Case Studies in Pediatric Infectious Diseases
Case Studies in Pediatric Infectious Diseases
Case Studies in Pediatric Infectious Diseases
Case Studies
in Pediatric
Infectious Diseases
Case Studies
in Pediatric
Infectious Diseases
Frank E. Berkowitz, BSc MBBCh, FCP(Paed)(SA), MPH
Professor of Pediatrics
Department of Pediatrics
Emory University School of Medicine
Atlanta, Georgia, USA
CAMBRIDGE UNIVERSITY PRESS
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, So Paulo
Cambridge University Press
The Edinburgh Building, Cambridge CB2 8RU, UK
First published in print format
ISBN-13 978-0-521-69761-3
ISBN-13 978-0-511-29516-4
Frank Berkowitz 2007
Every effort has been made in preparing this book to provide accurate and up-to-date
information that is in accord with accepted standards and practice at the time of
publication. Nevertheless, the authors, editors, and publisher can make no warranties that
the information contained herein is totally free from error, not least because clinical
standards are constantly changing through research and regulation. The authors, editors,
and publisher therefore disclaim all liability for direct or consequential damages resulting
from the use of material contained in this book. Readers are strongly advised to pay careful
attention to information provided by the manufacturer of any drugs or equipment that
they plan to use.
2007
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This book is dedicated
to the memory of my father,
Abraham Philip Berkowitz,
who first introduced me to the concept
of infectious diseases.
Contents
Preface xiii
PART 1: INTRODUCTION 1
The nature of the practice of infectious diseases 1
Components of a diagnosis 1
Microbiological diagnosis 2
Risk factors for infection 2
Methods for making a microbiological diagnosis 3
Principles of management of patients with infectious diseases 5
Principles of choosing antimicrobial therapy 8
Principles of addressing public health interests 10
PART 2: CLINICAL CASE EXERCISES 12
1. A teenage girl with nausea and abdominal pain 12
2. An 18-month-old child with fever, cough, and red eyes 17
3. An infant with runny nose, cough, and rapid breathing 24
4. A neonate with fever and cerebrospinal fluid pleocytosis 26
5. A 5-year-old boy with a limp 30
6. A teenage boy with sore throat and fever 34
7. A teenage boy with fever, headache, and bleeding 39
8. A teenage boy with agitation and altered level of consciousness 42
vii
9. A 6-year-old girl with a rash 44
10. A 12-year-old girl with fever and rapid breathing after renal transplantation 55
11. A 4-year-old boy with fever after heart surgery 58
12. A 6-year-old girl with sickle cell disease and worsening anemia 59
13. A 5-year-old girl with walking difficulty and speech deterioration 61
14. A 6-month-old boy with poor feeding, fever, and lethargy 63
15. A 2-year-old boy with recurrent hospitalizations for fever and cough 67
16. A neonate with a rash 69
17. A 6-year-old girl with weakness and muscle pain 72
18. A 48-year-old man with fever and multiorgan failure 75
19. A 6-month-old boy with diarrhea and fever 77
20. An 18-month-old girl with fever and a rash 87
21. A neonate with eye discharge 92
22. A 9-year-old boy with joint pain and swelling 94
23. A 3-year-old boy with eyelid swelling 97
24. A 6-year-old boy with fever and sore throat 99
25. A premature neonate with skin spots and ankle swelling 101
26. A 3-year-old boy with fever, confusion, and a rash 104
27. A 6-month-old girl with fever and altered level of consciousness 105
28. A neonate with failure to use one limb 110
29. A 6-month-old child with a ventriculoperitoneal shunt and fever 112
30. A 1-day-old infant with respiratory distress and shock 112
31. An 8-month-old infant with fever and shock 114
32. An infant, recovering from pneumonia, with a facial abnormality 117
33. A picture of an abnormal 5-day-old infant 119
34. A 10-year-old girl with a sore throat after returning to the United States
from Odessa 120
35. A 2-week-old neonate with fever and altered mental status 123
36. A 5-year-old girl with recurrent episodes of fever, cough, and chest pain 124
37. An 8-year-old boy with cough, chest pain, and fever after bone marrow
transplantation 125
38. A 4-month-old infant with constipation and floppiness 127
viii Contents
39. A 15-year-old Turkish shepherd with a sore on his arm 130
40. A 10-year-old girl with previous severe infections, presenting with leg swelling
and pain 131
41. Pictures of several infants 03 months old with the same diagnosis 133
42. A 13-year-old boy with repeated episodes of fever 137
43. A triathlete with fever and headache 139
44. A 13-year-old boy with knee pain 141
45. A 12-year-old girl with abdominal pain 143
46. An 18-month-old boy with fever and rash 146
47. A 24-year-old man with headache, fever, and rash 149
48. A 13-year-old girl with eye pain 151
49. An 18-month-old boy with a limp and fever 153
50. A 3-year-old South African boy with fever and abdominal pain 154
51. A 1-month-old infant with jaundice 157
52. A 12-year-old girl with fever and abdominal pain 158
53. A 16-year-old boy with a bad cough 159
54. A 10-year-old boy with fever and an axillary swelling 162
55. A 6-month-old infant with fever and irritability 163
56. A 12-year-old boy who develops fever and hypotension while in the
intensive care unit 165
57. A 10-year-old girl with recurrent episodes of pneumonia 166
58. A 4-year-old boy with fever and diarrhea 168
59. A 2-year-old boy with fever and purple skin lesions 171
60. A13-year-old boy with thalassemia, presenting with fever and hypotension 172
61. A 3-old boy with fever for 1 month and abdominal tenderness 174
62. A physician with abdominal discomfort and diarrhea 177
63. A 6-year-old boy with fever 181
64. An 18-year-old hunter with fever and lymphadenopathy 189
65. A 4-month-old infant with strabismus and developmental delay 191
66. An 8-year-old girl with seizures 194
67. A 10-year-old boy with hematuria 198
68. A 3-year-old girl with respiratory difficulty and fever 202
Contents ix
69. A 16-year-old Mexican boy with fatigue 203
70. A 6-year-old Liberian girl with a cutaneous cyst 205
71. An 18-month-old boy with a worm 207
72. A 2-year-old boy with altered mental status 209
73. An 18-month-old child, receiving treatment for tuberculosis, with respiratory
difficulty 215
74. An 11-year-old boy with AIDS, presenting with weight loss and fever 220
75. A 2-year-old boy with suspected tuberculosis 223
76. A 12-year-old boy with long-standing neck pain 225
77. An 18-month-old boy with fever, rash, and red eyes 228
78. A 5-year-old boy with shortness of breath 231
79. An 8-year-old boy with fever, cough, weight loss, and fatigue 233
80. A 9-year-old boy with a neck swelling 237
81. A 10-month-old boy, hospitalized for kwashiorkor, who develops fever 240
82. A 2-year-old boy with AIDS and skin lesions 242
83. A toddler with fever and abdominal pain 244
84. A 2-year-old girl with cough and fever 246
85. An 18-month-old girl with fever and vomiting 253
86. An 11-year-old boy with fever, headache, and confusion 255
87. A 6-year-old South African boy with fever, abdominal pain, and pallor 257
88. An 18-month-old girl with fever and neck swelling 260
89. A 17-year-old boy with back pain, incontinence, and leg weakness 262
90. An 18-month-old girl with fever and inability to move her neck 263
91. A 2-year-old boy with fever and a limp 266
92. A neonate with petechiae and hepatosplenomegaly 268
93. An 18-month-old boy with fever, respiratory difficulty, and grunting 269
94. A 5-year-old boy with unilateral facial swelling 271
95. A 2-year-old girl with abdominal pain and refusal to walk 273
96. An 8-month-old infant with meningitis refractory to therapy 274
97. A 10-year-old boy with progressive infection 275
98. A 17-year-old girl with development of renal failure during treatment for a
vascular catheter infection 277
x Contents
99a. A 3-year-old boy with a ventriculoperitoneal shunt infection who develops
a seizure 278
99b. A 10-year-old boy with asthma who develops a seizure 279
99c. A17-year-old girl with tuberculosis, presenting with nausea and vomiting 279
100. An 11-year-old Mexican girl with a painful, swollen knee 281
101. A very ill neonate with abdominal distension 284
102. A 6-year-old South African shepherdess with abdominal discomfort 287
103. A 9-year-old girl with fever, rash, and joint pain 291
104. A 21-year-old woman with fever, shock, and skin lesions 293
105. A 17-year-old boy with fever, rash, and headache after a South African
safari 300
106. A 10-year-old girl with a skin problem 303
107. A 5-year-old girl with recurrent episodes of fever 304
108. A 14-year-old boy with fever and hip pain 305
109. A 10-year-old boy with abdominal pain during treatment for meningitis 308
110. A4-year-old boy with autoimmune lymphoproliferative disorder who develops
a sore throat 310
111. A 16-year-old boy with fever, headache, muscle aches, and weakness 311
112. A 4-year-old boy with an eye injury complicated by infection 313
113. A 12-year-old boy with nephrotic syndrome who develops abdominal pain and
fever 315
114. An 18-month-old girl with stridor 316
115. A 15-year-old girl with abdominal pain 319
116. A 12-year-old boy with fever, cough, and pallor 323
117. A 6-year-old girl with meningitis 325
118. A 13-year-old girl with fever, headache, and depressed level of
consciousness 326
119. A 12-year-old girl, living in a rural area, with fever and respiratory
difficulty 329
120. A 12-year-old boy with a sore throat, fever, and poor perfusion 331
121. A 6-year-old girl, being treated for an epidural abscess, with persistent
fever 334
Contents xi
PART 3: APPENDIX 336
Table A1. Infectious diseases reportable in the United States 336
Table A2. Taxonomy of human pathogens, their ususal sources, and the main clinical
syndromes they cause 337
List 1. Animate and inanimate sources and infectious agents associated with
them 351
Table A3. Arthropods as vectors of infectious agents 352
General References 354
Index 355
xii Contents
Preface
THE PURPOSE of this book is to provide the pediatric practitioner with an
approach to the diagnosis and management of patients suspected of suffering
from an infection through the use of teaching case exercises.
These cases have been designed as teaching exercises in clinical infectious
diseases. Their sources are as follows:
(i) The majority are derived frommy own clinical experience. Because this
experience covers a period of 30 years, many of these are reconstructed
from memory, and therefore some of the details, especially the childs
age and sex, may not be accurate.
(ii) Three cases are based on reports in the Morbidity and Mortality Weekly
Reviews (MMWR).
(iii) Several cases are composites of different cases from my experience.
(iv) The remainder of the cases are hypothetical, basedon current knowledge
of the clinical manifestations of a particular illness. These include cases in
which I have constructed a clinical scenario to match a photograph.
Where names of the cases have been used, they are not the patients real
names, but they contain clinically important information.
Although these cases cover a wide range of infections, they do not neces-
sarily include cases of commonly encountered infections. They do, however,
include cases of uncommon infections. I make no apology for this because the
goal of the exercises is to encourage thought about diagnostic possibilities,
both within and outside the range of the usual clinical encounters in the
United States.
The first chapter addresses general principles in the diagnosis and man-
agement of patients suspected of suffering from an infectious disease.
In the second chapter the cases are presented and discussed. The emphasis
of the discussions is on clinical evaluation based on history, particularly on
xiii
risk factors, and on physical examination. This evaluation consists mainly of
considerations of diagnostic possibilities and of physiologic disturbances.
There is little mention of broad-spectrum laboratory testing such as blood
counts because it is my view that these seldom help in differentiating be-
tween the different diagnostic possibilities. The discussions often include
noninfectious diseases, because patients do not present waving a flag that
they have an infectious disease.
Management is discussed mainly as it relates to principles. Details of
management are not discussed for the following reasons: (i) optimal anti-
microbial therapy changes over time and is influenced by susceptibility
patterns of organisms in a particular location; (ii) one should consult a hand-
book for the dosages of drugs that one does not prescribe frequently.
Most cases have reading or references applicable to that case. These are
mostly recent review articles. A list of books that should be consulted as
reference sources is given in Chapter 3.
ACKNOWLEDGMENTS
I wish to acknowledge the following individuals who, over many years,
have stimulated my interest in and taught me microbiology and infectious
diseases: Hendrik J. Koornhof, Benny Miller, James H.S. Gear, Barry Schoub,
Walter O. Prozesky, Myron Levin, Mimi Glode, James Todd, and Brian Lauer.
I also wish to thank Dr. Carlos Abramowsky and Dr. Robert Jerris for
providing me with some of the pictures, and the librarians of the Grady
Memorial Hospital branch of the Emory University School of Medicine
library for their help in obtaining literature. Finally, I wish to thank W. Dean
Wilcox for all his encouragement.
xiv Preface
Part One
INTRODUCTION
THE NATURE OF THE PRACTICE OF INFECTIOUS DISEASES
The practice of infectious diseases depends on the application of informa-
tion, knowledge, skills, and judgment related to three areas, namely epide-
miology, clinical medicine, and clinical microbiology. This book is intended
to provide insights into infectious diseases in children, emphasizing the
importance of these considerations.
The goal of clinical practice is to cure patients or, at least, to ameliorate their
condition. The ultimate goal lies in a good or beneficial outcome, not only for
the individual patient but also for the public. The outcome depends to a large
extent on some kind of action being taken. For the individual this is usually
therapeutic. For the public the action might entail tracing of exposed contacts,
quarantining of exposed individuals, and providing vaccination or chemopro-
phylaxis. The action to be taken often, but not always, depends on an accurate
diagnosis being made. It is important to remember that the ultimate goal does
not lie in making an accurate diagnosis, nor in taking some action, but in
obtaining a favorable outcome. There are circumstances in which the accurate
diagnosis in an individual patient is not as important to that patient, for whom
there may be no available therapy, as to the community.
COMPONENTS OF A DIAGNOSIS
Giving appropriate therapy often depends on making an accurate diagnosis.
The diagnosis, like ancient Gaul, is divided into three parts (omnis diagnosis
in tres partes divisa est):
1. Anatomic diagnosis, for example, the lung, the middle ear, the urinary tract.
2. Physiologic diagnosis. This describes functional disturbances, for example,
respiratory failure, shock.
1
The physiologic diagnosis is important for determining what supportive
care the patient requires. In patients with severe illness providing appropri-
ate supportive care is more urgent than is providing antimicrobial therapy.
For example, in a patient with septic shock, the most urgent matter is to
restore adequate perfusion; in a patient with respiratory failure complicating
pneumonia, the most urgent matter is to ensure adequate ventilation and
oxygenation.
Making an anatomical and physiological diagnosis depends on the his-
tory, physical examination, and sometimes on laboratory and imaging tests.
3. Pathologic and/or etiologic diagnosis, for example, inflammation caused
by Streptococcus pneumoniae or purpura fulminans caused by Neisseria
meningitidis.
In the case of infectious diseases, the etiological diagnosis is represented
by the microbiological diagnosis.
MICROBIOLOGICAL DIAGNOSIS
In infectious diseases making an etiologic or microbiological diagnosis is very
important because specific therapy, where available, entails use of an anti-
microbial agent.
The microbiological diagnosis can often be made based on the anatomic
diagnosis. For example, if the diagnosis is otitis media, we can assume, based
on previous studies of middle ear fluid of children with otitis media, that the
likely causative organism is one of the following: Streptococcus pneumoniae,
Haemophilus influenzae, or Moraxella catarrhalis. This principle can be
applied to an infection at any anatomic site. An etiological diagnosis is
usually difficult to make in the absence of an anatomic diagnosis.
RISK FACTORS FOR INFECTION
The microbiological diagnosis also depends on the risk factors that the
patient has for acquiring a particular infection. Such risk factors can be con-
sidered in terms of (a) genetic factors, for example, sickle cell disease, and
(b) environmental factors or the epidemiological circumstances in which the
patients infection was acquired. This constitutes the patients exposures.
A list of possible exposures that should be inquired about is shown in
Table 1. When obtaining a history about exposures, I have found it useful to
explain to patients (or their parents) the purpose of the apparently bizarre
questions that I intend to ask.
2 Case Studies in Pediatric Infectious Diseases
There is an aphorism used in clinical medicine in the United States
regarding the likelihood of a particular disease among a differential diagnosis:
when you hear hoofbeats, think of horses, not zebras. One of the messages
of this book is:
Think about zebras as well as horses, because whether horses or zebras are
more likely depends on where you come from! (Figure 1).
Furthermore, zebras are found in groups. Therefore, when individuals are
exposed to exotic diseases, they may be exposed to more than one disease at
the same time.
Patients with defects in their host defenses (genetic or acquired) are at risk
for infections caused by certain microorganisms that are unlikely to infect
normal hosts. Different host defense defects predispose to different kinds of
infections. Table 2 lists some host defense defects and infections to which
they predispose.
METHODS FOR MAKING A MICROBIOLOGICAL DIAGNOSIS
There are several different methods for confirming a microbiological diag-
nosis, which are summarized in Table 3. They can be divided into (a) direct
methods, in which the organism is visualized, cultured, or a component of
nTAB. 1: Types of exposures to infectious agents.
Sick human beings family, friends, day care, shelter for the homeless,
immigrants, visitors from abroad, prison, military
Maternal infections intrauterine (transplacental), intrapartum, postnatal
Animals vertebrates fish, amphibians, reptiles, birds, mammals
arthropods ticks, mosquitoes, fleas, lice, flies, mites
Travel foreign or domestic; foreign-sounding names or accents
should prompt enquiry about foreign travel
Occupation of patient or parents
Recreational activities sports, hobbies, sexual activity, drug abuse
Hospitalizations and visits to health
care facilities
Injections legal and illicit, blood transfusions, vascular catheters
Surgery, foreign body insertions
Immunizations
Antimicrobial therapy
Food and water sources
Methods for Making a Microbiological Diagnosis 3
the organism is detected, for example, antigen, DNA; and (b) indirect meth-
ods, which depend on the hosts response to the infection (i.e. serological
methods). The direct methods are undergoing significant changes due to the
rapid advances being made in our ability to detect microbial nucleic acid.
In making a microbiological diagnosis, the optimal site for obtaining
material for diagnosis is from the site of infection, when possible. Although
this may seem intuitive, it is remarkable how frequently this principle is not
followed. This principle is frequently referred to as Suttons Law, named
for the bank robber, Willie Sutton, who, when asked why he robbed banks,
replied, Because thats where the money is.
In the diagnosis of infections, in general, the sicker the patient is, the less
room there is for making an error in diagnosis, and consequently the more
important it is to make a microbiological diagnosis. This may necessitate
invasive procedures. For example a normal child with otitis media does not
require a myringotomy to obtain middle ear fluid for culture. Most children
with this condition recover with or without antimicrobial therapy. On the
other hand, a child who has recently undergone bone marrow transplantation
and has a rapidly progressive pneumonia might need to undergo an invasive pro-
cedure such as a bronchoalveolar lavage or a lung biopsy in order to determine
the causative organism, considering the wide variety of possible pathogens and
the toxicity of some of the therapeutic agents that might be indicated.
FIG 1. Zebras.
4 Case Studies in Pediatric Infectious Diseases
PRINCIPLES OF MANAGEMENT OF PATIENTS WITH
INFECTIOUS DISEASES
The following five main principles should be considered in the management
of patients with infections, not all of them necessarily applying to all cases:
Supportive care. This is the most important aspect to consider, and, in
patients with life-threatening infections, it is the aspect that must be
addressed immediately. For example, in a patient with shock due to severe
bacterial infection, the most important first step in management is to ensure
adequate tissue perfusion with intravenous fluid. In a patient with respira-
tory failure due to pneumonia, the most important first step in management
is to ensure adequate oxygenation and ventilation.
nTAB. 2: Host defense defects and infections to which they predispose.
Defect Infection/Organism
Skin
Atopic dermatitis Staphylococcus aureus, Streptococcus pyogenes
Burn Staph. aureus, Strep. pyogenes, Pseudomonas aeruginosa
Varicella Strep. pyogenes, Staph. aureus
Vascular catheter staphylococci, Candida sp., enterococci, enteric bacilli
Endotracheal intubation pharyngeal flora, Gram-negative bacilli
Urinary catheter Gram-negative bacilli, enterococci, Candida spp.
Blood diseases
Sickle cell disease Streptococcus pneumoniae sepsis, salmonella
osteomyelitis
Iron overload enteric rod sepsis, especially Yersinia enterocolitica
Cancer chemotherapy with neutropenia staphylococci, streptococci, Gram-negative rods, fungi
Transplant herpes group viruses, adenovirus, many different
bacteria, including mycobacteria and Nocardia spp.,
Listeria monocytogenes, fungi, Pneumocystis jiroveci,
and Toxoplasma gondii
Congenital Immunodeficiencies
Immunoglobulin deficiencies pyogenic bacterial infections, pneumonia, sinusitis
Combined immunodeficiencies bacterial infections, severe viral infections, Pneumocystis
jiroveci
Chronic granulomatous disease infections with staphylococci, Gram-negative bacilli,
mycobacteria, fungi
HIV infection Pneumocystis jireveci, mycobacteria, Candida spp.,
Cytomegalovirus, bacteremia
Principles of Management of Patients with Infectious Diseases 5
Antimicrobial therapy. This is specifically intended to kill or inhibit the
growth of invading microorganisms. For many patients with infections,
especially viral infections, there is currently no available antimicrobial ther-
apy. The principles for choosing antimicrobial agents are discussed below.
nTAB. 3: Methods for making a microbiological diagnosis.
A. Direct visualization of the organism
Electron microscopy for viruses seldom performed
Gram stain for bacteria very useful; rapid, cheap, semi-quantitative
Wet preparations bacteruria, Trichomonas vaginalis
unstained, mixed with saline Entamoeba histolytica, ova, fungi
dark field spirochetes
cleared with 10%KOH fungi
Acid-Fast stain Mycobacteria
Cytology
Papanicolaou stain viral inclusions, viral cytopathic effects
Silver stain Pneumocystis jiroveci, fungi
Gram stain bacteria
Immunostaining viruses, bacteria, fungi, parasites
Blood smears (stained with a
Romanowsky stain Wrights, Leishmans,
Giemsa)
Plasmodium spp., Trypanosoma spp., Babesia spp.,
relapsing fever Borrelia spp., morula of Ehrlichia spp.,
Bartonella bacilliformis, microfilaria
Histology sections stained with hematoxylin
and eosin and the above-mentioned stains
B. Culture of the organism this is the gold standard for detection of many organisms,
especially bacteria and viruses
Tissue culture viruses, Chlamydia spp., Rickettsia spp.
Nutrient-containing agar and broths bacteria, fungi
Living tissue e.g. eggs viruses, Rickettsia spp.
Animal inoculation this is very seldom performed
C. Detection of microbial antigens in body fluids and tissues
D. Detection of nucleic acid in body fluids and tissues, by signal amplification, nucleic acid
amplification (e.g. polymerase chain reaction), and several other methods
E. Serology this detects the hosts response to the infection, that is the presence of antibodies. Although
not the optimal way in which to diagnose an infection, in some infections it is the only way. There are
many different methods for detecting antibody responses to infection. These include the following:
Neutralization
Complement fixation
ELISA
Immunofluorescence
Hemagglutination
READING: Winn WC Jr, Allen SD, Janda WM, Koneman EW, Procop GW, Schreckenberger PC, Woods GL: Molecular
Microbiology. Chapter 4 in Konemans Color Atlas and Textbook of Diagnostic Microbiology. 6th edition. Lippincott William
and Wilkins, Philadelphia, 2006, pp. 132165.
6 Case Studies in Pediatric Infectious Diseases
Surgery. This may be necessary for therapy or for diagnostic purposes. It
includes aspirating or biopsying infected lesions to obtain material for stain-
ing, culture, or histology, and draining of abscesses.
Addressing the interests of the community. The community may be the family,
friends, school attendees, other patients in a hospital or clinic, or members of
the broader community of the city, country, or world. For example, when a case
of tuberculosis is diagnosed, the local health department should be informed
so that contact tracing can be instituted. When a child with a contagious illness
is admitted to hospital, specific isolation precautions should be instituted.
Prevention. For the most part this entails immunization. Although this will
have failed if a patient is diagnosed with a preventable disease, making such
a diagnosis should lead to an examination of the possible reasons why this
failure occurred and how the problem can be rectified to prevent other
patients acquiring the same illness.
The Gram Stain
Remember, Oh! The Gram stain test.
Its quick, its cheap, it is the best!
Whenever you have secretions,
Exudates or draining lesions.
If its closed, suck some juice,
Then a diagnosis youll deduce.
Make a smear (not too high),
On a slide, and let it dry.
After each step you must rinse,
Purple, brown its a cinch.
Clear (few secs), then safranin.
Wash and dry: now examine.
Optimize the light. For vision
Use the oil immersion.
Cells are red, and germs all kind
Purple (pos), Pink (neg) you will find.
Remember, Oh! To hold in awe
The verity of Suttons Law,
Which from a robber may sound funny
In diagnostics:
GO FOR THE MONEY!
Principles of Management of Patients with Infectious Diseases 7
Dont throw pus, sputum, or pee down the drain
Until you have first done
A GRAM STAIN
With some purple, then brown; then red after alcohol
You can Gram stain anything, ANYTHING,
ANYTHING AT ALL.
PRINCIPLES OF CHOOSING ANTIMICROBIAL THERAPY
Antimicrobial therapy is different from other forms of medical therapy in
that its goal is to affect a biological process in an invading microorganism,
thus inhibiting its growth or resulting in its death. The goals of other forms of
medical therapy are directed at influencing a physiologic process in the
patient. The use of antimicrobial agents can result in microorganisms
developing resistance to such agents. Microorganisms in an individual pa-
tient can spread fromthat individual to colonize or infect another individual.
Any antimicrobial resistance that has developed among microorganisms
within this host will thus be carried to the new host. Thus antimicrobial
resistance can be spread to other members of the community and, in fact, to
other generations of hosts. Therefore prescribing antimicrobial agents carries
with it an awesome responsibility and should be carried out judiciously.
Once it has been determined that the patient has or probably has an
infection, AND that antimicrobial therapy is indicated, the main questions
to be answered are
1. What is (are) the most likely causative organism(s)?
2. What are their most likely antimicrobial susceptibilities?
These are the most important questions to ask, and the most challenging
to answer, particularly in situations in which a specific diagnosis has not been
made (a frequent situation in pediatrics). The answer to question 1 lies in the
diagnosis, discussed above. The answer to the question regarding antimicro-
bial susceptibilities is determined by local epidemiology and the patients
history of prior exposure to antimicrobial agents. The antimicrobial suscep-
tibilities may vary from country-to-country, community-to-community,
hospital-to-hospital, and ward-to-ward. For example ampicillin might be
indicated for empiric treatment of a patient with an E. coli infection acquired
in a community where the resistance rate of E. coli to ampicillin is 5%,
whereas it would not be indicated for someone with the same infection
acquired in a hospital ward where the resistant rate is 70%. Once a causative
organism has been isolated and its antimicrobial susceptibilities are known,
antimicrobial therapy usually becomes fairly simple.
8 Case Studies in Pediatric Infectious Diseases
The next question to be asked is:
3. What is the most appropriate agent to use?
In actually choosing a specific antimicrobial agent, several factors must be
considered. The overriding principle in choosing therapy, however, is the
following: USE AS NARROWA SPECTRUM AGENT AS POSSIBLE.
The other factors that should be taken into account are as follows:
1. Spectrum of antimicrobial activity. The drug must have the necessary spec-
trum as determined by questions 1 and 2 above.
2. Severity of infection. This determines the balance of risks between treat-
ment and no treatment or between treatment with one drug and another,
which is, in turn, determined by the adverse effect profile of the drugs.
The severity of the infection also determines the speed with which an
effect is necessary and, therefore, also influences the route of drug
administration. For example, it would not be appropriate to use chlor-
amphenicol, which has the rare side effect of causing aplastic anemia, to
treat a patient with simple otitis media, but it might be appropriate to use
it for treating a patient with a brain abscess. Similarly it would not be
appropriate to use intravenous cefotaxime for treating a child with simple
otitis media thought to be caused by Streptococcus pneumoniae, but it
would be appropriate to use such therapy in a toxic-appearing patient
with lobar pneumonia suspected to be caused by the same organism.
3. The pharmacokinetics of the drug.
(a) The distribution of the drug. The drug must attain an adequate con-
centration at the site of infection to eliminate the infection. Because
different drugs penetrate different tissues to different degrees, infec-
tions caused by the same organism but at different sites might neces-
sitate the use of different drugs. For example, clindamycin would be
suitable for treating a patient with a lung abscess but not for a patient
with meningitis caused by the same organism because it does not
enter the cerebrospinal fluid in a significant concentration.
(b) The elimination of the drug by metabolism or excretion. Dysfunction of
the liver or kidney might interfere with the elimination of certain
drugs. In such cases the drug might accumulate to toxic concentra-
tions. This might prevent the drug from being used safely.
4. The route of administration. This is usually determined by the severity of
infection (see 2 above) and the possible routes for administration of the
specific drug. Several drugs, especially those used for treating patients
Principles of Choosing Antimicrobial Therapy 9
with severe illness, can be given only intravenously, for example, vanco-
mycin. This places a constraint on the use of this drug.
1. Drugdrug interactions. Many patients, especially those with underlying
illnesses, receive multiple drugs. Several drugs, including over-the-
counter preparations, interfere with the pharmacokinetics of other
drugs, resulting in their blood levels being inadequate or excessive. The
general mechanisms by which these interactions occur are as follows:
(a) Interference with oral absorption, for example, antacids, such as alu-
minum hydroxide, interfere with the absorption of fluoroquinolones.
(b) Interference with hepatic metabolism. This applies particularly to
drugs that are metabolized by the cytochrome P450 enzyme systems.
Drugs that induce hepatic enzymes, for example, rifamycins and
anticonvulsants, speed up the metabolism of some other drugs, for
example, corticosteroids and warfarin, resulting in reduced effects.
Some drugs, for example, erythromycin, inhibit the metabolism of
other drugs, for example, theophylline, resulting in them reaching
toxic levels in the blood.
Antimicrobial agents that are frequently associated with drug
drug interactions include the rifamycins, imidazole antifungal agents,
macrolides, and antiretroviral protease inhibitors.
(c) Additive injury to the kidney, resulting in decreased excretion of the
drug, for example, a combination of an aminoglycoside and vancomycin.
2. Cost. When multiple drugs are equivalent in the above characteristics, the
cheapest option should be used.
PRINCIPLES OF ADDRESSING PUBLIC HEALTH INTERESTS
Members of a community often have an interest in the diagnosis of an
infection in an individual because they may be at risk for acquiring the same
infection. There are several situations in which this may occur, but essen-
tially there are two main reasons for community interest:
(a) the patient may be the index case of a broader outbreak or represent
a sentinel case, indicating the local presence of the disease. For example,
a child is generally the victim of tuberculosis spread from an adult.
Therefore the diagnosis of tuberculosis in a child indicates the presence
of an adult source who must be sought, so that he or she can be treated,
so that spread to additional individuals is interrupted, and so that other
individuals already infected can be identified and treated. The diagnosis
10 Case Studies in Pediatric Infectious Diseases
of certain infections in an individual indicates that several individuals
might harbor the causative agent and spread it without being ill or prior
to becoming ill. When the agent causes serious disease, prevention of
disease is highly desirable, for example, in the cases of Neisseria menin-
gitidis, Haemophilus influenzae type b, and Bordetella pertussis. In such
situations antimicrobial prophylaxis should be provided to high-risk con-
tacts such as members of the household.
(b) the patient is the potential source of spread of the infection to others,
such as in the case of a sexually transmitted disease, or measles.
Children admitted to hospital with a wide variety of infections should be
isolated or nursed with precautions designed to prevent the spread of
infection to other individuals.
There are four main types of isolation precautions, which should be used
on the presumption of the relevant diagnosis.
1. Standard (universal) precautions, which should be used in dealing with all
patients, entail washing hands after all patient contacts and wearing
gloves when there is a risk of having contact with body fluids. Hands
should be washed even if gloves have been worn.
2. Droplet precautions, which entails wearing a mask when within 3 feet of
the patient and are indicated for all viral respiratory tract infections
(except respiratory syncytial virus and parainfluenza virus infections
(see below)), Streptococcus pyogenes, Neisseria meningitidis, Bordetella
pertussis, and invasive Haemophilus influenzae infections.
3. Contact precautions, which entails wearing gloves and a gown and are
indicated when one comes into contact with patients who have infected
skin lesions or wound infections, who have diarrhea or other enteric-
transmitted infections, such as enteroviral meningitis, or who have res-
piratory syncytial virus or parainfluenza virus infection.
4. Airborne precautions, which entails nursing the patient in a room with neg-
ative air pressure and the door closed (except when people are entering and
leaving). It is used for patients with tuberculosis (in which case an appropri-
ate mask should be worn by those entering the room), and for measles and
varicella (in which case nonimmune individuals should not enter the room).
Individual clinicians can seldom perform the contact tracing and manage-
ment necessary for addressing community interests. Therefore cases of spe-
cific infections must be reported to the local health department, whether
city, county, or state. The urgency with which this should be done depends
on the nature of the infection.
Principles of Addressing Public Health Interests 11
Part Two
CLINICAL CASE EXERCISES
(WITH DISCUSSION)
The sources of these cases are as follows:
(i) The majority are derived from my own clinical experience. Because
this experience covers a period of 30 years, many of these are recon-
structed frommemory, and therefore some of the details, especially the
childs age and sex, may not be accurate.
(ii) Three cases are based on reports in the Morbidity and Mortality
Weekly Reviews (MMWR). This is indicated by (MMWR) with
the number of the case and in the reference.
(iii) Several cases are composites of different cases from my experience.
These are indicated by (COMP).
(iv) The remainder of the cases are hypothetical, based on current knowl-
edge of the clinical manifestations of a particular illness. These include
cases in which I have constructed a clinical scenario to match a photo-
graph. These are indicated by (HYP).
Where names of the cases have been used, they are not the patients real
names, but they contain clinically important information.
n
CASE 1. A previously well 13-year-old girl presents with a history of
nausea, anorexia, abdominal pain , and dark urine for 3 days. On examina-
tion she has mild right upper quadrant discomfort. Jaundice cannot be
detected. The rest of the examination is normal.
What is your differential diagnosis?
What quick (2-minute) test can you do to help you?
What further studies might you do?
12
The differential diagnosis in this patient includes the following:
1. acute hepatitis
2. cholecystitis, cholangitis, cholelithiasis
3. gastritis and peptic ulcer disease
4. pancreatitis
5. pyelonephritis
6. hepatic sludging/sequestration if she has sickle cell disease
7. liver abscess
The clinical features of nausea, anorexia, and right upper quadrant ten-
derness suggest disease of the liver or gallbladder, and the dark urine suggests
the possibility of bilirubinuria, which results from conjugated hyperbiliru-
binemia. The most likely cause of acute liver disease in a previously normal
teenager is acute hepatitis. Although cholecystitis is the most common dis-
ease of the gallbladder in a teenager, it is rare in the absence of an underlying
hemolytic disorder such as sickle cell disease.
The tests that can help to localize the site of disease are (a) the urinalysis,
which can be performed very quickly and can demonstrate evidence of
urinary tract infection (leukocyturia, hematuria, bacteruria) and evidence
of conjugated hyperbilirubinemia (bilirubinuria); conjugated hyperbilirubi-
nemia occurs in hepatitis as a result of the swollen hepatocytes compressing
the bile cannaliculi; and (b) the serum bilirubin (direct and indirect) and the
hepatic transaminases levels. These are elevated in hepatitis. They may also
be elevated in cholelithiasis, but generally the transaminases are not elevated
to levels greater than 1000 IU/ml in this condition, whereas they may reach
levels of several thousand in hepatitis. The other main causes of markedly
elevated transaminase levels are hepatic ischemia and drug/toxin-induced
hepatic injury.
An abdominal ultrasound can be helpful in diagnosing disease of the
gallbladder and of the biliary tract.
This patient had bilirubinuria and a mildly elevated conjugated serum
bilirubin, and her transaminases (alanine aminotransferase (ALT) and aspar-
tate aminotransferase (AST)) were elevated to approximately 1500 IU/dl.
Acute hepatitis was diagnosed.
Hepatitis implies inflammation of the liver. Although it may occur as part
of many systemic viral infections, it is usually caused by one of several
specific viral infections that primarily affect the liver. In the initial stages
these may not be clinically distinguishable, but they differ epidemiologically,
and their outcomes may be very different. They are compared in Table 1.1.
Hepatitis A is the most likely cause of acute hepatitis in this patient.
Hepatitis B and hepatitis C would be considerations if she were sexually
Case Study 1 13
active, engaged in intravenous drug abuse, or had received a blood trans-
fusion. Hepatitis E is very uncommon in the United States, but is particularly
prevalent in Asia.
Patients with viral hepatitis may be asymptomatic or they may present
with fever, anorexia, right upper quadrant discomfort or pain, and dark
urine. On examination they have jaundice and tender hepatomegaly. Hep-
atitis B may be associated with a prodromal illness characterized by arthral-
gias and a rash. The clinical illness of hepatitis may take one of several
courses: (a) mild-to-moderate illness with recovery over several weeks; (b)
severe illness associated with hepatic failure (fulminant hepatitis). This may
be associated with death, unless liver transplantation can be performed.
Patients with hepatitis B or C may develop chronic infection that may lead
to cirrhosis and hepatocellular carcinoma.
The diagnosis of hepatitis should be considered in terms of (a) Is there
hepatitis? (b) What is the cause of the hepatitis, the answer to which has
important public health implications?, and (c) Is there evidence of liver
decompensation?
The differential diagnosis of the causes of acute hepatitis and the tests
used to diagnose or differentiate between them are shown in Table 1.2.
Management of acute viral hepatitis
This consists essentially of supportive care, directed at ensuring adequate
hydration, blood glucose concentration, and overall nutrition, and of mon-
itoring the patient for the development of liver failure. Tests of liver
nTAB. 1.1: Comparison of viral hepatitides.
Virus Transmission
route
Incubation
period
Potential for
chronicity
Hepatitis A RNA fecaloral 1550 days
Hepatitis B DNA parenteral 28160 days +
Hepatitis C RNA parenteral 14160 days +
Hepatitis D DNA parenteral
coinfection with
hepatitis B
variable +
Hepatitis E RNA fecaloral 1545
14 Case Studies in Pediatric Infectious Diseases
synthetic function, in particular the prothrombin time, are important in
this regard. The management of liver failure and of chronic liver disease is
beyond the scope of this discussion.
Antiviral therapy is not generally used in cases of acute hepatitis, but there
is some evidence of the benefit of a combination of ribavirin and interferon
in cases of acute hepatitis C.
The decisions about management of chronic hepatitis B with nucleotide
analogues such as lamivudine, together with interferon, and of chronic hep-
atitis C with ribavirin and interferon should be made in consultation with
a hepatologist.
Public health issues
Hepatitis A: Since the spread is fecaloral, often from a child who is asymp-
tomatic, once this diagnosis is made the local public health department
should be notified. Therefore it is important to confirm a diagnosis of hep-
atitis A rapidly, by demonstration of antihepatitis A IgM in the blood.
Immune globulin should be offered to family contacts and may be indicated
for day-care contacts. Hepatitis A vaccine should be used routinely in high
prevalence areas and before travel to countries where the risk is high.
nTAB. 1.2: Differential diagnosis of the causes of acute hepatitis, and the tests used to
diagnose them.
