I also want to thank those individuals at the Centers for Disease Control and Prevention who generously have provided many photographs of the etiologic agents, vectors, and life cycles o
Trang 13 FE # PPL ¥
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Trang 3R ed B ook ® ATLAS
of pediatric infectious diseases
2nd Edition
EditorCarol J Baker, MD, FAAP
American Academy of Pediatrics
141 Northwest Point BlvdElk Grove Village, IL 60007-1019
Trang 4American Academy of Pediatrics Department of Marketing and Publications Staἀ
Maureen DeRosa, MPA, Director, Department of Marketing and Publications
Mark Grimes, Director, Division of Product Development
Martha Cook, MS, Sr Product Development Editor
Carrie Peters, Editorial Assistant
Sandi King, MS, Director, Division of Publishing and Production Services
Theresa Wiener, Manager, Publications Production and Manufacturing
Kate Larson, Manager, Editorial Services
Peg Mulcahy, Manager Graphic Design and Production
Linda Smessaert, Manger, Clinical and Professional Publications Marketing
Library of Congress Control Number LOC 2012941376
Printed in the United States of America
9-298/0513
1 2 3 4 5 6 7 8 9 10
Trang 5Table of Contents
Introduction VII
1/Actinomycosis 1
2/Adenovirus Infections 4
3/Amebiasis 7
4/ Amebic Meningoence phalitis and Keratitis (Naegleria fowleri, Acanthamoeba species, and Balamuthia mandrillaris) 12
5/Anthrax 17
6/ Arboviruses (Including California Serogroup, Chikungunya, Colorado Tick Fever, Eastern Equine Encephalitis, Japanese Encephalitis, Powassan, St Louis Encephalitis, Tickborne Encephalitis, Venezuelan Equine Encephalitis, Western Equine Encephalitis, and Yellow Fever Viruses) 22
7/Arcanobacterium haemolyticum Infections 29
8/Ascaris lumbricoides Infections 31
9/Aspergillosis 34
10/Astrovirus Infections 38
11/Babesiosis 40
12/Bacillus cereus Infections 43
13/Bacterial Vaginosis 45
14/Ba cteroides and Prevotella Infections 47
15/Ba lantidium coli Infections (Balantidiasis) 49
16/Baylisascaris Infections 51
17/Bla stocystis hominis Infections 54
18/Blastomycosis 56
19/B orrelia Infections (Relapsing Fever) 58
20/Brucellosis 60
21/B urkholderia Infections 62
22/Human Calicivirus Infections (Norovirus and Sapovirus) 65
23/Ca mpylobacter Infections 67
24/Candidiasis (Moniliasis, Thrush) 70
25/Cat-Scratch Disease (Bartonella henselae) 79
26/Chancroid 84
27/Chlamydophila (formerly Chlamydia) pneumoniae 86
28/Chl amydophila (formerly Chlamydia) psittaci (Psittacosis, Ornithosis) 87
29/Chlamydia trachomatis 89
30/C lostridium botulinum (Botulism and Infant Botulism) 94
31/Cl ostridium diἀ cile 99
32/C lostridium perfringens Food Poisoning 101
33/Clostridial Myonecrosis (Gas Gangrene) 103
34/Coccidioidomycosis 105
35/Coronaviruses, Including SARS 111
36/Cr yptococcus neoformans Infections (Cryptococcosis) 113
37/Cryptosporidiosis 116
38/Cutaneous Larva Migrans 120
39/Cyclosporiasis 122
40/Cytomegalovirus Infection 125
41/Dengue 130
42/Diphtheria 132
43/Ehrlichia and Anaplasma Infections (Human Ehrlichiosis and Anaplasmosis) 137
Trang 6IV RED BOOK ATLAS
44/ Enterovirus (Nonpoliovirus) and Parechovirus Infections (Group A and
B Coxsackieviruses, Echoviruses, Numbered Enteroviruses, and
Human Parechoviruses) 142
45/Epstein-Barr Virus Infections (Infectious Mononucleosis) 147
46/ Escherichia coli and Other Gram-Negative Bacilli (Septicemia and Meningitis in Neonates) 151
47/Escherichia coli Diarrhea (Including Hemolytic Uremic Syndrome) 155
48/Fusobacterium Infections (Including Lemierre Disease) 160
49/ Giardia intestinalis ( formerly Giardia lamblia and Giardia duodenalis) Infections (Giardiasis) 163
50/Gonococcal Infections 167
51/Granuloma Inguinale (Donovanosis) 173
52/Haemophilus influenzae Infections 175
53/Hantavirus Pulmonary Syndrome 179
54/Helicobacter pylori Infections 184
55/Hemorrhagic Fevers Caused by Arenaviruses 186
56/ Hemorrhagic Fevers and Related Syndromes Caused by Viruses of the Family Bunyaviridae 188
57/Hepatitis A 190
58/Hepatitis B 193
59/Hepatitis C 200
60/Hepatitis D 203
61/Hepatitis E 204
62/Herpes Simplex 206
63/Histoplasmosis 216
64/Hookworm Infections (Ancylostoma duodenale and Necator americanus) 220
65/Human Bocavirus 224
66/Human Herpesvirus 6 (Including Roseola) and 7 225
67/Human Herpesvirus 8 229
68/HIV Infection 230
69/Influenza 246
70/Isosporiasis (now designated as Cystoisosporiasis) 253
71/Kawasaki Disease 255
72/Legionella pneumophila Infections 262
73/Leishmaniasis 265
74/Leprosy 270
75/Leptospirosis 273
76/Listeria monocytogenes Infections (Listeriosis) 276
77/Lyme Disease (Lyme Borreliosis, Borrelia burgdorferi Infection) 280
78/Lymphatic Filariasis (Bancroftian, Malayan, and Timorian) 288
79/Lymphocytic Choriomeningitis 292
80/Malaria 294
81/Measles 300
82/Meningococcal Infections 304
83/Human Metapneumovirus 310
84/Microsporidia Infections (Microsporidiosis) 312
85/Molluscum Contagiosum 314
86/Mumps 316
87/Mycoplasma pneumoniae and Other Mycoplasma Species Infections 320
88/Nocardiosis 326
89/Onchocerciasis (River Blindness, Filariasis) 329
90/Human Papillomaviruses 331
Trang 791/Paracoccidioidomycosis (South American Blastomycosis) 336
92/Paragonimiasis 338
93/Parainfluenza Viral Infections 341
94/Parasitic Diseases 344
95/Parvovirus B19 (Erythema Infectiosum, Fifth Disease) 353
96/Pasteurella Infections 357
97/Pediculosis Capitis (Head Lice) 359
98/Pediculosis Corporis (Body Lice) 362
99/Pediculosis Pubis (Pubic Lice, Crab Lice) 363
100/Pertussis (Whooping Cough) 365
101/Pinworm Infection (Enterobius vermicularis) 370
102/Pityriasis Versicolor (Tinea Versicolor) 373
103/Plague 376
104/Pneumococcal Infections 380
105/Pneumocystis jiroveci Infections 388
106/Poliovirus Infections 392
107/Prion Diseases: Transmissible Spongiform Encephalopathies 395
108/Q Fever 399
109/Rabies 402
110/Rat-Bite Fever 406
111/Respiratory Syncytial Virus 409
112/Rickettsial Diseases 412
113/Rickettsialpox 413
114/Rocky Mountain Spotted Fever 415
115/Rotavirus Infections 418
116/Rubella 420
117/Salmonella Infections 426
118/Scabies 431
119/Schistosomiasis 436
120/Shigella Infections 440
121/Smallpox (Variola) 443
122/Sporotrichosis 447
123/Staphylococcal Infections 449
124/Group A Streptococcal Infections 473
125/Group B Streptococcal Infections 488
126/Non–Group A or B Streptococcal and Enterococcal Infections 493
127/Strongyloidiasis (Strongyloides stercoralis) 498
128/Syphilis 501
129/Tapeworm Diseases (Taeniasis and Cysticercosis) 516
130/Other Tapeworm Infections (Including Hydatid Disease) 521
131/Tetanus (Lockjaw) 526
132/Tinea Capitis (Ringworm of the Scalp) 530
133/Tinea Corporis (Ringworm of the Body) 534
134/Tinea Cruris (Jock Itch) 537
135/Tinea Pedis and Tinea Unguium (Athlete’s Foot, Ringworm of the Feet) 539
136/Toxocariasis (Visceral Larva Migrans, Ocular Larva Migrans) 541
137/Toxoplasma gondii Infections (Toxoplasmosis) 544
138/Trichinellosis (Trichinella spiralis) 553
139/Trichomonas vaginalis Infections (Trichomoniasis) 557
140/Trichuriasis (Whipworm Infection) 560
141/African Trypanosomiasis (African Sleeping Sickness) 561
142/American Trypanosomiasis (Chagas Disease) 564
Trang 8VI RED BOOK ATLAS
143/Tuberculosis 567
144/ Diseases Caused by Nontuberculous Mycobacteria (Atypical Mycobacteria, Mycobacteria Other Than Mycobacterium tuberculosis) 595
145/Tularemia 601
146/Endemic Typhus (Murine Typhus) 605
147/Epidemic Typhus (Louseborne or Sylvatic Typhus) 607
