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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_182_библиотеки_им_акад_М_И_Перельмана.pdf
LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION
This section from a fatal case of lymphocytic
choriomeningitis virus infection shows a mild
Viral Infections: Viral Infections Requiring Ancillary Tests
perivascular, predominantly lymphocytic pattern of
inflammation .
TERMINOLOGY
Abbreviations
Lymphocytic choriomeningitis virus (LCMV)
Definitions
Arenaviridae family: Derived from "arena" (sand),
describing grainy particles (ribosomes) seen by EM
ETIOLOGY/PATHOGENESIS
Infectious Agents
Viral infection transmitted by exposure to fresh urine,
droppings, saliva, or nesting materials from infected
rodents
Virus can also be transmitted from mother to fetus
during pregnancy and from human to human through
solid organ transplant
Primary viremia with extra-CNS seeding followed by
secondary viremia with CNS involvement
Symptoms due to natural killer cell and cytotoxic T
cell production of interferon and other inflammatory
mediators
Incubation: 8-13 days
CLINICAL ISSUES
Epidemiology
Mus musculus (house mouse) is predominant carrier
(up to 5% infected)
Cases reported in Europe, North America, South
America, Australia, and Japan
Prevalence of LCMV antibodies in human population
range from 2-5%
Seasonal peak in fall and winter
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Site
Brain, spinal cord
2
Mild, predominantly lymphocytic meningeal
inflammation is present in a section from a fatal case
of lymphocytic choriomeningitis virus infection.
Presentation
Typically asymptomatic or mild febrile illness
Biphasic febrile illness: Initial phase (3-5 days) fever,
anorexia, headache, myalgia, malaise, nausea, and
vomiting, recovery (~ 4 days), then fever, meningitis,
encephalitis, acute hydrocephalus, myelitis (rare)
Fetal involvement: Hydrocephalus, ventriculomegaly,
chorioretinitis, intracerebral hemorrhage
Laboratory Tests
CBC: Leukopenia and thrombocytopenia
CSF: Increased protein and WBC; decreased glucose
IgM and IgG antibodies (serum, CSF)
PCR or virus isolation (CSF)
Treatment
Primary prevention
Avoidance of contact with wild mice and
precautions when handling pet rodents
Presentation with symptoms
Hospitalization and supportive care
Ribavirin has been used in some cases
Prognosis
Mortality from meningitis or encephalitis rare (< 1%);
permanent neurological damage may occur
Infection during pregnancy may result in fetal loss
(35%) or birth defects (hydrocephalus, chorioretinitis,
mental retardation)
Infection in transplant recipients often results in death
MICROBIOLOGY
Virus Features
Enveloped, single-strand RNA virus
60-300 nm in size, with helical nucleocapsid
10,600 nucleotide genome
26
LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION
Etiology
Viral infection transmitted by exposure to infected
rodents (predominantly Mus musculus)
Clinical Issues
Human seroprevalence is 2-5%
Biphasic febrile illness (8-13 day incubation): Flu-like
symptoms (3-5 days), recovery (~ 4 days), then fever,
meningitis &/or encephalitis
CSF: protein, WBC, glucose
Key Facts
Self-limited (mortality < 1%); fetal loss and birth
defects common; high mortality in solid organ
transplants
Microscopic Pathology
Lymphocytic and histiocytic infiltrate involving
meninges, choroid plexus, ependyma, and VirchowRobin space; cerebromalacia, glial proliferation, and
perivascular edema
Confirm with serology, PCR or virus isolation
Viral Infections: Viral Infections Requiring Ancillary Tests
Culture
Forms plaques in Vero cells after 4 days
MICROSCOPIC PATHOLOGY
Histologic Features
Brain
Lymphocytic and histiocytic infiltrate with few
polymorphonuclear cells involving meninges,
choroid plexus, and ependyma
Infiltration of perivascular Virchow-Robin spaces,
cerebromalacia, glial proliferation, and perivascular
edema
Fetus
Lymphocytic myocarditis, extramedullary
hematopoiesis
ANCILLARY TESTS
Immunohistochemistry
Anti-LCMV and anti-Lassa fever virus antibodies
DIFFERENTIAL DIAGNOSIS
Viral Infections With Aseptic Meningitis
Enteroviruses, herpes simplex, mumps, HIV,
arboviruses, measles, parainfluenza, adenovirus,
varicella, Epstein-Barr, cytomegalovirus, influenza,
rubella, rotavirus
Presence of characteristic inclusions or detection by
IHC, serology, or PCR
Negative for LCMV serology, viral protein, or RNA
Perinatal Infections With Congenital
Malformations (TORCH Infections)
Toxoplasmosis, cytomegalovirus, herpes simplex,
varicella, syphilis, mumps, parvovirus, HIV
Negative for LCMV serology, viral protein, or RNA
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
History of rodent exposure
Confirm diagnosis by serology or viral isolation
SELECTED REFERENCES
1. Basavaraju SV et al: Encephalitis Caused by Pathogens
Transmitted through Organ Transplants, United States,
2002-2013. Emerg Infect Dis. 20(9):1443-51, 2014
2. Centers for Disease Control and Prevention. Lymphocytic
Choriomeningitis (LCM). http://www.cdc.gov/vhf/lcm/.