Etiology Diagnostic test
Viral hepatitis
A anti-HAV IgM
B anti-HBV core IgM, HBV surface antigen
C HCV RNA
D anti-HDV; genome detection
E anti-HEV IgM
EBV anti-EBV early antigen, anti-EBV VCA IgM
CMV anti-CMV IgM, urine culture for CMV, serum
CMV PCR or antigen
Bacterial hepatitis
Q fever (Coxiella burnetii) serology
Leptospirosis (Leptospira interrogans) serology
Drugs and Toxins exposure history
Isoniazid exposure history
Acetaminophen exposure history, serum level may or may not
be helpful
Mushrooms exposure history
Metabolic disease
Wilsons disease serum ceruloplasmin concentration, liver
copper content
Case Study 1 15
The epidemiology and clinical features of hepatitis Aare summarized in the
following song:
When your stomachs feeling funny
And right up you want to throw
But your bu-bu is not runny
And your liver starts to grow
Chorus:
Hepatitis gives your skin a yellow sheen
Your stool the color cream
Your liver turning green
If your food or water are not clean
Or you have poor hygiene
In most cases it is mild
And especially in a child
But it may be fulminant
So its something to prevent
Chorus
Hepatitis B: Hepatitis B vaccine should be given routinely to all children.
Unimmunized sexual contacts of acute cases should be given hepatitis B
immune globulin (HBIG) and active immunization should be initiated.
Infants born to women infected with hepatitis B virus have an extremely
high risk of developing chronic liver disease. Therefore such infants should
receive HBIG and hepatitis B vaccine at birth. This vaccine has resulted in
a marked reduction in the incidence of hepatitis B and hepatocellular carci-
noma in areas where it has been widely used. It is the first vaccine to reduce
the incidence of a cancer in human beings.
Readings:
Beckingham RSD: Acute hepatitis. Br Med J 2001; 322: 151153.
Aggarwal R, Krawczynski K: Hepatitis E: an overviewand recent advances in
clinical and laboratory research. J Gasteroenterol Hepatol 2000; 15: 920.
Hochman JA, Balistreri WF: Chronic viral hepatitis: always be current!
Pediatr Rev. 2003; 24: 399410.
Lauer GM, Walker BD: Hepatitis Cvirus infection. NEngl J Med 2001; 345:
4152.
16 Case Studies in Pediatric Infectious Diseases
Ganem D, Prince AM: Hepatitis B virus infection natural history and
clinical consequences. N Engl J Med 2004; 350: 11181129.
n
CASE 2. An 18-month-old child presents with a history of fever, cough,
and red eyes for 4 days.
He is shown in the picture (Figure 2.1).
What is your differential diagnosis?
What would you do?
The main differential diagnosis is:
Measles
Adenovirus infection
Kawasaki disease
The constellation of symptoms and signs in this child are highly suggestive
of measles. Questions about prior immunization against the infection and
possible risk factors, such as foreign travel, can help to make the diagnosis.
Adenoviral infections can cause conjunctivitis and respiratory tract infection
and rarely a rash. Kawasaki disease is generally not associated with significant
respiratory symptoms, which are very prominent in measles. In Kawasaki
disease the rash occurs earlier in the febrile illness than it does in measles, and
the conjunctival inflammation is primarily bulbal with perilimbic sparing
and is not associated with discharge. In measles the conjunctival inflamma-
tion is tarsal as well as bulbal, and there is a conjunctival discharge. Drug
eruption is not associated with a cough, and in StevensJohnson syndrome
the mucosal disease is associated with pseudomembrane formation, which
FIG. 2.1. Child with fever,
cough, and rash.
Case Study 2 17
does not occur in measles. Characteristic of measles, early in the infection
(12 days) is the presence of Koplik spots on the buccal mucosa (see below),
and late in the infection (47 days) is the development of the rash that is
almost confluent and that becomes darker with time.
This child had measles.
Measles is one of the most contagious and terrible diseases of humankind.
It has an attack rate of almost 100%, and in some areas of the world, it is
associated with a case fatality rate of up to 20%. Fortunately it has been
eliminated from many parts of the world and has the potential to be totally
eradicated. It is spread by the airborne route and has an incubation period of
about 10 days.
The virus is spread systemically but also throughout the respiratory tract,
where it can wreak havoc. It can also cause profound immunosuppression,
which can last for several weeks. Most of the complications (discussed be-
low) affect the respiratory tract.
Clinical manifestations: there is a prodromal illness (10th day from in-
fection) of fever, cough, coryza, and conjunctival inflammation. About 2
days later (12th day) Koplik spots appear. These are tiny white raised spots
on the very red background of the buccal mucosa including the gingival
sulcus. They have the appearance of salt sprinkled on red velvet.
The whole buccal mucosa is fiery red. The whole face is running. A vague
papular rash might be present at this time. (This is not the main measles rash.)
The patient looks very miserable. (The origin of the name measles is fromthe
Latin misellus, which means miserable.) The measles rash appears 2 days
later (14th day). This is a maculopapular rash, beginning behind the ears and
descending to cover the whole body, including the palms and soles (Figure 2.2).
The spots are not very discreet, and become slightly confluent. In the early
stages this rash can be difficult to see on a dark skin. However, after a few
days, it becomes darker and more readily visible (Figure 2.3).
Of particular importance among the clinical manifestations is the prom-
inence of cough.
Over the ensuing fewdays the rash becomes darker and desquamates. The
acute illness lasts about 7 days. However, the resulting debilitation, resulting
from the severe catabolic nature of the infection and its complications, may
last much longer.
Organs affected/complications:
1. The whole respiratory tract can be affected, resulting in
(a) otitis media
(b) laryngotracheobronchitis (croup) although initially caused by the
virus, this may be complicated by bacterial superinfection
18 Case Studies in Pediatric Infectious Diseases
(c) bronchitis this may lead to bronchiectasis
(d) pneumonia this is the main cause of death from measles. It can
result in chronic lung disease fromobliterative bronchiolitis and bron-
chiectasis. Measles virus itself causes pneumonia (Figure 2.4).
FIG. 2.2. The rash of measles infection.
FIG. 2.3. The measles rash in a dark-skinned child with late stage measles.
Case Study 2 19
Because histologically this demonstrates syncytial cells (see below), it is
called measles giant cell pneumonia.
The patient with measles is susceptible to secondary infection of the lung
due to the denuded respiratory epithelium and immunosuppression. Hos-
pitalization further exposes the patient to a variety of pathogens that might
be highly antibiotic resistant. The secondary pneumonia is caused by other
viruses, in particular adenovirus and herpes simplex virus, and bacteria,
including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus
influenzae, and enteric rods, in particular Klebsiella pneumoniae (Figure
2.5). Tuberculosis can also be reactivated during measles.
FIG. 2.4. Chest X ray
showing perihilar infiltrates
due to measles pneumonia.
20 Case Studies in Pediatric Infectious Diseases
2. Brain: Measles is associated with several different types of encephalitis.
(a) Acute encephalitis: This occurs during or within a few weeks of
the infection. In most cases it probably represents parainfectious
encephalitis, or what is now called acute disseminated encephalomy-
elitis (ADEM). When nonselected children with measles have had
electroencephalograms performed or cerebrospinal fluid (CSF)
examined, these have frequently been found to be abnormal.
Whether this represents mild encephalitis is unclear. Not all patients
with altered mental status associated with measles have encephalitis.
Other causes of altered mental status are shown in Table 2.1.
(b) Progressive encephalitis in immunocompromised individuals (e.g. those
receiving cancer chemotherapy): This has its onset about 6 months
after the infection. It is relentless and ultimately fatal.
(c) Subacute sclerosing panencephalitis (SSPE) (also called Dawsons en-
cephalitis): This is a very rare complication that begins to manifest
nTAB. 2.1: Causes of altered mental status in individuals with measles.
Metabolic
Hypoxia due to a respiratory complication
Hypoglycemia due to starvation or due to kwashiorkor
Hyponatremia due to malnutrition or diarrhea
Reyes syndrome
Encephalitis
Meningitis complicating bacterial pneumonia
FIG. 2.5. Chest X ray
showing bronchopneumonia
complicating measles. This
was ultimately fatal in this
child.
Case Study 2 21
more than 1 year after the infection. It is characterized by personality
changes and gradual intellectual deterioration and is ultimately fatal.
3. Malnutrition: Being a severely catabolic event, measles results in malnu-
trition. It can also be associated with diarrhea. In individuals with a bor-
derline nutritional status, measles can precipitate overt malnutrition such
as kwashiorkor. One of the nutrients whose blood concentrations
decreases during measles is vitamin A. Therapy with this vitamin can
reduce the fatality rate very significantly (see below).
4. Eye: Measles causes a punctate keratitis. In the face of vitamin A
deficiency, keratitis can progress to keratomalacia and corneal perforation
(Figure 2.6).
5. Heart: Myocarditis.
Diagnosis of measles: This should be suspected clinically in an individual
with fever, cough, conjunctivitis, and a rash, especially if he or she has been
in an area or in contact with someone from an area in which the disease is
prevalent. In the United States, presently all cases of measles are imported.
The main differential diagnosis is adenovirus infection. Kawasaki disease
shares several features with measles (fever, conjunctivitis, and rash), but it
is not associated with respiratory tract symptoms (see above). In the United
States, it is useful to consult older practitioners who are likely to have ex-
perience in managing patients with measles. For public health reasons it is
important to confirmthe diagnosis of measles. This is done by demonstrating
the presence of measles IgMin the blood. Other tests that might be helpful if
the results can be obtained sooner than those of the IgM include the follow-
ing: cytopathology of a buccal scraping, which may showmultinucleate giant
cells (Figure 2.7), and immunofluorescent staining for the virus of a buccal
scraping or of urinary sediment.
FIG. 2.6. A child with bilateral corneal perforations caused by measles keratitis.
22 Case Studies in Pediatric Infectious Diseases
Management: The diagnosis of measles represents a public health emer-
gency, because this is a highly contagious disease with a significant morbidity
and mortality rate. Therefore the local health department must be contacted
immediately so that contacts can be traced and managed (see below).
The management of the patient is supportive. In most patients this should
be done in the home. This should entail ensuring adequate hydration and
observing for complications. There is no currently available antiviral therapy
for measles. In individuals with malnutrition or borderline nutritional status,
or in those living in communities in which malnutrition is prevalent, vitamin
A should be administered, in the dosage of 100,000200,000 units orally. If
significant complications develop for which hospitalization is necessary, the
patient should be nursed with airborne isolation, and nonimmune individ-
uals should not enter the room.
Patients who develop complications should be treated as necessary for
those complications. This often entails antibiotics for presumed bacterial
superinfections.
Prevention: Measles can readily be prevented by active immunization.
The vaccine, which is a live, attenuated vaccine, is highly effective. Low
concentrations of immune globulin that infants have acquired transplacen-
tally from their mothers (or that children could have received from infu-
sions of blood products) can inactivate the vaccine. In the United States,
the vaccine is given routinely twice, at 12 months and at 4 years of age. In
countries where the risk of measles is higher, it is given earlier. If American
children are visiting such countries, they should be given the vaccine earlier
(as early as 6 months of age). Although this will not be considered as the first
dose for official purposes, it may be protective.
FIG. 2.7. A Papanicolaou
stained smear of a buccal
scraping from a child with
measles showing a
multinucleate giant cell.
Case Study 2 23
Postexposure prophylaxis for a susceptible individual: if the exposure
is less than 72 hours earlier, then vaccine should be given; if more than
72 hours earlier then immune globulin should be given (0.25 ml/kg
intramuscularly for normal hosts, 0.5 ml for immunocompromised hosts);
HIV-infected and HIV-exposed individuals of unknown infection sta-
tus should receive immune globulin irrespective of their immunization
status.
Reading:
Duke T, Mgone CS: Measles: not just another viral exanthema. Lancet 2003;
361: 763773.
Mulholland EK: Measles in the United States, N Engl J Med. 2006; 355:
440442.
n
CASE 3. A 4-month-old infant presents with a runny nose, cough, and
rapid breathing 5 days after receiving his 4-month immunizations. On ex-
amination he has a temperature of 38.6C, a respiratory rate of 60/minute,
and he has a diffuse expiratory wheeze.
What is your diagnosis?
How did he get this illness?
How would you treat him?
The likely diagnosis is bronchiolitis.
This is a common pediatric condition in which there is inflammation of
the small airways. The pathogenesis involves a combination of respiratory
viral infection and the hosts immune response to the infection. The phys-
iological effect is narrowing of the bronchioles, resulting in air-trapping. The
most common viral cause is respiratory syncytial virus (RSV), but other viral
pathogens, including parainfluenza virus, may cause this disease. This disease
affects primarily children younger than 1 year, although RSV infection
occurs in older individuals. Affected children present with fever and cough
(often following a short illness with rhinorrhea) and pulmonary findings of
varying degrees of severity: tachypnea, intercostal and subcostal retractions,
expiratory wheeze, and crackles. The lower edge of the liver may be dis-
placed inferiorly (the vertical span of the liver is normal), and normal cardiac
dullness to percussion may be absent, both these findings indicating hyper-
inflation. The clinical course of the illness lasts 12 weeks. Children with
bronchiolitis may have concurrent pneumonia. There is a wide range of
24 Case Studies in Pediatric Infectious Diseases
severity of disease. Most infants do not require hospitalization, a few require
hospitalization, and very few develop respiratory failure.
Diagnosis: Most infants with bronchiolitis can be diagnosed clinically.
Chest radiography is seldom helpful or necessary. If performed, it may show
hyperinflation (Figure 3.1).
The only value of knowing whether RSV is the cause of the illness is for
infection control precautions for hospitalized infants (contact isolation for
those with RSVand parainfluenza infections, and droplet isolation for those
with all other respiratory viral infections).
Differential diagnosis: In an infant with fever and tachypnea, the other
main cause of illness is pneumonia. This may be present concurrently in
children with bronchiolitis. (RSVis also the commonest cause of pneumonia
in infants). In children with wheezing, asthma is a consideration. It may be
difficult to differentiate bronchiolitis from asthma for the following reasons:
(a) the clinical findings of tachypnea, wheezing, and hyperinflation occur in
both conditions; (b) acute exacerbations of asthma are often precipitated by
viral respiratory infections that cause fever and rhinorrhea. The diagnosis of
FIG. 3.1. A chest X ray of
a child with bronchiolitis,
showing hyperinflation of
the lungs.
Case Study 3 25
bronchiolitis is more likely in patients younger than 1 year and in whom this
is the first episode of wheezing.
Management is primarily supportive: it consists of ensuring adequate
oxygenation and hydration (but not excessive hydration). Bronchodilator
therapy with a b-agonist may be of value in some patients but has not been
shown to result in improved pulmonary function in large studies. Cortico-
steroids are not of value, and antiviral therapy with inhaled ribavirin is of
doubtful value. Two groups of children are at high risk for severe morbidity
or mortality from infections with RSV, namely those with chronic lung
disease resulting from prematurity (formerly called bronchopulmonary dys-
plasia) and those with cyanotic congenital heart disease. These children
should receive anti-RSV prophylaxis with specific immune globulin (palivi-
zumab), which is given intramuscularly once per month during the RSV
season (October through March in the United States).
Reading:
Smyth RL, Openshaw PJM: Bronchiolitis. Lancet 2006; 368: 312322.
Wohl ME, Chernick V: Treatment of acute bronchiolitis. N Engl J Med:
2003; 349: 8283.
Breese Hall C: Respiratory syncytial virus and parainfluenza virus. N Engl J
Med 2001; 344: 19171928.
n
CASE 4. A 3-week-old infant is admitted to hospital in May 1998
because of fever. On examination she has a temperature of 38C, a red
right conjunctiva, and no other abnormalities. Cerebrospinal fluid reveals
50 leukocytes per microliter, of which the majority are lymphocytes, with
protein and glucose concentrations of 120 and 60 mg/dl, respectively.
What is your differential diagnosis?
What else would you like to know?
What would you do?
This infant has meningitis or meningoencephalitis. Although bacterial
meningitis is possible, it is unlikely given the predominance of lymphocytes
and the normal glucose concentration in the cerebrospinal fluid. It is very
likely that the infant has a viral meningitis or meningoencephalitis. The most
important viruses to consider are herpes simplex virus (HSV), which can
cause very severe brain damage and against which treatment is available, and
26 Case Studies in Pediatric Infectious Diseases
enteroviruses, which usually cause benign disease and against which treat-
ment is currently not available.
Examination of the eye might give useful information. If there is a corneal
ulcer, it would strongly suggest HSVinfection. HSVinfection in the neonate
is usually acquired from the mother during the birth process. A maternal
history of genital sores at the time of delivery would raise the likelihood of
HSV infection significantly, but lack of this history would not exclude this
possibility. The risk of HSV infection in a baby born vaginally to a mother
with a primary genital HSV infection at the time of delivery is about
60%, while the risk if the mother has a recurrence of this infection is only
about 2%.
Although rare, neonatal HSV infection is a very severe disease because it
can result in death or very severe brain damage. There are three main forms
of the infection.
(a) Skin, eye, and mouth disease: The skin lesions are vesicles with a red
base, which progress to pustules, often in clusters. They can occur
anywhere but are most frequent at the presenting site or where a break
in the skin might have occurred. Therefore the scalp, including the site
of a scalp fetal monitor probe, is often affected. When typical skin or
mucosal lesions are present, the diagnosis can be readily made clini-
cally. Such lesions should nevertheless be cultured. However, these
lesions are present in only about one-third of cases of neonatal HSV
infection. Therefore the possibility of HSV infection should be enter-
tained in any newborn with fever or evidence of serious disease for
which there is no other obvious explanation.
Other cutaneous lesions that can resemble HSV vesicles are (i) varicella
this is a generalized rash; (ii) bullous impetigo due to Staphylococcus aureus.
These are larger than herpetic vesicles, are often in different parts of the
body, and a Gram stain of a smear of the lesion fluid shows numerous poly-
morphonuclear leukocytes and Gram-positive cocci in clusters. (iii) Candida
infection these are usually confined to the diaper area and inner thighs, and
a Gram stain of fluid from the lesions shows yeasts. (iv) Other bullous
diseases of childhood, such as epidermolysis bullosa. These lesions are much
larger than those of HSVinfection. (v) Aplasia cutis: HSVinfection acquired
in utero can cause loss of skin that gives the appearance of aplasia cutis.
The mouth lesions are similar to those on the skin.
The ocular disease usually manifests as conjunctivitis or keratitis. The
typical herpetic corneal lesion is a dendritic ulcer, which has a serpiginous
border. (The name for herpes is derived from the Greek word for creeping
thing).
Case Study 4 27
(b) Brain disease (encephalitis): This often manifests with seizures and a
change in level of consciousness. However, early on in the herpetic
infection there may not be any specific neurological manifestation.
Most infants with perinatally acquired HSV encephalitis present be-
tween 15 and 19 days of age. The differential diagnosis includes several
metabolic diseases, such as hypoglycemia, hyponatremia, hypocalce-
mia, hypomagnesemia, pyridoxine deficiency, inborn errors of metab-
olism, hypoxic injury, hemorrhage, and other infections, including
bacterial meningitis and enteroviral meningoencephalitis. Differentiat-
ing HSV from enterovirus infection in infants with CSF pleocytosis is
a major challenge. The differences are shown in Table 4.1. The main
differences are that the cell count tends to be much higher and the
protein concentration much lower in enteroviral meningitis. Despite
these differences, I treat all neonates with CSF pleocytosis and with
a negative Gram stain for bacteria, for the possibility of HSVenceph-
alitis, pending the results of further studies (see below). HSVenceph-
alitis, even in infants who have been appropriately treated, is associated
with a very low probability for normal neurological outcome.
(c) Disseminated disease: This manifests with features of the sepsis syn-
drome, with fever, and progressive evidence of multiorgan dysfunc-
tion, including liver failure and coagulopathy. The other main causes
of this clinical scenario are enteroviral infection, bacteremia, and
inherited disorders of metabolism. Considering the life-threatening
state of patients presenting in this manner, they should be treated
nTAB. 4.1: Comparison of cerebrospinal fluid findings in neonatal HSV encephalitis and
enteroviral meningitis.
Reference No. of leukocytes 3 10
6
/l Protein conc. (mg/dl)
HSV
Nahmias 02500 up to 1000
Arvin 100262 (7095% mononuclear) 63210
Gutman 10315 95100 (initially)
Enterovirus
No. of leukocytes
(% of cases in each group)
% neutrophils
(% of cases in each group)
Protein conc.
(% of cases in each group)
Rorabaugh <10 (5) <50 (66) <50 (28)
1025 (22) 5075 (19) 5079 (40)
26100 (22) 7690 (10) 80119 (23)
101500 (31) >90 (5) 120170 (7)
5011000 (13) >170 (3)
>1000 (7)
28 Case Studies in Pediatric Infectious Diseases
with antiviral therapy as well as broad-spectrum antibiotics until a de-
finitive diagnosis can be made. Studies for metabolic diseases should
also be performed as part of the initial evaluation.
Enterovirus (Coxsackie and echovirus) infection is common, and entero-
viral meningitis usually has a benign course and outcome. Although the
infection can occur at any age, most cases are diagnosed within the first
few months of life. This is probably due, at least in part, to the frequency
with which young febrile infants undergo lumbar puncture. Enterovirus in-
fection in the first few days of life can cause very severe illness. In this case
the infection may have been acquired from the mother around the time of
delivery or in the nursery, soon after the infants birth. The infection man-
ifests as a rapidly progressive multiorgan system disease, with myocarditis,
hepatitis, pneumonia, and adrenal disease.
What would you like to know?
Considering the large number of diagnostic possibilities in such infants
and the rarity of HSV infection, several pieces of information might help in
increasing the probability of HSV infection, and thus of favoring initiating
empiric antiviral therapy with acyclovir:
History of exposure: (a) genital HSV infection in the mother at the time
of delivery (that was the case in this mother); (b) penile lesions in the
mothers sexual partner (that had also occurred in this patients case);
HSV infection in close contacts, such as fever blisters.
Examination: The skin should be thoroughly examined, including the
scalp. In this case careful examination of the red eye revealed a dendritic
ulcer, which is characteristic of HSV keratitis, and, thus clinically confirmed
the diagnosis of HSV infection.
What would you like to do?
Management: In suspected cases material from lesions, when available,
should be sent to the laboratory for viral culture. In this case the eye culture
was positive for HSV. In addition, swabs from the mouth and rectum should
also be cultured for HSV. Although laboratories might observe the cultures for
up to a week, they are often positive within 48 hours. Cerebrospinal fluid
should be tested for HSV by polymerase chain reaction (PCR). Pending the
results of tests, empiric therapy should be initiated. This consists of acyclovir
administered intravenously at a dosage of 20 mg/kg/dose given every 8 hours.
If the diagnosis is confirmed or considered likely this should be continued for
a total of 21 days in cases of encephalitis and for 14 days in cases without
encephalitis.
Prevention: Intrapartumacquired HSVinfection can largely be prevented
by performing caesarean sections on mothers in labor with overt genital
Case Study 4 29
HSV infection. If a baby is indeed born vaginally to such a woman, the
following should be considered: specimens should be taken about 24 hours
after delivery, from the mouth, nose, conjunctiva, and rectum for HSV
culture, and the parents be instructed to bring the child for care if there
are any signs of illness. If this occurs, or if the cultures are positive, antiviral
therapy should be initiated while further evaluation is conducted.
Some infants with neonatal HSV who have been appropriately treated
develop recurrences of cutaneous lesions. It is unclear how these patients
should be managed.
Reading:
Kimberlin DW: Neonatal herpes simplex infection. Clin Microbiol Rev
2004; 17: 113.
References:
Whitley RJ, Corey L, Arvin Aet al: Changing presentation of herpes simplex
virus infection in neonates. J Infect Dis 1988; 158: 109.
Arvin et al: Neonatal herpes simplex infection in the absence of mucocuta-
neous lesions. J Pediatr 1982; 100: 715.
Gutman LT, Wilfert CM, Eppes S: Herpes simplex virus encephalitis in
children: analysis of cerebrospinal fluid and progressive neurodevelopmental
deterioration. J Infect Dis 1986; 154: 415.
Rorabaugh ML, Berlin LE, Heldrich F et al: Aseptic meningitis in infants
younger than 2 years of age: acute illness and neurologic complications.
Pediatrics 1993; 92: 206.
Nahmias A et al: Herpes simplex. In: Remington J. Klein J (editors):
Infections of the fetus and newborn infant. WB Saunders. Philadelphia,
1983, pp. 66809.
Frenkel LM: Challenges in the diagnosis and management of neonatal
herpes simplex virus encephalitis. Pediatrics 2005; 115: 795797.
Fonseca-Aten M, Messina AF, Jafri HS, Sanchez PJ: Herpes simplex virus
encephalitis during suppressive therapy with acyclovir in a premature infant.
Pediatrics 2005; 115: 804.
n
CASE 5. (HYP). A 5-year-old boy presents with a limp. This was pre-
ceded by a febrile illness, but there has been no preceding trauma. On
30 Case Studies in Pediatric Infectious Diseases
examination he has weakness of all muscle groups in his right lower limb.
The limb is hypotonic, and deep tendon reflexes cannot be elicited. There is
no pain on movement of the joints nor is there tenderness. Sensory exam-
ination is normal.
What is your differential diagnosis?
What else would you like to know?
What would you do?
Since there is no pain, trauma or infection of the bones, joints or muscles
can be eliminated as causes of the limp. The finding of weakness indicates
a muscle or nervous system problem. The main acute disease of muscle is
myositis, which is usually associated with pain, and is usually more diffuse.
Therefore the disease is most likely one of the nervous system.
Where in the nervous system could a lesion be located that would cause
the present illness?
1. Brain: If a single lesion, it would have to be localized to the left motor
cortex, in the medial aspect of the brain. This would be associated with
hypertonia and increased deep tendon reflexes.
The clinical features are those of a lower motor neuron problem. The
anatomy of the lower motor neuron is shown in Figure 5.1.
2. Spinal cord: If a single lesion, it would have to be located at several levels
of the cord on the right side. This would be unlikely in the absence of
sensory changes.
However, multiple lesions affecting cells in the anterior horns at several
levels could explain this. This is what occurs in poliomyelitis.
3. Peripheral nerve: The most common acute peripheral nerve disease of
children is the Guillain-Barre syndrome. This presents as an ascending
weakness and is symmetrical.
4. Neuromuscular junction: Botulism, which presents with a descending,
symmetrical paralysis, is the main example of disease affecting this area.
One of the important abnormalities in this condition is ptosis.
This child has poliomyelitis. This is an enteroviral infection caused by polio
viruses 1, 2, and 3, which are transmitted by the fecaloral route. It affects
motor neurons of the spinal cord and the brain. The infection is characterized
by fever, myalgia, and backache, which may resolve completely or may
be followed by flaccid weakness. Aseptic meningitis is often present. Al-
though the weakness is usually localized to one limb or muscle group, it
Case Study 5 31
may be generalized. When the brainstem is involved (bulbar poliomyelitis)
swallowing and respiration are affected. There may be recovery, but paralysis
may persist, with wasting of the affected muscle group (Figure 5.2). Nonpolio
enteroviruses and West Nile virus can cause the same clinical syndrome.
A postpolio syndrome, characterized by weakness, muscle atrophy, and
generalized fatigue may develop decades after the acute infection.
Poliomyelitis is diagnosed primarily clinically. The diagnosis should be
confirmed by culture of the virus from the stool. This makes it possible to
examine the viral genome to determine whether the incriminated virus is
wild polio virus or oral vaccine virus, which can, rarely, cause paralytic
disease. The main exposure questions are (a) has he been adequately immu-
nized against the infection and (b) has he traveled recently to an area where
polio is still prevalent (e.g. India)?
Management: In this child the management is concerned with physical
therapy. Long-term care will depend on the degree of recovery that occurs.
However, in patients with bulbar involvement or involvement of the nerves
innervating the muscles of respiration, respiratory support is critical. It is
important to notify the case to the local health department because the virus
can be spread rapidly in both pharyngeal secretions and by the fecaloral
route. It is important to ensure that his contacts are immunized and that he
practices good hygiene. In the United States, polio vaccine is given thrice
during the first 18 months of life, and again at the age of 46 years. In the
FIG. 5.1. The different parts of the lower motor neuron unit.
32 Case Studies in Pediatric Infectious Diseases
United States, only the inactivated (Salk) vaccine is used, while in many
other parts of the world the oral, live, attenuated (Sabin) vaccine is used.
Although significant progress has been made in attempts to eradicate polio
from the earth, this has recently been hampered by objection to immuni-
zation by some communities in northern Nigeria, resulting in spread of
the virus to adjacent countries. Outbreaks can occur in unvaccinated com-
munities within countries with high vaccination rates, as shown by a recent
outbreak in the United States.
Reading:
Burk J, Agre J: Characteristics and management of postpolio syndrome.
JAMA 2000; 284: 412414.
Ogra PL: Poliomyelitis as a paradigm for investment in and success of vac-
cination programs, Pediatr Infect Dis J 1999; 18: 1015.
Centers for Disease Control and Prevention: Progress toward interruption
of wild poliovirus transmission worldwide, January 2004March 2005.
MMWR 2005; 54: 408412.
FIG. 5.2. Unilateral lower
limb wasting, typical of the
late effect of poliomyelitis.
This picture depicts a
Pharaoh of the 18th dynasty.
(Reprinted from: Loschiavo
F: The Lancet. Volume 347,
page 628, with permission
from Elsevier Publishers).
Case Study 5 33
Centers for Disease Control and Prevention: Poliovirus infections in four
unvaccinated children Minnesota, AugustOctober 2005. MMWR 2005;
54: 10531055.
n
CASE 6. (COMP). An 18-year-old boy presents with a history of severe
sore throat and fever for a few days. On examination he has a temperature
of 39C, very large, red tonsils with exudate, resembling that shown in
Figure 6.1, and large cervical lymph nodes.
What is your differential diagnosis?
What else would you like to know?
What would you do?
Differential diagnosis: Infectious mononucleosis, due to EpsteinBarr vi-
rus; Streptococcus pyogenes tonsillitis; gonococcal tonsillitis; diphtheria; re-
spiratory virus infection.
What would you like to know?
Is he sexually active? If so, does he engage in oro-genital sex, which could
expose him to gonococcal tonsillitis?
Is there splenomegaly? This would strongly support the diagnosis of in-
fectious mononucleosis. If he were sexually active, acute HIV infection
should also be considered.
Has he traveled to a country where diphtheria is endemic or been in
contact with an individual who has come from such a country? Is he immu-
nized against diphtheria?
Management of this patient: Streptococcal tonsillitis should be diagnosed
or excluded by performing a streptococcal test on a throat swab. If confirmed
FIG. 6.1. The pharynx of
a patient with the same
diagnosis as that of the
patient described above.
(with permission of James
H Brien, DO, Texas A and
M University College of
Medicine)
34 Case Studies in Pediatric Infectious Diseases
he should be treated with penicillin. If gonococcal tonsillitis is a consider-
ation, a throat culture, specifically for gonococcus, should be performed. This
requires use of a selective medium (Thayer-Martin). The diagnosis of infec-
tious mononucleosis caused by EBV can be confirmed with a heterophile
antibody test. In this condition a blood count may show lymphocytosis, and
a blood smear may show Downy cells (atypical lymphocytes) (Figure 6.2).
This patient had infectious mononucleosis caused by EpsteinBarr virus.
EpsteinBarr virus (EBV): This gamma herpes virus is spread from one
individual (who is usually asymptomatic, but in whom the virus has been
reactivated) to another by saliva, but it can be transmitted by blood trans-
fusion. The incubation period is 46 weeks.
It becomes latent in oral epithelial cells and B-lymphocytes, where it can
become oncogenic. Most individuals are infected in childhood, when the
infection is usually asymptomatic or has nonspecific manifestations, such
as fever. However, in older children and adults it can cause severe symptom-
atic disease. It is a cause of severe disease in immunocompromised individ-
uals. Because the virus results in the production of many nonspecific
antibodies (heterophile antibodies), infection can be complicated by auto-
immune diseases.
Pathogenesis: The virus enters oral epithelial cells and then B-lympho-
cytes, which proliferate. T-lymphocytes proliferate and attack the infected
B-lymphocytes. These T-lymphocytes constitute the primitive-appearing
atypical lymphocytes on the blood smear described above. The inflam-
mation occurring in the organs is largely the result of the T-lymphocyte
response.
FIG. 6.2. The characteristic
atypical lymphocytes
(Downy cells) in the blood
of a 6-year-old child with
infectious mononucleosis.
Case Study 6 35
Clinical manifestations of EBV infection
1. Infectious mononucleosis (glandular fever): This affects mainly older
children, teenagers, and young adults. It is characterized by:
(i) fever, which may persist for a few weeks;
(ii) pharyngotonsillitis: this may be very severe, associated with pseu-
domembrane formation, and may lead to obstruction of the oral
pharynx; this form is called anginose infectious mononucleosis;
(iii) cervical lymphadenopathy;
(iv) generalized lymphadenopathy;
(v) splenomegaly;
(vi) hepatitis: chemical evidence of hepatitis (elevated serum transam-
inase activity) is frequent, but clinical evidence of hepatitis can
also occur.
There may be significant malaise, which can persist for several weeks or
months.
2. Several organ systems can be affected as a result of acute EBV infection:
(i) blood: autoimmune hemolytic anemia; leucopenia; thrombocytopenia;
(ii) nervous system: Guillain-Barre syndrome; transverse myelitis; en-
cephalitis; ataxia; Alice-in-Wonderland syndrome (in which
objects appear larger or smaller than they should);
(iii) lungs: pneumonia;
(iv) kidneys: glomerulonephritis;
(v) heart: myocarditis;
(vi) skin: although a rash is unusual in this infection, a macular rash
occurs in about 90% of individuals who receive ampicillin or amox-
icillin during the infection. This occurs about 10 days after exposure
to these drugs.
(vii) splenic rupture: this a life-threatening complication of EBV infec-
tious mononucleosis. It should be considered in an individual with
features of infectious mononucleosis, who develops acute abdom-
inal, flank, or shoulder-tip pain, anemia, or shock. The risk period is
up to 1 month after diagnosis.
The differential diagnosis of infectious mononucleosis caused by EBV
includes the similar clinical syndrome caused by other agents, namely cyto-
megalovirus, toxoplasmosis, and HIV. In sexually active individuals, HIV is
36 Case Studies in Pediatric Infectious Diseases
the most important consideration. Pharyngotonsillitis due to Streptococcus
pyogenes and respiratory viruses is associated with the pharyngeal and cervi-
cal lymph node manifestations of infectious mononucleosis, but not gener-
alized lymphadenopathy or splenomegaly. The presence of anemia,
thrombocytopenia, or leucopenia would also suggest the possibility of leu-
kemia or lymphoma.
3. Fever, with no other manifestations.
4. Diseases in the immunocompromised host:
(a) X-linked lymphoproliferative disorder (Duncan syndrome): this dis-
order, affecting males only, is characterized by an immunodeficiency
limited to EBV. Affected boys, who cannot contain the infection,
develop progressive infection with organ dysfunction, or lymphoma,
both of which are fatal.
(b) posttransplant lymphoproliferative disease (PTLD): this results from
the therapeutic immunosuppression used to prevent organ rejection
in transplant recipients. It has been a particular risk with cyclosporine
therapy. It begins as a focus of polyclonal lymphoproliferation and can
progress to a lymphoma. It can affect any area including the trans-
planted organ or lymph nodes. The diagnosis depends on clinical
suspicion, which should lead to biopsy.
(c) malignancies (see below).
5. Malignancies:
(a) nasopharyngeal carcinoma
(b) Burkitts lymphoma (African type) (Figures 6.3 and 6.4)
(c) Nasal natural killer-T-cell lymphoma
(d) Hodgkins disease
(e) B-cell lymphoma in immunosuppressed individuals
(f) leiomyosarcoma in immunosuppressed individuals.
Diagnosis of EBV infection: In most normal children, confirming the
diagnosis of infectious mononucleosis caused by EBVis not always necessary.
There is value in making a specific diagnosis in the following circumstances:
(i) when a diagnostic work-up for prolonged, unexplained fever, or for
lymphadenopathy is planned. Having a specific diagnosis of EBV in-
fection can avert such a work-up.
(ii) advising children against contact sports for 1 month after diagnosis.
Case Study 6 37
Diagnostic tests:
(i) blood count and smear: this may show an absolute lymphocytosis and
characteristic atypical lymphocytes, described above (Figure 6.2).
(ii) heterophile antibody: these are antibodies that are unrelated to the
virus and cause agglutination of sheep red cells after absorption with
guinea pig kidney cells but not bovine red cells. There are several tests
for this such as the Monospot test. This test is fairly specific. It is
frequently negative in children younger than 4 years.
(iii) specific EBV antibodies: antibodies to several different EBV antigens
can be detected. Their profile can give an indication of when the in-
fection occurred.
These are shown in Table 6.1. As the table suggests, these tests are fre-
quently difficult to interpret.
FIG. 6.4. An African child
with Burkitts lymphoma
affecting the right maxilla
(internal view).
FIG. 6.3. An African child
with Burkitts lymphoma
affecting the right maxilla
(external view).
38 Case Studies in Pediatric Infectious Diseases
(iv) PCR: the detection and quantitation of EBV DNA in the patients
blood has made it possible to examine progression of disease and re-
sponse to management in immunocompromised patients, such as
those who have had transplants, and are suspected of having posttrans-
plant lymphoproliferative disease (PTLD).
(v) although the virus can be cultured in vitro, this cannot be done in most
diagnostic laboratories.
Management: There is currently no drug available that is very active
against EBV. Nevertheless acyclovir has some activity against the virus.
Treatment of normal hosts is supportive. Treatment of those with PTLD
depends on modification of immunosuppression, other forms of immuno-
modulation, and sometimes chemotherapy, the discussion of which is be-
yond the scope of this text.
In patients with severe tonsillar swelling and the threat of airway obstruc-
tion associated with infectious mononucleosis, administration of corticoste-
roids is beneficial.
Reading:
Cohen J: Epstein-Barr virus infection. N Engl J Med 2000; 343: 481492.
Okano M: Epstein-Barr virus infection and its role in the expanding spec-
trum of human diseases, Acta Paediatr 1998; 87: 1118.
Thorley-Lawson DA., Gross A: Persistence of Epstein-Barr virus and origins
of associated lymphomas. N Engl J Med 2004; 350: 13281337.
n
CASE 7. (MMWR). A 13-year-old previously healthy boy presents with
a history of fever and headache for about 3 days. Now he is generally getting
worse. On examination he looks very ill. He has a high fever, is slightly
obtunded, and has poor perfusion. During the examination he starts to
nTAB. 6.1: Interpretation of antibody tests to EBV antigens.
Test result
Time of infection Current Recent (weeks) Past
Antigen
Viral capsid antigen (VCA) IgM + +/
VCA IgG + + +
Early antigen (EA) + +/
EpsteinBarr nuclear antigen (EBNA) +/ +
Case Study 7 39
vomit blood. It is noticed that after blood is drawn, he continues to bleed at
the venipuncture site. There are no focal abnormalities.