148/Varicella-Zoster Infections 609
149/Vibrio cholerae Infections 616
150/Other Vibrio Infections 619
151/West Nile Virus 620
152/ Yersinia enterocolitica and Yersinia pseudo tuberculosis Infections (Enteritis and Other Illnesses) 624
Index 627
Trang 9Visual representations of common and atypical clinical manifestations of infectious diseases
provide diagnostic information not found in the print version of the Red Book The juxtaposition
of these visuals with a summary of the clinical features, epidemiology, diagnostic methods, and
treatment information serves as a training tool and quick reference The Red Book Atlas is not
intended to provide detailed treatment and management information but rather a big- picture approach that can be refined by consulting reference texts or infectious disease specialists
Complete disease and treatment information from the AAP can be found on Red Book® Online (www.aapredbook.org), the electronic version of the Red Book
This Red Book Atlas could not have been completed without the superb assistance of Martha
Cook at the AAP and of those physicians who photographed disease manifestations in their patients and shared these with the AAP Some diseases rarely are seen today because of improved preventive strategies, especially immunization programs While photographs can’t replace hands-
on experience, they have helped me to consider the likelihood of a correct diagnosis, and I hope this will be so for the reader I also want to thank those individuals at the Centers for Disease Control and Prevention who generously have provided many photographs of the etiologic agents, vectors, and life cycles of parasites and protozoa relevant to these largely domestic infections The study of pediatric infectious diseases has been a challenging and changing professional life that has brought me great joy To gather information with my ears and eyes (the history and physi-cal examination), place this into the context of relevant epidemiology and incubation, and then select appropriate diagnostic studies is still exciting Putting these many pieces together to arrive
at the correct diagnosis is akin to solving a crime On many occasions, just seeing the clue (eg, a
characteristic rash, an asymmetry, a swelling) will solve the medical puzzle, lead to recovery with the proper management, and bring satisfaction almost nothing can replace It is my hope that the
readers of the second edition of the Red Book Atlas might find a similar enthusiasm for the field.
Carol J Baker, MD, FAAP Editor
Trang 11Actinomycosis
Clinical Manifestations
Actinomycosis results from pathogen
intro-duction following a breakdown in
mucocuta-neous protective barriers Spread within the
host is by direct invasion of adjacent tissues,
typically forming sinus tracts that cross
tis-sue planes
There are 3 common anatomic sites of
infec-tion Cervicofacial is most common, often
occurring after tooth extraction, oral surgery,
other oral/facial trauma, or even from carious
teeth Localized pain and induration can
progress to cervical abscess and “woody hard”
nodular lesions (“lumpy jaw”), which can
develop draining sinus tracts, usually at the
angle of the jaw or in the submandibular
region Infection also may contribute to
chronic tonsillar airway obstruction Thoracic
disease can be an extension of cervicofacial
infection but most commonly it is secondary
to aspiration of oropharyngeal secretions It
rarely occurs after esophageal disruption
dur-ing or nonpenetratdur-ing trauma Presentations
include pneumonia, which can be complicated
by lung abscesses, empyema and, rarely,
pleurodermal sinuses Focal or multifocal
mediastinal and pulmonary masses may be
mistaken for tumors Abdominal
actinomyco-sis usually is attributable to penetrating trauma
or intestinal perforation The appendix and
cecum are the most common sites; symptoms
are similar to appendicitis Slowly developing
masses can simulate abdominal or
retroperito-neal neoplasms Intraabdominal abscesses and
peritoneal- dermal draining sinuses occur with
chronic infection often forming draining sinus
tracts with purulent discharge Other sites of
infection include liver, pelvis (which, in some
cases, has been linked to use of intrauterine
devices), heart, testicles, and brain (typically
associated with a primary pulmonary focus)
Noninvasive primary cutaneous actinomycosis
has occurred
Etiology
Actinomyces israelii is the most common
spe-cies causing human disease but at least 5 other
Actinomyces species are human pathogens All
are slow-growing, microaerophilic or tive anaerobic, gram-positive, filamentous
faculta-branching bacilli Actinomyces species
fre-quently are copathogens in tissues harboring multiple other anaerobic and/or aerobic spe-
cies Actinobacillus actinomycetemcomitans is
a frequent copathogen, and its isolation may predict the presence of actinomycosis
Epidemiology
Actinomyces species occur worldwide, being
components of endogenous oral
gastrointesti-nal tract and vagigastrointesti-nal flora Actinomyces species
are opportunistic pathogens (reported in patients with HIV and chronic granulomatous disease), with disease usually following pen-etrating and nonpenetrating trauma Infection
is uncommon in infants and children, with 80% of cases occurring in adults The male-to-female ratio in children is 1.5:1 Overt, micro-biologically confirmed, monomicrobial disease
caused by Actinomyces species is rare.
sug-in drasug-inage or loculations of purulent material also suggest the diagnosis A Gram stain of
“sulfur granules” discloses a dense aggregate
of bacterial filaments mixed with tory debris Immunofluorescent stains for
Actinomyces species and 16s rRNA sequencing
and polymerase chain reaction assay are able for tissue specimens Only normally sterile site specimens should be submitted for culture, and specimens must be obtained, transported, and cultured anaerobically on special media for greatest diagnostic sensitivity
Trang 12avail-2 AcTinOmycOSiS
tetracycline are alternative antimicrobial choices Surgical drainage or debridement often is a necessary adjunct to medical man-agement and may allow for a shorter duration
of antimicrobial treatment
Treatment
Initial therapy should include intravenous
penicillin G or ampicillin for 4 to 6 weeks,
followed by high doses of oral penicillin
typi-cally for a total of 4 to 12 months Amoxicillin,
erythromycin, clindamycin, doxycycline, and
Image 1.1
Tissue showing filamentous branching rods of
Actinomyces israelii (Brown and Brenn stain)
Actinomyces have fastidious growth
requirements Staining of a crushed sulfur
granule reveals branching bacilli
Image 1.2
A brain heart infusion agar plate culture of
Actinomyces sp, magnification x573, at 10 days
of incubation Courtesy of Centers for Disease Control and Prevention/Dr George
Image 1.3
A 10-year-old boy with chronic pulmonary,
abdominal, and lower extremity abscesses
with chronic draining sinus tracts from which
Actinomyces israelii was isolated Prolonged
antimicrobial treatment and surgical drainage
were required for resolution of this
infectious process
Image 1.4
Actinomycotic abscesses of the thigh of the
child in Image 1.3 Actinomyces infections are often polymicrobial Actinobacillus
actinomycetemcomitans, one of the HACEK
group of organisms, may accompany
Actinomyces israelii and may cause endocarditis.
