Case studies in infectious disease: Coxiella burnetti

34 Pages·2010·1.446 MB·English

by  Lydyard, Peter M

Coxiella burnetti
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.
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Vice President: Denise Schanck Peter M. Lydyard, Emeritus Professor of
Editor: Elizabeth Owen Immunology, University College Medical
Editorial Assistant: Sarah E. Holland School, London, UK and Honorary
Senior Production Editor: Simon Hill Professor of Immunology, School of
Typesetting: Georgina Lucas Biosciences, University of Westminster,
Cover Design: Andy Magee London, UK. Michael F. Cole, Professor
Proofreader: Sally Huish of Microbiology & Immunology,
Indexer: Merrall-Ross International Ltd Georgetown University School of
Medicine, Washington, DC, USA.
JohnHolton, Reader and Honorary
©2010 by Garland Science, Taylor & Francis Group, LLC Consultant in Clinical Microbiology,
Windeyer Institute of Medical Sciences,
University College London and University
This book contains information obtained from authentic and highly College London Hospital Foundation Trust,
regarded sources. Reprinted material is quoted with permission, and London, UK. William L. Irving, Professor
sources are indicated. A wide variety of references are listed. and Honorary Consultant in Virology,
Reasonable efforts have been made to publish reliable data and University of Nottingham and Nottingham
information, but the author and the publisher cannot assume University Hospitals NHS Trust,
responsibility for the validity of all materials or for the consequences of Nottingham, UK. Nino Porakishvili,
their use. All rights reserved. No part of this book covered by the Senior Lecturer, School of Biosciences,
copyright heron may be reproduced or used in any format in any form University of Westminster, London, UK
or by any means—graphic, electronic, or mechanical, including and Honorary Professor, Javakhishvili
photocopying, recording, taping, or information storage and retrieval Tbilisi State University, Tbilisi, Georgia.
systems—without permission of the publisher. Pradhib Venkatesan, Consultant in
Infectious Diseases, Nottingham University
Hospitals NHS Trust, Nottingham, UK.
The publisher makes no representation, express or implied, that the Katherine N. Ward, Consultant Virologist
drug doses in this book are correct. Readers must check up to date and Honorary Senior Lecturer, University
product information and clinical procedures with the manufacturers, College Medical School, London, UK and
current codes of conduct, and current safety regulations. Honorary Consultant, Health Protection
Agency, UK.
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
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ISBN 0-203-85378-4 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
Coxiella burnetii
In 1998 a 35-year-old woman underwent surgery for elevated levels of IgG (titer 6400) and IgA (titer 6400)
aortic coarctation with the interposition of a Gortex antibodies to phase I Coxiella burnetiiconsistent with the
tube. The operation was successful and there were no chronic Q fever diagnosis. IgMtiters were low confirming
complications. In summer 2006 the woman had spent a the chronic type of infection.
month living in a village in Sri Lanka where she had been Antibiotics were immediately prescribed: doxycycline
helping with charity work and was in close contact with 200 mg per day and ofloxacin 400 mg per day. After 1
newborn cows. In January 2007, the patient was admitted week, the fever decreased, but TEE still showed large
for investigation because of high fever (39.8∞C). It turned vegetations on the graft. The patient was referred for
out that during the previous year she had had several surgery where the prosthetic graft was resected and
episodes of fever, which resolved without medical help. several large vegetations revealed including those in the
On physical examination her pulse rate was 120 lumen of the tube. Due to the infection the prosthetic graft
beats/minute and an arterial pressure 110/46 mmHg. was replaced by a homograft. C. burnetiiwas later detected
Femoral pulses were present with a bruit on the left side, in the aortic specimen (Figure 1B) by polymerase chain
and distal pulses were perceptible. There were no reaction (PCR)and was isolated in Vero cell culture.
neurological abnormalities and the chest X-ray was After surgery, a different combination of antibiotics
normal. However, laboratory tests showed a white blood was prescribed: doxycycline and hydroxychloroquine. The
cell count of 8500 mm–3and creatinine of 1.9 mg dl–1. patient was discharged after 6 weeks and continued
Transthoracic echocardiography (TTE)ruled out the antibiotic treatment with serologic monitoring. After 10
diagnosis of cardiac endocarditis, but detected large months the patient was well, although antibiotic therapy
vegetations in the prosthetic tube (Figure 1A). Although was continuing. There was no recurrent infection of the
blood cultures were sterile, serological tests revealed homograft tube.
Figure 1. (A) Transthoracic
A B
echocardiography (TEE) with arrows
showing large vegetations in the
prosthetic graft. (B) Vascular tissue
with foreign material indicated by
arrows, and showing fibrosis and
nonspecific chronic inflammatory
infiltrate (hematoxylin and eosin
stain, ¥¥200).
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?
The patient is infected with Coxiellaburnetiiand is suffering from chronic
Q fever. C. burnetii is an obligate intracellular bacterium with a complex
life cycle and related morphological heterogeneity. It is a pleomorphic
coccobacillus 0.3–1.0 mm in size (Figure 2). C. burnetiihas a cell wall built
of approximately 6.5 nm thick outer and inner membranes, which are
2 COXIELLA BURNETII
separated by a peptidoglycan layer (Figure 3). A spore-like stage does not
have dipicolinic acid or a spore coat with cysteine characteristic for other
gram-positive bacterial spores. Due to these features C. burnetiiis consid-
ered to be a gram-negative bacterium, although it is almost impossible to