What disturbances are present and what might have caused them?
What else would you like to know?
What would you do?
The clinical features suggest the presence of an infection that is causing
shock, that is systemic, that might be affecting the brain, and that is associ-
ated with a coagulopathy. Infections that might do this are:
Viral: hemorrhagic fevers, including those caused by Ebola virus, Marburg
virus, Lassa virus, Rift Valley fever virus, Yellowfever virus and dengue virus,
and Congo-Crimean hemorrhagic fever;
Bacterial: rickettsioses, sepsis syndrome (in particular meningococcemia),
plague, and leptospirosis;
Parasitic: falciparum malaria and African trypanosomiasis.
Therefore it is very important to obtain a history of possible exposures to
the above infectious agents.
Additional history of exposures: he has recently returned from a 1-week
field trip with his school in a nonmalaria-endemic rural part of South
Africa. A tick was removed from him. Therefore, with the consideration
of a rickettsial infection, when his illness began, he was treated with tetra-
cycline. However, his symptoms progressed.
Management: The most important element of this is supportive care,
which should be directed at reversing the shock and the coagulopathy. Treat-
ment for possible treatable infections should be provided at the same time as
tests are being performed to make a diagnosis. (All laboratories to which
specimens are sent should be informed of the possibility of a viral hemor-
rhagic fever.) These tests should include blood cultures and, in circumstan-
ces in which possible exposure to malaria and trypanosomiasis has occurred,
a blood smear, to look for these parasites. Serum should be stored for pos-
sible future testing. Blood should be sent to a laboratory with facilities to
look for hemorrhagic fever viruses. Appropriate specimens also need to be
submitted to the laboratory for evaluation of his physiological derangements
(chemistry and hematologic studies). Antimicrobial therapy should be di-
rected at the above-mentioned pathogens (broad-spectrum antibiotic ther-
apy). Although his symptoms suggest the possibility of brain infection, his
condition (shock and coagulopathy) contraindicates the performance of
a lumbar puncture. Consideration should be given to the administration of
ribavirin intravenously, which has activity against some of the hemorrhagic
40 Case Studies in Pediatric Infectious Diseases
fever viruses, in particular Lassa fever (endemic in West Africa). Strict con-
tact isolation precautions should be employed, in addition to the use of mask
and eye protection when procedures are performed that have the potential
to cause splashes or aerosols.
The local health department should be notified immediately of a patient
with the possibility of a viral hemorrhagic fever, meningococcemia, or
plague. In the United States, the Centers for Disease Control and Prevention
should also be notified about any case of suspected hemorrhagic fever.
The viruses causing hemorrhagic fevers belong to four main virus families,
namely the Arenaviridae (Lassa fever, Argentinian hemorrhagic fever, Boli-
vian hemorrhagic fever), the Bunyaviridae (Congo-Crimean hemorrhagic
fever, Rift Valley fever), the Filoviridae (Ebola and Marburg), and the Fla-
viviridae (Yellow fever, dengue). Although their clinical manifestations vary,
as a group they include the following: fever, headache, sore throat, myalgia,
backache, macular rash, hemorrhage, multiorgan dysfunction, and shock.
The diagnosis in this patient was Congo-Crimean hemorrhagic fever
(tick-transmitted).
Viral hemorrhagic fever viruses are widespread in Africa and South Amer-
ica. The speed of international air travel facilitates the spread of such viruses.
An infected individual can present anywhere in the world. These infections
carry a very high fatality rate. Some can be spread fromperson-to-person and
can thus constitute an important nosocomial threat.
Reading:
Androniko S, Hopp M, Thompson PD et al: Congo-Crimean Hemorrhagic
Fever South Africa. MMWR 30: 34951, July 24, 1981.
Peters CJ: Role of the endothelium in viral hemorrhagic fevers. Crit Care
Med 2002; 30: S268S273.
Borio L, Inglesby T, Peters CJ et al: Hemorrhagic fever viruses as bio-
logical weapons. Medical and public health management. JAMA 2002;
287: 23912405.
Isaacson M: Viral hemorrhagic fever hazards for travelers in Africa. Clin
Infect Dis 2001; 33: 17071712.
Geisbert T, Jahrling PB: Exotic emerging viral diseases: progress and chal-
lenges. Nat Med. 2004; 10: S110S121.
Peters CJ: Marburg and Ebola arming ourselves against the deadly filovi-
ruses, N Engl J Med. 2005; 352: 25712573.
Case Study 7 41
n
CASE 8 (HYP). A 15-year-old boy presents with episodes of agitation
and anxiety, and confusion. On examination he has a temperature of 38.2 C
and shows slight obtundation and disorientation, but the rest of his exam-
ination is normal. A computer tomography (CT) scan is normal and an
extended drug-screen is negative. The cerebrospinal fluid reveals 70 leuko-
cytes per microliter of which 95% are lymphocytes, with protein and glu-
cose concentrations of 100 and 50 mg/dl, respectively.
What is your differential diagnosis?
What else would you like to know?
What would you do?
This patient has brain dysfunction and a cerebrospinal fluid (CSF)
pleocytosis, suggesting an inflammatory process involving the brain.
The following terminology (rightly or wrongly) is often used, according to
tradition, to describe disease associated with CSF pleocytosis and brain
disease:
(i) meningitis CSF pleocytosis with normal brain function. This may be
of bacterial or other origin.
nTAB. 8.1: A list of causes of encephalitis.
Agent Exposure Treatment
Viruses
Herpes simplex no specific acyclovir
Enterovirus no specific none
Arboviruses mosquitoes, ticks, flies none
HIV human (sexual) antiretrovirals
Rabies animal bite none
a
Bacteria
Borrelia burgdorferi tick ceftriaxone
Mycoplasma pneumoniae human doxycyline
Treponema pallidum human (sexual) penicillin
Fungi OI amphotericin B, fluconazole
Protozoa
Toxoplasma gondii cats, raw meat, OI pyrimethamine + sulfonamide
Naegleria fowleri fresh water amphotericin B + rifampin
Worms
Baylisascaris procyonis raccoon feces
Neurocysticercosis feces of human who has eaten
raw pork
albendazole, praziquantel
Noninfectious disease
Systemic lupus erythematosus corticosteroids
a
Recently a well-documented case of survival from rabies following treatment with ribavirin, interferon, and hypothermia has
been reported.
42 Case Studies in Pediatric Infectious Diseases
(ii) meningitis CSF pleocytosis with brain dysfunction that is thought to
be of bacterial, mycobacterial, or fungal origin.
(iii) encephalitis or meningoencephalitis CSF pleocytosis with brain dys-
function that is thought to be viral or parasitic in origin (that is not
bacterial, mycobacterial, or fungal)
(iv) cerebritis focal brain parenchymal inflammation (the equivalent of
cellulitis), thought to be of bacterial, fungal, or parasitic origin.
The lymphocytic predominance and normal glucose in the CSF suggest
the diagnosis of encephalitis. Although a parameningeal infection such as
a brain abscess or subdural empyema can result in this CSF picture, the
normal CT scan makes this unlikely. (A CT scan with contrast would be
a more sensitive test to detect these conditions.) A wide variety of infectious
agents and noninfectious diseases can cause encephalitis. These are shown in
Table 8.1.
It is important to obtain an exposure history to determine the possibility
of exposure to the above agents. This includes travel, occupational, recrea-
tional, and animal exposures.
When appropriate, tests to help to diagnose these infections or conditions
should be performed.
FIG. 8.1. Immunofluorescence of rabies virus in brain tissue. (Courtesy of
Dr Tierkel, Centers for Disease Control and Prevention)
Case Study 8 43
This patient was a spelunker and had frequently entered caves inhabited by
bats. This poses a risk of exposure to rabies virus, which could explain his illness.
Tests to diagnose rabies should be performed. These include submission
of saliva, CSF, and biopsies of the nape of the neck to a laboratory equipped
to perform the tests for rabies (Figure 8.1). In the United States, specimens
should be sent to the Centers for Disease Control and Prevention in Atlanta.
Management (a) Supportive; (b) antimicrobial therapy directed against
those agents that could cause this clinical picture, and for which therapy is
available. Pending the outcome of an epidemiologic enquiry and laboratory
tests, I employ the following regimen: (i) acyclovir for its activity against
HSV; (ii) cefriaxone for its activity against Neisseria meningitidis, Strepto-
coccus pneumoniae, and Borrelia burgdorferi; (iii) doxycycline for its activity
against Mycoplasma pneumoniae. (c) contact isolation precautions; (d) if
rabies is suspected, the health department should be notified.
Reading:
Hirsch MS, Werner B: Case 17-2003: a 38-year-old woman with fever,
headache, and confusion. N Engl J Med 2003; 348: 22392247.
Whitley RJ, Gnann JW: Viral encephalitis: familiar infections and emerging
pathogens. Lancet 2002; 359: 507514.
Warrell MJ, Warrell DA: Rabies and other lyssavirus diseases. Lancet 2004;
363: 959969.
Hemachudha T, Laothamatas J, Rupprecht C: Human rabies: a disease of
complex neuropathogenetic mechanisms and diagnostic challenge. Lancet
Neurol 2002; 1: 101109.
Jackson AC: Update on rabies. Curr Opin Neurol. 2002; 15: 327331.
Willoughby RE Jr, Tieves KS, Hoffman GM et al: Brief report: survival after
treatment of rabies with induction of coma. N Engl J Med 2005; 352: 2508
2514.
Romero JR, Newland JG: Diagnosis of viral encephalitides: nonzoonotic-
associated viruses. Pediatr Infect Dis J 2006; 25: 739740.
Romero JR, Newland JG: Diagnosis of viral encephalitides: zoonotic-
associated viruses. Pediatr Infect Dis J 2006; 25: 741742.
n
CASE 9. A 6-year-old girl presents with a mild fever and a few small
blisters on her shoulder and chest (Figure 9.1).
44 Case Studies in Pediatric Infectious Diseases
What is the diagnosis?
What are the main complications of this infection?
Observation: Lesions at different stages: tiny papule; vesicle; pustule;
crusted lesion.
Diagnosis: varicella (chickenpox).
Varicella is caused by the human herpes virus, varicella zoster virus
(VZV). It is a common infection affecting most individuals during childhood
(prior to the use of vaccine). It is highly contagious, being transmitted both
by direct contact and by the airborne route. The incubation period is 1021
days. If varicella zoster immune globulin (VZIG) has been administered to
an individual in an attempt to prevent infection (see below), the incubation
period may be prolonged up to 28 days.
Clinical features: There may be a prodrome of 1 or 2 days during which
fever occurs. This is followed by the appearance of skin lesions. These begin as
tiny papules, which progress rapidly to clear vesicles, and then, over a few
days, to pustules and then scabs. The number of lesions varies fromfewer than
10 to several hundred. The course of the illness usually lasts about 7 days. Of
importance in differentiating this infection from other infections are:
(i) different stage lesions are present at the same time (Figure 9.1);
(ii) the lesions tend to be distributed more centripetally than centrifugally,
but they can involve the palms and soles (Figure 9.2);
FIG. 9.1. Picture of the child with fever and blisters.
Case Study 9 45
(iii) they may be present inside the mouth (Figure 9.3); this can be helpful
diagnostically.
Fever usually lasts up to about 3 days. If fever persists longer than this
time, or if it abates and then recurs, the development of secondary bacterial
infection should be suspected. Most children are not very ill with this
infection, but adults tend to have more severe systemic illness.
Diagnosis: The diagnosis of chickenpox is made clinically. Although the
virus can be cultured, this is difficult and takes several weeks. In situations in
which a definitive diagnosis is particularly important, immunofluorescent
tests of scrapings from lesions can be used. The differential diagnosis includes:
Smallpox the lesions are deeper in the skin, are distributed more centrif-
ugally, and all are at a similar stage (Figure 9.4).
Vaccinia the lesions are usually localized to around the site of inoculation
(Figure 9.5).
Bullous impetigo the lesions start as pustules and do not form a dark red
crust. They are generally fewer in number and larger than those in varicella.
Herpes simplex the lesions appear the same as in chickenpox, but they are
localized.
Insect bites these tend to be papules. Although fire ant (Solemnopsis
invicta) bites can appear very similar to chickenpox lesions, they are local-
ized, and there is a distinct history of the bite incident (Figure 9.6).
FIG. 9.2. Varicella in the sibling of child shown in Figure 9.1, showing palmar lesions.
46 Case Studies in Pediatric Infectious Diseases
Management: In most cases symptomatic management is all that is re-
quired. This might include an antipyretic (NOT salicylate) and an antipru-
ritic (e.g. diphenhydramine). Cool baths may be soothing. Antiviral therapy
with acyclovir given orally (20 mg/kg/dose every 6 hours) has been shown to
reduce the duration of illness by about 1 day. This is not usually of clinical
significance.
Individuals with impairment of cell-mediated immunity should be trea-
ted aggressively, with acyclovir administered intravenously (500 mg/m
2
every 8 hours).
Complications: (i) The most serous complication is pneumonia. This is very
unusual in normal children, but is important in
adults and immunocompromised children. It is a diffuse
pneumonia that can lead to respiratory failure and death
(Figures 9.7 and 9.8).
It can be followed by pulmonary calcifications. The diagnosis of this com-
plication can usually be made readily. Management entails supportive care
(e.g. oxygen) and antiviral therapy with acyclovir.
(ii) Secondary bacterial infection of skin lesions (Figures 9.9 and 9.10).
This constitutes the most common complication of varicella. There
may be increasing erythema and induration around the lesion, but
the focus of secondary infection might not always be apparent. The
FIG. 9.3. A woman with the enanthem of varicella.
Case Study 9 47
infecting bacteria are usually Streptococcus pyogenes or Staphylococcus
aureus. These infections can progress to very severe infective compli-
cations, including cellulitis, necrotizing fasciitis, bacteremia, osteomy-
elitis, and staphylococcal toxic shock syndrome or streptococcal toxic
shock-like syndrome. This latter complication carries a very high fatal-
ity rate.
The diagnosis of secondary bacterial infection is based on clinical suspi-
cion. As alluded to above, fever persisting after 3 days, or recrudescence of
fever after it has abated should suggest that this complication has occurred.
Avery thorough examination of the skin should be made to look for a site of
secondary bacterial infection. This is important not only to assist in the di-
agnosis but also to determine whether there is a focus that requires surgical
drainage, or from which infected material can be obtained for culture and
FIG. 9.4. A child with
smallpox. (Courtesy of
James Hicks/Centers for
Disease Control and
Prevention)
48 Case Studies in Pediatric Infectious Diseases
FIG. 9.5. The appearance of a vaccinia lesion at the site of inoculation.
FIG. 9.6. Lesions caused by the bites of the fire ant (Solemnopsis invicta).
Case Study 9 49
antibiotic susceptibility testing. If there is a suspicion of severe infection,
bacteremia, or toxic shock syndrome, a blood culture should be performed,
as well as other tests deemed necessary to evaluate physiological functions.
Management: Patients with mild infections can be treated with cephalexin
or, where methicillin-resistant Staphylococcus aureus (MRSA) is prevalent,
clindamycin. Patients with moderately severe or severe infections should
FIG. 9.8. Chest X ray of
patient shown in the Figure
9.7, showing extensive
pulmonary infiltrates..
FIG. 9.7. A child with Hodgkins disease and a severe case of varicella and varicella
pneumonia; note the oxygen mask.
50 Case Studies in Pediatric Infectious Diseases
be hospitalized and receive supportive care as is indicated. Antimicrobial
therapy should be directed at the above-mentioned bacteria.
In locales with a low prevalence of MRSA, nafcillin may be used, but
where the prevalence of such resistant strains is high, vancomycin should
be administered.
(iii) Encephalitis: This can develop during or within a few weeks of chick-
enpox. In most cases it is probably a parainfectious encephalitis, im-
plying that the virus is not present in the brain.
(iv) Acute cerebellar ataxia: This is a form of encephalopathy characterized
by ataxia, suggesting disease of the cerebellum and/or its connections.
FIG. 9.9. A child with cellulitis of the neck and upper chest complicating varicella.
FIG. 9.10. A child with
periorbital cellulitis compli-
cating varicella. Note the
swelling of the left upper
eyelid and the healed lesions
on the forehead.
Case Study 9 51
The cerebrospinal fluid is generally normal, as are imaging studies.
Therefore it may not be an inflammatory disease. It lasts up to a few
weeks, but recovery is complete.
(v) Reyes syndrome.
(vi) Severe visceral disease (progressive varicella), including hepatitis and
myocarditis.
(vii) Zoster (shingles): Being a herpes virus, VZV becomes latent in sensory
or dorsal root ganglia. Zoster represents the recrudescence of the virus.
It is characterized by skin disease in a dermatomal distribution. It
begins as pain or burning, followed by the appearance of vesicles,
which progress to crusting (Figures 9.11 and 9.12).
It can be very painful, and, prior to the appearance of the rash, can be
confused with other diseases affecting that location, particularly if it involves
the chest or abdomen. Although most patients who develop zoster have no
recognized underlying predisposing factor, individuals with defects in cell-
mediated immunity are at increased risk of developing this complication.
The diagnosis of zoster is made clinically. This is facilitated by the distribu-
tion of the rash in one or more dermatomes on one side of the body. Asimilar
appearing rash can be caused by herpes simplex and by allergy to poison ivy.
FIG. 9.11. Zoster, affecting the skin in dermatome C6 distribution, in a child
with leukemia who had had varicella 6 months earlier.
52 Case Studies in Pediatric Infectious Diseases
Management: In most cases analgesia is all that is required. The lesion
should be covered to prevent spread to individuals who are susceptible to
VZV. (Spread is by direct contact.) In individuals with impaired cell-
mediated immunity, antiviral therapy should be administered. In severe
cases this should be with intravenously administered acyclovir (dosed as
for chickenpox, see above), while in mild cases this can be accomplished
by the oral route, with acyclovir, valacyclovir, or famcyclovir.
Complications of zoster: (a) Herpes zoster ophthalmicus: this is zoster af-
fecting the ophthalmic branch of the trigeminal nerve. This results in disease
around the eye, and sometimes of the cornea and uveal tract. If this occurs it
should be managed in conjunction with an ophthalmologist, because it can
be associated with severe intraocular inflammation and glaucoma. Antiviral
therapy (acyclovir or one of its derivatives) should be used. In most cases this
can be administered orally. A particularly severe complication of herpes
zoster ophthalmicus is contralateral hemiplegia, as a result of infection
extending along the sympathetic chain into the carotid artery.
(b) Postherpetic neuralgia: This is persistent severe pain following an epi-
sode of zoster. Patients with this complication should be managed in
conjunction with a neurologist. Carbamazepine can be of value in this
circumstance.
(c) Persistent zoster: This can occur in individuals with severe cell-mediated
immune defects, such as AIDS.
FIG. 9.12. Zoster affecting thoracic dermatomes in a child.
Case Study 9 53
(viii) Encephalopathy: There are several possible causes of encephalopathy
in patients with varicella. These are listed in Table 9.1.
(ix) Congenital varicella: Although uncommon, maternal varicella can re-
sult in fetal infection. This may result in severe scarring of the skin and
in brain atrophy (Figure 9.13).
nTAB. 9.1: Causes of encephalopathy during or following chickenpox.
Metabolic disease
Hypoxia due to pneumonia
Hypoglycemia due to:
Ketotic hypoglycemia
Liver failure
Reyes syndrome
Reyes syndrome
Infection
Sepsis syndrome caused by Streptococcus pyogenes or Staphylococcus aureus
Toxic shock or toxic shock-like syndromes
Encephalitis
Intoxication
Overdosage of diphenhydramine
Liver failure due to overdosage of acetaminophen
FIG. 9.13. A newborn baby
with left wrist scarring from
intrauterine varicella.
54 Case Studies in Pediatric Infectious Diseases
Reading:
Nguyen HQ, Jumaan AO, Seward JF: Decline in mortality due to varicella
after implementation of varicella vaccination in the United States. N Engl J
Med 2005; 352: 450458.
n
CASE 10. A 12-year-old girl develops malaise, fever, and rapid breathing
6 weeks after undergoing a renal transplant. On examination she is febrile,
tachypneic, and has bilateral crackles on auscultation. Examination of her
cardiovascular system is normal, and the rest of her examination is normal
other than for the presence of a well-healed abdominal surgical scar, a pal-
pable kidney in the right lower quadrant, and a cushingoid appearance.
What is the differential diagnosis?
What would you like to know?
Differential diagnosis: The clinical features in this child indicate pneumo-
nia. The challenge is to determine its microbial cause. In a renal transplant
patient, who is immunocompromised as a result of immunosuppressive
therapy, one should consider the following causes of pneumonia:
(a) those causing pneumonia in normal children Mycoplasma pneumoniae,
Chlamydia pneumoniae, and Streptococcus pneumoniae, respiratory
viruses, for example, adenovirus, influenza virus, parainfluenza virus,
and respiratory syncytial virus
(b) opportunistic viruses: respiratory syncytial virus, adenovirus, cyto-
megalovirus (CMV)
(c) opportunistic bacteria: Legionella pneumophila, Mycobacterium tubercu-
losis, Staphylococcus aureus, Nocardia asteroides, Rhodococcus equi
(d) opportunistic fungi: Histoplasma capsulatum, Cryptococcus neoformans,
Pneumocystis jiroveci
(e) opportunistic parasites: Toxoplasma gondii, Strongyloides stercoralis.
The following important questions should be asked to determine possible
exposures to unusual pathogens: travel, occupation, recreational activities,
exposures to animals and to sick human beings, and blood transfusions.
A very important factor in this patient is the CMV status of the patient
before transplantation and of the donor. In this case the patient was CMV
seronegative, indicating that she had not ever been infected with the virus,
while the donor was CMV positive, indicating prior infection with the virus.
This places her at high risk for developing CMV infection, which was ulti-
mately shown to be the case. Considering the number of microorganisms
Case Study 10 55
that might cause pneumonia in a transplant patient, and the potential toxicities
of antimicrobial therapy directed against them, serious consideration should be
given to performing an invasive procedure such as bronchoalveolar lavage or
lung biopsy in order to make a microbiological diagnosis. This was not done in
this patient. She was treated with ganciclovir intravenously and improved.
CMV infections in the immunocompromised host are discussed below.
Because CMV is markedly cell-associated, cell-mediated immunity is
important in controlling viral replication. Therefore individuals with impair-
ment of this defense system are at risk for significant CMV disease. These
include patients with AIDS and those who have undergone organ transplan-
tation. The infection manifests with fever, evidence of different organ in-
volvement (see below), leucopenia, and elevated transaminase levels. The
organ involvement includes the following:
pneumonia, which is the most serious (Figure 10.1);
retinitis, which is particularly important in patients with AIDS;
encephalitis;
kidney disease, which may lead to graft rejection in renal transplant patients;
hepatitis;
colitis, which may associated with bleeding or intestinal perforation.
Diagnosis: There are currently several types of tests available for diagnosing
CMV infection:
(i) Serological tests for antibodies: These are of very limited value. A pos-
itive anti-CMV IgG indicates that the patient has had the infection
FIG. 10.1. Lung tissue
from a patient with AIDS
complicated by pneumonia,
demonstrating the character-
istic large (megalo) alveo-
lar cell (cyte) with an
intranuclear inclusion, char-
acteristic of cytomegalovirus
infection. (Courtesy of the
Centers for Disease Control
and Prevention/Dr Edwin P
Ewing, Jr)
56 Case Studies in Pediatric Infectious Diseases
previously or has recently received a blood transfusion. Apositive anti-
CMVIgMindicates that the patient has recently been infected with the
virus or has had a reactivation of the virus. A negative serological test
indicates that the patient has not been infected or has been infected but
cannot mount an antibody response. The main value of the test lies in
determining a patients susceptibility to the virus prior to transplant,
whether a transplant donor has been infected with the virus and whether
the patient has seroconverted, implying acquisition of infection.
(ii) Culture: Although CMV takes several weeks to produce cytopathic
effects in tissue culture, the presence of viral antigens on tissue culture
cells can be detected within 48 hours after inoculation. This technique
is called the shell-vial technique. Body fluids that can be tested in this
manner include urine and bronchial fluid.
(iii) PCR: This detects viral genome. It is rapid, very sensitive, and can be
performed on blood and leukocyte preparations. This test can be used
not only for detecting viremia, but also for quantitating viremia (viral
load), and consequently, for evaluating response to therapy.
(iv) Detection of CMVantigenemia.
(v) Demonstration of virus-infected cells in tissue. Such cells show char-
acteristic inclusions and can be stained with CMV antigenlabeled
antibody.
Management: When CMV is diagnosed in an immunocompromised pa-
tient, antiviral therapy should be administered, initially with intravenous
gancyclovir. Failure of an expected response should suggest the possibility
of resistance to the drug. In such a case attempts should be made to culture
the virus from urine or blood so that its drug susceptibility can be deter-
mined. If resistance is suspected or demonstrated, the antiviral drug foscar-
net should be administered.
Various strategies can be considered for patients placed at risk of devel-
oping CMV infection through solid organ transplantation. These are as fol-
lows: (i) prophylaxis, which involves administering gancyclovir, with or
without CMV hyperimmune globulin, to patients at high risk (seronegative
recipient, seropositive donor); (ii) pre-emptive therapy, which involves
monitoring blood by CMV viral load measurement for the development
of infection and, if it occurs, to initiate therapy with ganciclovir; and (iii)
therapy for symptomatic disease with ganciclovir. In a situation such as the
one described for this patient, in which a seronegative recipient received an
organ from a seropositive donor, prophylaxis or pre-emptive therapy with
ganciclovir might have prevented her illness.
Case Study 10 57
Reading:
Danziger-Isakov LA, Storch GA: Prevention and treatment of cytomegalo-
virus infections in solid organ transplant recipients. Pediatr Infect Dis J 2002;
21: 432434.
Bueno J, Ramil C, Green M: Current management strategies for the pre-
vention and treatment of cytomegalovirus infection in pediatric transplant
recipients. Pediatr Drugs 2002; 4: 279290.
Pereyraa F, Rubin RH: Prevention and treatment of cytomegalovirus
infection in solid organ transplant recipients. Curr Opin Infect Dis 2004;
17: 357361.
n
CASE 11 (HYP). A 4-year-old boy develops fever 5 weeks after under-
going open-heart surgery for congenital heart disease. On examination he is
fairly well appearing and has a temperature of 38.4C. The surgical wound
and sites of previous vascular catheters are well healed. The heart exami-
nation reveals a 2/6 short ejection systolic murmur and no pericardial rub.
There are no petechiae, splinter hemorrhages, or palmar nodules. He has
generalized lymphadenopathy and splenomegaly, but no hepatomegaly, and
the rest of his examination is normal.
What is the differential diagnosis?
Differential diagnosis of a febrile illness in a patient who has undergone
cardiac surgery:
(a) Infective endocarditis: This is the main concern in a patient with con-
genital heart disease who has fever following heart surgery. Although
splenomegaly is a clinical feature of infective endocarditis, generalized
lymphadenopathy is not.
(b) Nosocomial infection complicating use of vascular catheters, a urinary
catheter, and ventilation: These usually manifest during hospitalization
or soon afterward. Therefore this is unlikely.
(c) Postpericardiotomy syndrome: This is characterized by fever, pericar-
ditis, and pleuritis. It usually develops 13 weeks after surgery. This
child lacks the clinical features of this condition.
(d) Postperfusion syndrome: This is an infectious mononucleosis syndrome
resulting from blood transfusions given during cardiopulmonary bypass.
It is usually caused by cytomegalovirus, but can be caused by Epstein
Barr virus, Toxoplasma gondii, and human immunodeficiency virus
58 Case Studies in Pediatric Infectious Diseases
(HIV). It is characterized by fever, splenomegaly, and lymphadenopa-
thy. Hepatomegaly and a rash may sometimes occur. This is the most
likely diagnosis in this patient.
The diagnosis of cytomegalovirus infection can be supported by demon-
strating CMV in the blood by PCR, CMV in the urine by culture, serocon-
version to CMV, or the presence of CMV IgM antibodies in the blood (see
Case 10). Infection with the other causes of infectious mononucleosis can be
diagnosed serologically or, in the case of acute HIV infection, by a PCR test.
Many infectious agents can be transmitted in transfused blood. Most of
these are present in the blood of the donor at the time of blood collection.
These include viruses (hepatitis B and C, cytomegalovirus, EpsteinBarr
virus, HIV, and West Nile virus), bacteria that are present in the donors
blood, including Treponema pallidum, and especially Yersinia enterocolitica
and Listeria monocytogenes, which can grow during cold storage of the blood,
and protozoa, including Plasmodium spp., Toxoplasma gondii, Trypanosoma
cruzi, and Trypanosoma brucei. The blood can also become contaminated
during collection and processing, in which case the infectious agents are
usually bacteria. Platelet units are particularly prone to bacterial infection
because they are stored at room temperature.
Reading:
Busch MP, Kleinman SH, Nemo GJ: Current and emerging infectious risks
of blood transfusions. JAMA 2003; 289: 959962.
n
CASE 12. A6-year-old girl with sickle cell disease is admitted with fever,
sore throat, and general malaise. She has no localizing signs of infection. She
is treated for the possibility of bacteremia with intravenous cefotaxime, but
her fever has persisted. The blood cultures have been negative. On day 3,
her hemoglobin concentration has decreased from 7.5 to 5.0 g/dl, and her
reticulocyte count has decreased from 10% to 1%.
What do you think has happened?
She has developed worsening anemia in the face of a decreased produc-
tion of red cells, as demonstrated by a decreasing reticulocyte count. This
suggests that the cause of the deterioration is bone marrow failure of red cell
production. Possible causes of this are infection, in particular that caused by
parvovirus B19, and drugs. Since this illness is associated with fever and she
has not received drugs that cause red cell hypoplasia, this is likely caused by
Case Study 12 59
parvovirus. This clinical scenario is called an aplastic crisis. Parvovirus B19
infects many individuals in childhood, sometimes causing an exanthem
called erythema infectiosum (fifth disease) characterized by a lacy erythem-
atous rash and red cheeks (Figures 12.1 and 12.2).
The virus infects red cell precursors in the bone marrow, resulting in
failure to produce red cells for about 1 week. This does not have a significant
effect on individuals with a normal red cell lifespan (about 120 days) but can
FIG. 12.1. The lacy rash associated with parvovirus B19 infection.
FIG. 12.2. A boy (sibling of the child in Figure 12.1) with red cheeks
(slapped cheeks) due to parvovirus B19 infection.
60 Case Studies in Pediatric Infectious Diseases
cause profound anemia in individuals whose red cell lifespan is short, that is,
those with chronic hemolytic anemias such as sickle cell disease and hered-
itary spherocytosis. This virus also causes severe anemia in the fetus, result-
ing in hydrops fetalis, and in individuals with immunodeficiencies that limit
their ability to eliminate the virus, such as AIDS.
Reading:
Young NS, Brown KE: Parvovirus B19. N Engl J Med 2004; 350: 586
597.
n
CASE 13. A 5-year-old girl presents with a history that she has difficulty
walking and that her speech is becoming difficult to understand. On exam-
ination she has generalized increase in muscle tone, her gait is wide-based,
and she is dysarthric. Disease of the brain is diagnosed, and a computer
tomography scan without contrast is performed (Figure 13.1).
What does the scan show?
What is your differential diagnosis?
What would you do?
FIG. 13.1. The computer tomography scan (without contrast) of the patients head.
Case Study 13 61
The scan shows calcification of the basal ganglia, in addition to cerebral
atrophy, as demonstrated by widened sulci. There are several metabolic
conditions that can cause this, such as pseudohypoparathyroidism. Intrauter-
ine infections such as toxoplasmosis and cytomegalovirus infection can cause
cerebral calcifications, but in such cases the clinical manifestations of cere-
bral injury are present in infancy. A particular infection that should be con-
sidered in such patients is human immunodeficiency virus (HIV) infection,
which would likely have been transmitted vertically. Therefore an HIVanti-
body test should be performed on the child.
She was shown to have HIV infection as was her mother.
Neurological disease is an important complication of HIV infection
in children. Most cases are due to direct damage to the brain by the virus,
resulting in encephalopathies with varying rates of progression. These can
result in failure to attain developmental milestones or loss of intellectual and
motor milestones, as in this case. Spasticity is often present, and movement
disorders may occur. In my experience, ankle clonus is often present.
Much less common causes of brain disease in HIV-infected children include
tumors (primarily lymphoma), stroke resulting from HIV vasculopathy, and
opportunistic infections, the most common of which is cytomegalovirus
infection.
Other nervous systemdiseases occurring in HIV-infected children include
vacuolar myelopathy and peripheral neuropathy, which is due mainly to
antiretroviral therapy.
Reading:
Zuckerman GB, Sanchez JL, Conway EE: Neurologic complications of HIV
infections in children. Pediatr Ann 1998, 27: 635639.
Zeichner SL, Read JS (editors): Handbook of pediatric HIV care. Lippincott
Williams and Wilkins, Philadelphia, 1999, pp. 336351.
Weisberg LA: Neurologic abnormalities in human immunodeficiency virus
infection. Southern Med J 2001; 94: 266275.
Antiretroviral therapy and medical management of pediatric HIV infection
and 1997 USPHS/IDSAreport on the prevention of opportunistic infections
in persons infected with human immunodeficiency virus. Pediatrics 1998;
102 (part 2): S 1005S 1085.
American Academy of Pediatrics and Canadian Paediatric Society. Evalua-
tion and treatment of the Human Immunodeficiency Virus-exposed infant.
Pediatrics 2004; 114: 497505.
62 Case Studies in Pediatric Infectious Diseases
n
CASE 14. A 6-month-old boy presents (in 1990) with a history of poor
feeding, fever, and decreased activity. He weighs 3 kg. He is diagnosed with
meningitis due to Listeria monocytogenes. He is treated with ampicillin and
recovers from this infection. While still in hospital he develops tachypnea
and respiratory difficulty. A chest X ray is performed (Figure 14.1).
What does the X ray show?
What is the differential diagnosis?
What would you do?
The clinical scenario is one of an infant with severe failure to thrive and
the development of pneumonia while he was recovering from a proven in-
fection (listeriosis) that is opportunistic in individuals with defective
cell-mediated immunity. The new respiratory symptoms therefore suggest
the possibility of another opportunistic infection. The chest radiograph
shows a diffuse alveolar infiltrate. This might be caused by many infectious
agents including respiratory viruses (respiratory syncytial virus, human
metapneumovirus, adenovirus, parainfluenza virus, and influenza virus)
and bacteria (Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia
pneumoniae, Legionella pneumophila, and Mycobacterium tuberculosis). In
FIG. 14.1. The infants
chest X ray.
Case Study 14 63
view of the likelihood that he is immunocompromised, an important con-
sideration is infection with Pneumocystis jiroveci (formerly called Pneumo-
cystis carinii). Considering the long time that it would have taken to
demonstrate the presence of the viruses in the pharynx by tissue culture
of pharyngeal secretions (rapid diagnostic tests were not readily available
at the facility at that time), and the lack of ability to obtain sputum from
an infant for examination of bacteria, the dilemma facing the clinicians was
the following: should the child be treated empirically for all the treatable
diagnostic possibilities or should he undergo an invasive diagnostic procedure
such as bronchoalveolar lavage or lung biopsy to obtain pulmonary material
for staining of bacteria and Pneumocystis jiroveci, culture, and histology?
He underwent open lung biopsy. The histological picture was typical of
pneumocystis infection (Figure 14.2), and the silver stain showed cysts of the
Pneumocystis jiroveci (Figure 14.3).
FIG. 14.3. Gomorri
methenamine stain of the
lung biopsy showing the
black-stained cysts of
Pneumocystis jiroveci.
FIG. 14.2. Hematoxylin
and eosin stained section of
lung tissue from the patient,
showing thickening and
hypercellularity of the inter-
stitium, and foamy material
within the alveoli, character-
istic of pneumocystis
pneumonia (formerly called
interstitial plasma cell
pneumonitis).
64 Case Studies in Pediatric Infectious Diseases
The child was treated with trimethoprim/sulfamethoxazole and im-
proved. Further investigation showed that he was infected with HIV, which
he had acquired vertically from his mother.
The clinical features of children with HIV infection are discussed
below. They can be considered in terms of those due to only the HIV in-
fection itself, those due to the consequences of loss of immune function
(mainly opportunistic infections), and those due to management (not dis-
cussed here).
Manifestations due to HIV infection itself: Since the virus infection is
systemic all parts of the body can be affected.
Growth and nutrition: Failure to thrive and loss of weight; this is due to
a combination of increased metabolic demands, in which cytokines play
a role, and opportunistic infections.
Reticuloendothelial system: Generalized lymphadenopathy, including epitro-
chlear lymphadenopathy, hepatomegaly, and splenomegaly.
Blood: Anemia, thrombocytopenia, and leucopenia; the leucopenia can re-
flect not only lymphopenia, but also neutropenia.
Lung: Lymphocytic interstitial pneumonitis, which is characterized by lym-
phocytic infiltration of the bronchial walls as well as the alveolar septa.
EpsteinBarr virus may play a role in the pathogenesis of this condition. This
condition can cause airway obstruction.
Central nervous system: Encephalopathies ranging in manifestations from
failure of brain growth and normal acquisition of milestones, to progressive
loss of acquired milestones, spasticity, and movement disorders (see Case
13). A vasculopathy predisposing to stroke can also occur.
Heart: Cardiomyopathy.
Skin: Inflammatory lesions resembling atopic or seborrheic dermatitis.
Kidney: Glomerulopathy due to a membranous glomerulonephritis. This is
a late manifestation of HIV infection.
Opportunistic infections: Many of these infections are the same as those in
normal children, such as frequent episodes of acute otitis media, and caused
by infectious agents that infect normal children, in particular Streptococcus
pneumoniae. However, HIV-infected children may have more severe disease,
have these infections more frequently, or be unable to eliminate the infec-
tious agent. Several opportunistic diseases are rare in children compared
with adults, probably because of lack of exposure to the organisms. These
Case Study 14 65
include toxoplasmosis, cryptococcosis, histoplasmosis, polyoma virus infec-
tions, Kaposi sarcoma, and bacilliary angiomatosis.
Virus infections:
The herpes viruses: Herpes simplex virus can cause severe infections of the
oral and esophageal mucosae and the skin, while varicella zoster virus can
cause severe chickenpox, as well as severe and chronic zoster infections.
Cytomegalovirus, which commonly affects many normal children, can
cause severe opportunistic infection of the esophagus, intestine, retina,
lung, liver, and nervous system. All three herpes viruses can cause a rad-
iculomyelopathy.
Respiratory viruses: Although the clinical diseases are the same as those
affecting normal children, pneumonia is common, and viral excretion may
be prolonged.
Parvovirus B19: HIV-infected children may not be able to eliminate
the virus, which infects red cell precursors in the bone marrow. This
can therefore be one of several potential causes of chronic anemia.
Bacterial infections: Although some bacterial infections affecting HIV-
infected children do not occur in normal hosts, many of the bacterial
infections in such children are the same as those in normal hosts, but they
occur significantly more frequently. Otitis media and pneumonia are
common. Bacteremia is caused by Streptococcus pneumoniae, Haemophilus
influenzae type b, and Pseudomonas aeruginosa, and occasionally, by Lis-
teria monocytogenes. Although tuberculosis occurs as in any exposed in-
dividual, the disease is more frequently extrapulmonary than in otherwise
normal hosts. Mycobacterium avium complex causes both pulmonary and
systemic disease, affecting the liver, intestine, and other organs. Nocardia
species cause opportunistic pneumonia and brain abscess.
