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
Trang 2Peter M Lydyard
Michael F Cole
John Holton William L Irving
Nino Porakishvili
Pradhib Venkatesan
Katherine N Ward
Plasmodium spp.
Trang 3Vice President: Denise Schanck
Editor: Elizabeth Owen
Editorial Assistant: Sarah E Holland
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©2010 by Garland Science, Taylor & Francis Group, LLC
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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 Diseases Case Reports WC 100 C337 2009]
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
Peter M Lydyard, Emeritus Professor of
Immunology, University College MedicalSchool, London, UK and HonoraryProfessor of Immunology, School ofBiosciences, University of Westminster,
London, UK Michael F Cole, Professor
of Microbiology & Immunology,Georgetown University School ofMedicine, Washington, DC, USA
John Holton, Reader and Honorary
Consultant in Clinical Microbiology,Windeyer Institute of Medical Sciences,University College London and UniversityCollege London Hospital Foundation Trust,
London, UK William L Irving, Professor
and Honorary Consultant in Virology,University of Nottingham and NottinghamUniversity Hospitals NHS Trust,
Nottingham, UK Nino Porakishvili,
Senior Lecturer, School of Biosciences,University of Westminster, London, UKand Honorary Professor, JavakhishviliTbilisi State University, Tbilisi, Georgia
Pradhib Venkatesan, Consultant in
Infectious Diseases, Nottingham UniversityHospitals NHS Trust, Nottingham, UK
Katherine N Ward, Consultant Virologist
and Honorary Senior Lecturer, UniversityCollege Medical School, London, UK andHonorary Consultant, Health ProtectionAgency, UK
ISBN 0-203-85400-4 Master e-book ISBN
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
Trang 4The idea for this book came from a successful course in a medical schoolsetting Each of the forty cases has been selected by the authors as beingthose that cause the most morbidity and mortality worldwide The casesthemselves follow the natural history of infection from point of entry ofthe pathogen through pathogenesis, clinical presentation, diagnosis, andtreatment 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 acommon sequence The initial set concerns the nature of the infectiousagent, how it gains access to the body, what cells are infected, and how theorganism spreads; the second set asks about host defense mechanismsagainst the agent and how disease is caused; the third set enquires aboutthe clinical manifestations of the infection and the complications that canoccur; 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 aged, and what preventative measures can be taken to avoid the infection
man-In order to facilitate the learning process, each case includes summary let points, a reference list, a further reading list and some relevant reliablewebsites Some of the websites contain images that are referred to in thetext Each chapter concludes with multiple-choice questions for self-test-ing with the answers given in the back of the book
bul-In the contents section, diseases are listed alphabetically under thecausative 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® mat at www.garlandscience.com/gs_textbooks.asp
for-We believe that this book would be an excellent textbook for any course inmicrobiology and in particular for medical students who need instantaccess to key information about specific infections
Trang 5Case 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 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
Table of Contents
The glossary for Case Studies in Infectious Disease can be found
at http://www.garlandscience.com/textbooks/0815341423.asp
Trang 6Guide 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
Trang 7The 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
Trang 81 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
plasmod-ium, P knowlesi, has been recently proven infective to humans P
falci-parum 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
intracel-lular and extracelintracel-lular 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 2
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
dur-ing feeddur-ing 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
Plasmodium spp.
A 26-year-old model went to see her doctor about 1 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 hadtachycardia She gave a history of having taken anti-malarial tablets before and during her stay in the Gambiabut was admitted to hospital with a provisional diagnosis
of malaria
Figure 1 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
Trang 9highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface ofthe of hepatocytes Other membrane molecules are important for thisbinding 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 stage
erythrocytic stage
infective stage
diagnostic stage
2 3
O O
liver cell
infected liver cell
schizont
schizont
P falciparum
immature trophozoite (ring stage)
mature trophozoite
gametocyte development gametocytes
exflagellated microgametocyte
ookinete
schizont ruptures, merozoites released
Figure 2 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
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)
Trang 10resting 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 2 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
com-plications 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 3
pro-tein for P falciparum P vivax has a specific reticular binding propro-tein to
enable it to attach and invade reticulocytes In addition, P vivax has
sur-face 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
asex-ual 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 3 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
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
sporo-zoites, which then migrate to the mosquito’s salivary gland
Trang 11Person to person spread
The sporozoites are injected into an individual when an infected female
Anopheles mosquito feeds and the whole cycle starts again
worsen-300 million carriers of the parasite Estimates made independently byothers using a combination of epidemiologic, geographic, and demo-graphic data have put the overall clinical episodes of malaria at up to 50%higher and 200% higher for areas outside Africa The higher values arebelieved to reflect the WHO’s reliance on passive national reporting forthese 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 allpeople that carry the parasite Malaria deaths have been estimated at
800 000 per year in children and a child dies every 30 seconds! Asia, LatinAmerica, the Middle East, and parts of Europe are also affected Withincreasing international travel, there continues to be a rise in the number
of cases of malaria in travelers returning to nonmalarious areas fromcountries where malaria is endemic During the last decade, there hasbeen an average of 1843 cases of malaria in Great Britain each year The
global incidence of P falciparum is shown in Figure 4 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 malariainfection during pregnancy HIV-infected pregnant women are atincreased risk
Human genetic factors that decrease the infection rates of Plasmodium
As already mentioned, the absence of DBPs in most West Africans
pre-vents 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 asyoung children grow during their first 10 years of life, although the mech-anism is currently unknown Glucose 6 phosphate dehydrogenase (G6PD)deficiency confers resistance to malaria; again, the mechanism is unknown
2 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 formsthrough its life cycle (Section 1) that are found both extracellularly andintracelluarly The organism can also modify its surface receptors to bind
to hepatocytes (sporozoites) and erythrocytes (merozoites) In addition,