Updated May 6 2014. Accessed November 18, 2014
3. Wilson MR et al: Diseases of the central nervous system
caused by lymphocytic choriomeningitis virus and other
arenaviruses. Handb Clin Neurol. 123:671-81, 2014
IMAGE GALLERY
(Left) CT in a microcephalic infant with a lymphocytic choriomeningitis virus infection shows scattered basal ganglia calcifications , features
that can mimic congenital cytomegalovirus infection. (From DI2: Brain.) (Center) CD45 immunohistochemistry highlights perivascular
inflammatory cells as well as numerous microglia in a fatal case of lymphocytic choriomeningitis. (Right) Perivascular inflammatory
infiltrate with LCMV infection consists of predominantly CD3(+) T cells .
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MUMPS VIRUS INFECTION
Necrosis of spermatogenic cells and interstitial edema and
inflammation are present in this case of mumps orchitis.
Viral Infections: Viral Infections Requiring Ancillary Tests
(Courtesy L.Rorke-Adams, MD.)
TERMINOLOGY
Definitions
Paramyxoviridae family: Derived from "para" (beyond)
and "myxo" (mucus)
ETIOLOGY/PATHOGENESIS
Infectious Agents
Transmitted through direct contact with respiratory
secretions (incubation period: 12-25 days)
Virus replicates in upper respiratory tract, regional
lymphoid tissue, then systemic dissemination
Infectious period: 1-2 days before until 5 days after
onset of parotitis
CLINICAL ISSUES
Epidemiology
USA: 186,000 cases per year (pre-vaccination era:
1949); now 20-6,500 cases per year (varies with
number and severity of outbreaks)
Occurs year round with peaks in late winter and spring
Site
Salivary glands, brain, spinal cord, testicles, ovaries,
breasts
Presentation
Fever, headache, malaise, anorexia, myalgia, swollen
salivary glands (parotitis) (30-40%)
Complications: Orchitis (30-40%), mastitis (31%),
meningitis (10%), oophoritis (5%), sensorineural
hearing loss (1 per 20,000 cases), encephalitis (< 2 per
100,000 cases)
I
Laboratory Tests
RT-PCR (buccal/oral swab, serum, urine, CSF)
2
Ultrasound shows an enlarged, diffusely hypoechoic
testis more pronounced in the perihilar region ,
suggestive of acute orchitis. (From DI: Ultrasound.)