Fungal infections: The most important of these by far is Pneumocystis
jiroveci (formerly P. carinii). This causes severe pneumonia, the peak
age incidence of which is 4 months. The other important fungal pathogen
is Candida. This causes oral as well as esophageal disease.
Parasites: In the United States, the most important are those protozoa
affecting the intestinal tract, namely Giardia lamblia, Cryptosporidium
parvum, and Isospora belli.
Opportunistic tumors are rare in children. These include B-cell lympho-
mas and leiomyosarcomas.
66 Case Studies in Pediatric Infectious Diseases
Reading:
Zeicher SL, Read JS: Handbook of Pediatric HIV Care. Lippincott Williams
and Wilkins, Philadelphia, 1999, pages 336352.
Domachowske JB: Pediatric human immunodeficiency virus infection. Clin
Microbiol Rev 1996; 9: 448468.
Antiretroviral therapy and medical management of pediatric HIV infection
and 1997 USPHS/IDSAreport on the prevention of opportunistic infections
in persons infected with human immunodeficiency virus. Pediatrics 1998;
102 (part 2); S 1005S 1085.
American Academy of Pediatrics and Canadian Paediatric Society. Evalua-
tion and treatment of the Human Immunodeficiency Virus-exposed infant.
Pediatrics 2004; 114: 497505.
n
CASE 15 (COMP). A 2-year-old boy presents with a history of having
a cough and fever for 2 days. He has been hospitalized on three previous
occasions for a similar problem, and he improved after being treated with
antibiotics. On examination he is mildly ill-appearing. His temperature is
38.5C, heart rate 120/minute, respiratory rate 40/minute, and blood pres-
sure 95/60 mm Hg. He has mild subcostal retractions and decreased breath
sounds in the right lower lobe, with crackles in that area. The trachea is
central. The ears and pharynx are normal, and the rest of his examination is
completely normal.
What is your differential diagnosis?
How would you evaluate him?
This patient has evidence of lobar pneumonia (fever, decreased breath
sounds, and crackles). He requires treatment for this episode of illness. How-
ever, this is recurrent, and he therefore requires evaluation for an underlying
disease predisposing him to this problem.
When evaluating a patient with recurrent pneumonia, one should ask
oneself several questions:
(a) Has there indeed been recurrent pneumonia, or have these episodes
really represented episodes of asthma or bronchitis? What is the
evidence that he has had recurrent pneumonia?
(b) Have these episodes affected the same area of the lung, or different areas?
Answering these two questions requires review of all records and chest
X rays available.
Case Study 15 67
If he has indeed suffered fromrecurrent episodes of pneumonia, and these
have affected the same area of the lung each time, this suggests an anatomical
abnormality in that area, particularly an abnormality causing obstruction of
the bronchus to that area. Causes of this can be considered in terms of
abnormalities within the lumen, those affecting the wall, and those causing
compression from outside the bronchus. These include the following:
Causes within the lumen:
Foreign body
Endobronchial tuberculosis
Tumor
Causes affecting the wall:
Asthma
Bronchomalacia
Causes from external compression:
Enlarged hilar lymph node due to:
Tuberculosis
Lymphoma
Enlargement of the left atrium compressing the left main bronchus
Other causes of recurrent focal pneumonia:
Bronchiectasis
Lung malformations
Sequestered lobe
If the pneumonias have affected different parts of the lung, a more gen-
eralized problem should be considered. The causes should be considered in
the following categories:
Heart disease
heart failure
left-to-right shunts, for example, ventricular septal defect
Gastrointestinal disease
Gastroesophageal reflux with aspiration
H-type tracheoesophageal fistula
Neurological disease
Lower motor neuron disorders, causing poor lung excursion and clearance
of secretions, for example, spinal muscular atrophy (Figure 15.1)
Severe spasticity, with pseudobulbar paresis
Systemic diseases affecting the lung:
Immotile cilia syndromes
Cystic fibrosis
Immune deficiencies
68 Case Studies in Pediatric Infectious Diseases
Many of these can be diagnosed or suspected clinically. Specific tests may
be required for diagnosing others, for example, gastroesophageal reflux,
cystic fibrosis, immotile cilia syndromes, and immune defects.
Reading:
Panitch HB: Evaluation of recurrent pneumonia. Pediatr Infect Dis J 2005;
24: 265266.
n
CASE 16 (HYP). A baby is born with a rash identical to that seen in the
baby shown in Figure 16.1.
Questioning reveals that the mother had a febrile illness during the second
trimester of pregnancy.
Examination reveals diffuse raised purple skin lesions. There is no pallor,
jaundice, or cyanosis. The eyes are normal externally, the heart has a 3/6
systolic murmur, and there is enlargement of both the liver and the spleen.
There is no lymphadenopathy.
What is your differential diagnosis?
What would you like to know?
FIG. 15.1. A 10-month-old infant with spinal muscular atrophy (Werdnig-Hoffman
type). Note the frog-leg position of the lower limbs, and the concavity of the lower
chest (Harrisons sulcus), a sign of lung disease beginning at a young age.
Case Study 16 69
This childs condition is characterized by a rash, a heart murmur, and
enlargement of the liver and spleen.
This rash is generalized and characterized by raised purple lesions.
Several infections may cause rashes that are present in babies at birth.
These include the following: congenital rubella, which causes a generalized
macular rash or raised purple lesions (blueberry muffin rash), which rep-
resent areas of extramedullary erythropoiesis; congenital cytomegalovirus
(CMV) infection and toxoplasmosis, which can cause the same type of rash
as rubella. The rash associated with congenital syphilis is macular or maculo-
papular, but does not consist of purple lesions; congenital listeriosis, which
produces multiple pustules (granulomatosis infantiseptica); candida, which
causes macules or generalized erythema; and herpes simplex virus, which pro-
duces focal vesicles. The lethal form of epidermolysis bullosa is associated
with denudation of areas of skin at birth. Nikolsky sign can be demonstrated
in this condition.
Candida and herpes simplex are usually due to ascending infection and are
not likely to result from a maternal infection in the second trimester. Con-
genital listeriosis is usually fatal, so the baby would not likely have survived
from the second trimester.
FIG. 16.1. New born baby with a rash. (Courtesy of the Centers for Disease
Control and Prevention).
70 Case Studies in Pediatric Infectious Diseases
Enlargement of liver and spleen occurs in congenital rubella, CMV in-
fection, toxoplasmosis, and syphilis, as well as in noninfectious conditions,
such as hemolytic disease of the newborn (which would be associated with
jaundice and pallor). The heart murmur could suggest a congenital heart
disease, such as that associated with congenital rubella, but at this age could
also represent a flow murmur.
Of the chronic intrauterine infections, congenital CMVinfection is, by far,
the most common. In considering congenital rubella an important question to
be asked is: Was the mother immune to rubella (was she seropositive) before
this pregnancy, and is she immune now? Knowledge of immunity only during
this pregnancy does not answer the question of whether the infection oc-
curred during this pregnancy (potentially affecting the baby) or previously.
In this case (Figure 16.1) the rash was caused by rubella. The congenital
rubella syndrome may be associated with abnormalities affecting many
organs: ocular abnormalities, including cataracts (the abnormality that led
to the recognition of the entity of congenital rubella infection) (Figure 16.2),
microphthalmia, and corneal opacity (Figure 16.3); deafness; congenital
heart disease; brain abnormalities, including microcephaly; hepatitis; anemia;
thrombocytopenia; and linear lucencies in the long bones (celery stalk
appearance).
The methods used to diagnose intrauterine infections are shown in
Table 16.1.
The development of PCR tests will render diagnosing these infections
easier.
FIG. 16.2. A child with a
congenital cataract. Note that
the opacity can be seen only
through the pupil, because the
lens is behind the iris.
Case Study 16 71
Congenital rubella can be prevented by immunization of all children so
that (i) the girls are not susceptible when they become pregnant and (ii) that
neither girls nor boys can bring the infection home to their pregnant moth-
ers. In the United States, the rate of congenital rubella syndrome decreased
from 10,000 cases per year in 1969 when vaccination was introduced to 1
case per year in 2002.
Reading:
Achievements in public health: elimination of rubella and congenital rubella
syndrome United States, 19692004. MMWR 2005;54:14.
n
CASE 17 (HYP). A 6-year-old girl complains of weakness and muscle
pain, and tightness in her thighs and legs. About 1 week earlier she had
a fever, sore throat, and cough. On examination she cannot stand nor walk
FIG. 16.3. Corneal opacities. Note that the opacities are in front of the pupil.
nTAB. 16.1: The usual methods used to diagnose intrauterine infections.
Infection Method
Rubella serology (IgM)
Cytomegalovirus infection urine viral culture, PCR on blood
Human immunodeficiency virus infection DNA PCR
Lymphocytic choriomeningitis virus serology
Syphilis serology (RPR, specific Treponemal test)
Toxoplasmosis serology (IgM)
Legend: PCR = polymerase chain reaction; RPR = rapid plasma reagin; IgM = immunoglobulin M.
72 Case Studies in Pediatric Infectious Diseases
due to weakness. Her thighs and calves are tender. Sensation and deep
tendon reflexes are normal. Examination of the back and upper limbs is
normal.
What might be wrong with her?
What would you like to know?
The differential diagnosis is one of generalized weakness but preserved
higher function. This suggests a lower motor neuron lesion affecting her
lower limbs. The possible levels of disease should be considered anatomically
(Figure 17.1).
It is useful to consider possible etiologies of diseases for each of these sites.
Diseases of the lower motor neuron may be generalized in which case
they may affect the muscles of respiration, leading to respiratory failure.
They may also be associated with autonomic dysfunction resulting in car-
diovascular instability. Therefore cardiorespiratory supportive care is the
most important component of management. Secondary infectious problems
may complicate the course, such as decubitus ulcers, and the complications
of intensive support such as artificial ventilation and intravenous therapy.
The differential diagnosis should include the infectious and noninfectious
diseases listed below in Table 17.1.
FIG. 17.1. The anatomy of the lower motor neuron unit.
Case Study 17 73
Management principles:
1. Observe respiratory function. In older individuals this can be done by
monitoring inspiratory force. In infants the strength of the cry is helpful.
Supporting ventilation may become necessary.
2. Monitor cardiovascular function, in particular heart rate and blood
pressure.
3. Make a diagnosis.
4. Provide specific therapy if possible.
5. Prevent decubitus ulcers.
6. Prevent contractures.
7. Ensure adequate nutrition.
The pain and muscle tenderness in this patient indicate muscle inflam-
mation (myositis) as the cause of the weakness.
Muscle disease: Acute muscle disease may be due to injury, inflammation
(myositis), or a metabolic disorder, for example, heat stroke. Acute myositis
is usually caused by a viral infection such as influenza, enterovirus infection,
or acute HIV infection. This is referred to as benign acute childhood myo-
sitis, which is to be distinguished from the myositis occurring with derma-
tomyositis or polymyositis, which have a prolonged course and can result in
nTAB. 17.1: Causes of acute flaccid weakness.
(A) Spinal cord Spinal shock (early stage of acute cord disease)
Transverse myelitis (mixed upper and lower motor)
(B) Anterior horn cell Poliomyelitis
Other enterovirus infections
West Nile virus infection
(C) Peripheral nerve Guillain-Barre syndrome
Diphtheria
Toxins n-toluene, glue-sniffing
Acute intermittent porphyria
(D) Neuromuscular junction Botulism
Elapid snake bite (cobra, mamba)
(E) Muscle Myositis
Electrolyte disturbance
Hypokalemia
Extreme hypocalcemia
Periodic paralysis (several types)
(F) Pseudoparesis (localized) Skeletal disease
Traumatic injury
Osteomyelitis
Septic arthritis
Congenital syphilis (osteitis)
(G) Unknown mechanism Tick paralysis
74 Case Studies in Pediatric Infectious Diseases
significant long-term disability. Patients with benign acute myositis present
with acute onset of weakness and muscle pain and tenderness, most fre-
quently affecting the calf muscles. The muscles may be swollen and the
weakness may be profound. The dangers of myositis are respiratory failure
and rhabdomyolysis, which leads to hyperkalemia and to myoglobinuria,
which, in turn, can lead to acute tubular necrosis and renal failure. The
diagnosis of myositis can be confirmed by the demonstration of elevated
creatine phosphokinase (CPK) activity in the serum. Myoglobinuria man-
ifests as red, clear urine (like rose wine) as opposed to red, cloudy urine that
occurs with hematuria. In this clinical circumstance a urine dipstick test
that is positive for blood in the absence red cells on microscopy is highly
suggestive of myoglobinuria. A microbiological diagnosis of the cause of
myositis is not usually helpful, unless HIV infection is suspected.
Treatment is primarily supportive, entailing analgesia and a very high
fluid intake. If myoglobinuria is present the urine should be alkalinized to
prevent injury to the renal tubules. Monitoring of respiratory function is
essential.
Reading:
King BA: Benign acute childhood myositis as a cause of failure to weight
bear. J Paediatr Child Health. 2003; 39: 378380.
Singh U, Scheld WM: Infectious etiologies of rhabdomyolysis: three case
reports. Clin Infect Dis 1996; 22: 642649.
n
CASE 18 (COMP-MMWR). Apreviously well 48-year-old man presents
with a 4-day history of fever, chills, photophobia, myalgia, arthralgia,
nausea, vomiting, constipation, and upper abdominal discomfort. On
examination he is ill-appearing and febrile. He is jaundiced and he has upper
abdominal tenderness, but has neither enlargement of liver or spleen nor
lymphadenopathy. He has several skin papules on his limbs, consistent with
insect bites. Laboratory testing reveals marked elevation of transaminases
(several thousand IU/dl), serum creatinine, and blood urea, as well as leu-
copenia and thrombocytopenia.
What is your differential diagnosis?
What would you like to know?
Case Study 18 75
This patient has a systemic infection of very acute onset with liver and
renal failure, but without shock. He does not have known underlying disease
predisposing him to severe infection. Therefore one should pursue a course
looking for exposures to specific infectious agents. We know that he has
probably been bitten by insects.
Arthropod-transmitted infections that cause acute systemic illness are
shown in Table 18.1.
Nonarthropod-borne infections that might cause this clinical scenario
include arenavirus infections such as Lassa fever, Argentinian hemorrhagic
fever and Bolivian hemorrhagic fever, and leptospirosis. The latter is usually
acquired from exposure to water into which animals have urinated.
Considering the differential diagnosis, the exposure history is very
important.
He had traveled to the jungle in the Amazon region of Brazil. He had not
been immunized against yellow fever. He was shown to have this infection,
from which he died.
nTAB. 18.1: Arthropod-borne infections causing acute systemic illness and their vectors.
Organism Vector
Viruses
Flaviviridae yellow fever, dengue, and others mosquito
Togaviridae equine encephalitides mosquito
Bunyaviridae
Congo-Crimean hemorrhagic fever tick
Rift Valley fever and others mosquito
Reoviridae Colorado tick fever tick
Rickettsiae
Rocky Mountain spotted fever and others tick
Epidemic typhus louse
Ehrlichiae
Ehrlichia chafeensis tick
Anaplasma phagocytophilum tick
Spirochetes
Borrelia relapsing fever tick, louse
Gram-negative rods
Francisella tularensis tick, fly
Yersinia pestis flea
Protozoa
Malaria mosquito
Babesia tick
Trypanosoma brucei fly
Trypanosoma cruzi reduviid bug
76 Case Studies in Pediatric Infectious Diseases
Yellowfever is one of the important global infectious diseases. It is caused by
yellow fever virus, which is a flavivirus (the prototypic virus of this group,
whence the name flavi, which is derived from the Latin for yellow). It is
transmitted by Aedes aegypti mosquitoes, in tropical Africa and tropical South
America. There are two epidemiologic patterns, namely the urban pattern in
which the virus is transmitted between mosquitoes and human beings, and the
sylvatic, in which it is transmitted between mosquitoes and monkeys, and in
which human beings are incidental hosts. The virus causes liver and renal
failure, and carries a very high case fatality rate. There is a very effective live
attenuated vaccine that should be administered to all travelers to endemic areas.
References:
Schwartz F, Drach F, Guroy ME et al: Fatal yellow fever in a traveler return-
ing from Venezuela, 1999. MMWR 49: 3035, April 14, 1999
Hall P, Fojtasek M, Pettigrove J et al: Fatal yellowfever in a traveler returning
from Amazonas, Brazil, 2002. MMWR 2002; 51: 324325.
Geisbert TW, Jahrling PB: Exotic emerging viral diseases: progress and chal-
lenges. Nat Med 2004; 10: S110S121.
n
CASE 19. A 6-month-old boy presents with watery diarrhea and a tem-
perature of 38.5C.
What is the most important aspect of the clinical evaluation?
What is the likely clinical diagnosis, and what are its possible causes?
What do you want to do?
(a) The most important question addresses the physiologic diagnosis,
namely: What is his hydration status? The signs of dehydration are:
decreased urine output;
sticky oral mucosa
decreased skin turgor (Figure 19.1)
sunken eyes
sunken fontanelle
tachycardia
poor peripheral perfusion and decreased level of consciousness (shock)
What is the likely diagnosis? This is most likely a case of acute infectious
diarrhea (acute gastroenteritis). The possible causes are listed in Table 19.1.
These agents are all spread by the fecaloral route. In addition, there are
several food intoxications (food poisonings) in which bacteria have been
Case Study 19 77
allowed to grow in food, and produce toxins, which cause vomiting and/or
diarrhea. These toxins are produced by Staphylococcus aureus and Bacillus
cereus.
Although these agents have different sources, sites of infection within the
intestine, and mechanisms of causing disease, they all cause diarrhea, and
hence water loss. Consequently, the most important aspect of evaluation is
to determine the state of hydration, and the most important component of
treatment is to ensure adequate hydration (see above).
There are risk factors that predispose individuals to acquiring infections
with enteropathic organisms:
Poor hygiene in those preparing food
All circumstances leading to poor hygiene
Squalid or crowded living circumstances
Absence of clean water supply and sewage disposal
Eating of uncooked or undercooked meat or seafood or other foods contam-
inated by these
Lack of refrigeration of foods that have been contaminated
Living or traveling to areas where enteric infections are prevalent (mostly for
the above reasons)
FIG. 19.1. Decreased skin turgor (tenting) in a dehydrated child.
78 Case Studies in Pediatric Infectious Diseases
Clinical features: The initial symptom is often vomiting followed within
a few hours by the development of diarrhea. The viral and invasive bacterial
infections are often associated with fever. Abdominal cramps may also occur.
In the cases of invasive bacterial infections, blood and pus may appear in the
stool after 1 or 2 days. Although most patients with acute enteric infection
begin to improve after about 2 days, some take several days to return to
normal health. In young children, the stool may remain loose for weeks.
Complications:
1. Dehydration. This is the main problem caused by acute diarrheal disease,
and the major cause of death fromsuch illnesses. The dehydration leads not
only to hypovolemic shock, but also to hemoconcentration. The combina-
tion of hypovolemia and hemoconcentration results in a decreased blood
flowrate, predisposing the patient tovascular occlusion. This canoccur any-
where in the circulation but is most devastating when it affects the brain.
nTAB. 19.1: Causes of acute infectious diarrhea.
Agent
Viruses
Rotavirus
Enteric adenovirus
Noroviruses
Astroviruses
Bacteria
Salmonella enteritidis
Shigella species
Campylobacter jejuni
Escherichia coli
Enteropathogenic (EPEC)
Enterotoxigenic (ETEC)
Enteroadherent (EAEC)
Enterohemorrhagic (EHEC)
Enteroinvasive (EIEC)
Yersinia enterocolitica
Vibrio cholerae
Vibrio parahaemolyticus
Clostridium difficile
Clostridium perfringens
Parasites
Giardia lamblia (intestinalis)
Cryptosporidium parvum
Cyclospora cayetanensis
Isospora belli
Entamoeba histolytica
Balantidium coli
Case Study 19 79
2. Metabolic and electrolyte disturbances: As a result of causing diarrhea by
different mechanisms, different organisms cause different degrees of salt
and other electrolyte losses in the stool. The main electrolyte disturban-
ces that can occur are hyponatremia, hypernatremia, hypokalemia, and
acidosis. Abnormalities of blood glucose, both hypoglycemia and hyper-
glycemia can also occur. These abnormalities should be sought in all
children with severe diarrhea in whom neurological disturbances are pre-
sent, such as changes in level of consciousness, seizures, muscle hyperto-
nia, or hypotonia.
3. Bacteremia: This can occur in gut-invasive bacterial infections and is most
common in cases of salmonella infection. In countries where water and
food hygiene are poor, salmonella enteric infections are very common,
and salmonellae are among the most common causes of bacteremia. Sal-
monellae occasionally cause metastatic infections such as septic arthritis,
osteomyelitis, and meningitis. Young infants are at greatest risk of suffer-
ing such complications. Individuals with sickle cell disease are also at risk
of developing salmonella osteomyelitis. Yersinia enterocolitica also causes
bacteremia in young infants, as well as in individuals with iron overload.
4. Hemolytic uremic syndrome: This is a condition characterized by a vascul-
opathy, affecting mainly the kidney and the brain, by renal failure and
hypertension, and by microangiopathic hemolytic anemia, and thrombo-
cytopenia. Most cases result from infections with enterohemorrhagic
E. coli, such as serotype O157; H7, but infections with shigella can also
cause the disease. It should be suspected in children who have recently
suffered from bloody diarrhea, and who develop oliguria, edema, pete-
chiae, pallor, or changes in mental state. The blood smear shows frag-
mented erythrocytes, helmet cells, and schistocytes (Figure 19.2).
5. Toxic encephalopathy: This is a frequent complication of shigellosis.
This frequently manifests with seizures but can be associated with a depressed
level of consciousness and even coma. Occasionally shigella encephalopathy
can be fatal, a condition known in Japan as ekiri. Causes of altered mental
state in children with acute infectious diarrhea are shown in Table 19.2.
6. Chronic diarrhea: Previously well children, who suffer an episode of
acute infectious diarrhea, may then continue to have diarrhea. By defini-
tion diarrhea lasting longer than 2 weeks is considered chronic. The most
important cause of chronic diarrhea in this circumstance is villous atro-
phy, with loss of disaccharidases, especially lactase. The inability of
the intestinal mucosa to hydrolyze lactase results in this sugar being
presented to the colon, where it causes an osmotic diarrhea. Chronic
80 Case Studies in Pediatric Infectious Diseases
diarrhea may also result from continued infection. This is most likely to
occur with parasitic infections such as giardiasis.
7. Colonic perforation: This is a complication of amebiasis and highlights the
importance that this infection be considered in individuals who have
traveled to high-risk areas and who have bloody diarrhea. It differs from
the bacterial causes of bloody diarrhea in that the stool does not have
many leukocytes (which are lysed by the parasites) and that the infection
may not be self-limited.
nTAB. 19.2: Causes of altered mental status in children who have or have had diarrhea.
Shock from dehydration
Metabolic and electrolyte disturbance
Hypoglycemia
Hyperglycemia
Hyponatremia
Hypernatremia
Vascular
Stroke
Hemolytic uremic syndrome
Iatrogenic
Too rapid correction of hypernatremia
Too rapid correction of hyponatremia (central pontine myelinosis)
Atropine-containing drugs
Antiemetic drugs
Complication of bacteremia
Meningitis
Shigellosis
FIG. 19.2. A blood smear
of a child with hemolytic
uremic syndrome. Note the
large spaces between the
erythrocytes, indicating
severe anemia (the
hemoglobin concentration
was 1.8 g/dl) and the
schistocytes.
Case Study 19 81
8. Reactive arthritis: This is a well-recognized, but unusual complication of
bacterial enteric infections. Individuals with the HLA B27 haplotype are
particularly predisposed to this complication.
9. Guillain-Barre syndrome: About one-third of cases of Guillain-Barre syn-
drome follow infections with Campylobacter jejuni.
Management: As mentioned above, the most important element of man-
agement is to ensure adequate hydration (Figure 19.3). In most circumstan-
ces this can be accomplished by the frequent administration of liquid by
mouth.
Diagnosis of enteric infections: There are two components of this. (a) Are
the clinical features due to an enteric infection or not? (b) If due to an enteric
infection, what is the likely cause?
(a) Noninfectious causes of intestinal symptoms and signs. Vomiting is
a common symptom in children. When accompanied by fever, it may
be a manifestation of a parenteral infection. Two conditions that should
always be considered when vomiting is NOT ACCOMPANIED BY
DIARRHEA are raised intracranial pressure, as may occur with menin-
gitis, and intestinal obstruction. Abdominal pain or cramps, WITHOUT
DIARRHEA, and with or without the passage of blood per rectum
should suggest the possibility of intussusception in children younger
FIG. 19.3. Dehydration with decreased turgor (left panel), and normal hydration
with good turgor (right panel).
82 Case Studies in Pediatric Infectious Diseases
than about 3 years of age. Chronic diarrhea, with obviously bloody
stools, or with hematological evidence of blood loss in young infants
should suggest the possibility of milk protein allergy. In older children
and teenagers, chronic diarrhea, with or without blood, and weight loss,
should suggest the possibility of inflammatory bowel disease. The dif-
ferential diagnosis of enteric infections is listed in Table 19.3.
(b) Differentiating between the different causes of infection is difficult and,
in most cases, is unnecessary. Examination of the stool macroscopically is
useful. If blood or pus is seen, then further evaluation of the stool is
indicated. This should consist of examination of the stool for leukocytes
and culture for pathogenic bacteria. Examination of a fecal smear for
leukocytes can be very useful because it can give an immediate clue as
to the type of agent causing the disease. This test is performed as follows:
the stool is inspected for blood, mucus, or pus; any areas containing these
elements are scraped on to a wooden spatula/tongue depressor, and a thin
smear of this is made on a microscope slide and allowed to dry; the slide is
stained with methylene blue for about 2 minutes, and examined micro-
scopically (Figure 19.4). The presence of large numbers or sheets of
leukocytes suggest that the illness is caused by an invasive bacterium.
However, this can also be seen in cases of milk protein allergy.
Culture of stool for bacteria usually takes several days, because various
selective processes are needed to eliminate the normal bacteria that are
present in feces. Most laboratories routinely culture for Salmonella spp.,
Shigella spp., Yersinia enterocolitica and Campylobacter jejuni. However, they
may not culture for enterohemorrhagic E. coli or for Vibrio cholerae. When
nTAB. 19.3: Differential diagnosis of intestinal symptoms and signs.
Vomiting, no diarrhea
Gastritis
Acute food poisoning
Raised intracranial pressure
Intestinal obstruction, in particular intussusception
Parenteral infection
Hematochezia, no diarrhea
Meckels diverticulum
Intussusception
Polyp
Profound upper intestinal bleeding
Bloody diarrhea
Milk protein allergy
Inflammatory bowel disease
Case Study 19 83
these organisms are suspected, based on epidemiological, clinical, or stool
features, they should be specifically sought. Testing the stool for viruses is
not usually very helpful, because no specific therapy is available. However,
the results may be of epidemiological value and may restrain one from
pursuing other causes of the disease.
The epidemiological, clinical, and stool features associated with different
enteric infections are shown in Table 19.4.
Testing the stool for protozoa: In the past this has depended on the obser-
vation of the organisms by microscopy of the stool. This is time-consuming
and requires significant expertise. Giardia lamblia and Cryptosporidium par-
vum can be detected by antigen detection methods. Because giardia forms
cysts, it is often the cysts that are seen in the stool rather than the trophozoites.
Cryptosporidium parvum and Cyclospora cayetanensis can be detected, after
centrifugation of the stool specimen, by staining with a modified acid-fast
stain (see Case 62). Entamoeba histolytica should be sought by microscopy.
Ideally fresh stool mixed with warmsaline is examined under the microscope.
Observation of erythrophagocytic trophozoites with ameboid movement con-
firms that these are invasive amebae. If this test cannot be done immediately,
the stool should be submitted in a fixative to the laboratory so that the
morphology of the parasite can be observed. However, antigen detection
methods are now available for the detection of this organism in stool.
Treatment of patients with enteric infections
1. The most important component of management is rehydration and main-
tenance of hydration.
2. Nutrition: In infants with acute diarrhea, especially those who may have
borderline malnutrition, it is very important that adequate nutrition be
FIG. 19.4. A methylene
bluestained fecal smear of
child with diarrhea caused by
both Salmonella enteritidis
and Yersinia enterocolitica.
84 Case Studies in Pediatric Infectious Diseases
provided. There is no sound basis for withholding food. Therefore, as
soon as the child has been re-hydrated, milk or another appropriate prep-
aration should be administered.
3. Antimicrobial: This can be of benefit in selected bacterial and protozoal
infections but plays no roll in viral infections. Because the specific etiol-
ogy is seldom known until a few days after the patient presents, initial
treatment should be based on the epidemiological and clinical features,
and on the appearance of the stool. The treatment of patients with dif-
ferent enteric infections is shown in Table 19.5. As a generalization, an-
tibacterial therapy is indicated for patients suspected of having shigellosis
or bacteremia, or in those with diarrhea associated with foreign travel.
Antiparasitic therapy is indicated in those with a demonstrated protozoal
infection for which therapy is available.
4. Antiperistalsis agents: These have limited value in children, although loper-
amide has been shown to reduce the volume of stool output in certain
circumstances. It should not be used in presumed toxigenic infections.
5. Public health measures: Because these agents are transmitted by the
fecaloral route, attention to hygiene should be emphasized to family
members. Those children who are hospitalized should be nursed with
nTAB 19.4: Epidemiological, clinical, and stool features associated with different enteric
infections, and tests used for their confirmation.
Microorganism Epidemiology Clinical Stool Test
Rotavirus winter acute no blood antigen
Enteric adenovirus acute no blood tissue
culture
Norovirus outbreak (human) acute, vomiting no blood RT-PCR
a
Salmonella animals, eggs, meat acute, fever +/ blood, pus culture
Shigella day care, human acute, fever +/ blood, pus culture
Campylobacter poultry acute +/ blood, pus culture
Yersinia pork acute +/ blood culture
EHEC meat acute blood specific
culture
Giardia day care, water acute-chronic no blood micro,
antigen
Cryptosporidium water, outbreak acute-chronic no blood micro,
antigen
Cyclospora outbreak acute-chronic no blood micro
E. histolytica travel acute-chronic blood micro,
antigen
a
RT-PCR, reverse transcriptase polymerase chain reaction; micro, microscopy.
Case Study 19 85
contact precautions. Patients with the suspicion of cholera should be
reported to the health department.
Reading:
Thielman NM, Guerrant RL: Acute infectious diarrhea. N Engl J Med 2004;
350: 3847.
Hines J, Nachamkin I: Effective use of the clinical microbiology laboratory
for diagnosing diarrheal diseases. Clin Infect Dis 1996; 23: 12921301.
Al-Abri SS, Beeching NJ, Nje FJ: Travellers diarrhea. Lancet Infect Dis
2005; 5: 349360.
Armon K, Stephenson T, MacFaul R et al: An evidence and consensus based
guideline for acute diarrhea management. Arch Dis Child 2001; 85:
132141.
Glass RI, Parashar UD, Bresee JS et al: Rotavirus vaccines: current prospects
and future challenges. Lancet 2006; 368: 323332.
nTAB. 19.5: Antimicrobial therapy of enteric infections.
Microorganism Antimicrobial agent(s)
Salmonella None, unless bacteremia suspected
Ceftriaxone, TMP/S
Shigella Ampicillin
a
; TMP/S; cefriaxone;
azithromycin, fluoroquinolone
b
Campylobacter jejuni Azithromycin, fluoroquinolone
b
Yersinia enterocolitica None, unless bacteremia suspected
Ceftriaxone, TMP/S; gentamicin
E. coli
c
ETEC, EPEC, EIEC TMP/S; fluoroquinolone
b
Clostridium difficile Metronidazole; oral vancomycin
Giardia lamblia Metronidazole, nitazoxanide
Cryptosporidium parvum Nitazoxanide
Cyclospora cayetanensis TMP/S
Entamoeba histolytica Metronidazole/tinidazole
ETEC = enterotoxigenic Escherichia coli, EPEC = enteropathogenic Escherichia coli; EIEC = enteroinvasive Escherichia
coli; TMP/S = trimethoprim/sulfamethoxazole.
a
Ampicillin-resistant Shigella are widely prevalent.
b
Fluoroquinolones are very useful, but still not widely used in children. In puppies they have been shown to cause joint
disease. This has not been a problem in children.
c
Rifaximin, a nonabsorbable rifamycin, has been shown to be of value in treating adults with travelers diarrhea.
86 Case Studies in Pediatric Infectious Diseases
n
CASE 20. An 18-month-old girl presents with fever of a few hours
duration and a rash that is spreading rapidly. Examination reveals a very
ill child with poor perfusion, temperature of 40C, and a hemorrhagic rash
(Figure 20.1).
What is the most likely diagnosis?
What would you do?
This child has septic shock as well as hemorrhagic skin lesions. This
scenario is typical of meningococcemia (meningococcal (Neisseria meningi-
tidis) septicemia). This is by far the most likely diagnosis, although
other infections can cause this clinical appearance, such as pneumococcal
bacteremia in an asplenic individual, Gram-negative rod bacteremia, staph-
ylococcal bacteremia or acute staphylococcal endocarditis, and septicemic
plague. Rocky Mountain spotted fever, which might be considered, does
not have such a short course from onset of symptoms to the appearance of
the rash.
Management:
(a) Institute supportive care immediately: Intravenous fluids, and, if there is
an inadequate response, vasopressor agents.
(b) Attempt to make a microbiological diagnosis: Aspirate a skin lesion and
culture the aspirate and make a smear for Gram stain (Figure 20.2).
Obtain blood for blood culture.
FIG. 20.1. The rash of the child presenting with fever and hypoperfusion.
Case Study 20 87
Performance of a lumbar puncture is contraindicated in this child at this
time, since she is unstable.
(c) Institute antimicrobial therapy with a third-generation cephalosporin.
Although Neisseria meningitidis is susceptible to penicillin, the other
possible causes of this childs illness may not be. Ceftriaxone has the
advantage that it eliminates carriage of meningococcus from the
nasopharynx. In considering the recently described syndrome of rapidly
progressive systemic infections caused by methicillin-resistant Staphylo-
coccus aureus, the addition of vancomycin should also be considered.
(d) Offer antimicrobial prophylaxis to household members and notify the
local health department immediately. This prophylaxis should consist of
rifampin (consider drug interactions), ciprofloxacin (if >18 years old),
or a single injection of ceftriaxone. Any contact who develops fever
should be evaluated, even if prophylaxis has been taken.
(e) Vaccination: Two vaccines are available in the United States, both
against serogroups A, C, Y, and W-135. The older vaccine is a polysac-
charide vaccine that is licensed for individuals older than 2 years of age.
Its use has been recommended for individuals who are at increased risk
of exposure to the organism (military recruits, travelers to high ende-
micity areas, and college students living in dormitories) and to those at
increased risk of disease (asplenic individuals and those with deficiencies
FIG. 20.2. Gram-negative cocci in a skin aspirate from a child with meningococcemia.
88 Case Studies in Pediatric Infectious Diseases
in terminal complement pathway components). The new vaccine is
a conjugate vaccine that is for use in children older than 11 years. In
the United States, it is recommended for all adolescents in addition to
the groups mentioned above who are candidates for the polysaccharide
vaccine.
Neisseria meningitidis is a Gram-negative coccus. It is often seen in pairs, as
shown in the Figure 20.3.
Its carbohydrate capsule is an important virulence factor, enabling it to
evade opsonization in the nonimmune host. It colonizes the hosts pharynx,
whence it may invade the bloodstream. Infection by this organism is highly
feared because the bacteremia it causes (meningococcemia) can rapidly de-
velop into a sepsis syndrome with progression to death within a few hours.
This syndrome is often associated with petechiae (Figure 20.4), echymoses,
and purpura fulminans, characterized by necrotic skin lesions, as shown in
this patient, and the patient shown in Figure 20.5.
Occlusion of large vessels can also occur as part of this syndrome, resulting
in gangrene of limbs (Figure 20.6).
FIG. 20.3. Contrasting the
Gram stain appearances of
Neisseria and Streptococci.
FIG. 20.4. A subconjuncti-
val hemorrhage in a child
with meningococcal
meningitis.
Case Study 20 89
FIG. 20.5. The hemorrhagic rash and necrotic skin lesions associated with
meningococcemia.
FIG. 20.6. Peripheral gangrene due to arterial occlusion in meningococcemia.
90 Case Studies in Pediatric Infectious Diseases
FIG. 20.7. The autopsy appearance of adrenal hemorrhage due to the
Waterhouse-Friderichsen syndrome.
FIG. 20.8. Gram-stain appearance of cerebrospinal fluid of a child with
meningococcal meningitis, showing numerous polymorphonuclear leukocytes and
Gram-negative cocci, many of which are inside polymorphonuclear leukocytes.
Case Study 20 91
A maculopapular rash may also occur. One of the dramatic clinico-
pathological complications of meningococcemia is adrenal hemorrhage,
called the Waterhouse-Friderichsen syndrome (Figure 20.7).
These clinical abnormalities are due to activation of inflammatory mediators
and of the coagulation and fibrinolytic systems initiated by the large amounts
of endotoxin elaborated by the organism. These disturbances result in endo-
thelial cell dysfunction, failure of vascular integrity, and myocardial depression.
The other main disease caused by this organism is meningitis, which gives
the organism its name, N. meningitidis or meningococcus. The Gram stain
appearance of cerebrospinal fluid in this infection is shown in Figure 20.8.
Other clinical syndromes it causes are encephalitis, pneumonia (which is
highly contagious), arthritis, which may be septic or reactive, pericarditis,
endocarditis, and anterior uveitis.
Reading:
Rosenstein NE, Perkins BA, Steohens DS, Popovic T, Hughes JM:
Meningococcal disease. N Engl J Med 2001; 344: 13781388.
Jodar L, Feavers IM, Salisbury D, Granoff DM: Development of vaccines
against meningococcal disease. Lancet 2002; 359: 14991508.
Warren HS, Gonzalez RG, Tian D: A 12-year-old girl with fever and coma.
New Engl J Med 2003; 349: 23412349.
Kirsch EA, Barton RP, Kitchen L, Giroir BP: Pathophysiology, treatment and
outcome of meningococcemia: a review and recent experience. Pediatr In-
fect Dis J 1996; 15: 967979.
deKleijn ED, Hazelzet JA, Kornelisse RF, de Groot R: Pathophysiology of
meningococcal sepsis in children. Eur J Pediatr 1998; 157: 869880.
n
CASE 21. A 5-day infant presents with a 1-day history of a red left eye
with a profuse discharge. Examination reveals a well-appearing child with
marked swelling and erythema of the left eyelids, a profuse green conjunc-
tival discharge, and marked chemosis (Figures 21.1 and 21.2).
What is the likely diagnosis?
What would you do?