Trang 13Image 1.5
An 8-month-old infant with pulmonary
actinomycosis, an uncommon infection in
infancy that may follow aspiration As in this
infant, most cases of actinomycosis are caused
by Actinomyces israelii. Image 1.6Clubbing of the thumb and fingers of the
8-month-old boy in Image 1.5 with chronic pulmonary actinomycosis Blood cultures were repeatedly negative without clinical signs of endocarditis Courtesy of Edgar O Ledbetter,
MD, FAAP
Image 1.7
The resected right lower lobe, diaphragm, and
portion of the liver in a 3-year-old previously
healthy girl with an unknown source for her
pulmonary actinomycosis Courtesy of Carol J
Baker, MD
Trang 144 ADEnOviRuS infEcTiOnS
2
Adenovirus Infections
Clinical Manifestations
Adenovirus infections of the upper respiratory
tract are common and, although often
sub-clinical, can result in symptoms of the
com-mon cold, pharyngitis, tonsillitis, otitis
media, and pharyngoconjunctival fever
Life-threatening disseminated infection, severe
pneumonia, hepatitis, meningitis, and
enceph-alitis occur occasionally, especially among
young infants and immunocompromised
hosts Adenoviruses occasionally cause a
pertussis-like syndrome, croup, bronchiolitis,
exudative tonsillitis, hemorrhagic cystitis, and
gastroenteritis Ocular adenovirus infections
can present as a follicular conjunctivitis or as
epidemic keratoconjunctivitis In epidemic
keratoconjunctivitis, there is an autoimmune
infiltration of the cornea in addition to the
fol-licular conjunctivitis In both cases,
ophthal-mologic illness frequently presents acutely in
one eye followed by involvement of the other
eye In epidemic keratoconjunctivitis, corneal
inflammation produces symptoms including
light sensitivity and vision loss
Etiology
Adenoviruses are double-stranded,
nonenvel-oped DNA viruses; at least 51 distinct serotypes
divided into 6 species (A through F) cause
human infections Some adenovirus types are
associated primarily with respiratory tract
dis-ease, and others are associated primarily with
gastroenteritis (types 40 and 41) Adenovirus
type 14 is emerging as a type that can cause
severe and sometimes fatal respiratory tract
illness in patients of all ages, including healthy
young adults, such as military recruits
Epidemiology
Infection in infants and children can occur at
any age Adenoviruses causing respiratory tract
infections usually are transmitted by
respira-tory tract secretions through person-to-person
contact, airborne droplets, and fomites, the
latter because adenoviruses are stable in the
environment The conjunctiva can provide a
portal of entry Community outbreaks of
ade-novirus-associated pharyngoconjunctival fever have been attributed to water exposure from contaminated swimming pools and fomites, such as shared towels Health care–associated transmission of adenoviral respiratory tract, conjunctival, and gastrointestinal tract infec-tions can occur in hospitals, residential insti-tutions, and nursing homes from exposures between infected health care personnel, patients, or contaminated equipment Adeno-virus infections in transplant recipients can occur from donor tissues Epidemic kerato-conjunctivitis commonly occurs by direct contact, has been associated with equipment used during eye examinations, and is caused principally by types 8 and 19 Enteric strains of adenoviruses are transmitted by the fecal-oral route Adenoviruses causing respiratory and enteric infections circulate throughout the year Enteric disease primarily affects children younger than 4 years Adenovirus infections are most communicable during the first few days of an acute illness, but persistent and intermittent shedding for longer periods, even months, is common Asymptomatic infections are common Reinfection can occur
adeno-be isolated from pharyngeal and eye secretions and feces by inoculation of specimens into sus-ceptible cell cultures A pharyngeal or ocular isolate suggests recent infection, but a fecal isolate indicates either recent infection or pro-longed carriage Rapid detection of adenovirus antigens is possible in a variety of body fluids
by commercial immunoassay techniques These rapid assays can be useful for diagnosis
of respiratory tract infections, ocular disease, and diarrheal disease Enteric adenovirus types
40 and 41 usually cannot be isolated in dard cell cultures Adenoviruses also can be identified by electron microscopic examination
stan-of respiratory tract or stool specimens, but this
Trang 15modality lacks sensitivity Polymerase chain
reaction assays for adenovirus DNA rapidly are
replacing other detection methods because of
improved sensitivity and increasing
commer-cial availability Adenovirus typing is available
from some reference and research laboratories
Treatment
Treatment of adenovirus infection is supportive Randomized clinical trials evaluating specific antiviral therapy have not been performed However, the successful use of intravenous cidofovir has been reported in immuno-compromised patients with severe adenovi-ral disease
Image 2.1
Transmission electron micrograph of adenovirus
Adenoviruses have a characteristic icosahedral
structure Courtesy of Centers for Disease
Control and Prevention/Dr William Gary, Jr Image 2.2Acute follicular adenovirus conjunctivitis
Adenoviruses are resistant to alcohol, detergents, and chlorhexidine and may contaminate ophthalmologic solutions and equipment Instruments can be disinfected by steam autoclaving or immersion in 1% sodium hypochlorite for 10 minutes
Image 2.3
Adenoviral pneumonia in an 8-year-old girl with
diffuse pulmonary infiltrate bilaterally Most
adenoviral infections in the normal host are
self-limited and require no specific treatment
Lobar consolidation is unusual
Trang 166 ADEnOviRuS infEcTiOnS
Image 2.4
Histopathology of the lung with bronchiolar occlusion in an immunocompromised child who died with adenoviral pneumonia Note interstitial mononuclear cell infiltration and hyaline membranes Adenoviruses types 3 and 7 can cause necrotizing bronchitis and bronchiolitis Courtesy of Edgar
O Ledbetter, MD, FAAP
Image 2.5
Pulmonary histopathology of the
immuno-compromised child in Image 2.4 showing multiple
adenovirus intranuclear inclusion cells Courtesy
of Edgar O Ledbetter, MD, FAAP Image 2.6A previously healthy 3-year-old boy who
presented with respiratory failure requiring intensive care for adenovirus type 7 pneumonia
He eventually recovered with mild impairment
in pulmonary function studies Note the mediastinum Courtesy of Carol J Baker, MD
Trang 17Amebiasis
Clinical Manifestations
Clinical syndromes associated with Entamoeba
histolytica infection include noninvasive
intes-tinal tract infection, intesintes-tinal amebiasis
(ame-bic colitis), ameboma, and liver abscess
Disease is more severe in young children, the
elderly , malnourished people, and pregnant
women Patients with noninvasive intestinal
tract infection can be asymptomatic or can
have nonspecific intestinal tract complaints
Patients with intestinal amebiasis generally
have a gradual onset of symptoms over 1 to
3 weeks The mildest form of intestinal tract
disease is nondysenteric colitis However,
amebic dysentery is the most common
mani-festation of amebiasis and generally includes
diarrhea with either gross or microscopic
blood in the stool, lower abdominal pain, and
tenesmus Weight loss is common, but fever
occurs in only about 8% to 38% of patients
Symptoms can be chronic and mimic those
of inflammatory bowel disease Progressive
involvement of the colon can produce toxic
megacolon, fulminant colitis, ulceration of the
colon and perianal area and, rarely,
perfora-tion Colonic progression can occur at multiple
sites and carries a high fatality rate
Progres-sion can occur in patients inappro priately
treated with corticosteroids or anti motility
drugs An ameboma may occur as an annular
lesion of the colon and may present as a
palpa-ble mass on physical examination Amebomas
can occur in any area of the colon but are more
common in the cecum Amebomas may be
mistaken for colonic carcinoma Amebomas
usually resolve with antiamebic therapy and
do not require surgery
In a small proportion of patients,
extraintes-tinal disease can occur The liver is the most
common extraintestinal site, and infection can
spread from there to the pleural space, lungs,
and pericardium Liver abscess can be acute,
with fever, abdominal pain, tachypnea, liver
tenderness, and hepatomegaly, or may be
chronic, with weight loss, vague abdominal
symptoms, and irritability Rupture of a liver
abscess into the abdomen or chest may lead to
death Evidence of recent intestinal tract infection usually is absent Infection also can spread from the colon to the genitourinary tract and the skin The organism rarely spreads hematogenously to the brain and other areas
of the body
Etiology
The genus Entamoeba includes 6 species that
live in the human intestine Three of these
species are identical morphologically: E
histo-lytica, Entamoeba dispar, and Entamoeba moshkovskii The pathogenic E histolytica and
the nonpathogenic E dispar and E moshkovskii
are excreted as cysts or trophozoites in stools
of infected people
Epidemiology
E histolytica can be found worldwide but is
more prevalent in people of lower nomic status who live in resource-limited countries, where the prevalence of amebic infection may be as high as 50% in some com-munities Groups at increased risk of infection
socioeco-in socioeco-industrialized countries socioeco-include immigrants from or long-term visitors to areas with endemic infection, institutionalized people,
and men who have sex with men E histolytica
is transmitted via amebic cysts by the fecal-oral route Ingested cysts, which are unaffected by gastric acid, undergo excystation in the alka-line small intestine and produce trophozoites that infect the colon Cysts that develop sub-sequently are the source of transmission, especially from asymptomatic cyst excreters Infected patients excrete cysts intermittently, sometimes for years if untreated Transmission has been associated with contaminated food
or water Fecal-oral transmission also can occur in the setting of anal sexual practices
or direct rectal inoculation through colonic irrigation devices
Trang 188 AmEBiASiS
serial specimens may be necessary Specimens
of stool can be examined microscopically by
wet mount within 30 minutes of collection or
may be fixed in formalin or polyvinyl alcohol
(available in kits) for concentration, permanent
staining, and subsequent microscopic
exami-nation Biopsy specimens and endoscopy
scrapings (not swabs) can be examined using
similar methods Polymerase chain reaction,
isoenzyme analysis, and monoclonal
antibody-based antigen detection assays can differentiate
E histolytica from E dispar and E moshkovskii.
