Book Cover......Page 1 Title......Page 2 Copyright......Page 3 Preface to Case Studies in Infectious Disease......Page 4 Table of Contents......Page 5 Plasmodium spp.......Page 8 Answers to Multiple Choice Questions......Page 21 cover Author(s): Lydyard, Peter M Publisher: Garland Science, Year: 2010 ISBN: 9781136986062,9780815341420,0203854004,0815341423,9780203854006,9781136986017,1136986014,9781136986055,1136986057,1136986065
Plasmodium 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 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 Communicable diseases Case studies I Lydyard, Peter M [DNLM: Communicable Diseases Case Reports Bacterial Infections Case Reports Mycoses Case Reports Parasitic Diseases-Case Reports 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 Park Square, Milton Park, Abingdon, OX14 4RN, UK Visit our web site at http://www.garlandscience.com ISBN 0-203-85400-4 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 Case Case Case Case Case Case Case Case 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 Herpes simplex virus 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 2+ 4+ 4+ Herpes simplex virus 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 Plasmodium spp A 26-year-old model went to see her doctor about week after returning from a job in the Gambia She complained of an abrupt onset of bouts of shivering and feeling cold, vomiting, rigors, and profuse sweating accompanied by a headache and nausea On examination she was noted to be pale with a temperature of 39.5∞C and had tachycardia She gave a history of having taken antimalarial tablets before and during her stay in the Gambia but was admitted to hospital with a provisional diagnosis of malaria 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 The organism causing malaria is Plasmodium, a eukaryotic protozoan that infects the erythrocytes of humans It has the characteristics of eukaryotes, with a nucleus, mitochondria, endoplasmic reticulum, and so forth Until recently four species of Plasmodium were identified as being able to infect humans: P falciparum, P ovale, P vivax, and P malariae A simian plasmodium, P knowlesi, has been recently proven infective to humans P falciparum is the most virulent species of malaria in humans All these species have similar life cycles in which the organisms undergo both sexual and asexual reproduction in the vector and host and alternate between intracellular and extracellular forms The female Anopheles mosquito is the vector for malaria The risk of malaria transmission is therefore restricted to those areas where mosquitoes can breed and where the parasite can develop within the mosquito The maximum extent of malaria risk is between approximately 60∞N and 30∞S (except areas higher than around 2500 meters), although this distribution has been reduced dramatically and is currently restricted mainly to the tropics and subtropics – see Epidemiology below Entry and spread within the body The transmission stage of Plasmodium is the sporozoite, which is injected into the bloodstream of a human when the female Anopheles mosquito takes a blood meal (Figure 1) The detailed life cycle is shown in Figure Following the mosquito bite, at least some of the sporozoites remain in the dermis for some time before entering the bloodstream and some pass into draining lymph nodes Only a few dozen sporozoites are transmitted during feeding but there is rapid translocation into the liver to begin the first stage of disease Liver stage (pre-erythrocytic stage) The blood-borne sporozoites localize in the liver via the sinusoids, where through their surface circumsporoite protein (CSP) they attach to the Figure Anopheles funestus mosquito taking a blood meal from its human host This mosquito species, together with Anopheles gambiae, is one of the two most important malaria vectors in Africa Note the blood passing through the proboscis 2 PLASMODIUM highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of the of hepatocytes Other membrane molecules are important for this binding The sporozoites actively enter the hepatocytes, (invade – rather than are taken up passively by endocytosis) and here they increase in number and develop into schizonts P vivax and P ovale also produce a liver cell i mosquito takes a blood meal (injects sporozoites) oocyst infected liver cell oocyst ruptures, sporozoites released liver stage oocyst develops i schizont ruptures, merozoites released vector stage schizont ookinete mosquito takes a blood meal immature trophozoite (ring stage) d (ingests gametocytes) microgametocyte enters macrogametocyte erythrocytic stage macrogametocyte d schizont exflagellated microgametocyte P falciparum d infective stage d diagnostic stage i mature trophozoite gametocyte development gametocytes Figure The life cycle of Plasmodium (1) The mosquito injects saliva containing sporozoites as it takes a blood meal and the parasite localizes in the liver (liver stage), where it undergoes a stage of development to produce a schizont in the infected liver cell, which contains merozoites (2) P vivax and P ovale also produce a resting stage within the liver cell called hypnozoites, which can persist in the liver and result in relapses months or even years later The dead liver cell breaks open and the shizont ruptures (3) releasing merozoites into the bloodstream These invade erythrocytes (erythrocytic stage) and undergo developmental stages as trophozoites, which mature and produce schizonts, at which stage the erythrocyte bursts rupturing the shizonts to release further merozoites (4) Further O O cycles of asexual development within uninfected erythrocytes occur, releasing more merozoites to infect further erythrocytes Differentiation of the immature trophozoite into male and female gametocytes occurs in some