Case Studies in Infectious Disease: Leishmania Spp

20 Pages·2009·1.757 MB·English

by  Lydyard, Peter;Cole, Michael;Holton, John;Irving, William L

Leishmania 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 Peter M. Lydyard, Emeritus Professor of
collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.
Immunology, University College Medical
Vice President: Denise Schanck School, London, UK and Honorary
Editor: Elizabeth Owen Professor of Immunology, School of
Editorial Assistant: Sarah E. Holland Biosciences, University of Westminster,
Senior Production Editor: Simon Hill London, UK. Michael F. Cole, Professor
Typesetting: Georgina Lucas of Microbiology & Immunology,
Cover Design: Andy Magee Georgetown University School of
Proofreader: Sally Huish Medicine, Washington, DC, USA.
Indexer: Merrall-Ross International Ltd JohnHolton, Reader and Honorary
Consultant in Clinical Microbiology,
Windeyer Institute of Medical Sciences,
©2010 by Garland Science, Taylor & Francis Group, LLC University College London and University
College London Hospital Foundation Trust,
London, UK. William L. Irving, Professor
This book contains information obtained from authentic and highly and Honorary Consultant in Virology,
regarded sources. Reprinted material is quoted with permission, and University of Nottingham and Nottingham
sources are indicated. A wide variety of references are listed. University Hospitals NHS Trust,
Reasonable efforts have been made to publish reliable data and Nottingham, UK. Nino Porakishvili,
information, but the author and the publisher cannot assume Senior Lecturer, School of Biosciences,
responsibility for the validity of all materials or for the consequences of University of Westminster, London, UK
their use. All rights reserved. No part of this book covered by the and Honorary Professor, Javakhishvili
copyright heron may be reproduced or used in any format in any form Tbilisi State University, Tbilisi, Georgia.
or by any means—graphic, electronic, or mechanical, including Pradhib Venkatesan, Consultant in
photocopying, recording, taping, or information storage and retrieval Infectious Diseases, Nottingham University
systems—without permission of the publisher. Hospitals NHS Trust, Nottingham, UK.
Katherine N. Ward, Consultant Virologist
and Honorary Senior Lecturer, University
The publisher makes no representation, express or implied, that the College Medical School, London, UK and
drug doses in this book are correct. Readers must check up to date Honorary Consultant, Health Protection
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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 0-203-85391-1 Master e-book ISBN
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 logi-
cal basis for understanding these diverse medically-important organisms.
Following the description of a case history, the same five sets of core ques-
tions 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 man-
aged, and what preventative measures can be taken to avoid the infection.
In order to facilitate the learning process, each case includes summary bul-
let 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-test-
ing 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 involve-
ment of each body system affected. Finally, there is a comprehensive glos-
sary to allow rapid access to microbiology and medical terms highlighted
in bold in the text. All figures are available in JPEG and PowerPoint® for-
mat 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 Aspergillus fumigatus
Case 2 Borellia burgdorferi and related species
Case 3 Campylobacter jejuni
Case 4 Chlamydia trachomatis
Case 5 Clostridium difficile
Case 6 Coxiella burnetti
Case 7 Coxsackie B virus
Case 8 Echinococcus spp.
Case 9 Epstein-Barr virus
Case 10 Escherichia coli
Case 11 Giardia lamblia
Case 12 Helicobacter pylori
Case 13 Hepatitis B virus
Case 14 Herpes simplex virus 1
Case 15 Herpes simplex virus 2
Case 16 Histoplasma capsulatum
Case 17 Human immunodeficiency virus
Case 18 Influenza virus
Case 19 Leishmania spp.
Case 20 Leptospira spp.
Case 21 Listeria monocytogenes
Case 22 Mycobacterium leprae
Case 23 Mycobacterium tuberculosis
Case 24 Neisseria gonorrhoeae
Case 25 Neisseria meningitidis
Case 26 Norovirus
Case 27 Parvovirus
Case 28 Plasmodiumspp.
Case 29 Respiratory syncytial virus
Case 30 Rickettsiaspp.
Case 31 Salmonella typhi
Case 32 Schistosomaspp.