Commercially available enzyme immuno assay
(EIA) kits for serum can diagnose amebiasis
The EIA detects antibody specific for
E histo-lytica in approximately 95% of patients with
extraintestinal amebiasis, 70% of patients with
active intestinal tract infection, and 10% of
asymptomatic people who are passing cysts of
E histolytica Positive serologic tests persist
even after adequate therapy
Ultrasonography, computed tomography, and
magnetic resonance imaging can identify liver
abscesses and other extraintestinal sites of
infection Aspirates from a liver abscess usually
show neither trophozoites nor leukocytes
Treatment
Treatment involves elimination of the
tissue-invading trophozoites as well as organisms
in the intestinal lumen E dispar and E
mosh-kovskii infections are considered to be
non-pathogenic and do not require treatment Corticosteroids and antimotility drugs admin-istered to people with amebiasis can worsen symptoms and the disease process The follow-ing regimens are recommended:
• Asymptomatic cyst excreters (intraluminal infections): treat with a luminal amebicide, such as iodoquinol, paromomycin, or dilox-anide Metronidazole is not effective
• Patients with intestinal tract symptoms or extraintestinal disease (including liver abscess): treat with metronidazole or tinida-zole, followed by a therapeutic course of a luminal amebicide (iodoquinol or paromo-mycin) An alternate treatment for liver abscess is chloroquine administered con-comitantly with metronidazole or tinida-zole, followed by a therapeutic course of a luminal amebicide
Percutaneous or surgical aspiration of large liver abscesses occasionally can be required when response to medical therapy is unsatis-factory In most cases of liver abscess, though, drainage is not required
Image 3.1
Trophozoites of Entamoeba histolytica with ingested erythrocytes Trichrome stain The ingested
erythrocytes appear as dark inclusions Erythrophagocytosis is the only characteristic that can
be used to differentiate morphologically E histolytica from the nonpathogenic E dispar In these
specimens, the parasite nuclei have the typical small, centrally located karyosome and thin, uniform peripheral chromatin Courtesy of Centers for Disease Control and Prevention
Trang 19Image 3.2
Cysts of Entamoeba histolytica and Entamoeba dispar Line drawing (A), wet mounts (B; iodine C),
and permanent preparations stained with trichrome (D, E) The cysts are usually spherical and often have a halo (B, C) Mature cysts have 4 nuclei The cyst in B appears uninucleate, while in C, D, and
E, 2 to 3 nuclei are visible in the focal plane (the fourth nucleus is coming into focus in D) The nuclei have characteristically centrally located karyosomes and fine, uniformly distributed peripheral chromatin The cysts in C, D, and E contain chromatoid bodies, with the one in D being particularly
well demonstrated, with typically blunted ends E histolytica cysts usually measure 12 to 15 µm
Courtesy of Centers for Disease Control and Prevention
Image 3.3
This amebiasis patient presented with tissue destruction and granulation of the anoperineal
region due to an Entamoeba histolytica
infection Courtesy of Centers for Disease Control and Prevention
Trang 2010 AmEBiASiS
Image 3.6
This patient presented with a case of invasive
extraintestinal amebiasis affecting the cutaneous
region of the right flank causing severe tissue
necrosis Here we see the site of tissue
destruction, pre-debridement Courtesy of
Centers for Disease Control and Prevention/
Kerrison Juniper, MD, and George Healy,
PhD, DPDx
Image 3.4
This patient presented with a case of invasive
extraintestinal amebiasis affecting the cutaneous
region of the right flank Courtesy of Centers for
Disease Control and Prevention/Kerrison Juniper,
MD, and George Healy, PhD, DPDx
Image 3.5
Gross pathology of amebic (Entamoeba
histolytica) abscess of liver Tube of
“chocolate-like” pus from abscess Amebic liver abscesses are usually singular, large, and in the right lobe of the liver Bacterial hepatic abscesses are more likely to be multiple Courtesy of Centers for Disease Control and Prevention/Dr Mae Melvin;
Dr E West
Trang 21Image 3.7
Cysts are passed in feces (1) Infection by Entamoeba histolytica occurs by ingestion of mature cysts
(2) in fecally contaminated food, water, or hands Excystation (3) occurs in the small intestine and trophozoites (4) are released, which migrate to the large intestine The trophozoites multiply by binary fission and produce cysts (5), which are passed in the feces (1) Because of the protection conferred
by their walls, the cysts can survive days to weeks in the external environment and are responsible for transmission (Trophozoites can also be passed in diarrheal stools, but are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment.) In many cases, the trophozoites remain confined to the intestinal lumen (A: noninvasive infection) of individuals who are asymptomatic carriers, passing cysts in their stool In some patients the trophozoites invade the intestinal mucosa (B: intestinal disease) or, through the bloodstream, extraintestinal sites such as the liver, brain, and lungs (C: extraintestinal disease), with resultant pathologic manifestations The
invasive and noninvasive forms represent 2 separate species, respectively E histolytica and E dispar; however, not all persons infected with E histolytica will have invasive disease These 2 species are
morphologically indistinguishable Transmission can also occur through fecal exposure during sexual contact (in which case not only cysts, but also trophozoites, could prove infective) Courtesy of Centers for Disease Control and Prevention
Trang 2212 AmEBic mEningOEncE phALiTiS AnD KERATiTiS
4
Amebic Meningoence
phalitis and Keratitis
(Naegleria fowleri, Acanthamoeba species,
and Balamuthia mandrillaris)
Clinical Manifestations
Naegleria fowleri causes a rapidly progressive,
almost always fatal, primary amebic
meningo-encephalitis Early symptoms include fever,
headache, vomiting, and sometimes
distur-bances of smell and taste, then progresses
rap-idly to signs of meningoencephalitis including
nuchal rigidity, lethargy, confusion,
personal-ity changes, and altered level of consciousness
Seizures are common, and death generally
occurs within a week of onset of symptoms
No distinct clinical features differentiate this
disease from fulminant bacterial meningitis
or other causes of meningoencephalitis
Granulomatous amebic encephalitis (GAE)
caused by Acanthamoeba species and
Balamu-thia mandrillaris has a more insidious onset
and progression of manifestations occurring
weeks to months after exposure Signs and
symptoms include personality changes,
sei-zures, headaches, nuchal rigidity, ataxia,
cra-nial nerve palsies, hemiparesis, and other focal