stain C. burnetiiby the Gram technique. The Gimenez staining method is
usually used instead.
C. burnetiihas been traditionally classified with the Rickettsiales order, the
Rickettsiaceae family, and theRickettsiae tribe, which it shared with the
genera Rickettsia and Rochalimaea. However, subsequent rRNA sequence
analysis has demonstrated that the Coxiella genusbelongs to the gamma
subdivision of Proteobacteriaand is closely related to the genera Legionella
and Rickettsiella. C. burnetii genomic analysis revealed more genes regulat-
ing metabolic processes than in other obligate intracellular bacteria such
as Chlamydia(see Case 4) and Rickettsia.
Q fever is a zoonosisandC. burnetiiis found in almost all animal species,
particularly in wild and domestic mammals, birds,and arthropods such as
Figure 2. C. burnetii,microscopic image
ticks. Infected animals most often shed C. burnetii into the environment
(¥¥2200).
during parturition. As many as 109bacteria can be found in 1 g of placenta
at birth. C. burnetii can also contaminate the environment via animal
urine, feces, and milk. Coxiellosis is more frequent in dairy cows and goats
than in sheep. More rarely C. burnetii infection has been identified in
horses, camels, buffalos, swine, rabbits,rats, and mice, and has been iso-
lated from chickens, ducks, geese,turkeys, and pigeons.
Humans usually become infected from cattle, goats,sheep, domestic rumi-
nants, and pets or contaminated dung and bedding. C. burnetii may be
transmitted to humans also from consumption of raw eggs, raw milk, and
cheese or inhalation of infected fomites. Cats and dogs can become
infected through tick bites, eating contaminated placentasor milk, and by
the aerosol route. There are over 40 tick species naturally infected with
C. burnetii. C. burnetii multiplies in the gutcells of infected ticks and is
shed with their feces onto the skinof the animal host. Although C. burnetii
in ticks are in highly infectious phase I stage (see below), the tick-mediated
route of infection is not considered essential in domestic animals com-
pared with their close contact. However, ticks may contribute to the infec-
tion of wild animals such as rodents and wild birds. The role of other
arthropods in coxiellosis transmission – mosquitoes, lice,mites, flies, and
fleas – is controversial. Unlike rickettsial diseases, C. burnetii is not
believed to be transmitted to humans via tick bites.
Genetic variability
There are a variety of C. burnetiistrains (genovars) that are closely associ-
ated with their virulence. Genomic groups I, II, and III belong to so-called
Figure 3. Diagrammatic illustration of
periplasmic space
C.burnetiicell structure.
core
intracellular membrane
peptidoglycan
outer membrane
COXIELLA BURNETII 3
acute strains, which infect animals, ticks, and humans and cause acute
Qfever in humans. Genomic groups IV and V belong to so-called chronic
strains and cause human Q fever endocarditis (see Section 3). Genomic
group VI C. burnetii was isolated from feral rodents in Dugway (Utah,
USA) and has unknown pathogenicity. Acute strains all have QpH1 plas-
mid, and chronic strains have QpRS plasmid or integrated QpRS
sequences. Although genomic strain variations are associated with the geo-
graphic distribution of isolates it appears that host susceptibility to C. bur-
netiiis more important for infection.
There are two variations of C. burnetti, based on their lipopolysaccharide
(LPS) structure, as has been shown in vitro. The virulent natural form
(called phase I variant or simply phase I) has ‘smooth’ LPS while an avir-
ulent laboratory strain (called phase II variant or phase II) has ‘rough’ LPS.
The LPS from the latter variation is truncated due to large chromosomal
deletions. Detection of antibodies to the antigens expressed by these two
forms is used in diagnosis (see Section 4).
Entry into the body
C. burnetii has a complex life cycle. It exists as two distinct forms called
‘small-cell variant’ (SCV) and‘large-cell variant’ (LCV). SCV is a form of
the bacterium that can exist extracellularly and resist environmental con-
ditions such as low or high pH, treatment with ammonium chloride,dis-
infectants, and UV radiation. Only exposure to high (≤to 5%) concentra-
tions of formalin for no less than 24 hours may kill C. burnetii SCV and
this can be used for sanitation. SCVs are small (204 ¥ 450 nmin size),
rod-shaped, and spore-like. This form is metabolically inactive and resist-
ant to osmotic pressure. Its cell wall is rich with proteinsand peptidogly-
can that may render the bacterium high resistance to harsh environmental
conditions.
C. burnetii is inhaled directly from aerosols of infected animals or their
contaminated body fluids, newborns, placenta, and wool. The SCV form
infects alveolar macrophages. It is believed that the organisms enter the
macrophages by attaching to integrin-associated proteins and Toll-like
receptor4 (TLR4) and complement receptor 3 (CR3) molecules. Which
of these is involved in attachment determines successful internalization
and survival in macrophages and monocytes (see Section 2).
After phagolysosomal fusion, the SCVs are activated, multiply, and may
transform into LCVs, which is the metabolically active intracellular form
of C. burnetii (Figure 4). LCVs are up to 2 mm long, more pleomorphic,
rounded,granular, sometimes with fibrillar cytoplasm and with dispersed
nucleoid filaments. Six strain types of LCV have been described:
Hamilton, Bacca, Rasche, Biothere, Corazon, and Dod.
LCVs also divide by binary fission and can undergo sporogenic differenti-
ation leadingto the formation of spore-like endogenous forms of bacteria.
These further develop into the metabolically inactive SCVs, which are
then released from the infected host cell eitherby cell lysisor possibly by Figure 4. Electron micrograph of large
exocytosis and can spread via the bloodstream to other body organs (see cell variant (LCV, indicated by an arrow)
below). At this stage multiplication of C. burnetti in the alveolar of C. burnetii multiplying in a human
macrophages may lead to pneumonia(see Section 3). macrophage.