Serology (IgM or increased IgG)
Natural History
Symptoms typically resolve after 1-2 weeks
Treatment
Primary prevention
MMR vaccine (12-15 months and 4-6 years of age)
Presentation with symptoms
Symptomatic treatment only
Prognosis
Typically self-limited
Permanent neurological sequelae and deaths are rare
IMAGE FINDINGS
Parotid
Enlarged parotid glands with surrounding fat
stranding
Testes
Enlarged, hyperemic testis on color Doppler US
MICROBIOLOGY
Virus Features
Enveloped, single-strand, RNA virus
200 nm in size, helical nucleocapsid
15,384 nucleotide genome (7 genes)
12 WHO recognized genotypes (A, B, C, D, F, G, H, I, J,
K, L, N)
Culture
Grow in primary monkey kidney cells and Vero cells
Detection of virus with immunofluorescent antibody
staining or RT-PCR
28
MUMPS VIRUS INFECTION
Etiology
Highly contagious virus transmitted through direct
contact with respiratory secretions
Clinical Issues
Incidence: 20-6,500 cases/year in USA (primarily in
outbreaks)
Fever, headache, malaise, anorexia, myalgia, parotitis,
orchitis, mastitis, meningitis, encephalitis
Key Facts
Diagnose with RT-PCR (buccal/oral swab, serum) or
by serology (IgM); biopsy rarely indicated
Symptoms typically resolve after 1-2 weeks
Primary prevention with MMR vaccine
Microscopic Pathology
Salivary gland: Hemorrhage, necrosis, chronic
inflammatory infiltrate
Testes: Edema, mixed interstitial inflammation and
lymphoid aggregation, congestion of tunica vasculosa
Viral Infections: Viral Infections Requiring Ancillary Tests
MICROSCOPIC PATHOLOGY
Histologic Features
Salivary gland
Hemorrhage, necrosis, chronic inflammatory
infiltrate
Testes
Edema, mixed interstitial inflammation and
lymphoid aggregation, congestion of tunica
vasculosa
Necrosis of spermatogenic cells (Sertoli cells spared)
DIFFERENTIAL DIAGNOSIS
Other Causes of Parotitis
Viral infections (parainfluenza, influenza, Coxsackie A
& B, echovirus, lymphocytic choriomeningitis virus)
Bilateral; lobular architecture maintained with
interstitial subacute infiltrate
No detection of mumps antibodies or nucleic acids
Bacterial infections (Staphylococcus aureus, Streptococcus,
Haemophilus, Escherichia coli, anaerobes)
Typically unilateral; usually due to ascending
infection, may result from adjacent cellulitis
Acinar degeneration with mixed inflammatory
infiltrate; microabscesses with necrotic amorphous
debris and neutrophils
Calculus induced
Unilateral with radiopaque stone in parotid duct
Other Causes of Orchitis
Ascending genitourinary tract infections: S. aureus,
E. coli, Chlamydia, Mycobacterium tuberculosis,
Pseudomonas, Klebsiella, Proteus mirabilis
Unilateral; secondary spread from adjacent
epididymis
Improvement with antibiotics
No detection of mumps antibodies or nucleic acids
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Determine genotype by sequencing to track outbreaks
and rule out vaccine strain
Immunization history
SELECTED REFERENCES
1. Bale JF Jr: Measles, mumps, rubella, and human parvovirus
B19 infections and neurologic disease. Handb Clin Neurol.
121:1345-53, 2014
2. Centers for Disease Control and Prevention. Mumps.
http://www.cdc.gov/mumps/. Updated July 1, 2014.
Accessed November 11, 2014
3. Hviid A et al: Mumps. Lancet. 371(9616):932-44, 2008
IMAGE GALLERY
(Left) Necroinflammatory debris and degeneration of the seminiferous tubules is present in this case of mumps orchitis. (Courtesy L.RorkeAdams, MD.) (Center) Subpial demyelination is present in the spinal cord of a child with mumps. (Courtesy L.Rorke-Adams, MD.) (Right)
Perivenous demyelination is present in the spinal cord of a child with mumps. (Courtesy L.Rorke-Adams, MD.)
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POLIOVIRUS INFECTION
Cresyl violet staining of lumbar spinal cord in acute
poliomyelitis shows infiltration with inflammatory cells
Viral Infections: Viral Infections Requiring Ancillary Tests
and destruction of anterior horn .