deficits Fever often is low grade and
intermit-tent Chronic granulomatous skin lesions
(pus-tules, nodules, ulcers) may be present without
central nervous system (CNS) involvement,
particularly in patients with acquired
immu-nodeficiency syndrome, and lesions on the
midface may present for months before CNS
involvement in immunocompetent hosts
The most common symptoms of amebic
kera-titis, usually attributable to Acanthamoeba
species, are pain (often out of proportion to
clinical signs), photophobia, tearing, and
foreign body sensation Characteristic signs
include radial keratoneuritis and stromal ring
infiltrate Acanthamoeba keratitis generally
follows an indolent course and initially can
resemble herpes simplex or bacterial keratitis;
delay in diagnosis is associated with
N fowleri is found in warm freshwater and
moist soil Most infections have been ated with swimming in warm freshwater, such
associ-as ponds, lakes, and hot springs, but other sources have included tap water from geother-mal sources and contaminated and poorly chlorinated swimming pools Disease has been reported worldwide but is uncommon In the United States, infection occurs primarily in the summer and usually affects children and young adults The trophozoites of the parasite invade the brain directly from the nose along the olfactory nerves via the cribriform plate In
infections with N fowleri, trophozoites but not
cysts can be visualized in sections of brain or
in cerebrospinal fluid (CSF)
Acanthamoeba species are distributed
world-wide and are found in soil; dust; cooling towers
of electric and nuclear power plants; heating, ventilating, and air-conditioning units; fresh and brackish water; whirlpool baths; and physiotherapy pools The environmental niche
of B mandrillaris is not delineated clearly,
although it has been isolated from soil CNS
infection attributable to Acanthamoeba occurs
primarily in debilitated and mised people However, some patients infected
immunocompro-with B mandrillaris have had no demonstrable
underlying disease or disability CNS infection
by both amebae probably occurs by inhalation
or direct contact with contaminated soil or water The primary foci of these infections most likely are skin or respiratory tract, fol-lowed by hematogenous spread to the brain
Acanthamoeba keratitis occurs primarily in
people who wear contact lenses, although it also has been associated with corneal trauma Poor contact lens hygiene or disinfection prac-tices as well as swimming with contact lenses are risk factors
Trang 23Incubation Period
Incubation period for N fowleri is typically 3 to
7 days Acanthamoeba and Balamuthia GAE
incubation periods are unknown but are
thought to range from several weeks to months
for CNS disease and within a few weeks for
Acanthamoeba keratitis
Diagnostic Tests
In N fowleri infection, computed tomography
scans of the head without contrast are
unre-markable or show only cerebral edema;
con-trast meningeal enhancement of the basilar
cisterns and sulci may be found However,
these changes are nonspecific CSF pressure
usually is elevated (300 to >600 mm H2O), and
CSF can have polymorphonuclear pleocytosis,
increased protein concentration, and a normal
to very low glucose concentration N fowleri
infection can be documented by microscopic
demonstration of the motile trophozoites on a
wet mount of centrifuged CSF Smears of CSF
should be stained with Giemsa, trichrome, or
Wright stains to identify the trophozoites, if
present; Gram stain is not useful
In infection with Acanthamoeba species and
B mandrillaris, trophozoites and cysts can be
visualized in sections of brain, lungs, and skin;
in cases of Acanthamoeba keratitis, they also
can be visualized in corneal scrapings and by
confocal microscopy in vivo in the cornea In
GAE infections, CSF indices typically reveal a
lymphocytic pleocytosis and an increased
pro-tein concentration, with normal or low glucose
concentrations Computed tomography and
magnetic resonance imaging scans of the head
reveal single or multiple space-occupying,
ring-enhancing lesions that can mimic brain
abscesses, tumors, cerebrovascular accidents,
or other diseases N fowleri and Acanthamoeba species, but not Balamuthia species, can be cultured on special media; B mandrillaris can
be grown using mammalian cell culture Like
N fowleri, immunofluorescence and PCR assays
can be performed on clinical specimens to
identify Acanthamoeba species and
Balamu-thia species; these tests are available through
the Centers for Disease Control and Prevention
Treatment
Although an effective treatment regimen for primary amebic meningoencephalitis due to
N fowleri has not been identified, amphotericin
B is the drug of choice However, treatment usually is unsuccessful, with only a few cases
of complete recovery documented Two vors recovered after treatment with amphoteri-cin B in combination with an azole drug Early diagnosis and institution of high-dose drug therapy is thought to be important for optimiz-ing outcome Effective treatment for infections
survi-caused by Acanthamoeba species and B
man-drillaris has not been established Several
patients with Acanthamoeba GAE and
Acan-thamoeba cutaneous infections without CNS
involvement have been treated successfully with a multidrug regimen consisting of various combinations of pentamidine, sulfadiazine, flucytosine, either fluconazole or itraconazole, trimethoprim-sulfamethoxazole, and topical application of chlorhexidine gluconate and ketoconazole for skin lesions Patients with keratitis should be evaluated by an ophthal-mologist Early diagnosis and therapy are important for a good outcome
Trang 2414 AmEBic mEningOEncE phALiTiS AnD KERATiTiS
Image 4.1
Naegleria fowleri trophozoite in spinal fluid Trichrome stain Note the typically large karyosome and the
monopodial locomotion Courtesy of Centers for Disease Control and Prevention
Image 4.2
Naegleria fowleri trophozoites cultured from cerebrospinal fluid
These cells have charac teristically large nuclei, with a large,
dark-staining karyosome The amebae are very active and
extend and retract pseudopods (trichrome stain) From a patient
who died of primary amebic meningoencephalitis in Virginia
Courtesy of Centers for Disease Control and Prevention
Trang 25Image 4.3
Acanthamoeba keratitis Courtesy of Susan Lehman, MD, FAAP.
Image 4.4
(A) Computed tomographic scan: note the right fronto-basal collection
(arrow) with a midline shift right to left (B) Brain histology: 3 large
clusters of amebic vegetative forms are seen (hematoxylin-eosin stain,
x250) Inset: positive indirect immunofluorescent analysis on tissue
section with anti-Naegleria fowleri serum Courtesy of Cogo PE, Scagli
M, Giatti S, et al Fatal Naegleria fowleri meningoencephalitis, Italy
Emerg Infect Dis 2004;10(10):1835–1837.