This child has neonatal conjunctivitis. The profuse discharge suggests the
possibility of gonococcal infection, but other bacteria can cause this
condition, in particular Staphylococcus aureus. Chemical conjunctivitis from
silver nitrate eyedrops occurs earlier in life and tends not to be very severe.
92 Case Studies in Pediatric Infectious Diseases
FIG. 21.1. The infants left
eye. Note the marked eyelid
swelling and yellow
discharge. (Courtesy of
Dr Timothy Vece, Emory
University)
FIG. 21.2. The infants left
eye. Note the marked
chemosis (conjunctival
swelling). (Courtesy of
Dr Timothy Vece, Emory
University)
Case Study 21 93
This is too early in the childs life for the presentation of chlamydial
conjunctivitis.
Management: Make a smear of the discharge for Gramstain (which, in the
case of gonococcal conjunctivitis might show Gram-negative diplococci
Figure 21.3) and send a swab to be cultured specifically for Neisseria gonor-
rhoeae (which requires a selective medium).
Infants in whom gonococcal conjunctivitis is suspected should be treated
with a single injection of ceftriaxone (125 mg) and frequent instillations of
saline eyedrops to rinse out the eyes. They should be re-evaluated the next
day. Some authorities recommend performance of blood cultures and lum-
bar puncture to exclude systemic disease, but I do not do this unless there is
evidence of systemic infection. Untreated, this condition can cause severe
corneal damage and blindness. Diagnosing this condition implies that the
mother is infected with the organism. She and her sexual partner should be
treated and the health department should be notified.
This infants eye swab showed many Gram-negative diplococci and the
culture grew out Neisseria gonorrhoeae. One day after being treated as de-
scribed above, the eye was almost normal.
Reading:
Woods CR: Gonococcal infections in neonates and young children. Semin
Pediatr Infect Dis 2005; 16: 258270.
n
CASE 22 (COMP). A 9-year-old boy presents with a history of pain and
swelling of the right knee followed by similar symptoms affecting the left
elbow. He also feels tired. On examination he has a temperature of 38.3C,
FIG. 21.3. Gram stain of
a conjunctival swab from
this child showing Gram-
negative cocci, which were
confirmed to be Neisseria
gonorrhoeae.
94 Case Studies in Pediatric Infectious Diseases
and a heart rate of 120/min. His apex beat is in the 5th left interspace,
anterior axillary line. The first and second heart sounds are normal, and
there is a 2/6 holosystolic murmur at the apex. He has swelling of the right
knee and left elbow joints with limitation of movement.
What is the likely diagnosis?
What would you do?
This boy has fever, migratory arthritis, tachycardia, and mitral valve
insufficiency. These features strongly suggest the diagnosis of acute rheu-
matic fever. They constitute two of the major Jones criteria for the diagnosis
of this condition (arthritis and carditis). The other conditions that might
cause these features are infective endocarditis and systemic lupus erythema-
tosus. The other major Jones criteria are Sydenhams chorea, erythema mar-
ginatum, and subcutaneous nodules. The diagnosis of acute rheumatic fever
depends on two major criteria in addition to evidence of a recent infection
with Streptococcus pyogenes. There are also minor criteria used for the di-
agnosis of acute rheumatic fever. These are arthralgia, fever, prolonged PR
interval on electrocardiogram, and elevated acute phase reactants. Although
one major and two minor criteria may be used for the diagnosis of acute
rheumatic fever, the minor criteria are very nonspecific, and one should be
wary of using them.
Rheumatic fever is an immunological complication of Streptococcus pyo-
genes (group A streptococcus) pharyngotonsillitis, resulting in inflammation
of cardiac valves. It is due to antibodies to streptococcal antigens that cross-
react with heart valve antigens. The valves most frequently affected are the
mitral and the aortic valves. In the acute phase of the illness, the valve leaflets
are swollen. In addition myocarditis or pericarditis may be present. The
inflammation may resolve without leaving sequelae, but scarring of the valve
can occur resulting in permanent cardiac damage called rheumatic heart
disease. Such damage is manifest as valvular insufficiency, and/or stenosis,
which, in turn lead to heart failure. Therefore rheumatic fever is a very
important cause of acquired heart disease (Figure 22.1).
In individuals who have had an episode of acute rheumatic fever, sub-
sequent episodes of streptococcal tonsillitis may be followed by another
episode of rheumatic fever, resulting in further cardiac damage. Treatment
of the acute episode entails symptomatic treatment of the arthritis with
salicylates or ibuprofen, and treatment of heart failure if this occurs. Pre-
vention of subsequent episodes requires the administration of penicillin until
the patient is at least 25 years old. This can be done with oral penicillin twice
per day, or with an intramuscular injection of long-acting bicillin every 34
weeks. As long as there is any cardiac valvular abnormality, these patients are
Case Study 22 95
susceptible to infective endocarditis. They therefore require additional anti-
biotic prophylaxis for procedures that may cause bacteremia, for example,
dental cleaning. The regular penicillin they receive is inadequate for this
purpose.
Because rheumatic fever is a potentially devastating albeit rare complica-
tion of streptococcal pharyngitis, all patients with streptococcal pharyngitis
should be treated with penicillin. Streptococcal pharyngitis cannot be read-
ily differentiated from viral pharyngitis clinically. Therefore throat cultures
to detect Streptococcus pyogenes should be performed on all patients with
pharyngitis to determine who should be treated with penicillin.
Reading:
Stollerman GH: Rheumatic fever. Lancet 1997; 349: 935942.
Bisno AL, Brito MO, Collins CM: Molecular basis of group A streptococcal
virulence. Lancet Infect Dis 2003; 3: 191200.
Bisno AL: Group A streptococcal infections and acute rheumatic fever. N
Engl J Med 1991; 325: 783793.
Kotloff KL, Dale JB: Progress in Group A streptococcal vaccine develop-
ment. Pediatr Infect Dis J 2004; 23: 765766.
FIG. 22.1. Chest X ray of
a child with severe rheumatic
heart disease. There is
cardiomegaly resulting from
severe mitral insufficiency.
96 Case Studies in Pediatric Infectious Diseases
Carapetis JR, Steer AC, Mulholland EKet al: The global burden of group A
streptococcal diseases. Lancet Infect Dis 2005; 5: 685694.
n
CASE 23. A3-year-old boy presents with swelling of the eyelids on rising
in the morning for 2 days. On examination he has swelling of the eyelids and
legs, and several healing sores on his legs (Figures 23.1 and 23.2).
FIG. 23.1. The eyelid swelling.
FIG. 23.2. The skin sores.
Case Study 23 97
What else would you like to know?
What is wrong with him?
Fluid balance between the intravascular space and the interstitial space is
dependent on the hydrostatic pressure that tends to force water out of the
capillary, the oncotic pressure of the fluid that tends to hold the water within
the vascular space, and the integrity of the capillary wall. Edema is the result
of one or more of three processes: (a) increased hydrostatic pressure, as
occurs in heart failure, or a decreased glomerular filtration rate; (b)
decreased oncotic pressure due to hypoalbuminemia, as occurs in the ne-
phrotic syndrome, malnutrition, or liver failure; or (c) increased capillary
permeability, as occurs in the sepsis syndrome and in anaphylaxis. Many of
these conditions can be diagnosed by history and physical examination alone.
Additional information that should be sought:
Is he short of breath? Is there evidence of pulmonary edema from heart
failure or fluid overload from renal failure? Is there elevation of the jug-
ulovenous pressure? What is the blood pressure? Is there evidence of liver
disease or malnutrition?
What is the color of the urine? If it is dark reddish brown this suggests
hematuria, which, in this case, would suggest the diagnosis of acute
glomerulonephritis.
This child has edema, a blood pressure of 150/95 mm Hg, a jugulovenous
pressure of about 7 cm water, and a respiratory rate of 30/minute, and the
urine is reddish brown and turbid.
These abnormalities are highly suggestive of glomerulonephritis, with
fluid overload. An important cause of acute glomerulonephritis is infection
with Streptococcus pyogenes, either impetigo (of which this patient has evi-
dence) or tonsillitis. The glomeruli are inflamed and swollen, and there is
a decrease in the glomerular filtration rate, leading to oliguria and edema.
The demonstration of red cell casts in the urine would confirm the diagnosis
of glomerulonephritis (although this is a very insensitive test), while the
demonstration of Streptococcus pyogenes infection in the throat or skin would
suggest this as the etiology of the glomerulonephritis. Culture of an infected
skin lesion or of a throat swab is the optimal way in which to confirm the
presence of Streptococcus pyogenes infection. However, serological tests (e.g.
antihyaluronidase titer) may be helpful in this regard.
Treatment of acute poststreptococcal glomerulonephritis consists of (a)
treatment of pulmonary edema, if present, with oxygen and furosemide; (b)
control of hypertension, for example, with nifedipine (furosemide might
98 Case Studies in Pediatric Infectious Diseases
help in this regard); (c) restriction of fluid intake; (d) penicillin for 10 days to
eliminate the streptococcus. Long-term penicillin is not necessary, because,
unlike rheumatic fever, this disease does not recur. The long-term prognosis
is excellent.
Reading:
Bisno AL, Brito MO, Collins CM: Molecular basis of group A streptococcal
virulence. Lancet Infect Dis 2003; 3: 191200.
Bisno AL: Group A streptococcal infections and acute rheumatic fever. N
Engl J Med 1991; 325: 783793.
Kotloff KL, Dale JB: Progress in group Astreptococcal vaccine development.
Pediatr Infect Dis J 2004; 23: 765766.
n
CASE 24. A 6-year-old boy presents with a sore throat and fever and is
found to have large, inflamed tonsils and tender cervical lymphadenopathy,
with the appearance of that shown in Figure 24.1 (from a different patient).
FIG. 24.1. The throat of a patient with sore throat and fever. Note the pharyngeal
erythema and palatal petechiae. (Courtesy of the Center of Disease Control and
Prevention/Dr Heinz F Eichenwald)
Case Study 24 99
What is the differential diagnosis?
What would you do?
This child has acute tonsillitis. The differential diagnosis of the cause of
acute tonsillitis in this patient is Streptococcus pyogenes, infectious mononu-
cleosis due to EpsteinBarr virus, and several respiratory viruses such as
adenovirus, respiratory syncytial virus, and parainfluenza virus. Diphtheria
should be considered in patients who have traveled to areas where this is
endemic. In teenagers and young adults Arcanobacterium haemolyticum also
causes pharyngotonsillitis and a generalized rash. Of the likely causes anti-
microbial therapy is available against only Streptococcus pyogenes. Although
this infection may spread to cause a peritonsillar abscess, retropharyngeal
abscess, otitis media, cervical lymphadenitis, and occasionally spread via the
bloodstream to cause metastatic infection such as osteomyelitis, the main
reason for confirming the diagnosis of this infection and providing antimi-
crobial therapy is to prevent the complication of acute rheumatic fever,
which can have devastating long-term effects on the heart. Streptococcus
pyogenes infections may be associated with a rash, characterized by fine
sandpaper-like papules and diffuse erythroderma, called scarlet fever. This
is mediated by a pyrogenic toxin (Figure 24.2).
FIG. 24.2. A child with scarlet fever (Courtesy of Dr Michael Radetsky)
100 Case Studies in Pediatric Infectious Diseases
The diagnosis of streptococcal tonsillitis can be confirmed with a throat
culture (Figure 24.3) or one of the rapid streptococcal antigen detection tests
performed on a throat swab.
Treatment consists of penicillin, given as a single dose of long-acting bicil-
lin or as oral phenoxymethyl penicillin administered for 10 days. Other
agents such as amoxicillin, cephalosporins, and macrolides may also be used.
Reading:
Bisno AL, Brito MO, Collins CM: Molecular basis of group A streptococcal
virulence. Lancet Infect Dis 2003; 3: 191200.
Bisno AL: Group A streptococcal infections and acute rheumatic fever. N
Engl J Med 1991; 325: 783793.
n
CASE 25. A premature infant in the neonatal intensive care unit being
ventilated for hyaline membrane disease is noted to have temperature
instability, dark red spots on the skin, and a swollen red ankle. Further
FIG. 24.3. A culture of Streptococcus pyogenes on blood agar. Note the b-hemolysis
(complete hemolysis) around the colonies. (Courtesy of the Centers for Disease
Control and Prevention/Richard R Facklam, PhD)
Case Study 25 101
examination reveals a 3/6 ejection systolic heart murmur, heard loudest at
the upper sternal border. She has a venous and arterial vascular catheter in
place. The abdominal examination is normal.
What is the differential diagnosis?
What would you do?
Dark red spots on the skin suggest the possibility of hemorrhage or infarc-
tions of the skin. The red, swollen ankle suggests a septic arthritis or osteo-
myelitis. Temperature instability suggests a systemic infection. A unifying
diagnosis would be a systemic (bloodstream) bacterial or fungal infection
associated with skeletal infection, and causing (a) a hemorrhagic tendency
through the mechanisms of thrombocytopenia or disseminated intravascular
coagulation or (b) emboli due to infective endocarditis. The heart murmur,
which is suggestive of a pathological murmur by its intensity, could be due to
a congenital heart disease that could predispose to infective endocarditis, or
be due to valvular damage caused by infective endocarditis affecting a pre-
viously normal valve. By definition, an infection in this infant is nosocomial.
The potential routes of infection are through vascular access sites, through
the lungs, especially since the infant is intubated, through the intestine, or
through the urinary tract, especially if the infant has a urinary catheter. The
likely organisms include staphylococci, Candida spp., enterococci, and
Gram-negative bacilli.
Specific clinical evaluation should include examination of the optic fundi
(to look for Roth spots) and examination of all vascular access sites (past and
present) for evidence of infection. The urine should be examined for hema-
turia. Blood cultures (three) should be performed over a period of 15
minutes, as should a blood count including a platelet count. The ankle and
one of the skin lesions should be aspirated and the aspirates should be sub-
mitted for culture and Gram stain. A cardiologist should be consulted for
both clinical and echocardiographic evaluation of the heart.
Initial (empiric) antimicrobial treatment should be directed at the most
likely pathogens, but guided by Gram-stain results, and more definitive
treatment should be based on culture and susceptibility results. Initial treat-
ment should be as follows:
(a) If the Gramstain shows Gram-positive cocci in clusters (staphylococci),
vancomycin + nafcillin + gentamicin should be used. The reason for using
both vancomycin and nafcillin is that for susceptible organisms, nafcillin is
superior to vancomycin. However, the vancomycin is necessary in case
the organism is resistant to b-lactam antibiotics (methicillin resistant).
Gentamicin accelerates the clearance of the staphylococci fromthe blood.
102 Case Studies in Pediatric Infectious Diseases
(b) If the Gram stain shows Gram-negative rods (which could be enteric
bacilli or Pseudomonas aeruginosa), ceftazidime + amikacin should
be used (gentamicin can be used instead of amikacin if the rate of
gentamicin resistance among Gram-negative bacilli is very low in the
unit);
(c) If the Gram stain shows yeasts, amphotericin B should be used. (In less
severely ill patients with intravascular-lineassociated fungemia, and
without endocarditis, and in whom the vascular line can be removed,
fluconazole would be appropriate).
(d) If the Gram stain does not reveal an organism, initial treatment
should be directed at staphylococci and Gram-negative rods with van-
comycin, nafcillin, gentamicin, or amikacin, and a third-generation
cephalosporin.
The Gram stain from a skin aspirate of this patient (Figure 25.1) shows
Gram-positive cocci in clusters, the typical appearance of staphylococci.
The skin, blood cultures, and ankle joint fluid grew out Staphylococcus
aureus susceptible to methicillin. Further evaluation revealed an aortic veg-
etation, providing additional evidence of infective endocarditis. She was
treated successfully with nafcillin.
FIG. 25.1. Gram-stained smear of a skin lesion aspirate from the above patient
revealing Gram-positive cocci in clusters.
Case Study 25 103
Reading:
Daher AH, Berkowitz FE: Infective endocarditis in neonates. Clin Pediatr
1995; 34: 198206.
Moreillon P, Que Y: Infective endocarditis. Lancet 2004; 363: 139149.
n
CASE 26 (HYP). A 3-year-old boy who broke out with chickenpox 5
days ago seems to be getting worse after initial improvement. He has a high
fever, his skin is red all over, and he seems a little confused.
What might be the problem?
The most likely problem is that this boy has developed a complication of
chickenpox. The most common complication is secondary bacterial infec-
tion of skin lesions with Streptococcus pyogenes or Staphylococcus aureus. The
childs illness is characterized by fever, confusion, and diffuse erythroderma.
The confusion could be due merely to delireum associated with the fever, to
a more severe problem affecting the brain, including meningitis, a metabolic
disturbance such as hypoglycemia or hyponatremia, or to poor brain perfu-
sion. The erythema could be due to scarlet fever, or to streptococcal toxic
shock-like syndrome or staphylococcal toxic shock syndrome. Given the
apparent severity of the childs condition and the combination of clinical
abnormalities, he probably has streptococcal toxic shock-like syndrome,
with or without bacteremia, or staphylococcal toxic shock syndrome.
Further clinical evaluation should be directed at determining the ade-
quacy of his perfusion and at finding a septic focus that might be drained.
This is very important in toxic shock syndrome.
Management should entail the following: (a) ensuring adequate perfusion
with intravenous fluid and vasopressors, if necessary; (b) draining any focus
of pus, and sending specimens for Gram stain and culture; a blood culture
should also be performed; and (c) antimicrobial therapy this should consist
of antibiotics active against Streptococcus pyogenes and Staphylococcus aureus,
and might consist of the following, depending on the local prevalence of
methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (for its
activity against MRSA) + oxacillin/nafcillin/cephazolin (for its activity
against Streptococcus pyogenes and methicillin-susceptible Staphylococcus
aureus) + clindamycin (for its ability to halt protein synthesis by the organ-
isms, and thus halt toxin production).
There is some evidence that intravenous immune globulin (IVIG) is ben-
eficial in patients with streptococcal toxic shock-like syndrome. I would use
it in a patient such as this.
104 Case Studies in Pediatric Infectious Diseases
Reading:
American Academy of Pediatrics. Committee on Infectious Diseases. Severe
invasive group A streptococcal infections: a subject review. Pediatrics 1998;
101: 136 140.
n
CASE 27. A 6-month-old previously well girl who attends day care
presents with a history of fever, irritability, and decreased activity. On
examination she has a temperature of 40C and is extremely irritable. In
addition, she does not interact with her parents as usual. There are no other
findings. The cerebrospinal fluid examination reveals 8000 leukocytes per
mm
3
with a differential count of 95%neutrophils and 5%lymphocytes. The
Gram stain is shown in Figure 27.1.
What is the likely diagnosis?
What would you do?
How might this illness have been prevented?
The Gram stain shows numerous Gram-positive diplococci, resembling
streptococci.
FIG. 27.1. Gram stain of the cerebrospinal fluid similar to that of the patient
described.
Case Study 27 105
The likely diagnosis is Streptococcus pneumoniae (pneumococcal)
meningitis.
Management consists of (a) supportive care, which might entail intrave-
nous fluids if the child is in shock, and ventilation if breathing is impaired
and (b) antimicrobial therapy.
The initial empiric antimicrobial therapy is determined by possible
resistance of the causative organism to penicillin and third-generation ceph-
alosporins. It should consist of vancomycin 20 mg/kg/dose q 8 hours intra-
venously plus ceftriaxone 50 mg/kg/dose q 12 hours intravenously (or
cefotaxime 75 mg/kg/dose q 6 hours intravenously). Some authors (myself
included) recommend the addition of rifampin 10 mg/kg/dose q 12 hours
orally.
Once the susceptibilities are known, therapy can be adjusted.
The use of a corticosteroid such as dexamethasone is controversial. I
recommend its use.
Acute bacterial meningitis is associated with significant vascular injury,
cerebral edema, and raised intracranial pressure. Consequently it can be
associated with the following complications:
1. various types of brain injury including hemiplegia, brainstem infarction,
and learning disabilities (Figures 27.227.4)
2. seizures
3. cranial nerve palsies
FIG. 27.2. A child with severe brain damage resulting from pneumococcal meningitis.
106 Case Studies in Pediatric Infectious Diseases
FIG. 27.3. The autopsy appearance of the brain of the child shown in figure 27.2.
Note the brain liquefaction resulting from ischemia.
FIG. 27.4. Autopsy appearance of the brain of an infant dying from pneumococcal
meningitis, showing severe damage.
Case Study 27 107
4. hydrocephalus
5. subdural fluid collection. This is common and does not usually warrant
drainage. However, it may progress to empyema in which case drainage is
indicated.
6. brain abscess is rarely a complication of bacterial meningitis, except in the
newborn, and particularly in cases caused by Proteus, Enterobacter, and
Citrobacter species.
FIG. 27.5. Histopathology
of bacterial meningitis,
showing the inflammatory
reaction in the subarachnoid
space. (Courtesy of Dr
Carlos Abramowsky, Emory
University).
FIG. 27.6. Computer tomography scan of a child with Haemophilus influenzae
meningitis and profound neurological deficit. The dark (hypodense) areas represent
infarctions, which affect both hemispheres.
108 Case Studies in Pediatric Infectious Diseases
7. inappropriate secretion of antidiuretic hormone (SIADH)
8. hearing loss. This is due to cochlear damage.
Fever may continue despite treatment in patients with bacterial menin-
gitis. One should consider several causes of fever in such patients.
(A) Those related to the meningitis:
(a) If the patient is otherwise improving, the fever is probably due to
the meningitis itself and may last up to about a week.
(b) If the patient is not improving as expected, the causative organism
may not be susceptible to the antimicrobial therapy; in such a case,
a repeat lumbar puncture should be performed to determine
whether the cerebrospinal fluid has been sterilized or not.
(c) Intracranial suppurative complications of the meningitis such as
subdural empyema or brain abscess. Brain imaging can help to di-
agnose these.
(B) Those related to therapy:
(a) Phlebitis from the intravenous catheter
(b) Drug fever due to the antibiotic
(c) Nosocomial infections such as phlebitis, respiratory tract infection
(C) Distant infections resulting from hematogenous spread of the same
organism that caused the meningitis, for example, septic arthritis
(D) Immune reactions to the infection, for example, arthritis, which is seen
particularly with meningococcal infections.
Evaluation of such patients should be guided by clinical findings.
Reading:
Bedford H, de Louvois J, Halket S et al: Meningitis in infancy in England and
Wales: follow up at age 5 years. BMJ 2001; 323: 533535.
Kaplan SL, Mason EO: Management of infections due to antibiotic-resistant
Streptococcus pneumoniae. Clin Microbiol Rev 1998; 11: 628644.
Swartz MN: Bacterial meningitis a viewof the past 90 years. NEngl J Med
2004; 351: 18261828.
Kaplan SL, Woods CR: Neurological complications of bacterial meningitis in
children. Curr Clin Top Infect Dis 1992; 12: 3755.
Case Study 27 109
n
CASE 28. A 1-month-old infant presents with a history of not
moving the right arm for 1 day. She is otherwise fine, eating well, and
afebrile. On examination the temperature is 36.5C, and the perfusion is
normal. The right upper limb is flaccid and there is mild swelling and
marked tenderness around the shoulder joint. The rest of the examination
is normal.
What is the differential diagnosis?
What would you do?
The differential diagnosis essentially consists of injury to the limb (acci-
dental or nonaccidental), involving the soft tissue or bone, or infection
involving the shoulder joint or bone on either side of the joint, that is, the
upper end of the humerus or the scapula, or both. Although an X ray cannot
exclude soft tissue injury, it can largely exclude a fracture. Skeletal infections
in children of this age typically manifest as failure of the use of the limb, as
seen in this patient. The infant usually appears otherwise well, feeds well,
and may be afebrile. Osteomyelitis and septic arthritis in children is almost
always hematogenous in origin. Osteomyelitis affects the bone metaphysis.
In young infants infection can spread through the growth plate into the joint,
but in children older than about 18 months the growth plate provides a sig-
nificant barrier to spread of infection into the joint (Figure 28.1). It can also
spread through the periosteum into the muscle and subcutaneous tissue
(Figure 28.2).
The common causative organisms of skeletal infection in a 1-month-old
infant are Streptococcus agalactiae (group B streptococcus), Staphylococcus
FIG. 28.1. The anatomy of a long bone in an infant and older child.
110 Case Studies in Pediatric Infectious Diseases
aureus, and Gram-negative bacilli. It is extremely important to make a
microbiological diagnosis in order to provide optimal therapy. This requires
obtaining specimens from the joint and the adjacent bone by inserting a
needle into the respective area and culturing the aspirated material. Material
should be submitted both on a swab or in a sterile tube, as well as inoculated
into a blood culture bottle, which can increase the chances of culturing an
organism. When the focus of disease is apparent, as in this child, further
studies to localize the disease are unnecessary, but when this is not the
case, a radionucleide bone scan should be performed to localize a site of
osteomyelitis. When the nature of the disease and the specific site are un-
clear, an MRI may be helpful. Blood cultures should also be performed.
Once appropriate specimens have been obtained, antibiotic therapy directed
against the above-mentioned organisms should be initiated. This can be
adjusted once an organism is isolated. In areas with a high prevalence of
methicillin-resistant Staphylococcus aureus (MRSA), vancomycin should be
used, in addition to a third-generation cephalosporin for its activity against
Streptococcus agalactiae and enteric Gram-negative bacilli. In areas with a low
prevalence of MRSA, nafcillin or oxacillin can be used instead of
vancomycin.
In this child, Streptococcus agalactiae was cultured fromthe shoulder joint.
She improved on therapy with ampicillin.
FIG. 28.2. MRI of the
femur of a young infant with
osteomyelitis, showing
inflammation within the
quadriceps muscle, resulting
from spread of the infection
from the femur through the
periosteum.
Case Study 28 111
n
CASE 29. A 6-month-old child, who is 3 weeks post placement of a ven-
triculoperitoneal (VP) shunt for hydrocephalus, presents with a 3-day his-
tory of fever and decreased appetite. On examination she has a temperature
of 38.2C and a large head. The shunt track is not inflamed and the surgical
wound is well healed. The rest of the examination is normal. Cerebrospinal
fluid taken through the shunt bulb shows 100 leukocytes per mm
3
of which
75% are neutrophils. The Gram stain reveals a few Gram-positive cocci.
What is the likely diagnosis and its likely cause?
What should be done?
The patient has ventriculitis due to a shunt infection. This is probably
caused by a staphylococcus, a coagulase-negative staphylococcus more likely
than Staphylococcus aureus.
Patients with VP shunt infections usually present with fever and evidence
of raised intracranial pressure due to shunt malfunction (headache, vomit-
ing, decreased level of consciousness) or abdominal pain caused by infected
fluid draining into the peritoneal cavity, causing peritonitis.
Of three different methods of management, namely (i) leaving the shunt in
place and using antimicrobial therapy only, (ii) removal of the shunt and
immediate replacement with a new shunt, in addition to the administration
of antibiotics, and(iii) removal of the shunt, placement of anexternal drain, in
addition to the administration of antibiotics, and replacement of the shunt
when the cerebrospinal fluid has become sterile, the last strategy ((iii)) is
preferable. The new shunt can usually be replaced within 37 days after the
infectedshunt has beenremoved andappropriate therapy has beeninstituted.
References:
Yogev R: Cerebrospinal fluid shunt infections: a personal view. Pediatr
Infect Dis J 1985; 4: 113118.
Schreffler RT, Schreffler AJ, Wittler RR: Treatment of cerebrospinal
fluid shunt infections: a decision analysis. Pediatr Infect Dis J 2002; 21:
632636.
n
CASE 30. A full-term newborn baby develops respiratory difficulty and
shock, and dies within 12 hours of birth, despite vigorous therapy. The
Gram stain of the blood culture broth after 12 hours of incubation is shown
in Figure 30.1.
What is the likely identification of the organism?
The Gram stain shows Gram-positive cocci in chains.
112 Case Studies in Pediatric Infectious Diseases
The most likely causative organism is Streptococcus agalactiae (group B
streptococcus). This organism is the most common cause of neonatal sepsis
in the United States at this time. It causes two main types of illness. (a) Early-
onset disease (i.e. presenting in babies <1 week, often within a few hours of
birth as in this patient), which is characterized by severe pneumonia and
septic shock. In this situation, the organism is acquired from the mothers
vagina. (b) Late-onset disease (i.e. presenting in babies older than >1 week),
which may occur in infants as old as 4 months. Such infants usually present
with fever. They usually have bacteremia and/or meningitis. Late-onset
disease may also cause skeletal infection (see Case 28).
Several strategies have been used to prevent early-onset infection with
this organism. The current strategy recommended by the US Public Health
Service entails screening of the mother in late pregnancy and treating colo-
nized mothers with ampicillin during labor. This strategy has been shown to
have been associated with a marked decline in the number of cases of early-
onset neonatal Group B streptococcal infections but not in that of late-onset
infections.
Reading:
Centers for Disease Control and Prevention. Prevention or perinatal group B
streptococcal disease. Revised guidelines from CDC. MMWR Recomm. Rep.
2002; 51 (RR 11): 122.
FIG. 30.1. The Gram stain of the blood culture broth after overnight incubation.
Case Study 30 113
n
CASE31. An 8-month-old African-American boy presents with a history
of fever for several hours. He is found to be in shock. There are no localizing
findings. He is treated with fluid resuscitation, pressors, and antibiotics
(ceftriaxone and vancomycin intravenously). He dies a few hours later. A
blood smear reveals the cause of death (Figure 31.1).
What does the blood smear reveal?
What are possible underlying condition predisposing him this disease?
The blood smear reveals diplococci. When this smear is stained with
Gram stain, these can be seen to be Gram-positive diplococci, resembling
Streptococcus pneumoniae (pneumococcus) (Figure 31.2).
When microorganisms are seen on a blood smear, this indicates at least
10
5
organisms per milliliter of blood and a very poor prognosis for survival.
The most likely identity of these organisms is Streptococcus pneumoniae. The
rapid progression of the illness and the high concentration of organisms in
the blood suggests the absence or hypofunction of the spleen. This can occur
congenitally (sometimes associated with congenital heart disease), or as a
result of sickle cell disease or surgical splenectomy. (The presence of Howell-
Jolly bodies (intraerythrocytic inclusions) on a blood smear indicates absence
of the spleen (Figure 31.3)). This was indeed a case of pneumococcal bac-
teremia and the child indeed had sickle cell disease (Figure 31.4), which had
not been previously diagnosed. This is the main cause of death in infants and
FIG. 31.1. The patients blood smear stained with Wrights stain.
114 Case Studies in Pediatric Infectious Diseases
young children with sickle cell disease. Children at highest risk are those
younger than 3 years. The reason for children with sickle cell disease to be
susceptible to fulminating pneumococcal sepsis syndrome is hyposplenism
resulting from splenic infarcts. This develops progressively during the first
year of life.
Pneumococci have a polysaccharide capsule. There are more than 80 dif-
ferent capsular types (serotypes). The hosts blood phagocytes (neutrophils,
FIG. 31.3. A Howell-Jolly
body inside an erythrocyte.
FIG. 31.2. The blood smear stained with Gram stain, revealing Gram-positive
diplococci, resembling Streptococcus pneumoniae.
Case Study 31 115
FIG. 31.4. A blood smear
of a child with sickle cell
disease. Note the sickle cells
and target cells.
FIG. 31.5. The role of the
spleen in removing pneumo-
cocci from the
circulation.
116 Case Studies in Pediatric Infectious Diseases
monocytes) depend on complement and capsule-specific antibody to opson-
ize pneumococci and remove them from the circulation. However, in the
absence of antibody, only the splenic macrophages can remove pneumococci
from the circulation. In the case of infants and young children, who have not
previously encountered the organism and therefore lack antibody, the spleen
is therefore very important (Figure 31.5).
Young children with sickle cell disease, who lack both antibody and nor-
mal splenic function, cannot prevent pneumococci in the circulation from
multiplying rapidly and causing a fulminating sepsis syndrome, as in this
case. Penicillin prophylaxis (before the era of significant rates of penicillin
resistance) was shown to be very effective in reducing the mortality fromthis
infection. In order to (a) institute penicillin prophylaxis and (b) educate the
parents about the importance of bringing such children for evaluation and
antibiotic treatment when they have fever, the children must be known to
have sickle cell disease. Therefore it is important that children are screened
for this hemoglobinopathy as newborns. An additional preventive measure is
immunization with the conjugated pneumococcal vaccine beginning at the
age of 2 months.
Reading:
American Academy of Pediatrics, Section on Hematology/Oncology, Com-
mittee on Genetics: Health supervision for children with sickle cell disease.
Pediatrics 2002; 109: 526535.
Overturf GD and the Committee on Infectious Diseases, American Acad-
emy of Pediatrics. Technical report: Prevention of pneumococcal infections,
including the use of pneumococcal conjugate and polysaccharide vaccines
and antibiotic prophylaxis. Pediatrics 2000; 106: 367376.
Gaston MH, Verter JI, Woods G et al: Prophylaxis with oral penicillin in
children with sickle cell anemia. A randomized trial. N Engl J Med 1986;
314: 15931599.
n
CASE 32. An infant presents with cough and high fever. On examination
she is very ill-appearing; the respiratory rate is 80/minute, and there is
dullness to percussion and decreased breath sounds on the left side of the
chest. A chest X ray reveals a large left pleural effusion and pneumonia
(Figure 32.1).
The effusion is tapped revealing purulent fluid, fromwhich Staphylococcus
aureus is cultured. A chest tube (intercostal drain) is inserted and she is
Case Study 32 117
treated with cloxacillin. She slowly improves. During her convalescence an
abnormality, shown in the picture, is noted (Figure 32.2).
What is the abnormality, and what is its pathogenesis?
This picture shows left-sided ptosis. This is part of a Horners syndrome
complicating a pleural empyema. Horners syndrome, consisting of ptosis,
enophthalmos, miosis, and loss of sweating of the forehead, is caused by
FIG. 32.2. Part of the childs face.
FIG. 32.1. The infants
chest X ray showing a
left-sided pleural effusion.
118 Case Studies in Pediatric Infectious Diseases
damage to the ipsilateral cervical sympathetic fibers or ganglion. The gan-
glion is located on the posterior chest wall. This, presumably, was damaged
by the empyema.
n
CASE 33. A 5-day-old infant presents with a history of not being able to
breathe properly for a few hours. On examination he appears as shown in
the picture (Figure 33.1).
What is the diagnosis?
What is the mechanism of disease?
What would you do?
How could this have been prevented?
This picture demonstrates an infant with stiffness, grimacing, and tight-
ness of the fists. This is characteristic of tetanus. Other diagnostic consid-
erations are: tetany, due to hypocalcemia, and seizures, which, in newborn
infants, are not associated with generalized tonic contractions. Tetanus is a
major health problem in many parts of the world. Almost all cases of tetanus
worldwide occur in newborns, and it accounts for about 7% of neonatal
deaths worldwide. The disease is caused by the organism Clostridium tetani
entering the umbilical stump, which provides an anaerobic environment.
FIG. 33.1. The infant with inability to breathe properly.
Case Study 33 119
There it elaborates a potent toxin called tetanus toxin (tetanospasmin),
which ascends along nerve fibers to the central nervous system. There it
causes inhibition of inhibitory neurons, resulting in excitation. This results
in the clinical manifestations of muscle spasms. The prolonged contraction
of respiratory muscles prevents the victim from inspiring. Infection of the
umbilicus occurs as a result of two main factors: (a) the cord is cut with an
instrument contaminated with spores of the organism; and (b) the common
practice in some cultures of putting dirt or dung, which contain spores of the
organism, on the umbilical stump.
Treatment entails sedation, for example, with diazepam, to enable the
child to breathe. Artificial ventilation for about 1 month is often necessary.
Although tetanus immune globulin (human or animal) and penicillin are
used, their value is questionable.
Prevention consists of education regarding cord care and immunization of
pregnant women, whose IgG antibodies will enter the fetus and protect it.
Later the baby will require active tetanus immunization. Patients who have
recovered from tetanus still require active tetanus immunization.
References:
Bryce J, Boschi-Pinto C, Shibuya K et al: WHO estimates of the causes of
death in children. Lancet 2005; 365: 11471152.
Brook I: Tetanus in children. Pediatr Emerg Care 2004; 20: 4851.
n
CASE 34. (HYP). A 10-year-old girl presents with a history of sore
throat and difficulty breathing of 1 days duration. She returned 2 days
ago from a trip to Odessa (Ukraine). On examination she is very ill-appear-
ing. She has some inspiratory stridor and thick white-gray material covering
her tonsils and faucial pillars, and she has swelling of her neck (Figures 34.1
and 34.2).
What is the likely diagnosis and how would you confirm it?
What is the mechanism of disease?
How would you manage her?
The likely diagnosis is diphtheria, which is caused by Corynebacterium
diphtheriae. A very large epidemic of diphtheria occurred in the former
Soviet Union in the early 1990s. Although other agents can cause a pseudo-
membrane on the tonsils, for example, Streptococcus pyogenes and Epstein
Barr virus, they do not usually cause stridor. Diphtheria causes stridor
120 Case Studies in Pediatric Infectious Diseases
because the pseudomembrane can descend into the larynx, causing respira-
tory obstruction, one of the main causes of death in this infection. The
organism is not invasive. It elaborates a toxin, diphtheria toxin, which is
an ATP ribosylase, which inhibits protein synthesis at the ribosomal site
of elongation factor 2. Other clinical effects of the toxin include the follow-
ing: (i) palatal palsy, which manifests clinically with nasal speech and
which may be present in the early stages of the infection; (ii) a toxic myo-
carditis (cardiomyopathy), which results in atrioventricular block and myo-
cardial failure. This begins 12 weeks after onset of the disease; (iii)
a peripheral neuropathy resembling that of Guillain-Barre syndrome, which
can become manifest 10 days to 3 months after onset of the disease; (iv)
renal failure. Fatalities are due to respiratory tract obstruction or cardiac
failure.
Diphtheria is confirmed by culture of the causative organismfroma throat
swab. Culture for C. diphtheriae is not routinely performed on throat speci-
mens in the United States. This must be specifically requested, since special
media are required.
Management of diphtheria, which highlights the general principles of
management of infectious diseases, consists of the following: (a) suppor-
tive care ensuring an adequate airway, which may require endotracheal
intubation or tracheostomy; (b) antimicrobial therapy erythromycin or
FIG. 34.1. The pharynx of
a different patient with the
same appearance as that of
the child described above.
(From Kadirova R, Kartoglu
HU, Strebel PM: Clinical
characteristics and
management of 676
hospitalized diphtheria
cases, Kyrgyz Republic,
1995. J Infect Dis 2000; 181
(suppl 1); S110115, with
permission of The University
of Chicago Press, 2000
by the Infectious Diseases
Society of America.
All rights reserved.)
Case Study 34 121
penicillin, and antidiphtheria globulin, which is made in an animal; (c) sur-
gery tracheostomy (see above); (d) community notification of the health
department; hospital isolation with droplet precautions; contacts should be
tested for carriage (by throat culture) and given antimicrobial prophylaxis
with erythromycin or penicillin; and (e) prevention active immunization.
Although this infection is very rare in the United States as a result of wide-
spread immunization, it is prevalent in many other countries and can be
imported into this country.
Reading:
Mattos-Guaraldi AL, Moreira LO, Damasco PV, Junior RH: Diphtheria
remains a threat to health in the developing world an overview. Mem Inst
Oswaldo Cruz 2003; 98: 987993.