Case 33 Staphylococcus aureus
Case 34 Streptococcus mitis
Case 35 Streptococcus pneumoniae
Case 36 Streptococcus pyogenes
Case 37 Toxoplasma gondii
Case 38 Trypanosoma spp.
Case 39 Varicella-zoster virus
Case 40 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 L/H
Bacteria
Borrelia burgdorferi 4+ 1+ 1+
Campylobacter jejuni 4+ 2+
Chlamydia trachomatis 2+ 4+ 2+
Clostridium difficile 4+
Coxiella burnetti 4+ 4+
Escherichia coli 4+ 4+ 4+ 4+
Helicobacter pylori 4+
Leptospira spp. 4+ 4+ 4+
Listeria monocytogenes 2+ 4+ 2+ 4+
Mycobacterium leprae 2+ 4+
Mycobacterium tuberculosis 4+ 2+
Neisseria gonorrhoeae 4+ 2+
Neisseria meningitidis 4+ 4+
Rickettsia spp. 4+ 4+ 4+
Salmonella typhi 4+ 4+
Staphylococcus aureus 1+ 1+ 2+ 1+ 4+ 1+
Streptococcus mitis 1+ 4+
Streptococcus pneumoniae 4+ 4+
Streptococcus pyogenes 3+ 4+ 3+
Viruses
Coxsackie B virus 1+ 1+ 4+ 1+
Epstein-Barr virus 2+ 4+
Hepatitis B virus 4+
Herpes simplex virus 1 2+ 4+ 4+
Herpes simplex virus 2 4+ 2+ 4+
Human immunodeficiency virus 2+ 2+ 4+
Influenza virus 4+ 1+ 1+
Norovirus 4+
Parvovirus 2+ 3+ 4+ 2+
Respiratory syncytial virus 4+
Varicella-zoster virus 2+ 2+ 4+
Protozoa/Fungi/Worms
Aspergillusfumigatus 4+ 1+ 2+
Echinococcus spp. 2+ 4+
Giardia lamblia 4+
Histoplasmacapsulatum 3+ 1+ 4+
Leishmania spp. 4+ 4+
Plasmodium spp. 4+ 4+
Schistosoma spp. 4+ 4+ 4+
Toxoplasma gondii 2+ 4+
Trypanosoma spp. 4+ 4+ 4+
Wuchereria bancrofti 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
Leishmania spp.
A 72-year-old gentleman retired to the south of Spain but
returned to the UK for the summer months. He began to
develop fever, malaise, loss of appetite, and weight loss.
He was admitted to hospital and had temperatures
reaching 39∞C. Both his liver and spleen were palpable. No
lymph nodes could be felt. Blood tests showed a
pancytopenia. Routine investigations for an infection
were negative and he did not improve with broad-
spectrum antibiotics. His condition deteriorated and the
size of the liver and spleen increased (Figure 1). A bone
marrow examination did not show any sign of
hematological malignancy. No organisms were seen on
staining. His history was explored again. Four months
before his illness he had been on a camping break in Spain
to a coastal area. He recalled seeing many thin dogs in the
vicinity. Part of his bone marrow sample was sent to a
reference laboratory for Leishmania polymerase chain
reaction(PCR). This returned positive. He was successfully
treated with a course of liposomal amphotericin B and
over the ensuing 3 months his liver and spleen became
impalpable and his blood tests returned to normal. His
diagnosis was visceral leishmaniasis probably due to
Leishmania infantum.
Figure 1. A child with visceral leishmaniasis. As in the
patient described in the case history the liver and spleen
are enlarged, causing distension of the abdomen.
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
Leishmaniaare protozoan parasites. They have an intracellular form called
an amastigote (Figure 2) and an extracellular, flagellated form called a pro-
mastigote (Figure 3).
There is variety in the clinical diseases caused, geographical distribution,
and animal reservoirs. The genus Leishmania is divided into groups,
species, and complexes. Classification was classically determined by isoen-
zyme typing; molecular methods (using DNA) are now more common. Figure 2. A skin biopsy showing
Table 1 lists species and the diseases they cause. Leishmaniaamastigotes (arrowed).