Trang 2616 AmEBic mEningOEncE phALiTiS AnD KERATiTiS
Image 4.5
Free-living amebae belonging to the genera Acanthamoeba, Balamuthia, and Naegleria are important causes of disease in humans and animals Fowleri produces an acute, and usually lethal, central nervous system disease called primary amebic meningoencephalitis N fowleri has 3 stages: cysts (1),
trophozoites (2), and flagellated forms (3), in its life cycle The trophozoites replicate by promitosis
(nuclear membrane remains intact) (4) N fowleri is found in freshwater, soil, thermal discharges of
power plants, heated swimming pools, hydrotherapy and medicinal pools, aquariums, and sewage Trophozoites can turn into temporary flagellated forms, which usually revert back to the trophozoite stage Trophozoites infect humans or animals by entering the olfactory neuroepithelium (5) and
reaching the brain N fowleri trophozoites are found in cerebrospinal fluid (CSF) and tissue, while flagellated forms are found in CSF Acanthamoeba spp and B mandrillaris are opportunistic free-living
amebae capable of causing granulomatous amebic encephalitis in individuals with compromised
immune systems Acanthamoeba spp have been found in soil; fresh, brackish, and sea water; sewage;
swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air-conditioning systems; mammalian cell cultures; vegetables; human nostrils
and throats; and human and animal brain, skin, and lung tissues B mandrillaris, however, has not
been isolated from the environment but has been isolated from autopsy specimens of infected humans
and animals Unlike N fowleri, Acanthamoeba and Balamuthia have only 2 stages: cysts (1) and
trophozoites (2), in their life cycle No flagellated stage exists as part of the life cycle The trophozoites replicate by mitosis (nuclear membrane does not remain intact) (3) The trophozoites are the infective forms and are believed to gain entry into the body through the lower respiratory tract or ulcerated or broken skin and invade the central nervous system by hematogenous dissemination (4)
Acanthamoeba spp and B mandrillaris cysts and trophozoites are found in tissue Courtesy of Centers
for Disease Control and Prevention
Trang 27Anthrax
Clinical Manifestations
Depending on the route of infection, anthrax
can occur in 3 forms: cutaneous, inhalational,
and gastrointestinal Cutaneous anthrax
begins as a pruritic papule or vesicle that
enlarges and ulcerates in 1 to 2 days, with
sub-sequent formation of a central black eschar
The lesion itself characteristically is painless,
with surrounding edema, hyperemia, and
painful regional lymphadenopathy Patients
may have associated fever, lymphangitis, and
extensive edema Inhalational anthrax is a
frequently lethal form of the disease and is a
medical emergency A nonspecific prodrome of
fever, sweats, nonproductive cough, chest pain,
headache, myalgia, malaise, and nausea and
vomiting may occur initially, but illness
pro-gresses to the fulminant phase 2 to 5 days later
In some cases, the illness is biphasic with a
period of improvement between prodromal
symptoms and overwhelming illness
Fulmi-nant manifestations include hypotension,
dyspnea, hypoxia, cyanosis, and shock
occur-ring as a result of hemorrhagic mediastinal
lymphadenitis, hemorrhagic pneumonia, and
hemorrhagic pleural effusions, bacteremia,
and toxemia In addition, the liver and central
nervous system (CNS) may be involved A
widened mediastinum is the classic finding on
imaging of the chest Chest radiography also
may show pleural effusions and/or infiltrates,
each of which may be hemorrhagic in nature
Gastrointestinal tract disease can present as 2
clinical syndromes—intestinal or
oropharyn-geal Patients with the intestinal form have
symptoms of nausea, anorexia, vomiting, and
fever progressing to severe abdominal pain,
massive ascites, hematemesis, bloody diarrhea,
and submucosal intestinal hemorrhage
Oro-pharyngeal anthrax also may have dysphagia
with posterior oropharyngeal necrotic ulcers,
which may be associated with marked, often
unilateral neck swelling, regional adenopathy,
fever, and sepsis Hemorrhagic meningitis can
result from hematogenous spread of the
organ-ism after acquiring any form of disease and
may develop without any other apparent
clini-cal presentation The case-fatality rate for patients with appropriately treated cutaneous anthrax usually is less than 1%, but for inhalation
or gastrointestinal tract disease, mortality often exceeds 50% and approaches 100% for meningi-tis in the absence of antimicrobial therapy
Etiology
Bacillus anthracis is an aerobic, gram-positive,
encapsulated, spore-forming, nonhemolytic,
nonmotile rod B anthracis has 3 major
viru-lence factors: an antiphagocytic capsule and 2 exotoxins, called lethal and edema toxins The toxins are responsible for the significant mor-bidity and clinical manifestations of hemor-rhage, edema, and necrosis
Epidemiology
Anthrax is a zoonotic disease most commonly affecting domestic and wild herbivores that occurs in many rural regions of the world
B anthracis spores can remain viable in the
soil for decades, representing a potential source
of infection for livestock or wildlife through ingestion In susceptible hosts, the spores germinate to become viable bacteria Natural infection of humans occurs through contact with infected animals or contaminated animal products, including carcasses, hides, hair, wool, meat, and bone meal Outbreaks of gas-trointestinal tract anthrax have occurred after ingestion of undercooked or raw meat from infected animals Historically, most (~95%) cases of anthrax in the United States were cuta-neous infections among animal handlers or mill workers Discharge from cutaneous lesions potentially is infectious, but person-to-person transmission rarely has been reported The incidence of naturally occurring human anthrax decreased in the United States from
an estimated 130 cases annually in the early 1900s to 0 to 2 cases per year by the end of the first decade of the 21st century Recent cases
of inhalation, cutaneous, and gastrointestinal tract anthrax have occurred in drum makers working with animal hides contaminated with
B anthracis spores or people exposed to
drum-ming events where spore-contaminated drums were used
Trang 2818 AnThRAx
B anthracis is one of the most likely agents to
be used as a biological weapon because (1) its
spores are highly stabile; (2) spores can infect
via the respiratory route; and (3) the resulting
inhalational anthrax has a high mortality rate
In 1979, an accidental release of B anthracis
spores from a military microbiology facility
in the former Soviet Union resulted in at least
69 deaths In 2001, 22 cases of anthrax (11
inha-lational, 11 cutaneous) were identified in the
United States after intentional contamination
of the mail; 5 (45%) of the inhalational anthrax
cases were fatal In addition to aerosolization,
there is a theoretical health risk associated with
B anthracis spores being introduced into food
products or water supplies Use of B anthracis
in a biological attack would require immediate
response and mobilization of public health
resources Anthrax meets the definition of a
nationally and immediately notifiable
condi-tion as specified by the US Council of State
and Territorial Epidemiologists; therefore,
every suspected case should be reported
imme-diately to the local or state health department
Incubation Period
Typically 1 week or less for cutaneous or
gastrointestinal tract anthrax: for inhalational
1 to 43 days in humans
Diagnostic Tests
Depending on the clinical presentation, Gram
stain, culture, and PCR for anthrax should be
performed on pleural fluid, cerebrospinal fluid,
and tissue biopsy specimens or on swabs of
vesicular fluid or eschar material from
cutane-ous or oropharyngeal lesions, rectal swabs, or
stool These tests should be obtained before
initiating antimicrobial therapy because
previ-ous treatment with antimicrobial agents makes
isolation by culture unlikely Definitive
identi-fication of suspect B anthracis isolates can be
performed through the Laboratory Response
Network in each state Additional diagnostic
tests for anthrax can be accessed through state
health departments, including tissue
immuno-histochemistry, an enzyme immunoassay that
measures immunoglobulin G antibodies
against B anthracis protective antigen in paired
sera, or a MALDI-TOF mass spectrometry
assay measuring lethal factor activity in serum
samples The commercially available ELISA Anthrax-PA Kit can be used as a screen-ing test
to validate current treatment tions for anthrax Case reports suggest that naturally occurring cutaneous disease can
recommenda-be treated effectively with a variety of microbial agents, including penicillins and tetracyclines for 7 to 10 days For bioterrorism- associated cutaneous disease in adults or chil-dren, ciprofloxacin or doxycycline (for children
anti-8 years of age or older) is recommended for initial treatment until antimicrobial suscepti-bility data are available Because of the risk of spore dormancy in mediastinal lymph nodes, the antimicrobial regimen should be continued for a total of 60 days to provide postexposure prophylaxis, in conjunction with administra-tion of vaccine A multidrug approach is rec-ommended if there also are signs of systemic disease, extensive edema, or lesions of the head and neck
Ciprofloxacin (intravenously) is recommended
as the primary antimicrobial agent as part of
an initial multidrug regimen for treating inhalational anthrax, anthrax meningitis, cutaneous anthrax with systemic signs or extensive edema, and gastrointestinal tract/ oropharyngeal anthrax until results of anti-microbial susceptibility testing are known Meningitis treatment requires agents with known CNS penetration; meningeal involve-ment should be suspected in cases of inhala-tional anthrax or other systemic anthrax infections The addition of 1 or 2 other agents with adequate CNS penetration is recom-mended for use in conjunction with ciprofloxa-cin; the list of additional antimicrobial agents
to consider includes clindamycin, rifampin, penicillin, ampicillin, vancomycin, merope-nem, chloramphenicol, and clarithromycin Because of intrinsic resistance, cephalosporins and trimethoprim-sulfamethoxazole should
Trang 29not be used Treatment should continue for at
least 60 days, but a switch from intravenous to
oral therapy may occur when clinically
appro-priate For severe anthrax, anthrax-specific
hyperimmune globulin 5% should be
consid-ered in consultation with the Centers for
Dis-ease Control and Prevention (CDC) under the CDC-sponsored investigational new drug use protocol In addition, aggressive pleural fluid drainage is recommended if effusions exist and
is recommended for treatment of all patients with inhalational anthrax
Image 5.1
A photomicrograph of Bacillus anthracis bacteria
using Gram stain technique Courtesy of Centers
for Disease Control and Prevention
Image 5.2
Sporulation of Bacillus anthracis, a gram-positive,
nonmotile, encapsulated bacillus
Image 5.3
Bacillus anthracis tenacity positive on sheep
blood agar B anthracis colony characteristics:
Consistency sticky (tenacious) When teased
with loop, colony will stand up like beaten egg
white Courtesy of Centers for Disease Control
and Prevention/Larry Stauffer, Oregon State
Public Health Laboratory
Image 5.4
An electron micrograph of spores from the
Sterne strain of Bacillus anthracis bacteria These
spores can live for many years, enabling the bacteria to survive in a dormant state Courtesy
of Centers for Disease Control and Prevention/Janice Haney Carr
Trang 3020 AnThRAx
Image 5.5
Cutaneous anthrax Notice edema and typical lesions Courtesy of Centers for Disease Control and Prevention
Image 5.6
Cutaneous anthrax on the hand Courtesy of Gary Overturf, MD
Trang 31Image 5.12
Photomicrograph of meninges demonstrating hemorrhagic meningitis due to fatal inhalational anthrax (magnification x125) Courtesy of Centers for Disease Control and Prevention/Dr LaForce
Image 5.7
Cutaneous anthrax Vesicle development occurs
from day 2 through day 10 of progression
Courtesy of Centers for Disease Control and
Prevention
Image 5.8
Posteroanterior chest radiograph taken on the fourth day of illness, which shows a large pleural effusion and marked widening of the mediastinal shadow Courtesy of Centers for Disease Control and Prevention
Image 5.9
Photomicrograph of lung tissue demonstrating
hemorrhagic pneumonia in a case of fatal human
inhalation anthrax (magnification x50) Courtesy
of Centers for Disease Control and Prevention/Dr
LaForce
Image 5.10
This micrograph reveals submucosal hemorrhage
in the small intestine in a case of fatal human anthrax (hematoxylin-eosin stain, magnification x240) The first symptoms of gastrointestinal (GI) anthrax are nausea, loss of appetite, bloody diarrhea, and fever, followed by severe stomach pain One-fourth to more than half of GI anthrax cases lead to death Note the associated arteriolar degeneration Courtesy of Centers for Disease Control and Prevention/Dr Marshal Fox
Image 5.11
Gross pathology of fixed, cut brain showing
hemorrhagic meningitis secondary to inhalational
anthrax Courtesy of Centers for Disease Control
and Prevention
Trang 32(Including California Serogroup, Chikungunya,
Colorado Tick Fever, Eastern Equine
Enceph-alitis, Japanese EncephEnceph-alitis, Powassan, St
Louis Encephalitis, Tickborne Encephalitis,
Venezuelan Equine Encephalitis, Western
Equine Encephalitis, and Yellow Fever Viruses)
Clinical Manifestations
More than 150 arthropodborne viruses
(arbo-viruses) are known to cause human disease
Although most infections are subclinical,
symptomatic illness usually manifests as 1 of
3 primary clinical syndromes: systemic febrile
illness, neuroinvasive disease, or hemorrhagic
fever (Table 6.1)
• Systemic febrile illness Most arboviruses
are capable of causing a systemic febrile ness that often includes headache, arthral-gia, myalgia, and rash Some viruses also can cause more characteristic clinical manifes tations, including severe joint pain (eg, chikungunya) or jaundice (yellow fever) With some arboviruses, fatigue, malaise, and weakness can linger for weeks following the initial infection
ill-• Neuroinvasive disease Many arboviruses
cause neuroinvasive diseases, including aseptic meningitis, encephalitis, or acute flaccid paralysis Illness usually presents with a prodrome similar to the systemic febrile illness followed by neurologic symp-toms and signs The manifestations vary
by virus and clinical syndrome but can include vomiting, stiff neck, mental status
Table 6.1Clinical Manifestations for Select Domestic and
International Arboviral DiseasesVirus
Systemic Febrile Illness
Neuroinvasive Disease a Hemorrhagic Fever
Domestic
Eastern equine
encephali-tis
Western equine
encephali-tis
International
Venezuelan equine
encephalitis
a Aseptic meningitis, encephalitis, or acute flaccid paralysis.
b In this group, most human cases are caused by La Crosse virus Other known or suspected human pathogens in the group include California encephalitis, Jamestown Canyon, snowshoe hare, and trivittatus viruses.
c
Trang 33changes, seizures, or focal neurologic
defi-cits The severity and long-term outcome of
the illness vary by etiologic agent and the
underlying characteristics of the host, such
as age, immune status, and preexisting
medical condition
• Hemorrhagic fever Hemorrhagic fevers can
be caused by dengue or yellow fever viruses
After several days of nonspecific febrile
ill-ness, the patient may develop overt signs of
hemorrhage (eg, petechiae, ecchymoses,
bleeding from nose and gums, hematemesis,
and melena) and septic shock (eg, decreased
peripheral circulation, azotemia,
tachycar-dia, and hypotension) Hemorrhagic fever
caused by dengue and yellow fever viruses
can be confused with hemorrhagic fevers
transmitted by rodents (eg, Argentine
hem-orrhagic fever, Bolivian hemhem-orrhagic fever,
and Lassa fever) or those caused by Ebola or
Marburg viruses For information on other
infections causing hemorrhagic
manifesta-tions, see pages 186–189
Etiology
Arboviruses are RNA viruses that are
trans-mitted to humans primarily through bites of
infected arthropods (mosquitoes, ticks,
sand-flies, and biting midges) The viral families
responsible for most arboviral infections in
humans are Flaviviridae (genus Flavivirus),
Togaviridae (genus Alphavirus), and
Bunya-viridae (genus Bunyavirus) ReoBunya-viridae (genus
Coltivirus) also is responsible for a smaller
number of human arboviral infections
(eg, Colorado tick fever) (Table 6.2)
Epidemiology
Most arboviruses maintain cycles of
transmis-sion between birds or small mammals and
arthropod vectors Humans and domestic
ani-mals usually are infected incidentally as
“dead-end” hosts (Table 6.2) Important exceptions
are dengue, yellow fever, and chikungunya
viruses, which can be spread from person to
arthropod to person (anthroponotic
transmis-sion) For other arboviruses, humans usually
do not develop a sustained or high enough level
of viremia to infect arthropod vectors Direct
person-to-person spread of arboviruses can
occur through blood transfusion, organ
trans-plantation, intrauterine transmission, and possibly human milk Percutaneous and aero-sol transmission of arboviruses can occur in the laboratory setting
In the northern United States, arboviral tions occur during summer and autumn, when mosquitoes and ticks are most active In the southern United States, cases occur throughout the year because of warmer temperatures, which are conducive to year-round arthropod activity The number of domestic or imported arboviral disease cases reported in the United States varies greatly by specific etiology and year (Table 6.2)
infec-Overall, the risk of severe clinical disease for most arboviral infections in the United States
is higher among adults than among children One notable exception is La Crosse virus infec-tions, for which children are at highest risk of severe neurologic disease and possible long-term sequelae Eastern equine encephalitis virus causes a low incidence of disease but high case-fatality rate (40%) across all age groups
Incubation Period
Typically ranges between 2 and 15 days Longer incubation periods can occur in immunocom-promised people and for tickborne viruses
Diagnostic Tests
Arboviral infections are confirmed most quently by measurement of virus-specific anti-body in serum or cerebrospinal fluid (CSF) Acute-phase serum specimens should be tested for virus-specific immunoglobulin (Ig) M using an enzyme immunoassay (EIA) or microsphere immunoassay (MIA) With clini-cal and epidemiologic correlation, a positive IgM test has good diagnostic predictive value, but cross-reaction with related arboviruses from the same family can occur For most arboviral infections, IgM is detectable 3 to
fre-8 days after onset of illness and persists for
30 to 90 days A positive IgM test result sionally may reflect a past infection Serum collected within 10 days of illness onset may not have detectable IgM, and the test should be repeated on a convalescent sample IgG anti-body generally is detectable shortly after IgM and persists for years A plaque-reduction neu-tralization test (PRNT) can be performed to
Trang 34for Selected Domestic and International Arboviral Diseases
and Hawaii
Worldwide in tropical areas Mosquitoes 45 (20–71)b
Eastern equine encephalitis Alphavirus Eastern and gulf states Canada, Central and South America Mosquitoes 8 (3–21)
California serogroup Bunyavirus Widespread, most prevalent
in midwest and east
and South America
Mosquitoes 21 (2–79)
International
Venezuelan equine encephalitis Alphavirus Imported only Mexico, Central and South America Mosquitoes <1
a Average annual number of domestic and/or imported cases from 2000 to 2009 unless otherwise noted.
b Domestic and imported cases from 1997–2006; excludes indigenous transmission in Puerto Rico.
c Neuroinvasive disease only.
d
Trang 35measure virus-specific neutralizing antibodies
A fourfold or greater increase in virus-specific
neutralizing antibodies between acute- and
convalescent-phase serum specimens collected
2 to 3 weeks apart may be used to confirm
recent infection or discriminate between
cross-reacting antibodies in primary arboviral
infections For some arboviral infections
(eg, Colorado tick fever), the immune response
may be delayed, with IgM antibodies not
appearing until 2 to 3 weeks after onset of
ill-ness and neutralizing antibodies taking up to
a month to develop Immunization history,
date of symptom onset, and information
regarding other arboviruses known to circulate
in the geographic area that may cross-react in
serologic assays should be considered when
interpreting results
Viral culture and nucleic acid amplification
tests (NAATs) for RNA can be performed on
acute-phase serum, CSF, or tissue specimens
Arboviruses that are more likely to be detected using culture or NAATs early in the illness include chikungunya, dengue, and yellow fever viruses Immunohistochemical staining (IHC) can detect specific viral antigen in fixed tissue Antibody testing for common domestic arbo-viral diseases is performed in most state public health laboratories and many commercial labo-ratories Confirmatory PRNTs, viral culture, NAATs, IHC, and testing for less common domestic and international arboviruses are performed only at the Centers for Disease Control and Prevention
Treatment
The primary treatment for all arboviral disease
is supportive Although various therapies have been evaluated for several arboviral diseases, none have shown specific benefit
Image 6.1
An electron micrograph of yellow fever virus
virions Virions are spheroidal, uniform in shape,
and 40 to 60 nm in diameter The name “yellow
fever” is due to the ensuing jaundice that affects
some patients The vector is the Aedes aegypti or
Haemagogus spp mosquito.
Image 6.2
This colorized transmission electron micrograph depicts a salivary gland that had been extracted from a mosquito that was infected by the eastern equine encephalitis virus, which has been colorized red (magnification x83,900) Courtesy
of Centers for Disease Control and Prevention/Dr Fred Murphy; Sylvia Whitfield
Trang 37Image 6.5
Geographic distribution of Japanese encephalitis
Courtesy of Centers for Disease Control and Prevention
Image 6.6
Global spread of chikungya virus during 2005–2009 Courtesy of Morbidity and Mortality
Weekly Report.
Trang 3828 ARBOviRuSES
Image 6.9
Cutaneous eruption of chikungunya infection, a generalized exanthema comprising non-coalescent lesions occurs during the first week of the disease as seen in this patient with erythematous
maculopapular lesions with islands of normal skin Courtesy of Hochedez P, Jaureguiberry S,
Debruyne M, et al Chikungunya infection in travelers Emerg Infect Dis 2006;12(10):1565–1567.
Image 6.8
Digital gangrene in an 8-month-old girl during week 3 of hospitalization She was admitted to the hospital with fever, multiple seizures, and a widespread rash; chikungunya virus was detected in her plasma (A) Little finger of the left hand; (B) index finger of the right hand; and (C) 4 toes on the right
foot Courtesy of Centers for Disease Control and Prevention/Emerging Infectious Diseases.
Image 6.7
A close-up anterior view of a Culex tarsalis mosquito as it was about to begin feeding The
epidemiologic importance of C tarsalis lies in its ability to spread western equine encephalitis, St Louis
encephalitis, and California encephalitis, and is currently the main vector of West Nile virus in the western United States Courtesy of Centers for Disease Control and Prevention/James Gathany
Trang 39Arcanobacterium
haemolyticum Infections
Clinical Manifestations
Acute pharyngitis attributable to
Arcanobacte-rium haemolyticum often is indistinguishable
from that caused by group A streptococci
Fever, pharyngeal exudate, lymphadenopathy,
rash, and pruritus are common, but palatal
petechiae and strawberry tongue are absent
In almost half of all reported cases, a
maculo-papular or scarlatiniform exanthem is present,
beginning on the extensor surfaces of the distal
extremities, spreading centripetally to the chest
and back, and sparing the face, palms, and
soles Rash is associated primarily with cases
presenting with pharyngitis and typically
develops 1 to 4 days after onset of sore throat,
although cases have been reported with rash
preceding pharyngitis Respiratory tract
infec-tions that mimic diphtheria, including
mem-branous pharyngitis, sinusitis, and pneumonia,
and skin and soft tissue infections, including
chronic ulceration, cellulitis, paronychia, and
wound infection, have been attributed to
A haemolyticum Invasive infections, including
septicemia, peritonsillar abscess, Lemierre
syndrome, brain abscess, orbital cellulitis,
meningitis, endocarditis, pyogenic arthritis,
osteomyelitis, urinary tract infection,
pneumo-nia, spontaneous bacterial peritonitis, and
pyo-thorax have been reported No nonsuppurative
sequelae have been reported
Etiology
A haemolyticum is a catalase-negative, weakly
acid-fast, facultative, hemolytic, anaerobic,
gram-positive, slender, sometimes club-shaped
bacillus formerly classified as Corynebacterium
haemolyticum
Epidemiology
Humans are the primary reservoir of
A haemolyticum, and spread is person to
per-son, presumably via droplet respiratory tract
secretions Severe disease occurs almost
exclu-sively among immunocompromised people Pharyngitis occurs primarily in adolescents and young adults Although long-term pharyn-
geal carriage with A haemolyticum has been
described after an episode of acute pharyngitis, isolation of the bacterium from the nasophar-ynx of asymptomatic people is rare An esti-mated 0.5% to 3% of acute pharyngitis is
attributable to A haemolyticum
Incubation Period
Unknown
Diagnostic Tests
A haemolyticum grows on blood-enriched agar,
but colonies are small, have a narrow band of hemolysis, and may not be visible for 48 to
72 hours Detection is enhanced by culture
on rabbit or human blood agar rather than
on more commonly used sheep blood agar because of larger colony size and wider zones
of hemolysis Growth also is enhanced by addition of 5% carbon dioxide Routine throat cultures are inoculated onto sheep blood agar,
and A haemolyticum may be missed if
labora-tory personnel are not trained to look for the organism Pits characteristically form under the colonies on blood agar plates Two biotypes
of A haemolyticum have been identified: a
rough biotype predominates in respiratory tract infections and a smooth biotype is most commonly associated with skin and soft- tissue infections
Treatment
Erythromycin is the drug of choice for treating
tonsillopharyngitis attributable to
A haemolyti-cum A haemolyticum is also susceptible in
vitro to azithromycin, clindamycin, ime, vancomycin, and tetracycline Failures in treatment of pharyngitis with penicillin have been reported, perhaps because of this intracel-lular residing pathogen In the rare case of dis-seminated infection, susceptibility tests should
cefurox-be performed In disseminated infection, enteral penicillin plus an aminoglycoside may
par-be used initially as empirical treatment
Trang 4030 ARCANoBACtERIuM HAEMolytICuM INFECTIONS
Image 7.5
Although not present in this patient with facial
skin lesions associated with Arcanobacterium
haemolyticum pharyngitis, a pharyngeal
membrane similar to that of diphtheria may
occur with A haemolyticum pharyngeal
infection Copyright Williams/Karofsky
Image 7.1
Arcanobacterium haemolyticum (Gram stain)
A haemolyticum appears strongly gram-positive
in young cultures but becomes more
gram-variable after 24 hours of incubation as in
this photograph Copyright Noni MacDonald,
MD, FAAP Image 7.2Arcanobacterium haemolyticum was isolated on
pharyngeal culture from this 12-year-old boy with
an erythematous rash that was followed by mild desquamation Copyright Williams/Karofsky
Image 7.3
Arcanobacterium haemolyticum–associated
rash on dorsal surface of hand in the 12-year-old
boy in images 7.2, 7.4, and 7.5 Copyright
Williams/Karofsky
Image 7.4
Note that the palms are affected in this patient, though they are often spared Copyright Williams/Karofsky