erythrocytes (5) and these are ingested when a mosquito takes a blood meal The male (microgametocyte – exflagellated) fertilizes the female macrogametocyte (6) to form a zygote within the intestine of the mosquito (vector stage) and this becomes an ookinete that invades the intestinal wall where it develops into an oocyte (7) The oocyte matures into sporozoites, which are released and migrate to the salivary gland of the mosquito Here they will be transmitted to a new human host when the mosquito takes a blood meal and the cycle starts again (1) PLASMODIUM resting stage within the liver cell called hypnozoites, which are responsible for the relapses that occur with these forms of malaria (see later) This asexual stage takes up to weeks Rupture of the liver cells releases the schizonts into the bloodstream as merozoites (with about 10–40 000 being released from the liver) Erythrocytic stage These invade and destroy erythrocytes giving rise to symptoms (see complications later) The entry of the merozoites into erythrocytes is achieved through attachment of a number of surface molecules (merozoite surface proteins, MSPs) to structures on the erythrocyte, for example band protein for P falciparum P vivax has a specific reticular binding protein to enable it to attach and invade reticulocytes In addition, P vivax has surface molecules (Duffy binding proteins – DBPs) that bind to Duffy blood group antigens on the erythrocytes The lack of this antigen in some human populations, mostly West Africans, explains their resistance to P vivax Within the erythrocyte, the merozoites undergo further development as a trophozoite (seen as a ‘ring’ stage – see Figure 2) and then undergo asexual reproduction to produce schizonts, at which stage the erythrocyte bursts releasing merosomes containing 16–32 daughter merozoites into the bloodstream Each asexual cycle takes 44–48 hours, and is followed by cell rupture and re-invasion steps that induce periodic waves of fever in the patient (see Figure and Section 3) This erythrocytic cycle may continue for months or years However, in some erythrocytes the trophozoites differentiate into male and female gametocytes and a mosquito taking a blood meal will take up some of gametocyte-containing erythrocytes, heralding the sexual developmental phase in the vector temperature °C Vector stage Within the intestine of the insect, male (exflagellated microgametocytes) and female gametes (macrogametocytes) fuse to become a zygote These become an ookinete, which then invades the intestinal wall where it develops into an oocyte The oocyte develops into thousands of sporozoites, which then migrate to the mosquito’s salivary gland 41 Figure Cyclical fever coincident with the release of merozoites 40 39 38 37 36 am pm day pm am day am pm day P vivax, P ovale, P falciparum (if synchronous) P malariae am pm day 4 PLASMODIUM Person to person spread The sporozoites are injected into an individual when an infected female Anopheles mosquito feeds and the whole cycle starts again Non-mosquito spread Malaria can also be transmitted through blood transfusion, hypodermic needle sharing or accidents, and from mother to fetus Epidemiology According to the World Health Organization (WHO), malaria is worsening or barely contained in many parts of the world Global incidence is estimated to be 350–500 million cases of clinical malaria each year, with 300 million carriers of the parasite Estimates made independently by others using a combination of epidemiologic, geographic, and demographic data have put the overall clinical episodes of malaria at up to 50% higher and 200% higher for areas outside Africa The higher values are believed to reflect the WHO’s reliance on passive national reporting for these countries Most malaria infections and deaths occur in sub-Saharan Africa, where it is estimated to account for 80% of all clinical cases and about 90% of all people that carry the parasite Malaria deaths have been estimated at 800 000 per year in children and a child dies every 30 seconds! Asia, Latin America, the Middle East, and parts of Europe are also affected With increasing international travel, there continues to be a rise in the number of cases of malaria in travelers returning to nonmalarious areas from countries where malaria is endemic During the last decade, there has been an average of 1843 cases of malaria in Great Britain each year The global incidence of P falciparum is shown in Figure Pregnancy has a high risk of malaria An estimated 10 000 pregnant women and 200 000 of their infants die annually in sub-Saharan Africa as a result of malaria infection during pregnancy HIV-infected pregnant women are at increased risk Human genetic factors that decrease the infection rates of Plasmodium As already mentioned, the absence of DBPs in most West Africans prevents infection by P vivax, since it uses the Duffy blood group antigen as a means of attachment Sickle cell trait (heterozygous for HbS with HbA) gives an increasing amount of immunological protection against malaria as young children grow during their first 10 years of life, although the mechanism is currently unknown Glucose phosphate dehydrogenase (G6PD) deficiency confers resistance to malaria; again, the mechanism is unknown What is the host response to the infection and what is the disease pathogenesis? Plasmodium has a number of ‘escape mechanisms’ that allow it to avoid the immune response For example, it has numerous morphological forms through its life cycle (Section 1) that are found both extracellularly and intracelluarly The organism can also modify its surface receptors to bind to hepatocytes (sporozoites) and erythrocytes (merozoites) In addition, PLASMODIUM Figure Global incidence of P falciparum Dark red areas: ≥0.1 per thousand of the population; pink areas: