeriosis and a high index of suspicion should be held in at-risk groups.

●

Disease in immunocompromised adults presents as a meningitis or bacteremia.

5. How is the disease managed and prevented?

●

Disease caused by L. monocytogenes in otherwise healthy adults is infrequent but may present as a brainstem meningoencephalitis or as a febrile gastroenteritis.

●

Bacteremia may be complicated by abscesses or endocarditis.

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

7

●

Treatment is with ampicillin and gentamicin.

●

Co-trimoxazole is an alternative treatment in case of penicillin hypersensitivity.

●

In penicillin hypersensitivity in pregnancy a glycopeptide should be used.

●

At-risk individuals (pregnancy, neonates, immunocompromised) should avoid food in which Listeria can grow to high cell numbers.

Disease caused by Listeria is diagnosed by

FURTHER READING Cimolai N. Laboratory Diagnosis of Bacterial Infections. Marcel Dekker, NY, 2001: 333–375.

Murphy K, Travers P, Walport M. Janeway’s Immunobiology, 7th edition. Garland Science, New York, 2008.

Mandell GL, Bennet JE, Dolin R. Principles & Practice of Infectious Diseases, 6th edition, Vol 2. Churchill Livingstone, Philadelphia, 2005: 2478–2484.

Wilson M, McNab R, Henderson B. Bacterial Disease Mechanisms: An Introduction to Cellular Microbiology. Cambridge University Press, London, 2002: Chapter 8.

Mims C, Dockrell HM, Goering RV, Roitt I, Wakwlin D, Zuckerman M. Medical Microbiology, 3rd edition. Mosby, London, 2004.

REFERENCES Bahjat KS, Liu W, Lemmens EE, et al. Cytosolic entry controls CD8+-T-cell potency during bacterial infection. Infect Immun, 2006, 74: 6387–6397. Bierne H, Cossart P. Listeria monocytogenes surface proteins: from genome predictions to function. Microbiol Mol Biol Rev, 2007, 71: 377–397. Bierne H, Cossart P. InlB a surface protein of Listeria monocytogenes that behaves as an invasin and a growth factor. J Cell Sci, 2002, 115: 3357–3367. D’Orazio SE, Troese MJ, Starnbach MN. Cytosolic localization of Listeria monocytogenes triggers an early IFN gamma response by CD8 T cells that correlates with innate resistance

to infection. J Immunol, 2007, 177: 7146–7154. Foulds KE, Rotte MJ, Seder RA. IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes infection. J Immunol, 2006, 177: 2565–2574. Gandhi M, Chikindas ML. Listeria: a foodborne pathogen that knows how to survive. Int J Food Microbiol, 2007, 113: 1–15. Kim KP, Jagadeesan B, Burkholder KM, et al. Adhesion characteristics of Listeria adhesion protein (LAP)-expressing Escherichia coli to Caco-2 cells and of recombinant PAP to eukaryotic receptor Hsp60 as examined in a surface plasmon resonance sensor. FEMS Microbiol Lett, 2006, 256: 324–332.

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REFERENCES Lecuit M. Understanding how Listeria monocytogenes targets and crosses host barriers. Clin Microbiol Infect, 2005, 1: 430–436. Ramaswamy V, Cresence VM, Rejitha JS, et al. Listeria – review of epidemiology and pathogenesis. J Microbiol Immunol Infect, 2007, 40: 4–13.

Shaughnessy LM, Swanson JA. The role of activated macrophages in clearing Listeria monocytogenes infection. Front Biosci, 2007, 12: 2683–2692.

WEB SITES Centers for Disease Control and Prevention, Division of Foodborne, Bacterial and Mycotic Diseases, Atlanta, GA, USA: http://www.cdc.gov/nczved/dfbmd/disease_listing/listeriosis _gi.html Centre for Infections, Health Protection Agency, HPA Copyright, 2008: http://www.hpa.org.uk/infections/topics_az/ listeria/menu.htm

Agriculture: http://www.fsis.usda.gov/Fact_Sheets/Listeriosis _and_Pregnancy_What_is_Your_Risk/index.asp Food and Drug Administration, United States Department of Health and Human Services: http://www.fda.gov/FDAC/ features/2004/104_bac.html World Health Organization, © 2003 WHO/OMS: http://www.who.int/topics/listeria_infections/en/

Food Safety and Inspection Service, United States Department of

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. 1. Which of the following are true of Listeria species?

4. Which of the following are true of the clinical presentation of diseases caused by L. monocytogenes? A. Granulomatosis infantiseptica may occur. B. Infection in pregnant women may lead to spontaneous abortion. C. It is typically associated with necrotizing fasciitis.

A. They are gram-positive.

D. Meningitis is common in pregnant women.

B. L. monocytogenes is nonmotile.

E. Outbreaks are uncommon.

C. L. monocytogenes can grow at 4∞C. D. All Listeria species are pathogenic for humans. E. L. monocytogenes is alpha-hemolytic.

5. Which of the following are useful in the diagnosis of Listeria? A. Gram stain.

2. Which of the following are true concerning Listeria monocytogenes?

B. Culture. C. Serology.

A. It is ubiquitous in the environment.

D. PCR.

B. Infection is a zoonosis.

E. Gas-liquid chromatography.

C. Soft cheese is a low risk food that is unlikely to be contaminated with large numbers of L. monocytogenes. D. Infection may be acquired transplacentally. E. Infection is associated with certain at-risk groups.