FIG. 34.2. Appearance of
a child with the same
diagnosis as the child
described. (From Emond
RTD: Color Atlas of
Infectious Diseases. 1974.
Year Book Medical
Publishers, Chicago. With
permission from Elsevier.)
122 Case Studies in Pediatric Infectious Diseases
Reading:
Kadirova R, Kartoglu HU, Strebel PM: Clinical characteristics and manage-
ment of 676 hospitalized diphtheria cases, Kyrgyz Republic, 1995. J Infect
Dis 2000; 181 (Suppl 1): S 110115.
n
CASE 35. A 2-week-old infant presents with a history of fever, poor
feeding, and decreased activity over the past 2 days. On examination she
looks very ill and is barely responsive. The anterior fontanelle is bulging and
tense. The cerebrospinal fluid reveals the following: 1200 leukocytes/mm
3
of which 90% are neutrophils, a protein concentration of 200 mg/dl, and
a glucose concentration of 15 mg/dl. The blood glucose concentration is 70
mg/dl. Gram stain reveals Gram-positive rods.
What is the likely diagnosis?
What else would you like to know?
How would you manage the child?
This newborn infant has Gram-positive rod meningitis, which is most
likely caused by Listeria monocytogenes. This organism is acquired from the
mothers vagina, usually during delivery. The mother acquires the organism
by ingestion, resulting in intestinal colonization followed by vaginal coloni-
zation. Although the organism can be present in many foods including veg-
etables, an important source is unpasterurized dairy products, including
semisolid cheeses, and undercooked meat. Although pregnant women may
have transient symptoms such as fever when they become infected, they are
often only colonized and asymptomatic. An intrauterine form of listeriosis
called granulomatosis infantiseptica, characterized by the presence of mul-
tiple abscesses, is usually fatal. Listeria monocytogenes is one of the bacteria
that can remain within macrophages without being killed, and cell-mediated
immunity is therefore necessary for its elimination. (Other bacteria requir-
ing cell-mediated immunity for their elimination include salmonella,
brucella, legionella, and mycobacteria.) Therefore individuals with impair-
ment of this arm of immunity due to, for example, AIDS, corticosteroids,
and transplantation immunosuppression are at risk for this infection. The
elderly are also at risk for this infection.
The treatment of listeriosis consists of ampicillin with or without
gentamicin.
Prevention of neonatal listeriosis entails education of pregnant women to
avoid the risk factors described above.
Case Study 35 123
Reading:
Braden CR: Listeriosis. Pediatr Infect Dis J 2003; 22: 745746.
Southwick FS, Purich DL: Intracellular pathogenesis of listeriosis. N Engl J
Med 1996; 334: 770776.
n
CASE 36. A 5-year-old girl presents with fever, chest pain, and cough
and is found to have a pulmonary infiltrate on X ray. She is treated with
erythromycin and seems to improve a little. However, her symptoms recur
a few weeks later and she is treated with amoxicillin, again with some
improvement. She presents a few weeks later with a swelling on the right
side of her chest. A chest X ray shows the presence of consolidation in the
same place as initially. The swelling is biopsied and the Gram stain has the
appearance of that shown in the picture (Figure 36.1).
What is the diagnosis?
How should she be treated?
The biopsy reveals inflammation and a clump of branching Gram-positive
bacilli. These are characteristic of actinomyces and nocardia species (both
belong to the family Actinomycetales). This patient, who had no known
immunodeficiency, is more likely to have had an infection with actinomyces
FIG. 36.1. Biopsy (from another patient) showing a clump of branching,
Gram-positive bacilli. (Courtesy of Carlos Abramowsky, MD, Emory University)
124 Case Studies in Pediatric Infectious Diseases
than with nocardia. The culture grew out Actinomyces israelii, confirming
the diagnosis of actinomycosis, which is a bacterial not a fungal infection.
There are several species of actinomyces, including A. israelii (the most
important), A. naeslundi, A. viscosus, A. odontolyticus, and A. meyeri. These
bacteria, which are considered anaerobes, although they grow best micro-
aerophilically, form part of the normal flora of mucosal surfaces. They cause
chronic infections, which may spread across tissue plains. Clumps of bacteria
become mineralized, resulting in grains called sulfur granules. These infec-
tions arise particularly in the mouth (usually as a result of injuries), large
bowel, and female genital tract (usually as a complication of intrauterine
contraceptive devise usage). However, the organisms can spread to the lung
by aspiration and they can spread hematogenously. These organisms require
special media for growth in the laboratory, and they are susceptible to many
antibiotics. Treatment consists of penicillin for a prolonged period, and
sometimes entails surgical drainage. This child improved with penicillin
treatment.
Reading:
Mabeza GF, Macfarlane J: Pulmonary actinomycosis. Eur Respir J 2003; 21:
545551.
n
CASE 37. An 8-year-old boy, who underwent bone marrow transplan-
tation for leukemia about 1 year ago, presents with cough, chest pain, and
fever for a few days. He is currently receiving immunosuppressive therapy.
On examination he has evidence of consolidation in his left upper lobe,
which is confirmed radiologically.
What is your differential diagnosis?
What would you do?
Considering that he is immunosuppressed, there are several possible causes
of his lung disease, including the following: (a) bacteria, such as Streptococcus
pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Gram-
negative rods, including Legionella spp.; (b) bacteria causing more indolent
infections such as Mycobacterium tuberculosis, Nocardia spp., and Rhodococ-
cus equi; and (c) fungi, in particular Aspergillus species. Pneumonias caused
by viruses such as the respiratory viruses and cytomegalovirus, by bacteria
such as Mycoplasma pneumoniae and Chlamydia pneumoniae, and by Pneu-
mocystis jiroveci should be considered, but they tend to be diffuse more than
focal.
Case Study 37 125
Considering the wide microbiologic differential diagnosis, the lack of
practicability of providing antimicrobial therapy directed at all the possible
causes of pneumonia, and the high probability of significant adverse effects
if such broad spectrum therapy were instituted, it is important to make
a microbiological diagnosis in such a patient.
The methods for making a microbiological diagnosis are staining, antigen
detection, nucleic acid detection, and culture of potentially infected material
for the wide variety of pathogens described above. The major problem is in
obtaining appropriate specimens. The specimens used are (i) sputum this is
difficult to obtain in children, and is, by its nature, contaminated with saliva;
(ii) bronchoalveolar lavage fluid; and (iii) lung biopsy material, which
requires the most invasive procedure. The latter may become necessary if
the other procedures fail to provide a diagnostic answer.
This patient underwent bronchoalveolar lavage. Gram stain of the fluid
revealed fine, beady, branching Gram-positive rods, with the same appear-
ance as those, from a different patient, shown in Figure 37.1.
Now what is the most likely diagnosis?
This picture reveals beaded, branching, Gram-positive rods, which are
highly suggestive of Nocardia spp. The genus Nocardia includes N. asteroides,
FIG. 37.1. Gram-stained preparation of bronchoalveolar lavage fluid, from another
patient with the appearance of that seen in the fluid from this patient. (From Smilock
JD: Pulmonary and disseminated nocardiosis. N Engl J Med 1999; 341: 885.
Copyright 1999 Massachusetts Medical Society. All rights reserved, with permission.)
126 Case Studies in Pediatric Infectious Diseases
N. farcinica, N. nova, N. otitidiscaviarum, N. brasiliensis, and N. transvalensis.
They may stain with Kinyouns modified acid-fast stain, which can help to
differentiate them from Actinomyces spp., which are also branching Gram-
positive rods, but do not stain with this stain. Nocardia spp. grow on regular
media such as blood agar. They are present in the environment, and they
cause infection mainly in immunocompromised hosts. They enter the host
via the lung but may spread hematogenously, particularly to the brain.
However, N. brasiliensis causes cutaneous infections in normal hosts follow-
ing skin inoculation. Although Nocardia spp. are usually susceptible to tri-
methoprim/sulfamethoxazole, their antimicrobial susceptibilities are very
variable, so it is very important to have isolates tested for their antimicrobial
susceptibilities. They are sometimes susceptible to cephalosporins, minocy-
cline, imipenem, fluoroquinolones, and amikacin. Treatment should be ini-
tiated with trimethoprim/sulfamethoxazole, with or without amikacin,
pending results of susceptibility tests, which may take several weeks. All
patients with pulmonary nocardiosis should undergo brain imaging to look
for evidence of spread there.
This patient was treated with trimethoprim/sulfamethoxazole and
improved.
Reading:
Lerner PI: Nocardiosis. Clin Infect Dis 1996; 22: 891903.
Choucino C, Goodman SA, Greer JP et al: Nocardial infection in bone
marrow transplant recipients. Clin Infect Dis 1996; 23: 10121019.
n
CASE 38. A4-month-old breast-feeding infant presents with a history of
constipation for a few days. Now she does not move much and seems
floppy. On examination she is indeed hypotonic and very weak. She does
not open her eyes, but when you open them, she seems to look at you.
Her cry is very weak. She has the appearance of the infant shown in Figure
38.1.
What is your differential diagnosis?
What would you do?
This child has an acute diffuse lower motor neuron problem. Although
infants with acute cerebral disease, such as bacterial meningitis or hemor-
rhage, can be hypotonic, in such circumstances they are encephalopathic and
do not look at you. The differential diagnosis of acute lower motor diseases
should be considered anatomically (Figure 38.2).
Case Study 38 127
(a) anterior horn cell:
poliomyelitis in this infection the weakness is usually focal and asym-
metric, but may be generalized;
spinal muscular atrophy although this is a disease of the anterior horn
cell, it does not manifest acutely.
(b) peripheral nerve:
Guillain-Barre syndrome and toxic peripheral neuropathies.
(c) neuromuscular junction
botulism, which, in infants, can present exactly as this child has presented.
myasthenia gravis which does not usually present acutely.
FIG. 38.1. A hypotonic infant. (Courtesy of the Centers for Disease Control and
Prevention)
128 Case Studies in Pediatric Infectious Diseases
(d) muscle:
acute muscle disease, such as myositis, is usually associated with muscle
tenderness.
Considering this infants age, the most likely diagnosis is infant botulism.
Infant botulism is an infection caused by Clostridium botulinum. Spores of the
causative organism are ingested by the infant. In the gut they germinate
producing botulinum toxin, which is absorbed. The toxin, which, like many
bacterial exotoxins, has a light (toxic) component and a heavy (attachment)
component, prevents release of acetylcholine from the presynaptic end of
the neuromuscular junction, resulting in weakness. Clinically, infant botu-
lism presents with constipation and hypotonia, as in this case. Classic botu-
lism typically presents with descending paralysis. Ptosis is a notable feature.
The diagnosis is confirmed by the demonstration of toxin in the stool
(performed at reference laboratories). Honey fed to the infant is an identi-
fied risk factor and should therefore not be given to infants, but specific risk
factors are identified in few cases.
Management: This is mainly supportive, consisting of ensuring adequate
ventilation and nutrition. Antibiotics are not indicated. Botulinum immune
globulin, obtainable from the California State Health Department, has been
shown to ameliorate the condition.
Classic botulism is an intoxication in which the toxin, produced by the
organismin contaminated food, such as home canned vegetables, is ingested.
FIG. 38.2. Diagram showing the lower motor neuron unit.
Case Study 38 129
Wound botulism, in which the organism is inoculated into a wound where it
produces toxin, is an infection, like infant botulism.
Botulinum toxin is used therapeutically in conditions associated with
muscle spasm and for cosmetic purposes to remove wrinkles. It also has
the potential to be used as a biological weapon.
Reading:
Arnon SS, Schechter R, Inglesby T et al: Botulinum toxin as a biological
weapon. Medical and public health management. JAMA 2001; 285:
10591070.
Arnon SS, Schechter R, Maslanka SE et al: Human botulism immune glob-
ulin for the treatment of infant botulism. N Engl J Med 2006; 354: 462471.
n
CASE 39 (HYP). A 15-year-old Turkish shepherd develops a sore on his
forearm. This progressively enlarges and appears as shown in Figure 39.1
(from a different patient).
This sore is characterized by an ulcer with a black center.
What might have caused this?
What would you do?
Sores on the arm can be caused by many microorganisms as a result of
minor trauma, for example, Staphylococcus aureus. These do not usually have
black centers. Specific diseases for which this individual may be at risk due to
his place of residence and his occupation are rickettsial infection, cutaneous
FIG. 39.1. A sore that has
the appearance of that noted
in the patient described.
(Courtesy of the Center for
Disease Control and
Prevention/James H Steele)
130 Case Studies in Pediatric Infectious Diseases
leishmaniasis, and cutaneous anthrax. (In central Africa, African trypanoso-
miasis would also be a consideration.) Being a shepherd is a specific risk
factor for acquiring anthrax, the diagnosis in this case.
Anthrax is caused by the spore-forming Gram-positive rod Bacillus
anthracis, which may be present in soil and on the hides of animals. It causes
three clinical forms of disease. (a) Cutaneous, which is the most common.
The organism is inoculated into the skin by a mild abrasion, and causes
a painless sore that develops into a black eschar associated with significant
swelling. (The term anthrax is derived from the Greek word for black).
(b) Inhalation anthrax, which is characterized by a rapidly progressive
mediastinitis that is usually fatal. This form is difficult to diagnose and is
frequently complicated by bacteremia and meningitis. (c) Ingestion anthrax,
caused by ingestion of contaminated meat. Bacillus anthracis has several
virulence factors including a polygluconate capsule and three exotoxins
which act synergistically.
The diagnosis is confirmed by culture of the organism. Laboratory staff
should be informed of the clinical suspicion, because aerosolized organisms
pose a significant risk to them. Management is antimicrobial, with cipro-
floxacin or doxycycline. Public health authorities must be informed imme-
diately about the suspicion of anthrax, especially in light of its use as an agent
of bioterrorism.
Reading:
Dixon TC, Meselson M, Guillemin J, Hanna PC: Anthrax. N Engl J Med
1999; 341: 815826.
Swartz MN: Recognition and management of anthrax an update. NEngl J
Med 2001; 345: 16211626.
Mock M, Fouet A: Anthrax. Annu Rev Microbiol 2001; 55: 647671.
n
CASE 40. A 10-year-old girl presents with a history of pain and swelling
of her calf for a few hours. Her history is significant for several severe
bacterial infections, including meningitis, leading to the assumption that
she has an immunodeficiency. A specific immune defect has not been dem-
onstrated despite very extensive testing. On examination the swelling of the
leg is confirmed, in addition to which purple discoloration is also noted. She
is diagnosed with a deep venous thrombosis, hospitalized, and treated with
heparin intravenously. Over the ensuing few hours the swelling and pain
progress to the thigh and she develops brownish cutaneous bullae. An
aspirate of a bulla reveals, on Gram stain, what is shown in the Figure 40.1.
Case Study 40 131
What is the diagnosis?
What would you do?
The picture shows Gram-positive rods and the absence of leukocytes. The
clinical and Gram-stain appearance of the organism are characteristic of
clostridial gas gangrene (myonecrosis).
Clostridial myonecrosis is caused by histotoxic clostridia, the most
important of which is C. perfringens. This organism elaborates an exotoxin,
which is a lecithinase and lyses cellular membranes, including those of eryth-
rocytes. It thus causes tissue necrosis and intravascular hemolysis. The caus-
ative organism in this case was C. septicum, which is recognized to cause
infections in immunocompromised individuals.
Management consists of antimicrobial therapy and aggressive surgical
debridement. Although several drugs, including penicillin, clindamycin,
metronidazole, and carbapenems are active against the histotoxic clostridia,
a combination of penicillin and clindamycin is considered preferable. Hy-
perbaric oxygen therapy is also sometimes used. This patient was treated
with penicillin, underwent a hindquarter amputation and hyperbaric oxygen
therapy, and survived.
Reading:
Stevens DL, Musher DM, Watson DA: Spontaneous, nontraumatic gangrene
due to Clostridium septicum. Rev Infect Dis 1990; 12: 286296.
FIG. 40.1. The Gram stain of fluid from a bulla.
132 Case Studies in Pediatric Infectious Diseases
Brook I: Microbiology and management if infectious gangrene in children.
J Pediatr Orthop 2004; 24: 587592.
n
CASE 41. Infants between the ages of 0 and 3 months present as shown
in the pictures.
What is the diagnosis, and what would you do?
These are all features of congenital syphilis, which is a form of secondary
syphilis acquired transplacentally from the mother, and which manifests
during the first few months of life. These represent the following:
1. Snuffles: this is rhinorrhea caused by mucosal ulcers;
2. Peeling soles: this is one of several cutaneous manifestations of congenital
syphilis. Macular rashes are also a feature of congenital syphilis;
3. Condylomata lata;
4. Pitting edema: this is caused by the nephrotic syndrome due to syphilitic
glomerulonephritis.
Other manifestations or sites of infection in congenital syphilis are the
following:
meningitis;
pneumonia alba this is a severe form of pneumonia that is frequently fatal;
enlargement of the liver and spleen, and hepatitis;
anemia and thrombocytopenia;
generalized lymphadenopathy, including involvement of the epitrochlear
nodes; chorioretinitis;
osteitis, which may manifest with pseudoparesis (Figure 41.5).
Syphilis is caused by the spirochete Treponema pallidum, which is spread
sexually and vertically. It can also be spread through blood transfusion.
Other congenital infections, notably cytomegalovirus infection, toxoplas-
mosis, rubella, and human immunodeficiency virus (HIV) infection may
manifest with some of these abnormalities, including chorioretinitis, hepa-
tosplenomegaly, hepatitis, anemia, thrombocytopenia, and cerebrospinal
fluid pleocytosis, but they do not cause mucosal disease, nephrotic syn-
drome, or symptomatic bone disease. In addition, in these infections (with
the exception of HIV infection), the abnormalities are present at birth, and
their cutaneous manifestations are characterized by purple raised lesions
(blueberry muffin lesions) caused by extramedullary hematopoiesis.
Late manifestations of congenital syphilis, in untreated individuals,
include interstitial keratitis, joint effusions (Charcots joints), Hutchinsons
Case Study 41 133
FIG. 41.1. Cracked lips; runny nose.
FIG. 41.2. Peeling soles.
134 Case Studies in Pediatric Infectious Diseases
FIG. 41.3. Perianal swellings.
FIG. 41.4. Pitting edema.
Case Study 41 135
teeth (which are peg-shaped permanent incisors), sensory deafness, and
manifestations of tertiary syphilis, namely brain disease and aortitis of the
ascending aorta.
The diagnosis of congenital syphilis is confirmed by (a) dark-field micros-
copy of specimens from mucous membrane lesions to detect spirochetes
(seldom available) and (b) serology positive nonspecific serological tests
in the mother (e.g. rapid plasma reagin (RPR)) should be confirmed with
a specific antibody test (e.g. microhemagglutination test or fluorescent trep-
onemal antibody-absorption test (FTA-ABS)). The nonspecific test titers
return to negative over time after treatment, but the specific antibody tests
do not. Because the mothers specific IgG will be present in the infant, even
if she has been adequately treated, the serological confirmation of infection
in the infant requires demonstration of a nonspecific antibody (RPR) titer
FIG. 41.5. X ray of the
lower limbs showing marked
periosteal reactions of the
femora and tibias, and
metaphysitis of the upper
ends of the tibias, caused by
congenital syphilis. The lytic
lesions of the proximal tibial
metaphyses are called
Wimbergers sign.
136 Case Studies in Pediatric Infectious Diseases
fourfold or greater than in the mother. In suspected cases the cerebrospinal
fluid should also be examined for evidence of meningitis (with measure-
ments of cell count, and glucose and protein concentrations) and of antibody
production within the central nervous system using the Venereal Disease
Research Laboratory (VDRL) test. The presumptive diagnosis and the de-
cision to treat the infant should be guided by the serological test results of
the mother and infant, the mothers treatment status (adequate treatment
requires parenteral penicillin at least 4 weeks before delivery), and the clin-
ical and laboratory findings in the infant.
Treatment of congenital syphilis consists of parenteral penicillin adminis-
tered for 10 days.
Reading:
Stoll BJ: Congenital syphilis: evaluation and management of neonates born
to mothers with reactive serologic tests for syphilis. Pediatr Infect Dis J 1994;
13: 845853.
Fiumara NJ, Lessell S: Manifestations of late congenital syphilis. An analysis
of 271 patients. Arch Derm 1970; 102: 7883.
Woods CR: Syphilis in children: congenital and acquired. Semin Pediatr
Infect Dis 2005; 16: 245257.
American Academy of Pediatrics. Syphilis. In: Pickering LK (editor). Red
Book: 2006 Report of the Committee on Infectious Diseases. 27th edition.
American Academy of Pediatrics, Elk Grove Village, IL, 2006, pp. 631644.
n
CASE 42. (HYP). A 13-year previously healthy boy presents with fever,
headache, myalgia, and general malaise lasting about 3 days. There has not
been a sore throat or other respiratory tract symptoms. He improves, but
after a week the fever returns. On examination he has a temperature of
39Cand enlargement of the liver and spleen. The rest of the examination is
normal.
What would you like to know?
What would you do?
The main cause of fever and hepatosplenomegaly in a teenager is infec-
tious mononucleosis, caused by EpsteinBarr virus (EBV). This illness is also
associated with a sore throat and cervical lymphadenopathy.
Acute human immunodeficiency virus (HIV) infection, as well as cyto-
megalovirus infection and toxoplasmosis can cause a similar syndrome.
Case Study 42 137
What is unusual about this presentation is fever that remits for a few days
and then relapses. This suggests the possibility that this patient has an in-
fection that is associated with a cycle of waxing and waning in the number of
organisms in the host or of clinical manifestations being caused by an im-
mune response to the organism. Such infections include malaria, babesiosis,
relapsing fever, and leptospirosis. Therefore a history of exposure to such
pathogens should be sought, including a history about travel and recreational
activities.
Exposure history: This boy was staying in a cabin in the Colorado Rocky
Mountains a few days before his symptoms began. This environment is not
endemic for malaria or babesiosis but is for borrelial relapsing fever.
The type of relapsing fever occurring in the United States, as in this case,
is caused by several species of borrelia, including B. hermsii, B. parkeri, and
B. turicatae. These are transmitted by soft ticks of the genus Ornithodoros
between rodents and human beings. Two types of relapsing fever carry a high
fatality rate. These are caused by B. recurrentis, which is louse-borne, and has
a worldwide distribution, being most prevalent in Africa, and B. duttoni,
which is tick-borne and occurs in East Africa. Both of these borrelia are
transmitted between humans beings and their respective arthropod vectors.
The reason for the relapsing nature of the infection is the phenomenon of
antigenic variation. The organism has the genetic ability to change an
FIG. 42.1. A positive fluorescent antibody test for Borrelia. (From: Cooper RI,
Neuhauser T: Images in clinical medicine. Borreliosis. N Engl J Med 1998; 338: 231.
Copyright 1998. Massachusetts Medical Society. All rights reserved, with permission.)
138 Case Studies in Pediatric Infectious Diseases
antigenic coat protein, called variant major protein, so that, as the host
makes antibodies to the organismand the clinical illness remits, the antigenic
surface of the organism changes and its numbers rise, causing a relapse of
clinical symptoms. Each successive relapse becomes milder.
The diagnosis can be made by examination of a Giemsa-stained blood
smear on which spirochetes can be seen. The sensitivity of this test is,
however, only about 50%. This is increased by the use of fluorescent anti-
body staining of the blood smear (Figure 42.1).
Serological tests can also be performed. Several drugs can be used to treat
such patients, including penicillin, macrolides, and tetracyclines. It is impor-
tant to note that patients may experience the Jarisch-Herxheimer reaction,
characterized by high fever, chills, and hypotension, after initiation of ther-
apy. They should therefore be monitored for about 12 hours after initiation
of therapy.
Reading:
Dworkin MS, Schwan TG: Anderson DE: Tick-borne relapsing fever in
North America. Med Clin N Am 2002; 86: 417433.
n
CASE 43 (HYP, based on two reports in the MMWR). Soon after return-
ing from a competition in Borneo, a 20-year-old triathlon athlete presents
with a history of fever, myalgia, and abdominal pain. He improves after
about 3 days, and he concludes that he has had a virus. However, the
illness returns with a vengeance 5 days later, causing very severe headache
and photophobia. On examination he is ill-appearing with neck stiffness,
abdominal tenderness, muscle tenderness, and a macular rash.
What is your differential diagnosis?
What would you do?
In patients with simultaneous potential exposures to multiple infectious
agents, such as living in the tropics and exposure to unclean fresh water, as
is the case in this patient, one should consider the possibility that the patient
has more than one illness, with one illness not necessarily explaining
all the clinical features. Although he has evidence of a systemic disease,
there is evidence of focal infection in the meninges. The differential
diagnosis should include arbovirus infection, in particular dengue, entero-
virus infection, meningococcal meningitis and bacteremia, typhoid fever,
leptospirosis, malaria, the early stage of schistosomiasis, acute human im-
munodeficiency virus (HIV) infection, and rickettsial infection. Of these,
enterovirus infections and leptospirosis may have a biphasic pattern of fever,
Case Study 43 139
while malaria has a multiphasic pattern. Schistosomiasis is not endemic in
Borneo.
The following tests should be performed, in order of their priority in
contributing to the management of the patient:
Lumbar puncture with Gram stain and culture of the cerebrospinal fluid;
Blood smears for malaria;
Blood culture for Salmonella typhi and Neisseria meningitidis;
Serology for dengue (Culture of blood for the virus can be performed but is
rarely available.). Serology for Leptospira interrogans (Blood can be cultured
in the early phase of infection and urine in the later phase; however, special
medium is required.).
Treatment should be directed at the likely causes of illness after the initial
test results have become available. This should consist of a combination of
doxycycline, for its activity against Leptospira interrogans and rickettsiae,
and a third-generation cephalosporin, such as ceftriaxone or cefotaxime,
for its activity against Neisseria meningitidis and Salmonella typhi. Once cul-
ture results have become available, therapy can be adjusted. Serological test
results may not be available for days or weeks.
This patient had leptospirosis. This is often a biphasic illness, affecting
many organ systems. The illness is characterized initially by fever, myalgia,
headache, abdominal pain, vomiting and diarrhea and conjunctival injection.
In the later stage meningitis, kidney, liver, and pulmonary disease may occur.
The causative organismis a spirochete, Leptospira interrogans, of which there
are many serovars, that causing the most severe disease being serovar L.
icterohaemorrhagiae. Leptospira organisms are excreted in the urine of ani-
mals, such as dogs and rodents. Bodies of water are often the sites of urinary
contamination, and thus frequently the source of infection. In athletic events
such as the one described many individuals are often infected. Penicillin or
doxycycline are the preferred treatments.
Readings:
Katz AR, Ansdell VE, Effler PVet al: Assessment of the clinical presentation
and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii,
19741998. Clin Infect Dis 2001; 33: 18341840.
Kaul DR, Flanders SA, Saint S: Clear as mud. N Engl J Med 2005; 352:
19141918.
CDC: Public health dispatch: outbreak of acute febrile illness among partici-
pants in EcoChallenge Sabah 2000 Malaysia, 2000. MMWR2000; 49: 816817.
140 Case Studies in Pediatric Infectious Diseases
CDC: Update: outbreak of acute febrile illness among participants in Eco-
Challenge-Sabah 2000-Borneo, Malaysia, 2000. MMWR 2001; 50: 2124.
CDC: Update: leptospirosis and unexplained acute febrile illness among
athletes participating in triathlons Illinois and Wisconsin, 1998. MMWR
1998; 47: 673 676.
n
CASE 44 (HYP). A 13-year-old boy presents with a history of a painful
left knee. On examination he has a swollen, tender left knee with slight
limitation of movement. He is afebrile. The rest of his examination is normal.
What is your differential diagnosis?
What else would you like to know?
What would you like to do?
This boy has acute arthritis. The differential diagnosis includes:
traumatic hemarthrosis there is no history of trauma;
septic arthritis unlikely in view of the lack of fever;
acute rheumatic fever;
rheumatoid arthritis;
reactive arthritis following an enteric infection there is no history of a
recent infection, except that there is a history of a large red area on his skin
about 2 months ago;
Lyme disease he lives in Connecticut, where he walks in the woods fre-
quently. This exposure history and the history of a skin lesion makes Lyme
disease very likely, likely enough to provide treatment with doxycycline or
amoxicillin for 1 month. The diagnosis can be confirmed serologically.
Lyme disease is caused by the spirochete Borrelia burgdorferi. It is trans-
mitted to human beings by ticks of the genus Ixodes. (I. scapularis in the
eastern US, and I. pacificus in the western US.) Reservoir hosts are mainly
rodents and deer. The clinical illness occurs in two overlapping phases:
(a) Early stage (<8 weeks after exposure): the most characteristic clinical fea-
ture and that most useful in the diagnosis is erythema chronicum migrans.
This is a skin lesion characterized by an area of erythema without eleva-
tion extending for several centimeters fromthe site of the tick bite. It may
develop central clearing (Figure 44.1). There may be associated itching or
a burning sensation in the area. Mild constitutional symptoms may occur.
Disseminated disease is manifested by the following:
(i) Multiple skin lesions of erythema chronicum migrans;
Case Study 44 141
(ii) Neurological disease manifesting with cranial nerve palsies, espe-
cially of the facial nerve, other neuropathies, aseptic meningitis,
optic neuritis, and encephalitis;
(iii) Heart disease, usually manifesting with conduction abnormalities
such as heart block. This constitutes the only potential cause of
death in cases of Lyme disease.
(b) Late stage (> 8 weeks after exposure):
(i) Arthritis: this may occur during the early stage. It presents acutely,
but may become chronic or have a waxing and waning course. It
affects mainly large joints, especially the knee.
(ii) Late neurological disease: the manifestations are cognitive deficits,
peripheral neuropathies, and low-grade encephalopathy. This is rare
in children and difficult to diagnose.
FIG. 44.1. Erythema chro-
nicummigrans. (From: Smith
RP, Schoen RT, Rahn DW
et al: Clinical characteristics
and treatment outcome of
early Lyme disease in
patients with microbiologi-
cally confirmed erythema
migrans. Ann Intern Med
2002; 136: 421428, with
permission.)
142 Case Studies in Pediatric Infectious Diseases
The diagnosis of Lyme disease is based on a history of exposure, clinical
manifestations (arthritis following a history highly suggestive of erythema
chronicum migrans is sufficient to make the diagnosis), and sometimes
serological tests. Although the organism can be detected by culture and
polymerase chain reaction (PCR), this testing is not widely available. There-
fore testing largely depends on serology. Serological tests can be very mis-
leading and should not be undertaken for screening, because in situations
in which the pretest probability of infection is low, a positive test is very
likely to be a false-positive. Positive ELISA tests must be followed by a
Western blot test, which is more specific.
The recommended treatment of Lyme disease depends on the stage and
the type of involvement. In most situations children should be treated with
amoxicillin (or doxycycline in those older than 8 years). In those with neu-
rological disease (other than isolated facial nerve palsy) ceftriaxone should
be used.
Prevention depends on avoidance of tick bites and removal of ticks from
the skin (transmission occurs only after about 24 hours of tick attachment).
Reading:
Sood SK: Lyme disease. Pediatr Infect Dis J 1999; 18: 913925.
n
CASE 45. A 12-year-old girl presents with a history of severe abdominal
pain and fever for 2 days. On examination she is in significant pain and
febrile. There is no specific area of abdominal tenderness, but the liver
and spleen are enlarged. There is also marked enlargement and tenderness
of a left axillary lymph node, and a healed sore on the dorsum of her left
hand.
What is your differential diagnosis?
What more would you like to know?
What would you do?
This patient clearly has a systemic disease, based on the enlargement of
the liver and spleen. Fever, abdominal pain, and hepatosplenomegaly should
suggest the diagnostic possibilities of typhoid fever, infectious mononucle-
osis, and leukemia or lymphoma. However, neither typhoid fever nor
infectious mononucleosis is associated with localized lymphadenopathy. Lo-
calized lymphadenopathy, which is tender indicates lymphadenitis, which
suggests an infection occurring in the areas drained by the node. These are
the upper limb and chest wall in the case of an axillary node. The sore on the
left hand might well have been the site of inoculation of an infectious agent.
Case Study 45 143
The most common infections causing this are staphylococcal and strepto-
coccal infections of the skin. Systemic infections associated with these organ-
isms would imply bacteremia, with or without infective endocarditis, in
which case the patient would appear very ill. Infective endocarditis may
be associated with splenomegaly but not hepatomegaly, unless heart failure
is present. Infections associated with localized lymphadenopathy and evi-
dence of systemic infection include cat-scratch disease, tularemia, and
plague. Plague is associated with marked toxicity and not associated with
enlargement of the liver and spleen. The bacteremic (typhoidal) form of
tularemia may be associated with such visceromegaly. Cat-scratch disease,
which is caused by Bartonella henselae, usually manifests with localized
lymphadenopathy and, in cases with the hepatosplenic form, is associated
with enlargement of liver or spleen. This form may be associated with severe
abdominal pain.
Considering the above differential diagnosis, obtaining a history of possi-
ble risk factors for these infections is very important. The questions should
address the following: Has there been exposure to any animals (asking
whether the family has pets may not adequately address this question),
and what has been the nature of the exposure? Has the patient been exposed
to arthropods (fleas, ticks)? Has she traveled to areas where plague is
endemic (southwestern United States, Africa, Asia, South America)?
Further history from this patient revealed that she has several cats and has
been scratched frequently. This illness was preceded by the presence of
a pustule on the left hand. A clinical diagnosis of cat-scratch disease with
hepatosplenic involvement was therefore made.
The diagnosis of cat-scratch disease can be confirmed by the demonstra-
tion of antibodies against the causative organism, Bartonella henselae. In cases
with hepatosplenic involvement focal lesions can often be demonstrated in
these organs by ultrasound or computer tomography (CT), as was the case in
this patient. The CT appearance of the liver in hepatosplenic cat-scratch
disease in such a patient is shown in Figure 45.1.
Cat-scratch disease is usually self-limited, but it can be associated with
severe complications, including an encephalopathy (associated with seiz-
ures), retinitis (Figure 45.2), and osteomyelitis. It is an important cause of
prolonged unexplained fever in children. In such cases treatment is worth
trying, although it may not prove successful. Antimicrobial agents that are
sometimes effective include gentamicin, trimethoprim/sulfamethoxazole
plus rifampin, a fluoroquinolone, and azithromycin. The only controlled
trial for the treatment of patients with cat-scratch disease has demonstrated
that lymphadenitis improves more rapidly in patients treated with azithro-
mycin than in those treated with a placebo.
144 Case Studies in Pediatric Infectious Diseases
FIG. 45.1. CT scan of another patient showing multiple microabscesses in the liver
due to cat-scratch disease. (Courtesy of Dr Gillian Sherbourne)
FIG. 45.2. The retinitis and optic neuritis associated with cat-scratch disease.
Note the blurring of the disc margin and the radial streaking around the macula.
(Courtesy of Hans Grossniklaus, MD, Emory University)
Case Study 45 145
Bartonella henselae also causes bacillary angiomatosis, which is character-
ized by wart-like vascular lesions, in immunocompromised individuals, such
as those with AIDS. The possibility of the elaboration of an angiogenic
substance by this organism is particularly interesting. Bartonella bacilliformis,
the first recognized bartonella species, is transmitted by flies and infects
erythrocytes causing Oroya fever (Carrions disease), which is endemic
in parts of the Andes Mountain range. This infection is characterized by a
hemolytic anemia, followed by the development of hemangioma-like
lesions, called verruga peruana.
Reading:
Bass JW, Vincent JM, Person DA: The expanding spectrum of Bartonella
infections: II. Cat-scratch disease. Pediatr Infect Dis J 1997; 16: 163179.
Loutit JS: Bartonella infections. Curr Clin Topics Infect Dis 1997; 17:
269290.
n
CASE 46. An 18-month-old boy presents with a history of rash and fever
for about 1 week. He was seen by his primary care doctor during this illness
and diagnosed with a viral exanthem. His general condition has deterio-
rated. On examination he is febrile, ill-appearing, extremely irritable, and
he has a generalized petechial rash as shown in the pictures (Figures 46.1
and 46.2). The rest of his examination is normal.
FIG. 46.1. The childs rash.
146 Case Studies in Pediatric Infectious Diseases
What might be wrong with him?
What would you do?
Differential diagnosis:
(a) The most imminently life-threatening condition that this might be is
meningococcal bacteremia and meningitis. This diagnosis is unlikely,
however, because the history of a week is a long period for this child to
have had this infection without his condition having significantly de-
teriorated.
(b) Rocky Mountain spotted fever (infection with Rickettsia rickettsii):
Although this disease usually begins with a fever and severe headache,
followed a few days later by the appearance of a rash, typically be-
ginning around the wrists and ankles, the progression of this childs
illness, especially considering the evidence of brain disease (extreme
irritability), strongly suggests this diagnosis.
(c) Ehrlichiosis: These are tick-transmitted infections, caused by Ehrli-
chia chaffeensis, Anaplasma phagocytophilum, and Ehrlichia ewingii,
which cause systemic disease febrile illness, often associated with
leukopenia, thrombocytopenia, and elevated hepatic transaminases.
Treatment is the same as for rickettsial disease (see below).
FIG. 46.2. The childs rash and an echymosis, partially covered by a bandage,
on the left heel.
Case Study 46 147
(d) Viral exanthems, including rubella, parvovirus infection, and human
herpes virus 6 and human herpes virus 7 infections are possible but
unlikely given the progressive nature of this childs illness. Further-
more, the rashes in these conditions are macular (blanching), except
for the petechial rash occurring in a glove and stocking distribution
sometimes associated with parvovirus infection. Measles does not
cause a petechial rash and is associated with very prominent respira-
tory tract symptoms.
Management: After blood cultures have been drawn, treatment with both
ceftriaxone (for its activity against Neisseria meningitidis) and doxycycline
(for its activity against Rickettsia rickettsii) should be initiated immediately.
This child was treated with ceftriaxone and doxycycline. He developed seiz-
ures within a few hours of admission to hospital and a hemiplegia, but he sur-
vived. The diagnosis of Rocky Mountain spotted fever was later confirmed.
Rickettsiae are small Gram-negative bacilli that can multiple only intra-
cellularly. They are transmitted by arthropods, in most cases by ticks. There
are three groups of rickettsial diseases:
(a) Typhus group consisting of R. prowazekii, the cause of epidemic typhus,
which is louse-borne, and R. mooseri (typhi), the cause of endemic
typhus, which is flea-borne.
(b) Spotted fever group: Most areas of the world have their peculiar spotted
fever rickettsia, for example R. rickettsii (Rocky Mountain spotted fever
the Americas), R. conori (Mediterranean spotted fever), R. africae (African
tick bite fever), R. sibirica (northern Asia), and R . australis (Australia).
(c) Rickettsialpox (R. akari)
R. rickettsii is present in Canada, the United States, Mexico, Central
America, and South America. In the United States, it is most prevalent in
the southeastern and southern states, where it is transmitted by species of
Dermacentor, the dog tick.