TERMINOLOGY
Definitions
Poliovirus: Derived from "polio" (gray) referring to gray
matter of spinal cord
Picornaviridae family: Derived from "Pico" (small) and
"RNA virus"
ETIOLOGY/PATHOGENESIS
Infectious Agents
Fecal-oral route of infection; viral replication in
alimentary tract with shedding in feces
Incubation period is 6-20 days; infectivity occurs
from 7-10 days before until 7-10 days after onset of
symptoms
Transient viremia with rare (5%) spread to brown fat,
reticuloendothelial tissue, and muscle
Rarely (1%), virus spreads within nerve fiber pathways,
replicating in and destroying motor neurons
Virus binds immunoglobulin-like receptor CD155 on
cell surface of host cells
Autopsy section from cer vical cord in the chronic phase of
poliomyelitis shows selective destruction of anterior horns
, cavitation, gliosis, and complete destruction of motor
neurons.
Mild illness in ~ 25% including fever, fatigue, nausea,
headache, flu-like symptoms, stiffness in neck and
back, and pain in limbs
< 1% have permanent paralysis of limbs (usually legs)
Laboratory Tests
Cell culture/viral amplification (stool, oropharyngeal
swab, CSF)
Serology (neutralizing antibodies)
CSF: Increased WBC (10-200 cells/mm, primarily
lymphocytes) and mildly elevated protein (40-50
mg/100 mL)
Natural History
5-10% with paralysis will die from respiratory paralysis
Treatment
Primary prevention
Inactivated polio vaccine (IPV): 4 doses (2, 4, 6-18
months, and 4-6 years)
Oral polio vaccine (OPV): No longer available in
USA
Presentation with symptoms
Supportive therapy only
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CLINICAL ISSUES
Epidemiology
Mainly affects children < 5 years old; peaks in summer
USA: 35,000 cases per year of paralysis (1940s-1950s);
eradicated in 1979
Worldwide: Reported cases decreased > 99% from 1988
(~ 350,000) to 2013 (406), but remains endemic in
parts of Africa, Asia, and Middle East
Site
Brain, spinal cord
Presentation
Majority are asymptomatic
Prognosis
Nonparalytic infections recover completely
Some function regained in 4-6 weeks, but permanent
paralysis (~ 50%) and death (5-10%) can occur
Postpolio syndrome: New muscle pain, exacerbation of
existing weakness, and development of new weakness/
paralysis after 30-40 years
MICROBIOLOGY
Viral Features
Single-stranded, positive sense, RNA virus
30 nm icosahedral, nonenveloped
7,500 bp genome (~ 10 viral proteins)
3 serotypes identified (PV1-3)
POLIOVIRUS INFECTION
Etiology
Virus with fecal-oral route of infection
Rarely spreads within nerve fiber pathways,
replicating and destroying motor neurons
Clinical Issues
Eradicated in USA in 1979; remains endemic in parts
of Africa and Asia
Majority are asymptomatic, ~ 25% have mild illness,
< 1% have permanent paralysis
Key Facts
Primary prevention with inactivated polio vaccine
(IPV)
Microscopic Pathology
Acute phase: Mononuclear inflammation of spinal
gray matter with perivascular cuffing, neuronophagia,
and meningeal inflammation
Chronic phase: Loss of motor neurons, atrophy and
fibrosis of anterior nerve root, and neurogenic muscle
atrophy
Viral Infections: Viral Infections Requiring Ancillary Tests
Culture
Cell lines: L20B (poliovirus specific) and RD or Hep2
(other enteroviruses)
Viral cytopathic effects within 14 days
Identification with neutralization tests or PCR
MACROSCOPIC FEATURES
Acute Phase
Brain and spinal cord typically normal
Chronic Phase
Wasting of affected muscles, thinning and gray
discoloration of anterior nerve roots
MICROSCOPIC PATHOLOGY
Histologic Features
Acute phase
Mononuclear inflammation of spinal gray matter
with perivascular cuffing
Neuronophagia
Meningeal inflammation
Chronic phase
Loss of motor neurons
Atrophy and fibrosis of anterior nerve roots
Neurogenic muscle atrophy
DIFFERENTIAL DIAGNOSIS
Paraneoplastic (Autoimmune) Encephalitis
Involves limbic system, brainstem, cerebellum, and
spinal cord (less common); no detection of poliovirus
Rasmussen Encephalitis
Chronic inflammation, perivascular cuffing, microglial
nodule formation, rarefaction (single hemisphere); no
detection of poliovirus
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Culture is gold standard
Genotype to identify vaccine-related vs. imported
source of infections
Lack of vaccination history
SELECTED REFERENCES
1. Centers for Disease Control and Prevention: Global Health
- Polio: polio eradication. http://www.cdc.gov/polio/.