2 LEISHMANIA
Table 1. Species of Leishmaniaand the diseases they cause
Disease Species
Cutaneous leishmaniasis L. aethiopica
L. killicki
L. major
L. tropica
L. amazonensis
L. columbiensis
Figure 3. Elongated Leishmania L. guyanensis
promastigotes. L. lainsoni
L. mexicana
L. naiffi
L. shawi
L. venezuelensis
Mucocutaneous leishmaniasis L. braziliensis
L. panamensis
Visceral leishmaniasis L. donovani
L. infantum
L. chagasi
Entry and spread within the body
People are infected after the bite of a sandfly laden with Leishmania pro-
mastigotes. Under the skin the promastigotes are rapidly phagocytosed by
macrophages. For cutaneous disease lesions are confined to the locality of
the sandfly bite. For L. braziliensisand L. panamensiscutaneous spread can
occur and later this can involve mucous membranes of the mouth or nose.
L. donovani and L. infantum are capable of deeper spread within
macrophages to the rest of the mononuclear phagocytic system, mainly
present in organs such as the liver, spleen, and bone marrow. They are
responsible for visceral leishmaniasis. In India, visceral leishmaniasis is
called kala-azar. Relapse of infection after an interval may be manifest as
a widespread cutaneous form of disease, called post kala-azar dermal leish-
maniasis (PKDL). This occurs in India and East Africa. The life cycle of
Leishmaniais shown in Figure 4.
Person to person spread
In areas with visceral leishmaniasis sandflies can ingest protozoa when they
feed from the skin. Numbers of Leishmania in the skin are even higher in
PKDL. However, leishmaniasis is largely a zoonosis. Different animal
reservoirs occur in different regions. They include rodents, gerbils,
hyraxes, sloths, and the domestic dog.
The sandfly vector is aPhlebotomus species in the Old World and Lutzomyia
species in the New World. Sandflies are small, less than 5 mm in size, and
bite at dusk or during the night (Figure 5). They are not capable of flying
great heights above the ground and usually bite individuals sleeping close
to the ground. In the case described above the patient was probably
infected through sandflies when he was lying near the ground on his camp
bed. He normally lived in a flat. The sandflies will have carried infection
from the local dog population.
LEISHMANIA 3
sandfly stages 1 sandfly takes a blood meal human stages
(injects promastigote stage into
the skin)
i
8 promastigotes divide in
midgut and migrate to
2 promastigotes are
proboscis
phagocytosed by
macrophages
d
3 promastigotes transform
into amastigotes inside
7 amastigotes transform
macrophages
into promastigotes
inside midgut
d
4 amastigotes multiply in cells
6 ingestion of
(including macrophages) of
parasitized cell
various tissues
5 sandfly takes a blood meal
i infective stage
(ingests macrophages infected
d diagnostic stage with amastigotes)
Figure 4. Life cycle of Leishmaniaspp.Leishmania promastigotes transform into amastigotes (3). Amastigotes can
promastigotes are inoculated by sandflies into human and other multiply in various cell types (4). Macrophages containing
animal hosts at the time of taking a blood meal (1). Promastigotes amastigotes are ingested by sandflies taking a blood meal (5) and
are phagocytosed by macrophages (2). Within macrophages the life cycle continues within the sandfly vector (6–8).
Female sandflies bite and take blood from their target host. Any
amastigotes ingested from the skin change into promastigotes. These pass
into the sandfly midgut, proliferate, cause damage to the digestive valve
system, and are regurgitated to the biting mouthparts and then onto the
skin of the next host to be bitten.
Another form of transmission for visceral leishmaniasis has been described
among intravenous drug users in Southern Europe. Infection can be
passed on with shared needles and equipment. In one study about half of
discarded needles in Madrid were positive by PCR for Leishmania.
Epidemiology
Notification of cases of leishmaniasis occurs in only 32 of 88 endemic coun-
tries. Numbers of people afflicted by the disease are therefore estimates.
There are about 0.5 million new cases of visceral leishmaniasis annually,
and 90% of these are seen in Bangladesh, Brazil, India, Nepal, and Sudan.
Another 1.5 million individuals get cutaneous or mucocutaneous disease. Figure 5. Phlebotomussandfly.