The diagnosis of Rocky Mountain spotted fever is, for management pur-
poses, a clinical one. There is currently no readily available, rapid, and sen-
sitive laboratory test that is useful for diagnosing this infection, or, more
importantly, for excluding this diagnosis. Laboratory tests such as serum
sodium concentration and platelet count can be misleading and their value
lies only in evaluating the patient for physiological disturbances. Untreated
patients have a case fatality rate of about 10%. Only a minority of patients
have a known history of a tick bite. Therefore, when Rocky Mountain spot-
ted fever is suspected, treatment with a tetracycline MUST be instituted
immediately. Doxycycline is usually used. Although there may be concern
148 Case Studies in Pediatric Infectious Diseases
about staining of the teeth in children younger than 9 years, this is a minor
concern with a 57 day course, and should NOT deter one from prescribing
this agent in children of any age. Rickettsiae invade endothelial cells, and
therefore the infection can affect every organ, including the brain, heart,
lungs, liver, and kidneys (Figure 46.3).
The diagnosis can be confirmed serologically in retrospect, using acute
and convalescent sera. This information is only of epidemiological value, and
of no value to the patient.
Reading:
Sexton DJ, Kaye KS: Rocky Mountain spotted fever. Med Clin N Am 2002;
86: 351359.
Dumler JS, Walker DH: Rocky Mountain spotted fever changing ecology
and persisting virulence. N Engl J Med 2005; 353: 551553.
n
CASE 47. (Adapted from the patients account) A 24-year-old man
presents with a history of severe headache, fever, myalgia, and abdominal
pain, followed after about 5 days by the development of a rash, which
started on his upper trunk and then spread to his limbs. Examination
FIG. 46.3. An electron
micrograph of a cross
section of a capillary with
rickettsiae (in this case
Orientia tsutsugamushi).
(Courtesy of the Centers
for Disease Control and
Prevention/Dr Edwin P
Ewing, Jr)
Case Study 47 149
confirms these findings. The rash is maculopapular, petechial in areas, and
widespread, sparing his face, palms, and soles.
What is your differential diagnosis?
What would you like to know?
The differential diagnosis includes meningococcal disease, rickettsial
infection, a systemic viral infection such as West Nile virus infection and
dengue, acute human immunodeficiency virus (HIV) infection, leptospirosis,
and syphilis.
Young, presumably healthy, adults are not at great risk for the develop-
ment of infectious diseases unless they have had specific exposures such as
animal, arthropod, geographic, environmental, occupational, and recrea-
tional, including sexual. The exposure history is therefore very important.
This patients history is that one of his coworkers had developed a similar
illness a few days earlier. Their occupations were working in a microbiology
laboratory, making vaccine against Rickettsia prowazekii, the cause of
epidemic typhus.
The diagnosis in this patient was laboratory-acquired epidemic typhus.
He recovered without antimicrobial therapy, which was not available at the
time (about 1943).
Epidemic typhus is a disease that has had a significant impact on human
history. It is transmitted by the body louse, Pediculus humanus corporis
(Figure 47.1), the infestation of which is associated with crowded living
conditions, particularly during wars. The louse lives and lays its eggs (nits)
in clothing (Figure 47.2).
FIG. 47.1. A body louse
(Pediculus humanus
corporis). (Courtesy of the
Centers for Disease Control
and Prevention)
150 Case Studies in Pediatric Infectious Diseases
It depends on blood meals from the human host and transmits the
infection through its feces. The infection is characterized, as in this case,
by fever, headache, myalgia, conjunctival injection, rash, which may be
petechial, and mental status changes, which accounts for the name (from
the Greek for stupor). The rickettsial organism can remain dormant in the
human host for many years after he or she has recovered from the infection
and cause a recrudescence, called Brill-Zinsser disease. If such a host is
infested with body lice, an outbreak can be initiated. The diagnosis is gen-
erally made clinically, and the treatment is doxycycline. Even a single dose of
this drug can be effective.
Reading:
Raoult D, Woodward T, Dumler JS: The history of epidemic typhus. Infect
Dis Clin N Am 2004; 18: 127140.
Raoult D, Roux V: The body louse as a vector of reemerging human diseases.
Clin Infect Dis 1999; 29: 888911.
n
CASE 48. A 13-year-old girl presents with a history of a painful left eye.
There is no history of trauma or foreign body entering the eye. There is no
significant past medical history. On examination she has photophobia,
marked conjunctival injection, and some corneal clouding on the left. Her
FIG. 47.2. Nits of the body louse in clothing. (Courtesy of Reed and Carnrick
Pharmaceuticals)
Case Study 48 151
visual acuity is markedly decreased on the left and slightly decreased on the
right. She is also noted to have a swollen left knee, which contains fluid, but
which is not painful, and which does not have limitation of movement. Her
teeth have an unusual shape (Figure 48.1).
What is your differential diagnosis?
How would you manage this patient?
The combination of a painful, red eye and photophobia suggests corneal
inflammation (keratitis) and/or anterior uveitis (iridocyclitis), not merely
conjunctivitis. Keratitis is confirmed by the presence of corneal clouding.
Keratitis can cause significant visual impairment, and such patients should be
referred to an ophthalmologist immediately. In the absence of trauma or
a foreign body, it is usually due to a virus infection, in particular herpes
simplex virus. Herpes simplex keratitis may have a suggestive appearance,
with the corneal ulcer having a serpiginous outline (dendritic ulcer). The
joint effusion might have been caused by trauma or reaction to an infection,
such as parvovirus or an enteric infection. There was no history to suggest
that one of these preceding events had occurred.
Examination by the ophthalmologist revealed bilateral interstitial keratitis.
This can be caused by untreated congenital syphilis. Therefore a Rapid
Plasma Reagin (RPR) test was performed, which was strongly positive, sug-
gesting the diagnosis of syphilis. The diagnosis of syphilis was confirmed by
a positive treponemal test. The joint effusion probably represented a Clut-
tons joint, also a manifestation of late, untreated congenital syphilis.
She was treated with corticosteroid eyedrops and intravenous penicillin
for 10 days, and her mother was referred to the health department for man-
agement and contact tracing. Her eyes improved markedly. Her notched
upper incisors are called Hutchinsons teeth, also a manifestation of
late congenital syphilis. The molars may have multiple cusps, giving rise to
the name mulberry molars. The combination of interstitial keratitis,
FIG. 48.1. The small teeth,
with notching of the
upper central incisors.
152 Case Studies in Pediatric Infectious Diseases
Hutchinsons teeth, and sensorineural deafness (which she did not have)
constitutes Hutchinsons triad of manifestations of late congenital syphilis.
Patients with congenital syphilis may progress to develop tertiary syphilis,
the manifestations of which are cardiovascular (aortitis of the ascending
aorta) and cerebral (tabes dorsalis and dementia).
Other manifestations of late congenital syphilis include frontal bossing of
Parrot and saber shins, due to localized periostitis; rhagades, which are linear
scars radiating from the corners of the eyes and mouth; and consequences of
nasal inflammation, including saddle nose and short maxilla.
Reading:
Fiumara NJ, Lessell S: Manifestations of late congenital syphilis. An analysis
of 271 patients. Arch Derm 1970; 102: 7883.
n
CASE 49. An 18-month-old boy presents with a limp and fever for 1 day.
He has had no previous significant illnesses. He is fully immunized with oral
polio, diphtheria, tetanus and pertussis, Haemophilus influenzae type b,
measles, mumps and rubella, and hepatitis B vaccines. On examination
there is fever and a swollen, slightly red knee joint with markedly limited
range of movement. A diagnostic knee tap is performed, which reveals
turbid fluid. The fluid has 5 3 10
4
leukocytes per microliter and a negative
Gram stain. The child is treated with antibiotics. After 2 days a Gram-
negative rod is grown from the knee fluid.
What is the diagnosis and the likely causative organism?
This child has septic arthritis of the knee. Prior to the advent of the
vaccine against Haemophilus influenzae type b, this organism, a small, pleo-
morphic Gram-negative rod, was a common cause of septic arthritis in young
children. In communities in which the children have received this vaccine,
this infection has become very rare. Therefore, in this child, although
H. influenzae should be considered (which would render this a case of
vaccine failure), one should consider other Gram-negative rods, including
enteric rods, particularly Salmonella spp. An organism that has become
prominent as a cause of both septic arthritis and osteomyelitis in young
children is Kingella kingae. This organism is one of the HACEK group of
organisms, which constitute part of the normal oral flora and which should
be considered as causes of infective endocarditis. They are
Haemophilus aphrophilus
Actinobacillus actinomycetemcomitans
Case Study 49 153
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae
Kingella kingae is usually susceptible to all b-lactam antibiotics, although
some strains have been shown to elaborate a b-lactamase. The treatment
of children with skeletal infections caused by this organism should consist
of amoxicillin/clavulanic acid, or a third-generation cephalosporin.
This child had septic arthritis caused by Kingella kingae, and he responded
well to therapy with amoxicillin.
Reading:
Moylett EH, Rossmann SN, Epps HR, Demmler GJ: Importance of Kingella
kingae as a pediatric pathogen in the United States. Pediatr Infect Dis J 2000;
19: 262265
Lundy DW, Kehl DK: Increasing prevalence of Kingella kingae in osteoartic-
ular infections in young children. J Pediatr Orthop 1998; 18: 262267.
n
CASE 50. A 3-year-old boy presents with a 1-week history of fever and
headache. These symptoms started 1 week after he had returned from
a visit to a rural part of South Africa with an altitude of about 5000 feet.
On examination he is febrile, he has enlargement of the liver and spleen, and
he has a few blanching pink spots on his abdomen and chest (Figure 50.1).
There is no lymphadenopathy, and the rest of his examination is normal.
What is the differential diagnosis?
What would you do?
Fever and enlargement of the liver and spleen in the absence of jaundice
are features of the following:
(A) Infectious diseases:
(i) viral: infectious mononucleosis caused by EpsteinBarr virus, cyto-
megalovirus, and acute human immunodeficiency virus (HIV) in-
fection, (which would likely imply sexual molestation in this child);
(ii) bacterial: subacute systemic bacterial infections such as typhoid
fever and infective endocarditis (in which case the hepatomegaly
would be due to heart failure) and chronic systemic bacterial infec-
tions such as tuberculosis (miliary) and brucellosis;
154 Case Studies in Pediatric Infectious Diseases
(iii) parasitic infections: malaria, toxoplasmosis, and the early egg-laying
stage of schistosomiasis;
(iv) fungal: systemic fungal infections such as histoplasmosis.
A rash can occur in patients with infectious mononucleosis, especially if
they have received ampicillin or amoxicillin; however, it is not a feature of
tuberculosis, brucellosis or malaria. The spots occurring in infective endo-
carditis are nonblanching and are most marked peripherally. The high alti-
tude where this patient has visited would be an unlikely area for malaria
transmission. The migrating stage of schistosomiasis is associated with
a marked blood eosinophilia, which can readily be demonstrated.
(B) Noninfective conditions, including leukemia, lymphoma, and juvenile
rheumatoid disease.
Appropriate tests would be a blood count with differential count, blood
culture, and a chest X ray. Depending on their findings, serological tests
might be indicated.
This patients blood culture grewout a Gram-negative bacillus, which was
identified as Salmonella typhi, the cause of typhoid fever.
Typhoid fever is a common food and water-borne infection in many parts
of the world. It is spread by the fecaloral route. After the organism is
ingested, it multiplies in the lymphoid tissue of the small bowel, then
spreads, via the mesenteric nodes, to the reticuloendothelial system, where
its numbers are amplified. It continues to multiply in the lymphoid tissue of
the small bowel eventually causing ileal ulcers. Clinical symptoms begin
when the organism, having multiplied in the reticuloendothelial system,
spills into the bloodstream (secondary bacteremia). Clinical features include
fever, abdominal pain and diffuse abdominal tenderness, enlargement of the
liver (particularly in children) and spleen, and slight clouding of conscious-
ness. At the time of acquisition of the infection diarrhea may occur, and after
23 weeks this becomes a prominent feature. The main complications of
typhoid fever are related to ulceration of the bowel, namely bowel hemor-
rhage and perforation.
Other complications include encephalopathy (the origin of the term
typhoid is from the Greek for stupor), pneumonia, myocarditis, and Zenkers
degeneration of muscle.
This diagnosis should always be considered in febrile patients from Latin
America, Asia, or Africa. The diagnosis is best confirmed by blood culture.
Stool culture becomes positive after 23 weeks of illness. Serology (Widal
test) can be helpful but is less so in individuals who have lived in endemic
areas.
Case Study 50 155
In the past, antibiotic therapy consisted of amoxicillin, trimethoprim/
sulfamethoxazole, or chloramphenicol. However, due to the high rates of
resistance to these drugs, a fluoroquinolone or ceftriaxone should be used
until antibiotic susceptibilities are known. Despite appropriate therapy
relapse of illness can occur.
The diagnosis of typhoid fever carries important public health implica-
tions. The causative organism is strictly a human pathogen. Therefore cases
should be notified to the health department, so that a source can be identi-
fied. Such a source may be an asymptomatic intestinal carrier. Long-term
excretion is due to colonization of the liver or gallbladder. This occurs more
frequently in adults than in children.
Hospitalized patients should be nursed with contact precautions.
Reading:
Parry CM, Hien TT, Dougan G et al: Medical progress: typhoid fever. N Engl
J Med 2002; 347: 17701782.
Bhan MK, Bahl R, Bhatnagar S: Typhoid and paratyphoid fever. Lancet 2005;
366: 749762.
FIG. 50.1. The spots and markings of the liver and spleen edges.
156 Case Studies in Pediatric Infectious Diseases
Basnaya B, Maskey AP, Zimmerman MD, Murdoch DR: Enteric (typhoid)
fever in travelers. Clin Infect Dis 2005; 41: 14671472.
n
CASE 51. A 1-month-old infant presents with a history of poor feeding
and generally appearing ill to the parents. They think he looks a little yellow
and his urine is darker than usual. On examination he is ill-appearing, and
afebrile. His sclerae are yellowish-green in color. There is enlargement of the
liver, but not of the spleen. There is no pallor. The rest of his examination is
normal. The urine is indeed dark.
What is the most imminently life-threatening diagnosis?
This infant has evidence of biliary tract obstruction based on greenish
jaundice and dark urine. The differential diagnosis includes the following:
(A) Hepatitis caused by:
Infections:
(a) intrauterine infections: cytomegalovirus infection; rubella; toxoplas-
mosis; syphilis;
(b) hepatitis viruses: these do not usually cause clinical hepatitis in
infants of this age, and the incubation period is too short for post-
natally acquired hepatitis B or C;
(c) sepsis syndrome, in particular urosepsis caused by enteric bacilli
such as Escherichia coli;
(d) neonatal hepatitis of unknown etiology;
(B) Metabolic diseases: galactosemia, tyrosinemia, a-1-antitrypsin defi-
ciency, hypothyroidism
(C) Biliary atresia
(D) Choledochal cyst
Among these conditions, the only one that is imminently life threatening
is urosepsis due to Escherichia coli. Therefore the investigation of such cases
must include blood and urine cultures to exclude this condition. Urinalysis
and urine microscopy and Gram stain are rapid diagnostic tests that can be
used to guide decisions about therapy. The fact that this child is ill-appearing
suggests that he might have the sepsis syndrome and that empiric antimi-
crobial therapy should be initiated immediately with an agent such as
a third-generation cephalosporin. Meningitis should also be considered.
Case Study 51 157
Reading:
Seeler RA, Hahn K: Jaundice in urinary tract infection in infancy. Am J Dis
Child 1969; 118: 553558.
n
CASE 52. A 12-year-old girl has had fever for 1 week. About 1 month
ago she had severe abdominal pain and fever, which improved after she had
been treated with amoxicillin/clavulanic acid for a few days. On examina-
tion she has fever and looks mildly ill. She has some central abdominal
tenderness, but no other abnormal physical findings. Blood cultures, per-
formed because of the prolonged fever, have grown a Gram-negative rod
and Gram-positive cocci in pairs.
What organ is the likely source of the bacteremia?
What is the likely diagnosis?
What are the likely identities of the isolates?
The isolation of two organisms from the blood (polymicrobial bacter-
emia) suggests that the bacteremia arose from a mucosal surface. The mor-
phology of these isolates suggests the likelihood of an enteric rod and
a streptococcus. This suggests, in turn, that the source of infection is the
intestine. In a child with no history given of underlying disease, but a history
FIG. 52.1. Gallium scan
showing increased intra-
abdominal uptake due to an
appendix abscess. (Courtesy
of Dr Andrew Wiesenthal)
158 Case Studies in Pediatric Infectious Diseases
of severe abdominal pain recently, the most likely diagnosis is a perforated
appendix, leading to a focal abscess. This child underwent a Gallium-
scan study, which showed an area of increased uptake in the abdomen
(Figure 52.1).
An appendix abscess was confirmed at surgery. The antimicrobial therapy
that she received initially (amoxicillin/clavulanic acid) has broad-spectrum
activity, including activity against E. coli and enterococci (which were the
identities of the organisms isolated from the blood cultures), and anaerobes.
Therefore it is likely that the initial infection following the appendiceal
perforation had been suppressed by amoxicillin/clavulanic acid and had
flared up after the antimicrobial effects of this agent had waned.
Reading:
Solemkin JS, Mazuski JF, Baron EJ et al: Guidelines for the selection of anti-
infective agents for complicated intra-abdominal infections. Clin Infect Dis
2003; 37: 9991005.
n
CASE 53. A 16-year-old boy presents with an annoying cough, which
he has had for about 3 weeks. The illness started with a runny nose. On
examination he is completely normal, but he exhibits several episodes of
severe coughing.
What is the differential diagnosis?
What would you do?
Differential diagnosis:
Respiratory tract infection:
Virus:
Adenovirus
Other respiratory viruses
Bacteria:
Mycoplasma pneumoniae
Chlamydia pneumoniae
Bordetella pertussis
Mycobacterium tuberculosis
Fungal:
Histoplasma capsulatum
Other dimorphic fungi
Noninfectious diseases:
Asthma
Foreign body inhalation
Case Study 53 159
The course of this childs illness, beginning with a runny nose, followed
by episodes of severe coughing, suggests a respiratory tract infection. This
clinical picture, in particular the 3-week duration of the cough, is highly
suggestive of pertussis (whooping cough). Pertussis is a severe, contagious
infection that causes significant morbidity and mortality worldwide. It is
caused by the small Gram-negative bacillus, Bordetella pertussis. This organ-
ism becomes attached to the columnar epithelium of the respiratory tract
causing effacement of the brush border and necrosis of epithelial cells, result-
ing in the accumulation of debris within the airway. Pertussis causes mainly
bronchitis, but pneumonia may also occur. Classic pertussis has three clinical
stages: (a) the catarrhal stage, characterized by a runny nose, which is
indistinguishable fromthat of the common cold. This is followed after about
a week by (b) the paroxysmal stage, characterized by paroxysms of
FIG. 53.1. A child with a
paroxysmof coughing caused
by pertussis. (Courtesy of the
Centers of Disease Control
and Prevention)
160 Case Studies in Pediatric Infectious Diseases
prolonged cough during which the patient cannot catch his/her breath. At
the end of the paroxysm, air is inspired through a partially closed glottis
resulting in the characteristic whoop. During the paroxysm the patient may
become hypoxic and lose consciousness. Such an attack is frightening to
experience or to witness (Figure 53.1). Young infants may not experience
the coughing paroxysm, but may just become apneic. The paroxysmal stage
lasts for several weeks. This stage is followed by (c) the convalescent stage,
during which the paroxysms become less frequent. If the patient develops
a viral upper respiratory infection during this time paroxysms may recur.
This stage lasts for several weeks.
Complications of pertussis
hypoxia, with hypoxic brain injury;
pneumonia;
bronchiectasis;
death. Most deaths occur in infants younger than 6 months of age and are
due to pneumonia or apnea.
Teenagers and young adults with pertussis often present with a prolonged
cough, as in this case. Although such individuals are not at high risk for
significant morbidity, they pose an important source of spread of the
organism.
Diagnosis: This should be suspected clinically in cases demonstrating the
classic whooping cough. A blood count may reveal an absolute lymphocy-
tosis, which can be very marked. The diagnosis is confirmed by culture
specifically for the causative organism. A nasopharyngeal swab should be
inoculated at the bedside on to a specific selective medium or appropriate
transport medium. A direct fluorescent antibody test can be used. This is
more rapid than culture, but not as specific nor as sensitive as culture. Poly-
merase chain reaction tests of respiratory specimens are also available in
some laboratories.
Treatment: There is no proven treatment for paroxysms, other than arti-
ficial ventilation, which is occasionally necessary. Antimicrobial therapy
consisting of erythromycin, given for 14 days, or azithromycin given for 5
days, is used with the following aims: (a) to abort infection if diagnosed
in the catarrhal stage; (b) to eliminate carriage and thus infectivity in a pa-
tient with the disease; (c) to prevent the development of disease in close
contacts.
Prevention: The most important health intervention regarding pertussis
is active immunization. Pertussis vaccine has had a significantly beneficial
impact on the incidence of this disease. This has been highlighted by the rise
in incidence when vaccination rates have dropped, and the decrease in rates
Case Study 53 161
associated with its widespread use. In the United States, the rates of this
infection prior to vaccination were 450/100,000, while current rates are
12/100,000. The older vaccine is the killed whole cell vaccine. The newer
vaccine, currently used in the United States, is an acellular vaccine composed
of several purified pertussis antigens. This has fewer adverse effects than the
whole cell vaccine. It is combined with tetanus and diphtheria vaccines, the
combination being referred to as DTaP. In the United States, it is adminis-
tered at ages 2, 4, 6, and 1218 months, and at 46 years. Because teenagers
and adults play a major role in the spread of the infection, they should also
receive a vaccine booster, in the form of Tdap (tetanus, diphtheria, and
acellular pertussis vaccine).
All cases of pertussis should be reported to the health department, and
close contacts should be treated with a course of a macrolide antibiotic.
Individuals who are hospitalized should be nursed with droplet precautions.
Reading:
Hewlett E, Edwards KM: Pertussis not just for kids. N Engl J Med 2005;
352: 12151222.
Greenberg DP: Pertussis in adolescents. Increasing incidence brings attention
to the need for booster immunization of adolescents. Pediatr Infect Dis J
2005; 24: 721728.
Halperin SA: Pertussis a disease and vaccine for all ages. N Engl J Med
2005; 353: 16151617.
Crowcroft NS, Pebody RG: Recent developments in pertussis. Lancet 2006;
367: 19261936.
n
CASE 54 (HYP). A 10-year-old boy develops a tender swelling in his
right armpit, and fever. On examination he is toxic-appearing and has
a large, red, tender lymph node in his right axilla. The rest of the examina-
tion is normal.
What is the differential diagnosis?
What questions would you like to ask?
What would you do?
The clinical diagnosis is one of a suppurative lymphadenitis. The differ-
ential diagnosis relates to its microbial cause. Most cases of suppurative
lymphadenitis are caused by Staphylococcus aureus and Streptococcus
162 Case Studies in Pediatric Infectious Diseases
pyogenes, complicating an infected skin lesion or wound drained by the af-
fected node, in this case on the upper limb or chest wall. The other causes
require specific exposures. These are: Francisella tularensis, the cause of
tularemia, Yersinia pestis, the cause of plague, and Bartonella henselae, the
cause of cat-scratch disease. Since they are all transmitted by animals or
arthropod vectors, obtaining a history of possible exposures to animals is
of the utmost importance. Other questions about exposure are related to
travel, occupation, and recreational activities.
This boy had been hunting in Colorado. He had shot and skinned
a hare.
This information strongly suggests the diagnosis of tularemia. Francisella
tularensis is acquired by direct inoculation from infected material as in this
case, by the bite of an infected tick or fly, by inhalation, or by ingestion of
infected food. There are several clinical syndromes associated with infection
with this organism: glandular or ulceroglandular, as in this patient; oculo-
glandular (Parinauds syndrome); oropharyngeal, characterized by pharyngi-
tis; typhoidal; and pneumonic. The diagnosis of glandular disease can be
confirmed by Gram stain and culture of material from an aspirate of the
lymph node. In this case the laboratory personnel should be made aware of
the suspicion of tularemia, which poses a laboratory hazard, so that appro-
priate precautions can be taken. Serology can also be used. Antimicrobial
therapy should consist of streptomycin or gentamicin.
Reading:
Dennis DT, Inglesby TV, Henderson DA et al: Tularemia as a biological
weapon. Medical and public health management. JAMA 2001; 285:
27632773.
n
CASE 55. A 6-month-old infant presents with a high fever and irritabil-
ity. On examination she looks toxic, is very irritable, and has a bulging
anterior fontanelle. The cerebrospinal fluid reveals the following: leuko-
cytes 1200/ll (95% neutrophils), protein 150 mg/dl, and glucose 24 mg/dl;
the Gram stain is shown in Figure 55.1.
What is the likely diagnosis?
This child has bacterial meningitis. The Gram stain shows pleomorphic
Gram-negative rods, most likely Haemophilus influenzae type b. Prior to the
advent of a vaccine against this organism, this was the most common cause of
Case Study 55 163
bacterial meningitis in children in the United States. This serotype of
Haemophilus influenzae is considered contagious and not part of the normal
pharyngeal flora. It is spread by droplets from one child to another. It colo-
nizes the pharynx whence it enters the bloodstream. From the bloodstream
it can spread to the meninges, joints, pericardium, and other foci. Buccal
cellulitis and periorbital cellulitis are focal infections that may also be caused
by this organism. These invasive infections affect mainly children younger
than 3 years. Acute epiglottitis, a life-threatening disease of the airway,
caused by this organism, affects older children, mainly those 46 years
old. Antimicrobial therapy for patients with haemophilus meningitis con-
sists of a third-generation cephalosporin. Dexamethasone, preferably started
15 minutes before the first dose of antibiotic, reduces the frequency of
neurological sequelae, especially of hearing loss.
Because Haemophilus influenzae type b is contagious, when a case of
invasive disease is diagnosed, the local health department should be notified.
Members of families with a case of invasive haemophilus infection and in
which a child younger than 5 years lives should be offered chemoprophylaxis
with rifampin.
This infection has been largely eliminated in areas where the vaccine
is widely used. The vaccine is a conjugate of the polysaccharide capsule,
a very important virulence factor for the organism, and a protein such as
FIG. 55.1. A Gram stain of the cerebrospinal fluid.
164 Case Studies in Pediatric Infectious Diseases
meningococcal outer membrane protein, a mutant diphtheria toxin or tet-
anus toxoid. It is administered in the first and second years of life.
For further discussion of bacterial meningitis, see Case 27.
Reading:
Peltola H: Worldwide Haemophilus influenzae type b disease are the begin-
ning of the 21st century: global analysis of the disease burden 25 years after
the use of the polysaccharide vaccine and a decade after the advent of
conjugates. Clin Microbiol Rev 2000; 13: 302317.
n
CASE 56. (COMP). A 12-year-old child is in the pediatric intensive care
unit for multiple injuries following a motor vehicle accident. She has been
improving, but on the 8th hospital day she develops a high fever and
becomes hypotensive. On examination she is on a ventilator and receiving
vasopressors. She has an arterial catheter, several venous catheters, and
a urinary catheter in place. There is a red line with swelling extending
proximally from one of the venous catheters.
What is the likely diagnosis?
How would you confirm the diagnosis?
What would you do?
The clinical features of high fever and hypotension suggest septic shock.
This child has many risk factors predisposing her to different nosocomial
infections: (a) vascular catheters, (b) ventilator,; (c) a urinary catheter. This
type of patient is shown in Figure 56.1.
Many such patients have tubes in every natural orifice (mouth, nose,
urethra) except the anus, and tubes in man-made holes. Each of these con-
stitutes a breach in the patients defenses against infection. The examination
of this patient demonstrates a focus of inflammation, namely phlebitis,
which is the likely cause of the childs infection, and which may well have
led to a bloodstream infection. The most common organisms to cause vas-
cular catheter infection are staphylococci (S. aureus and coagulase-negative
staphylococci). In patients who have received antibiotics, Enterococcus spp.
and Candida spp. are also important, as are Gram-negative rods, including
enteric bacilli and Pseudomonas spp.
Management should consist of the following:
(a) Supportive care correct hypotension;
(b) Making a microbiological diagnosis: (i) Culture the blood and urine;
(ii) remove the catheter and culture its tip; milk the vein toward the
Case Study 56 165
exit site of the catheter and collect any fluid (blood or pus) that
emerges. If no material can be obtained in this manner, insert a hypoder-
mic needle percutaneously into the affected area, as if you were drawing
blood, and aspirate. Perform a Gram stain and culture of this material.
(c) Initiate antimicrobial therapy with agents active against the likely patho-
gens. The results of the Gram stain can be very helpful in narrowing the
spectrumof suchtherapy. If noorganismis seen, theninitial therapyshould
be directed against methicillin-resistant staphylococci (with vancomycin)
and hospital-acquired multiresistant Gram-negative rods (e.g. amikacin).
Once culture results are available the therapy may be adjusted. If a yeast is
seen, amphotericin B or fluconazole should be administered.
(d) Surgery: If pus is expressed from the vein, a diagnosis of suppurative
(septic) thrombophlebitis should be made and the affected part of the
vein should be excised.
Although infection of intravascular catheters cannot be totally prevented,
the rate of infection can be reduced by meticulous cleanliness at the time of
catheter insertion and adequate immobilization of the catheter.
n
CASE 57 (HYP). A 10-year-old child who has had many admissions for
episodes of pneumonia in different parts of the lungs, from which she does
FIG. 56.1. A patient such as the one described above.
166 Case Studies in Pediatric Infectious Diseases
not completely recover, presents yet again with a fever and worsening
cough. On examination she is thin, cyanosed without supplemental oxygen,
tachypneic with intercostal retractions, and she has digital clubbing. Her
lungs are hyperinflated, and she has diffuse pulmonary crackles. Her spu-
tum grows very mucoid colonies of a Gram-negative rod. A chest X ray of
such a patient is shown in Figure 57.1.
What is the likely diagnosis?
What is the likely identity of the isolate?
This history suggests that she has a generalized disease of the lungs asso-
ciated with bronchiectasis. The most likely causes are cystic fibrosis and an
immunodeficiency. Bronchiectasis may also complicate other conditions
such as pertussis, measles, adenoviral infections, and tuberculosis. The pres-
ence of very mucoid colonies of a Gram-negative rod suggests mucoid strains
of Pseudomonas aeruginosa that are characteristic of isolates from patients
with cystic fibrosis. Such strains form microcolonies within the lung of such
individuals, rendering the organism impossible to eliminate. Children with
cystic fibrosis initially acquire pneumonia with Haemophilus influenzae and
Staphylococcus aureus, and later develop infections with Pseudomonas aeru-
ginosa. Other pathogens that infect such patients are Burkholderia cepacia,
FIG. 57.1. A chest X ray of
a patient similar to the one
presented.
Case Study 57 167
which portends imminent deterioration of the patients condition, and Sten-
otrophomonas maltophilia.
Management of patients with cystic fibrosis must address several issues,
including the following: malabsorption and malnutrition due to pancreatic
exocrine failure; bronchial obstruction and chronic and recurrent pneumo-
nia, leading to bronchiectasis and cor pulmonale; and living with a severe
chronic illness that results in shortened longevity. Of particular relevance to
this case is the management of a patient with recurrent pneumonia caused by
Pseudomonas aeruginosa. Therapeutic strategies include: treatment of acute
exacerbations (which manifest with increased respiratory symptoms and
crackles on lung examination) with parenteral antipseudomonal antimicro-
bial agents, such as a combination of ceftazidime and tobramycin. With
recurrent use of these agents, resistance often develops. Other suitable
agents are fluoroquinolones and carbapenems. Tobramycin administered
by inhalation is useful in suppressing the growth of the organism. Azithro-
mycin is useful in suppressing the chronic inflammation that results in lung
damage. DNAse administered by inhalation is also of value. It lyses the DNA
derived from the cells involved in the inflammation, which contributes
toward the high viscosity of the sputum and which, in turn, contributes
toward the airway obstruction.
Reading:
Davis PB: Cystic fibrosis. Pediatr Rev 2001; 22: 257264.
Orenstein DM, Winnie GB, Altman H: Cystic fibrosis: a 2002 update.
J Pediatr 2002; 140: 156164.
Lyczak JB, Cannon CL, Pier GB: Lung infections associated with cystic
fibrosis. Clin Microbial Rev 2002; 15: 194222.
Miller MB, Gilligan PH: Laboratory aspects of management of chronic
pulmonary infections in patients with cystic fibrosis. J Clin Microbiol
2003; 41: 40094915.
n
CASE 58. A 4-year-old boy presents with a history of diarrhea, abdom-
inal cramps, and fever starting a few days after he acquired a turtle for a pet.
What is the likely cause of the diarrhea?
This child has acute gastroenteritis (acute infectious diarrhea). The
diagnostic challenge lies in determining its microbiologic cause. Many
168 Case Studies in Pediatric Infectious Diseases
different organisms (viral, bacterial, and protozoal) could have caused this
childs illness. In most circumstances making a microbiological diagnosis is
not very important to the patient. Ensuring adequate hydration is the most
important component of management (see Case 19). The exposure history
suggests very strongly that he has become infected with salmonella, which is
excreted by most reptiles.
A rapid diagnostic test that can help to limit the microbiological differ-
ential diagnosis is the fecal smear stained with methylene blue. If it reveals
many leukocytes (Figure 58.1), an invasive bacterial cause such as Salmonella
spp., Shigella spp., Campylobacter jejuni, or Yersinia enterocolitica is likely.
In such cases the stool should be cultured for these bacteria. The method
of performing the fecal smear test is important. The part of the stool con-
taining mucus, pus, or blood should be smeared thinly on a microscope slide
and allowed to dry. After the methylene blue stain has been applied for
12 minutes, the slide should be rinsed with water, allowed to dry, and
examined.
Nontyphoid salmonellae are excreted by many different animals. Human
beings become infected by ingesting undercooked meat, eggs, unpasteurized
dairy products, and contaminated water. There are over 2500 different sero-
types of these organisms, many having interesting names, including those of
FIG. 58.1. A methylene bluestained fecal smear showing large numbers of
polymorphonuclear leukocytes. This was from a child with enteric infection
caused by both Salmonella enteritidis and Yersinia enterocolitica.
Case Study 58 169
animals (such as S. gallinarum and S. pullorum), of diseases they cause in
animals (such as S. typhimurium and S. choleraesuis), and of cities (such as
S. kaapstad and S. montevideo). Most salmonella infections are characterized
by acute gastroenteritis. Although salmonella bacteremia is not unusual,
metastatic infection is unusual. When it occurs it affects mostly young
infants. Such infections include meningitis, septic arthritis, and osteomyeli-
tis. Patients with sickle cell disease are at particular risk of developing sal-
monella osteomyelitis (Figure 58.2). In parts of the world where a clean
water supply is lacking, intestinal and systemic salmonella infections are very
common.
Antimicrobial therapy of patients with salmonella gastroenteritis does not
hasten recovery but may prolong the duration of excretion of the pathogen.
Therefore it is not usually indicated. However, if systemic infection is sus-
pected, antimicrobial therapy should be used. Because of widespread anti-
microbial resistance, empiric therapy in children should usually consist of
a third-generation cephalosporin. If the isolate is susceptible, amoxicillin or
trimethoprim/sulfamethoxazole should be used. In adults a fluoroquinolone
can be used.
Salmonellae can live within macrophages. They therefore require cell-
mediated immunity for their elimination. Therefore individuals with defects
in this arm of immunity, such as those with AIDS, are at risk for persistent
salmonella infections. Chronic salmonella bacteremia can occur in individ-
uals with schistosomiasis, in which the worm, which lives within venous
plexuses, serves as an infected intravascular foreign body.
Salmonella typhi, which is solely a human pathogen, causes typhoid fever
(see Case 50).
FIG. 58.2. The hand X ray
of a child with sickle cell
disease and chronic
salmonella osteomyelitis of
the second metacarpal.
170 Case Studies in Pediatric Infectious Diseases
Reading:
Stam F, Romkens THE, Hekker TAM et al: Turtle-associated human salmo-
nellosis. Clin Infect Dis 2003; 37: e167169.
n
CASE 59. A 2-year-old boy presents with fever and skin lesions of 1-day
duration. On examination he is febrile and toxic-appearing but not in shock.
There are no localizing findings, except for the skin lesions shown in the
picture (Figure 59.1).
What are these lesions called?
What do they represent?
What organisms should be considered in the microbiological differential
diagnosis?
These skin lesions are called ecthyma gangrenosum. They are metastatic
skin infections complicating bacteremia caused by Gram-negative bacilli, in
particular Pseudomonas aeruginosa, which was the case in this patient. They
are caused by infection of the adventitia of subcutaneous blood vessels. They
resemble the lesions seen in meningococcemia and acute staphylococcal
endocarditis. It is important to aspirate the lesion to get material for Gram
stain and culture, the former of which can give immediate information as to
FIG. 59.1. The childs skin lesions. (Reprinted from: Anderson MG: Pseudomonas
septicaemia and ecthyma gangrenosum. S Afr Med J 1979; 55: 504, with permission.)
Case Study 59 171
whether this is likely caused by a Gram-negative rod, meningococcal, or
staphylococcal infection.
Aspiration is performed as follows: (i) a few drops of nonbacteriostatic,
sterile saline is aspirated into a 10 or 20 ml syringe, using a 21- or 22-gauge
needle (this is to provide enough volume of aspirate to perform the Gram
stain and culture); (ii) the needle is inserted into the lesion and as much
suction as possible is applied for about 30 seconds; usually a drop or two of
blood-stained fluid will be aspirated into the syringe; this fluid is mixed with
the saline, and then a drop is used to prepare a slide for Gram stain, and the
remainder is injected onto a culture swab or into a blood culture bottle.
Antimicrobial treatment should include an aminoglycoside and a beta-
lactam active against Pseudomonas aeruginosa, for example, ceftazidime,
and, if staphylococcal infection is suspected, vancomycin.
Reference
Anderson MG: Pseudomonas septicaemia and ecthyma gangrenosum. S Afr
Med J 1979; 55: 504508.
n
CASE 60. A 13-year-old boy with b-thalassemia major, for which he has
received many blood transfusions, presents with a high fever and malaise, of
1 days duration. He had a mild diarrheal illness a few days earlier. On
examination he is ill-appearing, with a temperature of 38.7C, heart rate
of 140/minute, and blood pressure of 80/40. He is pale, mildly jaundiced
(his usual color), and his face has a slightly greyish color (also his usual
color). His heart is enlarged, and both his liver and spleen are markedly
enlarged (all usual for him).
What is the likely cause of his acute problem?
What is the likely underlying abnormality predisposing himto this problem?
What would you do?
This patients clinical picture suggests that he is in septic shock and that
he might also be significantly anemic.
The immediate management should address ensuring adequate perfu-
sion, with intravenous fluids and adequate hemoglobinization with a blood
transfusion. (A hemoglobin concentration measurement can rapidly deter-
mine whether this is necessary.) The second issue to address is the likely
cause of his septic shock and, based on this, optimal empiric antimicrobial
management.
172 Case Studies in Pediatric Infectious Diseases
This patient has three particular risk factors for infections:
(a) Previous intravenous catheters for blood transfusion. A long-term cen-
tral venous catheter would be a very likely focus of infection. The most
likely causes of infection of such sites are staphylococci.