Reviewed January 27, 2014. Updated January 27, 2014.
Accessed August 27, 2014
2. Gonzalez H et al: Management of postpolio syndrome.
Lancet Neurol. 9(6):634-42, 2010
3. Nathanson N et al: From emergence to eradication:
the epidemiology of poliomyelitis deconstructed. Am J
Epidemiol. 172(11):1213-29, 2010
IMAGE GALLERY
(Left) Section of cresyl violet-stained lumbar cord in acute poliomyelitis shows mononuclear infiltrate in gray matter and perivascular cuffing
. (Center) Meningeal inflammation is a typical feature of acute poliomyelitis. (Right) Neuronophagia of anterior horn neurons is
characteristic of acute poliomyelitis.
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ROTAVIRUS INFECTION
A duodenal biopsy shows mild villous blunting and
marked increase in the number of intraepithelial
Viral Infections: Viral Infections Requiring Ancillary Tests
lymphocytes, findings consistent with but not specific for
rotavirus gastroenteritis.
TERMINOLOGY
Definitions
Derived from "rota" (wheel) shape
Reoviridae family: Derived from "respiratory enteric
orphan viruses"
ETIOLOGY/PATHOGENESIS
Infectious Agents
Virus transmitted by fecal-oral route
Infects and replicates in enterocytes of villi of small
intestine
Malabsorption due to destruction of epithelium,
villus ischemia, NSP4 (viral enterotoxin) action, and
activation of enteric nervous system
Incubation period: 2 days
Virus begins shedding in stool prior to development of
symptoms and stops 3 days after resolution
High-magnification image of a biopsy shows markedly
increased intraepithelial lymphocytes , which can also
be seen in gluten-sensitive enteropathy, H. pylori gastritis,
and other viral infections.
Laboratory Tests
Enzyme immunoassay (stool)
RT-PCR (stool)
Natural History
Self limited
1 out of 70 children will require hospitalization
Treatment
Primary prevention: 2 oral vaccines available
RotaTeq (RV5): 3 doses (2, 4, and 6 months)
Rotarix (RV1): 2 doses (2 and 4 months)
Presentation with symptoms: Supportive; rehydration
(oral or IV)
Prognosis
Full recovery if adequate hydration is maintained
Less severe symptoms manifest in subsequent
infections due to partial immunity
MICROBIOLOGY
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CLINICAL ISSUES
Epidemiology
Rotavirus A is endemic worldwide (90% of infections)
Symptomatic infections are highest in children < 2
years old
USA: 2.7 million cases, 60,000 hospitalizations, and
20-60 deaths annually prevaccine era (pre-2006)
Worldwide: 500,000 deaths (children < 5 years old)
annually in developing countries
Site
Small intestine
Presentation
Mild to severe gastroenteritis with vomiting, watery
diarrhea, and low-grade fever lasting 3-8 days
Virus Features
Nonenveloped, double-stranded RNA virus
76.5 nm in size, 3-layered icosahedral capsid
18,555 nucleotides (11 genes, 12 proteins)
5 species (rotavirus A, B, C, D, and E)
Rotavirus A serotypes defined by glycoprotein VP7
(G1-G27) and protease-sensitive protein VP4 (P[1]P[35]) sequences
Example: G1P[8]
Culture
Not routinely used for diagnosis
MICROSCOPIC PATHOLOGY
Histologic Features
Small intestine
ROTAVIRUS INFECTION
Etiology
Virus transmitted by fecal-oral route
Infects and replicates in enterocytes of villi of small
intestine
Symptoms due to malabsorption
Clinical Issues
Rotavirus A endemic worldwide (90% of infections)
Mild to severe gastroenteritis with vomiting, watery
diarrhea, and low-grade fever lasting 3-8 days
Key Facts
Diagnosis: Enzyme immunoassay or RT-PCR (stool)
2 oral vaccines available
Treat with oral or IV hydration
Microscopic Pathology
Small intestine
Viral Infections: Viral Infections Requiring Ancillary Tests