6. Which of the following are used in the treatment or prevention of Listeria? A. Vaccination. B. Co-trimoxazole.

3. Which of the following are true for Listeria?

C. Gentamicin.

A. The bacteria are rapidly killed by antibodies.

D. Education leaflets.

B. Listeria has a tropism for the CNS.

E. Good kitchen practices.

C. Listeria induces uptake into nonphagocytic cells. D. Listeria hydrolyzes actin in the cytoplasm. E. Listeria infection is controlled by cytotoxic CD8 cells.

Answers to Multiple Choice Questions 1. Which of the following are true of Listeria species? A. They are gram-positive. TRUE: Listeria are nonsporing gram-positive bacilli. B. L. monocytogenes is nonmotile. FALSE: Listeria are motile and L. monocytogenes has flagella and a characteristic tumbling motility at 25∞C. C. L. monocytogenes can grow at 4∞C. TRUE: and this means that refrigeration does not prevent bacterial multiplication. Also this attribute can be used to enrich for Listeria. D. All Listeria species are pathogenic for humans. FALSE: L. monocytogenes causes most human disease. E. L. monocytogenes is alpha-hemolytic. FALSE: L. monocytogenes produces a narrow zone of betahemolysis surrounding the colony. 2. Which of the following are true concerning Listeria monocytogenes? A. It is ubiquitous in the environment. TRUE: it is found on vegetation, in water, and colonizes a wide variety of animals. B. Infection is a zoonosis. TRUE: infection can be acquired from animal sources. C. Soft cheese is a low risk food that is unlikely to be contaminated with large numbers of L. monocytogenes. FALSE: some soft cheeses have high counts of L. monocytogenes. D. Infection may be acquired transplacentally. TRUE: giving rise to fetal disease. E. Infection is mostly associated with certain at-risk groups. TRUE: pregnant women, neonates, immunocompromised subjects. 3. Which of the following are true for Listeria? A. The bacteria are rapidly killed by antibodies. FALSE: as Listeria is an intracellular pathogen. B. Listeria has a tropism for the CNS. TRUE: and causes meningoencephalitis. C. Listeria induces uptake into nonphagocytic cells. TRUE: and is taken up into a phagosome from which it escapes with the aid of listeriolysin O. D. Listeria hydrolyzes actin in the cytoplasm. FALSE: it polymerizes actin, which it uses to move from one cell to an adjacent cell. E. Listeria infection is controlled by cytotoxic CD8 cells. TRUE: and is also killed by activated macrophages. 4. Which of the following are true of the clinical presentation of diseases caused by L. monocytogenes? A. Granulomatosis infantiseptica may occur. TRUE: following transplacental transmission. B. Infection in pregnant women may lead to spontaneous abortion. TRUE: as the placenta becomes infected and the fetus develops widespread abscesses.

C. It is typically associated with necrotizing fasciitis. FALSE: this is typically caused by Streptococcus pyogenes. D. Meningitis is common in pregnant women. FALSE: meningitis is uncommon in pregnant women. E. Outbreaks are uncommon. TRUE: although a number or outbreaks of listeriosis have been reported in association with pate, coleslaw, chocolate milk, compared with many other food-borne pathogens such as Salmonella and E. coli O157, outbreaks caused by Listeria are uncommon. 5. Which of the following are useful in the diagnosis of Listeria? A. Gram stain. TRUE: it can be helpful but in some specimens the organism may be regarded as a diphtheroid or appear as a coccus. B. Culture. TRUE: producing a narrow zone of beta-hemolysis of blood agar. C. Serology. FALSE: it is not helpful. D. PCR. FALSE: it is not part of the routine clinical diagnosis but is available. E. Gas-liquid chromatography. FALSE: this is used to detect anaerobic infection in pus. 6. Which of the following are used in the treatment or prevention of Listeria? A. Vaccination. FALSE: a vaccine does not yet exist. B. Co-trimoxazole. TRUE: it can be used in patients with penicillin hypersensitivity. C. Gentamicin. TRUE: it is used with ampicillin as part of the routine first-line treatment. D. Education leaflets. TRUE: as part of the education of pregnant women not to eat high risk foods. E. Good kitchen practices. TRUE: as they can prevent contamination of cooked food from raw food and correct cooking temperatures will kill the organism.

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Figure Acknowledgements Figure 1. Reprint permission kindly granted by Science Photo Library. Additional photographic credit given as CC Studio / Science Photo Library (M874/658). Figure 2. Reprint permission kindly granted by Science Photo Library. Additional photographic credit given as A.B. Dowsett / Science Photo Library (B220/273). Figure 3. Reprint permission kindly granted by Science Photo Library. Additional photographic credit given as Maximilian Stock Ltd / Science Photo Library (H110/1266).

Figure 4. This figure is the creation of the case study author, Professor John Holton, and was produced specifically for this publication. Figure 5. Reprint permission kindly granted by Barrow Neurological Institute, Barrow Quarterly, 19 (4): 20–24, Figure 3, 2003. © Barrow Neurological Institute. Figure 6. Reprint permission kindly granted by Becton, Dickinson and Company, http://www.bd.com/ © Becton, Dickinson and Company.