(b) Blood transfusion: Many infectious agents can be transmitted in blood,
including the following:
(i) Viruses such as hepatitis B and C viruses, human immunodeficiency
virus (HIV), EpsteinBarr virus, cytomegalovirus, and West Nile virus.
(ii) Bacteria, either from the donors blood, for example, Treponema pal-
lidum, or contaminating the blood during collection from the donor.
Since a well or mildly ill bacteremic donor would likely have a very low
concentration of bacteria in the blood, these would likely not grow to
large numbers during refrigeration of the blood. Exceptions are Listeria
monocytogenes and Yersinia enterocolitica, which can multiply in the
cold (this is in fact one of the methods used to selectively culture
Yersinia enterocolitica from feces).
(iii) Protozoa, such as Plasmodium spp., Babesia microti, Trypanosoma cruzi,
Trypanosoma brucei, and Toxoplasma gondii.
(c) Iron overload: This patient is at risk for iron overload, and his greyish
complexion suggests that he indeed has this complication of repeated blood
transfusions. Iron overload predisposes to bacterial infections, in particular
that due to Yersinia enterocolitica. The preceding diarrheal illness might have
been a bacterial enteric infection caused by Salmonella spp., Yersinia enter-
ocolitica, Shigella spp., or Campylobacter jejuni.
Therefore this childs blood should be examined for protozoal parasites
(by blood smear) and cultured for bacteria. Antimicrobial therapy against
Gram-negative bacilli, such as Salmonella spp. and Y. enterocolitica should be
instituted, with, for example, a third-generation cephalosporin and genta-
micin, or with a fluoroquinolone. If a long-term central venous catheter is in
place, vancomycin should also be administered.
Reading:
Berkowitz FE : Hemolysis and infection: categories and mechanisms of their
interrelationship. Rev Infect Dis 1991; 13: 11511162.
Busch MP, Kleinman SH, Nemo GJ: Current and emerging infectious risks
of blood transfusions. JAMA 2003; 289: 959962.
Case Study 60 173
n
CASE 61. Musa Noormohamed, a 3-year-old boy, who has no previous
medical history, presents to a hospital in Colorado, USA, with a history of
fever for approximately 1 months duration. He has undergone many
diagnostic tests, including blood counts, blood cultures, urine cultures,
and intravenous pyelography, but a diagnosis has not been made. On exam-
ination he has a temperature of 38.5C and a slightly tender, enlarged liver.
There is no jaundice, pallor, splenomegaly, or lymphadenopathy, and the
rest of the examination is normal.
What is the differential diagnosis?
How would you make a diagnosis?
The clinical features suggest disease in the liver or gallbladder, most likely
an infection, although cancer, such as hepatoblastoma or lymphoma, would
also be a consideration. Infections of the gallbladder tend to be more acute
than this childs illness suggests and is unlikely in a 3-year-old previously well
boy. Although hepatitis is a consideration, one would expect some jaundice
or a history of jaundice in the presence of an enlarged tender liver. A hepatic
abscess should be considered. This is not usually associated with jaundice.
There are four types of hepatic abscess: (a) pyogenic abscess, which usually
results from hematogenous spread of bacteria either from the systemic cir-
culation (as in staphylococcal bacteremia) or from the portal circulation,
arising, for example, from appendicitis; (b) amebic abscess, resulting from
trophozoites of Entamoeba histolytica, present in the colon, being carried to
the liver in the portal circulation; (c) an abscess forming in a site of hema-
toma within the liver; (d) an abscess complicating ascending cholangitis. The
patients name should suggest the possibility of travel outside the United
States and such a history should be sought. He visited Libya, his native
country, about 1 month before the onset of symptoms. This travel history
increases the probability of an amebic liver abscess. The easiest and least
invasive test to look for this possibility is an abdominal ultrasound of the
liver. The result is shown in Figure 61.1.
This showed a hepatic abscess. Considering his travel history, this was
presumed to be amebic. He was treated with metronidazole and made a rapid
recovery.
Amebiasis is a very important infection with a worldwide distribution. It
is caused by the ameba Entamoeba histolytica. This parasite is transmitted by
the fecaloral route. The infectious form is the cyst, which is formed in the
colon or in the stool of an infected individual. After ingestion in stool-
contaminated food or water, it excysts, and invades the colonic mucosa,
producing ulcers. This is associated with diarrhea, which may be bloody
174 Case Studies in Pediatric Infectious Diseases
(amebic dysentery). These ulcers can extend through the colonic wall,
resulting in colonic perforation, which carries an extremely high fatality rate.
The clinical features of colitis include abdominal tenderness, distension, and,
on rectal examination, a rough mucosa, which feels like sandpaper or cob-
blestones. Other manifestations of colonic disease are toxic megacolon and
ameboma, which is a focal annular area of granulation tissue. The organism
can enter the portal venous blood and spread systemically. This spread is
primarily to the liver, resulting in a liver abscess, as in this patient. Such
abscesses can extend to the surface of the liver and rupture into the perito-
neal cavity, or they may extend through the diaphragminto the pleural space
or the pericardium (Figure 61.2).
The abscess is a collection of liquefied tissue, rather than a pus-filled
cavity. Most cases of amebic liver abscess respond to medical therapy only.
Surgical drainage is indicated only if rupture appears imminent. The diag-
nosis of amebiasis can be confirmed by the detection of erythrophagocytic
amebae in a fresh stool specimen. Because this is difficult to accomplish,
a fresh stool specimen should be placed in a container with a fixative and
sent thus to the laboratory (Figure 61.3).
Antigen and PCR techniques have been developed for detecting the
organismin the stool or liver abscess fluid. Serological tests are useful in con-
firming the diagnosis of invasive disease. Therapy consists of metronidazole
FIG. 61.1. Ultrasound showing an abscess within the liver.
Case Study 61 175
FIG. 61.2. The pathogenesis of amebiasis and its complications.
176 Case Studies in Pediatric Infectious Diseases
or tinidazole for tissue invasion and iodoquinol for eliminating luminal
parasites.
Reading:
Stanley SL: Amoebiasis. Lancet 2003; 361: 10251034.
Haque R, Huston CD, Hughes M et al: Amebiasis. N Engl J Med 2003; 348:
15651573.
n
CASE 62. A 35-year-old physician with three young children, living in
the United States, presents with a history of acute onset of upper abdominal
discomfort and nonbloody diarrhea, which began 1 week earlier and has
persisted. On examination he appears well, is afebrile, and well-hydrated.
The abdominal examination shows very mild distension, but no tenderness,
and the rest of the examination is normal.
What might be the cause of his illness?
How would you make a diagnosis?
FIG. 61.3. A fecal specimen showing a trophozoite of Entamoeba histolytica with
ingested erythrocytes. (Courtesy of Dr NJ Wheeler, Jr/Centers for Disease Control
and Prevention)
Case Study 62 177
Many viruses, bacteria, and protozoa cause diarrhea in human beings. A
physician is potentially exposed to these more than the general population as
a result of his/her occupation. In addition, this patient has the potential
exposures from his own children, who might attend day care, an important
site for spread of infections. Intestinal pathogens of particular importance in
day-care centers are rotavirus and other enteric viruses, Shigella spp., Giardia
lamblia, a flagellated protozoan, and Cryptosporidium parvum, a sporozoan.
Other possible exposures to diarrheal agents, such as travel to another coun-
try, should be sought. The patients well appearance and mild symptoms
suggests that this is probably not a bacterial infection. In a normal adult, one
would not expect a viral intestinal infection to have persisted for 1 week
without signs of abatement. Therefore protozoal infections become more
likely. Specific antimicrobial therapy is available for treating patients with
some of them; so diagnostic tests should be directed toward these pathogens.
They are Giardia lamblia (intestinalis), Cryptosporidium parvum, and Cyclo-
spora cayetanensis, which all affect the small intestine. Entamoeba histolytica,
which affects the colon, is not frequently transmitted in the United States
and is often associated with bloody stools. Giardia lamblia trophozoites or
cysts can be visualized in fresh or preserved stool specimens (Figures 62.1
FIG. 62.1. Fixed, stained fecal specimen showing a trophozoite of Giardia lamblia.
(Courtesy of Dr Mae Melvin/the Centers for Disease Control and Prevention)
178 Case Studies in Pediatric Infectious Diseases
FIG. 62.2. Unstained fecal specimen showing a cyst of Giardia lamblia. (Courtesy
of the centers for Disease Control and Prevention)
FIG. 62.3. Acid-fast stain of a stool specimen showing cysts of Cryptosporidium
parvum.
Case Study 62 179
and 62.2). However, antigen detection methods are more sensitive than
microscopy.
Cryptosporidium parvum and Cyclospora cayetanensis can be seen after
staining the specimen with an acid-fast stain (Figure 62.3). Antigen detec-
tion and PCR tests for detecting cryptosporidium have also been developed.
Therapy for patients with giardiasis is metronidazole or tinidazole and for
those with cyclospora is trimethoprim/sulfamethoxazole. A newly available
treatment for patients with cryptosporidium infection is nitazoxanide,
which can also be used for treating patients with giardiasis.
Examination of this patients stool revealed cysts of Giardia lamblia. He
was treated with metronidazole. His children, one of whom had diarrhea,
were treated with furazolidone.
The different protozoa that can cause diarrhea and treatment of affected
patients are listed in Table 62.1.
Reading:
Schuster H, Chiodini PL: Parasitic infections of the intestine. Curr Opin
Infect Dis 2001; 14: 587591.
The Medical Letter. Drugs for parasitic infections. The Medical Letter.
August 2004.
nTAB. 62.1: Enteric protozoal infections causing diarrhea.
Family Treatment
Ameba
Entamoeba histolytica metronidazole or tinidazole
Flagellate
Giardia lamblia metronidazole, nitazoxanide, tinadazole,
paromomycin, furazolidone, quinacrine
Sporozoa
Cryptosporidium parvum nitazoxanide
Cyclospora cayetanensis trimethoprim/sulfamethoxazole
Isospora belli trimethoprim/sulfamethoxazole
Microsporidia
Enterocytozoon bieneusi fumagillin
Encephalitozoon intestinalis albendazole
Ciliate
Balantidium coli tetracycline, iodoquinol, metronidazole
180 Case Studies in Pediatric Infectious Diseases
n
CASE 63. Etienne Kabila, a 6-year-old boy, presents with a history of
fever for 3 days. There are no other symptoms. On examination he has
a temperature of 39C and appears moderately ill. There is no pallor,
cyanosis, jaundice, lymphadenopathy, enlargement of liver or spleen, or
rash. The rest of his examination is normal.
What is your differential diagnosis?
How would you make a diagnosis?
How would you treat the child?
Differential diagnosis: The patients name should suggest the possibility
of travel to or of living in a country other than the United States, especially
a former French or Belgian colony in Africa. This patient came to the United
States 1 week earlier from Zaire (currently called the Democratic Republic
of the Congo). This history suggests the possibility of exposure to several
different infectious agents that are absent or less common in the United
States, including the following:
Viruses: hepatitis A virus, Ebola virus, yellow fever virus, dengue virus
Bacteria: Salmonella typhi (typhoid fever), Leptospira interrogans (leptospi-
rosis)
Protozoa: Plasmodium spp. (malaria), Trypanosoma brucei (African trypano-
somiasis).
When evaluating a patient with a febrile illness who has traveled from an
area endemic for infectious agents not endemic in your own area, you should
consider possible (and multiple) diagnoses in terms of potential morbidity
and mortality and public health implications. Of the above list, which is not
exhaustive, that with the greatest public health implications is Ebola virus
infection, which has the potential for significant nosocomial and community
spread. Hepatitis A and Salmonella typhi infections are of importance but
spread can be controlled with appropriate hygiene and enteric precautions.
Ebola fever and yellow fever have extremely high case fatality rates. Malaria,
caused by Plasmodium falciparum, can be fatal if the patient is untreated, as
can typhoid fever and trypanosomiasis.
Management should consist of appropriate isolation while evaluation is
taking place, and performance of a blood smear to diagnose malaria and
trypanosomiasis, and a blood culture to diagnose typhoid fever. Serumchem-
istries, in particular serum transaminases, may provide a screen for the viral
infections listed above. When viral hemorrhagic fevers are considered as
possible diagnoses, the laboratory should be notified, and the appropriate
Case Study 63 181
public health authority should be consulted. In the United States, this is the
Centers for Disease Control and Prevention in Atlanta.
Figure 63.1. shows the thin blood smear of another child with the same
problemas this patient, and Figure 63.2 shows this childs thick blood smear.
The blood smear revealed a heavy parasitemia with Plasmodiumfalciparum.
He was treated with quinine for 5 days and a single dose of pyrimeth-
amine and sulfadoxine, and he made an uneventful recovery.
Malaria is one of the most important diseases of humankind, considering
the number of individuals at risk of infection, the number of individuals
actually infected, and the number of deaths it causes (>1 million per year),
especially among children. It occurs across the tropics and subtropics of the
world, its distribution being shown in Figures 63.3 and 63.4.
There are four species of plasmodiumthat cause malaria in human beings:
P. falciparum, P. vivax, P. ovale, and P. malariae. Their life cycle is shown in
Figure 63.5.
The vector, a female mosquito of the Anopheles genus, injects a sporozoite
into the bloodstream of the vertebrate host, while she is taking a blood meal.
This rapidly enters a hepatocyte, where it multiplies by binary fission into
many merozoites. These leave the hepatocyte and enter erythrocytes, where
they progress from ring forms (trophozoites) to schizonts. By binary fission
FIG. 63.1. Thin blood smear showing numerous ring forms of Plasmodium
falciparum.
182 Case Studies in Pediatric Infectious Diseases
these divide into 624 merozoites (depending on the species), which cause
rupture of the erythrocytes. They then enter other erythrocytes. Thus there
is an amplification process, which is asexual. During this process, some mer-
ozoites form male and female gametocytes, which are haploid cells. When
a mosquito feeds and ingests this blood, the gametocytes unite forming
a diploid oocyte, which forms an oocyst in the intestinal wall of the mos-
quito. Thus the mosquito, in which the sexual cycle is completed, is the
definitive host, while the vertebrate is the intermediate host.
In the cases of P. falciparum and P. malariae all merozoites leave the liver
at the same time. In the cases of P. vivax and P. ovale some of the liver stage
parasites remain in the hepatocytes. These are called hypnozoites. They
emerge from the liver at intervals over several months to a few years,
accounting for clinical relapses.
The clinical manifestations of malaria can be explained by the following:
(a) destruction of erythrocytes (hemolysis), leading to hemolytic anemia,
and hyperplasia of the reticuloendothelial system;
(b) elaboration of cytokines leading to chills and fever;
(c) in the case of P. falciparum, the species that causes the most severe
disease and accounts for almost all malaria deaths, adhesion of infected
erythrocytes to the endothelium. This results in vascular obstruction in
FIG. 63.2. Thick blood smear revealing numerous ring forms of Plasmodium
falciparum.
Case Study 63 183
all organs. The clinical manifestations include the following: (i) enceph-
alopathy (cerebral malaria); (ii) acute renal failure; (iii) liver failure; (iv)
diarrhea; (v) pulmonary edema; (vi) adrenal failure;
(d) immune stimulation, resulting in (i) splenomegaly in areas where re-
current episodes occur, this can lead to chronic massive splenomegaly,
a condition called tropical splenomegaly; (ii) autoantibody production,
directed against erythrocytes, resulting in hemolysis of nonparasitized
cells, and against platelets, resulting in thrombocytopenia; (iii) nephrotic
syndrome complicating P. malariae infection.
As mentioned above, falciparum malaria is potentially a life-threatening
disease. Therefore it constitutes a medical emergency. The causes of mor-
bidity and mortality are organ failure, as described above, hypoglycemia, and
severe anemia.
FIG. 63.3. Eastern hemisphere countries in which malaria is endemic in part or all of the
country. (fromCenters for Disease Control and Prevention. Health Information for International
Travel 20052006. Atlanta: US Department of Health and Human Services. Public Health
Service, 2005)
184 Case Studies in Pediatric Infectious Diseases
FIG. 63.4. Western hemisphere countries in which malaria is endemic in part
or all of the country. (from Centers for Disease Control and Prevention. Health
Information for International Travel 20052006. Atlanta: US Department of
Health and Human Services. Public Health Service, 2005)
Case Study 63 185
The diagnosis of malaria depends on demonstration of the organisms in
a blood smear stained with a Romanowsky stain such as Giemsa stain. Two
types of smear should be made:
(i) A thin smear, which is fixed before staining, and in which the parasite
morphology is well seen. This allows for speciation of the parasite. If
parasites are seen on this smear, examination of a thick smear is
unnecessary. Examination of this smear should enable one to estimate
the degree of parasitemia (proportion of erythrocytes parasitized).
FIG. 63.5. The life cycle of Plasmodium spp.
186 Case Studies in Pediatric Infectious Diseases
This is done by counting the numbers of parasitized and nonparasitized
erythrocytes in a given number of fields. A more accurate method
involves counting the numbers of parasites and of leukocytes seen in
a given number of fields and using the results of a leukocyte count to
calculate the proportion of erythrocytes parasitized.
(ii) A thick smear, which should be just thick enough for newsprint to
be read through it. This is not fixed before staining. Because one
looks through multiple layers of blood simultaneously, the sensitivity
of the test is higher than that of a thin smear examination. How-
ever, the morphology of the parasites is not well seen. In P. falciparum
infection the degree of parasitemia may reach greater than 5% of red
cells (considered a heavy parasitemia), ring forms are usually the only
forms seen in the peripheral blood, and more than one ring may be
seen within one red cell (Figure 63.1). In infections caused by the
other species of plasmodium, parasitemia rarely reaches 5% (unless
the patient is asplenic), stages more advanced than ring forms can
be seen in the peripheral blood (Figure 63.6), and more than one
parasite per red cell is not seen. Other tests such as antigen detection
have been used in the field but are not superior to blood smear
examination. Genome detection can be done, but is not routinely
available.
FIG. 63.6. A thin blood smear showing a schizont of Plasmodium vivax from a
patient with malaria acquired in India.
Case Study 63 187
Management:
(i) supportive care: ensure adequate oxygenation, hydration, and hemo-
globinization, and normoglycemia (both severe malaria itself, and ther-
apy with quinine can cause hypoglycemia);
(ii) antimicrobial therapy: this consists of treatment of the acute attack,
and, in the case of infection with P. vivax and P. ovale, radical cure.
Treatment of the acute attack:
(a) Falciparum malaria: This formerly consisted of chloroquine. However,
because chloroquine resistance in P. falciparum is so frequent in almost
all malaria-endemic areas, one should assume chloroquine resistance.
Currently recommended therapy in the United States is a fixed combi-
nation of atovoquone and proguanil. An alternative is quinine. When
quinine is used, a second drug is also recommended. Doxycycline, sulfa-
doxine plus pyrimethamine or clindamycin can be used for this purpose.
If the medication cannot be given by mouth or by nasogastric tube, for
example if the patient is vomiting, then intravenous therapy should be
given. Quinine for intravenous use is not available in the United States.
Instead quinidine should be used. In such cases the patient should ideally
be nursed in an intensive care unit, because the side effects of the drug
include dysrhythmias. In other parts of the world single drugs and drug
combinations that are used for treatment of malaria include mefloquine,
artemether-lumefantrine, artesunate-mefloquine, artesunate-amodia-
quine, and artesunate-sulfadoxine-pyrimethamine.
(b) Other species: Chloroquine can be used (although chloroquine-resistant
P. vivax is reported in Asia and South America). However, if there is
any concern about the possibility of falciparum malaria, quinine should
be used. This is effective against non-falciparum species of plasmodium.
(c) Radical cure for vivax and ovale malaria: This is aimed at eliminating the
hypnozoite stage in the liver and thus preventing relapses and consists of
primaquine. This drug is contraindicated during pregnancy, and in indi-
viduals with glucose-6-phosphate dehydrogenase deficiency. In such
individuals, relapses should be treated as described above.
(iii) Contacts: Malaria is not contagious fromperson-to-person, unless blood
from a parasitemic individual is introduced into another individual, as
can occur with shared needles or by blood transfusion. In such cases
radical cure is not necessary because the liver stage of the life cycle has
been omitted. However, when an individual is diagnosed with malaria
outside of an endemic area, co-travelers should be observed for illness.
188 Case Studies in Pediatric Infectious Diseases
(iv) Prevention: Malaria can be largely prevented by the following
methods: (a) Avoidance of mosquito bites by sleeping under insecticide-
impregnated mosquito nets, keeping indoors fromdusk to dawn, and use
of mosquito repellents containing DEET on skin, and permethrins on
clothing. (b) Chemoprophylaxis several drugs are available for this
purpose. Those recommended by the US Public Health Service for
Americans traveling to endemic areas are mefloquine, atovoquone/
proguanil, and doxycycline. (c) Reducing the ability of the mosquitoes
to multiply, using insecticides, and draining of bodies of water.
Reading:
Greenwood BM, Bojang K, Whitty CJM, Targett GA: Malaria. Lancet 2005;
365: 14871498.
Baird JK: Effectiveness of antimalarial drugs. N Engl J Med 2005; 352:
15651577.
Stauffer W, Fischer PR: Diagnosis and treatment of malaria in children. Clin
Infect Dis 2003; 37: 13401348.
Chen Q, Schlichtherle M, Wahlgren M: Molecular aspects of severe malaria.
Clin Microbiol Rev 2000; 13: 439450.
Hostetter MK: Epidemiology of travel-related morbidity and mortality in
children. Pediatr Rev 1999; 20: 228233.
Ryan ET, Wilson ME, Kain KC: Illness after international travel. N Engl J
Med 2002; 347: 505516.
McLellan SLF: Evaluation of fever in the returned traveler. Primary Care
Clin Office Pract 2002; 29: 947969.
n
CASE 64 (HYP). An 18-year-old boy presents with fever of 2 weeks
duration. One month ago he accompanied his father on a hunting trip to
Botswana. During the trip he developed a sore on his arm, which he as-
cribed to an insect bite. On examination he is moderately ill-appearing
with a temperature of 39C. He has generalized lymphadenopathy, but
no hepatomegaly or splenomegaly, and the rest of his examination is
normal.
What is the differential diagnosis?
What would you do?
Case Study 64 189
A sore suggests the possibility of a common skin infection following
minor trauma, for example that due to Staphylococcus aureus. Such an in-
fection would cause localized but not generalized lymphadenopathy. An
arthropod bite might cause such trauma and might also provide a site of
inoculation of an infectious agent. The travel and recreational history and
such a sore should lead to consideration of anthrax, rickettsial infection
(Rickettsia africae or R. conori), and African trypanosomiasis (sleeping sick-
ness). In anthrax and rickettsial infection, the fever does not develop weeks
after the appearance of the sore nor is generalized lymphadenopathy a fea-
ture of these infections. These features suggest trypanosomiasis. However,
considering the patients travel history, other ADDITIONAL infections
should also be considered, in particular malaria.
The test for diagnosing trypanosomiasis is examination of a Giemsa-stained
blood smear, and lymph node and skin lesion aspirate.
The smear of such a patient is shown in Figure 64.1.
This shows many flagellated protozoa, characteristic of Trypanosoma
brucei, the cause of African trypanosomiasis or sleeping sickness.
African sleeping sickness, which is present in many parts of tropical
Africa, is one of the major global health problems. It is transmitted by the
tsetse fly (Glossina spp.). The organism enters the lymphatics and then the
circulation. It causes systemic disease characterized by fever, a rash, and
FIG. 64.1. Blood smear showing Trypanosoma brucei. (Courtesy of Dr Mae
Melvin/Centers for Disease Control and Prevention)
190 Case Studies in Pediatric Infectious Diseases
generalized lymphadenopathy. The organism eventually enters the central
nervous system where it causes a progressive encephalitis, which is associ-
ated with disturbance of normal sleep patterns. This infection is fatal if un-
treated. Two subspecies of African trypanosomes infect human beings,
namely T. brucei rhodesiense and T. brucei gambiense. The main reservoirs
of T. brucei rhodesiense are cattle and antelope, while T. brucei gambiense is
transmitted between human beings. T. brucei rhodesiense causes a more rap-
idly progressive infection than does T. brucei gambiense. The treatment
according to the species and whether or not central nervous system disease
has developed is shown in Table 64.1.
Reading:
Barrett MP, Burchmore RJS, Stich A et al: The trypanosomiases. Lancet
2003; 362: 14691480.
Uslan DZ, Jacobson KM, Kumar N et al: A woman with fever and rash after
African safari. Clin Infect Dis 2006; 43: 609, 661662.
Drugs for Parasitic Diseases. The Medical Letter. August 2004.
n
CASE 65 (HYP). A 4-month-old girl is noted to have developmental
delay and strabismus. On examination she is microcephalic and her limbs
are hypertonic. She does not interact with you and clearly has delayed
motor and social milestones. The appearance of the optic fundus is similar
to that shown in Figure 65.1.
Fundoscopy shows a scar from healed chorioretinitis over the posterior
pole of the eye, involving the macula.
The differential diagnosis of microcephaly and psychomotor retardation
in a 4-month-old infant can be considered in terms of intrauterine, intra-
partum, and postnatal insults.
The major causes within each stage are shown in Table 65.1.
nTAB. 64.1: Treatments for African trypanosomiasis (Trypanosoma brucei) infection.
Subspecies Hemolymphatic Nervous system
T. b. gambiense Pentamidine isethionate Melarsoprol
Suramin Eflornithine
T. b. rhodesiense Suramin Melarsoprol
Case Study 65 191
Of the above causes, only cytomegalovirus and Toxoplasma gondii infec-
tions cause chorioretinitis. That caused by cytomegalovirus can affect any
part of the retina, including the periphery, whereas that caused by toxo-
plasma typically occurs in the posterior pole, as shown in this case. The
nTAB. 65.1: Major intrauterine, intrapartum, and postnatal causes of psychomotor retardation.
Intrauterine Intrapartum Postnatal
Infection
Cytomegalovirus
Rubella
Herpes simplex (very unusual) Herpes simplex
Toxoplasmosis
Lymphocytic choriomeningitis virus
Varicella (uncommon) Bacterial meningitis Bacterial meningitis
Metabolic
Hypoxia-ischemia Hypoxia-ischemia Hypoxia-ischemia
Hypoglycemia
Inborn error
Vascular
Occlusion Occlusion
Hemorrhage
Trauma Hemorrhage Hemorrhage
FIG. 65.1. The posterior
pole of the optic fundus.
(Reprinted from: Scheie HG
and Albert DM (editors):
Adlers Textbook of
Ophthalmology. 8th edition.
WB Saunders, Philadelphia,
1969, p. 143, with
permission from Elsevier.)
192 Case Studies in Pediatric Infectious Diseases
strabismus is probably due to very poor visual acuity, but could also be
related to the psychomotor retardation.
Toxoplasmosis is caused by the sporozoan parasite Toxoplasma gondii.
This organism has a life cycle similar to that of the other important sporo-
zoans affecting human beings, namely Cryptosporidium parvum and Plasmo-
dium spp. It is acquired by ingestion of infected meat (asexual cycle) or cat
feces (sexual cycle). The organism is spread in the blood, in the form of
tachyzoites (Figure 65.2), and can be deposited in any tissue, where it forms
cysts containing many bradyzoites (Figure 65.3). These can remain dormant
indefinitely, but can become active and cause disease in immunocompro-
mised hosts such as individuals with AIDS.
The fetus can be infected transplacentally if the mother is infected. The
main clinical features in the fetus are brain disease (brain atrophy, hydro-
cephalus), ocular disease, and disease of reticuloendothelial system (hepa-
tosplenomegaly and anemia).
The diagnosis is confirmed serologically. This requires the demonstration
of IgM or IgA antibodies in the infants blood. Although imaging of the brain
may show areas of calcification and volume loss, this is not likely to be of
value in managing the infant. Treatment has been shown to ameliorate the
FIG. 65.2. Tachyzoites of Toxoplasma gondii. (Courtesy of Dr LL Moore, Jr,
Centers for Disease Control and prevention)
Case Study 65 193
disease or prevent progressive damage. This consists of a combination of
pyrimethamine and sulfadiazine. Folinic acid supplements should be used
concurrently to prevent folate deficiency.
Prevention depends on the mother avoiding eating undercooked meat and
exposure to cat feces.
Reading:
Montoya JG, Liesenfeld O: Toxoplasmosis. Lancet 2004; 363: 19651976.
n
CASE 66. Maria Cortez, an 8-year-old girl, presents with a generalized
seizure. She has a history of having had such seizures previously. Initially she
is confused, but after a few hours she wakes up and then has a completely
normal neurological and general examination.
What is your differential diagnosis?
What risk factors for having seizures would you like to enquire
about?
What would you like to do?
FIG. 65.3. Bradyzoites of Toxoplasma gondii within a pseudocyst in cardiac muscle.
(Courtesy of Dr Edwin P Ewing, Jr, Centers for Disease Control and Prevention)
194 Case Studies in Pediatric Infectious Diseases
The differential diagnosis of seizures in a child can be considered in the
following categories, shown in Table 66.1. Some of them can be eliminated
from consideration on the basis of her rapid return to a normal state or her
normal state prior to the event.
The patients name suggests Hispanic ancestry and the possibility that she
lived in Latin America.
Further history reveals that she grew up in Guatemala and has been in the
United States for about 6 months.
In a patient presenting with a seizure, the most important aspects of
management are to ensure that the patient has an adequate airway (A), is
breathing adequately (B), has adequate circulation/perfusion (C), and an
adequate blood glucose (dextrose) concentration (D).
In many parts of the world, including Latin America, one of the most
common causes of seizures, where a cause is found, is neurocysticercosis, the
larval stage of the pork tapeworm, Taenia solium. A computer tomography
(CT) scan can demonstrate the cysts produced by these larvae. The CT scan
of this patients brain reveals multiple densities within the parenchyma,
highly suggestive of this diagnosis (Figure 66.1).
nTAB. 66.1: Differential diagnosis of seizures in a child.
A. Structural abnormalities
Cyst
Lyssencephaly
B. Metabolic abnormality
Hypoglycemia
Hyponatremia
Hypoxia
Inborn metabolic error
C. Infection
Meningitis
Encephalitis
Focal infection
Brain abscess
Neurocysticercosis
Hydatid cyst
Tuberculoma
D. Vascular lesion
Arteriovenous malformation
Vascular occlusion
Hypoxic-ischemic insult (previous)
E. Neoplasm
F. Toxin/drug
Case Study 66 195
Cysticercosis is acquired in human beings when the human being acts as
the intermediate host instead of the definitive host of Taenia solium. This
means that the human is infected with the larva rather than the adult worm.
The life cycle of the wormis as follows (Figure 66.2). The adult worm(in the
human intestine) lays eggs, which are eaten by pigs, which are copraphagic.
The eggs develop into larvae that penetrate the bowel mucosa, enter the
portal blood, and become disseminated within the animal and form small
cysts. When the uncooked pork is eaten by the human, the larvae grow into
adult worms within the human intestine. If a human eats the feces (like the
pig), it develops cysticercosis like the pig (Figure 66.2).
FIG. 66.1. Computer
tomography scan of the brain
showing multiple cysts
representing
neurocysticercosis.
196 Case Studies in Pediatric Infectious Diseases
Therefore this disease is not due to eating uncooked pork but due to
eating the feces (fecally contaminated food) of a person who has eaten un-
cooked pork. Thus two conditions contribute toward the prevalence of this
disease: (a) the eating of raw pork and (b) poor hygiene. The cysts often
affect the brain. When the larvae die, the cyst contents leaks out, resulting in
inflammation and focal edema, which results in many of the symptoms,
including seizures.
Antimicrobial therapy with albendazole or praziquantel kills the larvae,
which may lead to edema around the cyst. Therefore therapy has been
controversial, the controversy revolving around whether treatment is bene-
ficial or deleterious. Currently therapy is favored. If there are many cysts,
corticosteroids (e.g. dexamethasone) should be given simultaneously with
antimicrobial therapy to reduce cerebral edema.
FIG. 66.2. The life cycle of Taenia solium.
Case Study 66 197
Reading:
Garcia HH, Gonzalez AE, Evans CAW et al: Taenia solium cysticercosis.
Lancet 2003; 361: 547556.
n
CASE 67. Farouk Mahmoud, a 10-year-old boy, presents with a 1-month
history of passing blood on urination. There is no history of fever. On
examination he is completely normal. You collect urine from him in the
examination room and notice something very interesting. At the beginning
of urination the urine appears normal, but toward the end of urination it
becomes red.
Where is the likely site of disease?
What is its likely cause?
This symptom is called terminal hematuria. It indicates pathology within
the bladder. The differential diagnosis includes cystitis, a papilloma, and
schistomiasis. The history alone might give a clue to the specific diagnosis.
The patients name suggests that he might be from North Africa or the Mid-
dle East.
He is, in fact, from Egypt, where schistosomiasis is very common. This is
the cause of his illness. This fluke (trematode) infection is prevalent in most
of Africa, parts of South America, and southeast Asia. It is one of the major
global health problems. Several species of schistosome affect human beings.
Their life cycle, which involves fresh water, is as follows.
Eggs are passed in urine or feces into fresh water, where the eggs hatch.
The miracidia that are released enter a specific water snail where they mul-
tiply. The stage that emerges from the snail, the cercaria, requires a verte-
brate host within 24 hours. The cercaria enter the vertebrate host through
the skin, and travel through the lymphatics to the circulation whence they
reach the respective venous plexuses (superior mesenteric in the case of
S. mansoni, inferior mesenteric and superior hemorrhoidal in the case of
S. japonicum, and vesical and periureteral in the case of S. haematobium),
where they mature and mate. The female lays hundreds of eggs per day.
While the female is attached to the wall of the venule, the eggs burrow
through the wall of the respective organ (bowel in the case of S. mansoni,
S. japonicum, and S. mekongi, or bladder in the in the case of S. haematobium).
When she detaches herself from the endothelium, they are carried proxi-
mally to the liver.
The pathology is caused primarily by the eggs, which become trapped
in tissue, and around which granulomas are formed (Figure 67.1). In the
198 Case Studies in Pediatric Infectious Diseases
FIG. 67.2. The autopsy appearance of schistosomiasis affecting the liver. Note the
pipestem fibrosis around the veins. (Courtesy of Dr Carlos Abramowsky,
Emory University)
FIG. 67.1. The histology of schistosomiasis of the liver. Note the inflammation
around the egg. (Courtesy of Dr Carlos Abramowsky, Emory University)
Case Study 67 199
nTAB. 67.1: Species, geographic distribution, venous plexus and organs affected,
complications, and therapy of different schistosome infections.
Species Geography Venous
plexus
Organs Complications Therapy
S. mansoni Africa intestinal liver, lung portal
hypertension
praziquantel
S. America pulmonary
hypertension
oxamniquine
S. japonicum East Asia intestinal " " praziquantel
S. mekongii SE Asia intestinal " " praziquantel
S. haematobium Africa urinary
bladder
urinary tract
obstruction
praziquantel
FIG. 67.3. Countries in which schistosomiasis occurs. (from Centers for Disease Control
and Prevention. Health Information for International Travel 20052006. Atlanta:
US Department of Health and Human Services. Public Health Service, 2005)
200 Case Studies in Pediatric Infectious Diseases
liver this results in fibrosis (Figure 67.2) and the development of portal
hypertension, while in the urinary tract this results in bladder scarring, uri-
nary tract obstruction, and, ultimately, can lead to bladder cancer.
The world distribution of schistosomiasis is shown in the map (Figure
67.3), and the venous plexuses and organs that they affect, complications,
and therapy are shown in Table 67.1.
The diagnosis of schistosomiasis is preferably made by the demonstration
of ova in excreta, either urine, in the case of S. haematobiuminfection (Figure
67.4), or the stool in the cases of infection caused by the other species.
Sometimes rectal biopsy is necessary to confirm the diagnosis of infection
caused by non-haematobium species. Serology can demonstrate evidence of
previous infection. The additional value of microscopy for ova is that the
viability of the ova can be determined.
Antimicrobial treatment of the different species is shown in Table 67.1.
In highly endemic areas, periodic mass population treatment is also used.
Reading:
Allen R, Bartley PB, Sleigh AC et al: Current concepts: schistosomiasis. N
Engl J Med 2002; 346: 12121220.
FIG. 67.4. Microscopic appearance of Schistosoma haematobium egg. Note the
characteristic terminal spine. (Courtesy of the Centers for Disease Control and
Prevention)
Case Study 67 201
Vennervald B, Dunne DW: Morbidity in Schisosomiasis: an update. Curr
Opinion Infect Dis 2004; 17: 439447.
n
CASE 68. A 3-year-old girl presents with difficulty breathing and fever.
On examination she is found to be hypoxic and to have diffuse wheezing
and crackles in her lungs. A blood count reveals a total leukocyte count
of 20,000/mm
3
with 50% eosinophils, 25% neutrophils, and 25%
lymphocytes.
What is your differential diagnosis?
What would you do?
This child has the clinical features of pneumonia together with airway
obstruction. This might be caused by an infection or a hypersensitivity re-
action. Her marked eosinophilia strongly suggests that she has a worm in-
fection, although a hypersensitivity pneumonitis should still be considered.
Further history should explore possible exposures to (i) worms: Does she eat
or play in soil where animals or other human beings might have defecated?
(ii) Is she exposed to moldy vegetation or dust from bird feathers?
Several intestinal roundworms affect the lung because, during their larval
stage, they pass through this organ. Human beings become infected by eating
soil contaminated with feces from infected animals or other human beings.
The most important of these are the human, dog, and cat ascarids, namely
Ascaris lumbricoides, Toxocara canis, and Toxocara cati, respectively. The dog
and cat ascarids as well as the raccoon ascarid Baylisascaris procyonis cannot
complete their life cycles in humans beings. The larval stages travel through
the viscera but cannot reach the intestine. During this migration through the
viscera, a condition called visceral larva migrans, they can cause severe
pneumonitis (as in this case) and affect the brain (particularly in the case
of B. procyonis, which causes a severe encephalitis) and the eye, where they
cause focal nodular lesions that can resemble retinoblastoma. The liver and
spleen also may be enlarged. Children are the main victims because they play
in contaminated dirt and lick their fingers. The diagnosis should be suspected
in individuals with visceral disease and marked eosinophilia. Confirmation is
not usually necessary but can be accomplished by serology.
Therapy should be supportive, for example with oxygen, and antimicro-
bial, namely with the antihelminthic agent albendazole.
Reading:
Despommier D: Toxocariasis: clinical aspects, epidemiology, medical ecol-
ogy, and molecular aspects. Clin Microbiol Rev 2003; 16: 265272.
202 Case Studies in Pediatric Infectious Diseases
Sorvillo F, Ash LR, Berlin OG et al: Baylisascaris procyonis: an emerging
helminthic zoonosis. Emerging Infect Dis 2002; 8: 355359.
n
CASE 69. A 16-year-old Mexican immigrant to the United States
presents with a history of fatigue, headache, and weight loss for 2 weeks.
On examination his height is 157 cm (<5th percentile), his weight is 51 kg
(10th percentile), and he is afebrile. The rest of his examination is normal.
A blood count reveals a hemoglobin concentration of 9.9 g/dl, an MCVof
61 fL, and a total leukocyte count of 10.9 3 10
6
/l, with a differential count
of 13% neutrophils, 30% lymphocytes, and 57% eosinophils.