Reactive and degenerative epithelium
Villous blunting
Increased intraepithelial lymphocytes
Reactive and degenerative epithelium
Villous blunting
Increased intraepithelial lymphocytes
ANCILLARY TESTS
Electron Microscopy
Wheel-shaped viral particles
DIFFERENTIAL DIAGNOSIS
Gluten-Sensitive Enteropathy (Celiac
Disease)
Clinical suspicion &/or serological correlation with
celiac disease-associated antibodies
Antitissue transglutaminase (tTG) antibodies,
endomysial antibodies (EMA), and deamidated
gliadin peptide (DGP) antibodies
Helicobacter pylori-Associated Duodenitis
Commonly occurs in setting of H. pylori gastritis;
organisms seen in associated gastric biopsies
Other Viral Infections
Adenovirus, coronavirus, echovirus, enterovirus,
astrovirus, and Norwalk virus
Identification of specific active viral infection by
PCR, culture, serology, or immunohistochemistry
Most likely infection varies with age, geographic
location, and immune status
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Low clinical suspicion for gluten-sensitive enteropathy
&/or negative serological studies
No history of H. pylori infection or organisms
identified in gastric biopsies
Rotavirus antigen or nucleic acid detection from stool
to confirm diagnosis
SELECTED REFERENCES
1. Centers for Disease Control and Prevention: Vaccines and
Immunizations: Rotavirus: epidemiology and prevention of
vaccine-preventable diseases. http://www.cdc.gov/vaccines/
pubs/pinkbook/rota.html. Reviewed July7, 2014. Updated
May 7, 2012. Accessed August 27, 2014
2. Desselberger U: Rotaviruses. Virus Res. 190C:75-96, 2014
3. Parashar UD et al: Diagnosis, management, and prevention
of rotavirus gastroenteritis in children. BMJ. 347:f7204,
2013
4. Patton JT: Rotavirus diversity and evolution in the postvaccine world. Discov Med. 13(68):85-97, 2012
IMAGE GALLERY
(Left) Correlation with viral studies is necessary to confirm acute rotavirus infection in duodenal biopsies showing villous blunting and increased
intraepithelial lymphocytes. (Center) This biopsy shows normal duodenal mucosa without villous blunting. (Right) This biopsy shows normal
duodenal mucosa with only occasional intraepithelial lymphocytes .
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RUBELLA
Sensorineural deafness, heart defects, and nuclear
cataracts (shown here) are typical features of congenital
Viral Infections: Viral Infections Requiring Ancillary Tests
rubella syndrome. (Courtesy H. Wainwright, MBChB,
FFPath [SA].)
TERMINOLOGY
Synonyms
German measles; 3-day measles
Definitions
Rubella: Derived from Latin ("little red")
Togaviridae family: Derived from "toga" (garment
covering), which describes the viral envelope
ETIOLOGY/PATHOGENESIS
Infectious Agents
Virus transmitted by respiratory droplets, replicates
in nasopharynx and lymph nodes, and spreads
hematogenously
Incubation period: 12-23 days
Contagious period: From 7 days before until 7 days
after appearance of rash
Virus crosses placenta, then kills or prevents
replication of cells (risk decreases with increasing
gestational age at time of maternal infection)
CLINICAL ISSUES
Epidemiology
Mostly affects children 5-9 years old; peaks in spring;
epidemics every 6-9 years
USA: 12.5 million cases (1964-1965 epidemic) with
11,250 therapeutic or spontaneous abortions, 2,100
neonatal deaths, and 20,000 infants with congenital
rubella syndrome (CRS); 11 cases annually (2005-2011)
Worldwide: 100,000 infants with CRS annually
Site
I
Skin, respiratory tract, lymph nodes
2
"Blueberry muffin" lesions consist of foci of erythrocyte
precursors within the dermis and subcutis and are
characteristic of infants with congenital rubella syndrome.
(Courtesy L. Rorke-Adams, MD.)
Presentation
Children: Pink or light red rash that begins in face and
spreads to rest of body (fades after 3 days), low fever (<
38.3 C), posterior cervical lymphadenopathy
Adults: Prodrome of low-grade fever, headache,
malaise, mild coryza, and conjunctivitis; arthralgia or
arthritis (70% of women)
Neonates: Miscarriage, fetal death/stillbirth, and
"blueberry muffin" skin lesions
CRS: sensorineural deafness, cataracts, heart defects
(patent ductus arteriosus, interventricular septal
defects, and pulmonic stenosis)
Laboratory Tests
RT-PCR
Serology (IgM, IgG)
Natural History
Mild, self-limited infection, often asymptomatic
Treatment
Primary prevention
Measles, mumps, rubella vaccine (MMR) (doses at
12-15 months and 4-6 years)
Screening prior to conception; MMR deferred to
postpartum period in susceptible pregnant women
Active infection: Supportive therapy
Congenital infection: Management of complications
Prognosis
Acquired: Complete recovery
Congenital: Varies with severity of complications;
neurological symptoms typically permanent
MICROBIOLOGY
Virus Features
Single-strand, positive-sense RNA virus
50-70 nm enveloped icosahedral capsid
34
Etiology
Virus transmitted by respiratory droplets; spreads
hematogenously and crosses placenta
Clinical Issues
Rare (~ 11/year) imported cases in USA
Light red rash spreads from face to body; low fever,
lymphadenopathy
Perinatal morbidity/mortality decreases with later
gestational age at time of maternal infection
RUBELLA
Key Facts
Congenital rubella syndrome (CRS) includes deafness,
cataracts, and heart defects
RT-PCR, serology, or viral culture for diagnosis
MMR vaccine to prevent infection
Microscopic Pathology
Placenta: Necrosis; immature hypoplastic villi
Infant/fetus: Thrombi and widespread ischemia,
necrosis, and chronic inflammation
Viral Infections: Viral Infections Requiring Ancillary Tests
9,762 bp genome (5 proteins)
Culture
Immunofluorescence in Vero cells (1-2 weeks)
MACROSCOPIC FEATURES
Skin
Generalized maculopapular erythematous eruption
MICROSCOPIC PATHOLOGY
Histologic Features
Placenta: Noninflammatory necrosis in epithelium
of chorion and in endothelial cells; immature villous
pattern with villous hypoplasia
Infant/fetus: Necrotizing chorioretinitis, myocardial
necrosis, interstitial pneumonitis, swelling and
vacuolization of liver cells, chronic inflammation of
leptomeninges, lung, and uveal tract of eye
Blueberry muffin lesion: Foci of erythrocyte
precursors within dermis and subcutis
DIFFERENTIAL DIAGNOSIS
Infections Presenting With Fever and Rash
Measles, scarlet fever (Streptococcus pyogenes), erythema
infectiosum (parvovirus B19), meningococcemia,
typhoid fever, varicella
Negative for rubella serology, viral protein or RNA
Perinatal Infections Presenting With Rash
and Ocular Findings (TORCH Infections)
Toxoplasmosis, cytomegalovirus, herpes simplex,
varicella, syphilis, mumps, parvovirus, HIV
Negative for rubella serology, viral protein, or RNA
DIAGNOSTIC CHECKLIST
Pathologic Interpretation Pearls
Confirm diagnosis with serology or viral isolation
Molecular genotyping to track source of infection
Lack of vaccination history
SELECTED REFERENCES
1. Bouthry E et al: Rubella and pregnancy: diagnosis,
management and outcomes. Prenat Diagn. Epub ahead of
print, 2014
2. Centers for Disease Control and Prevention. Rubella
(German Measles, Three-Day Measles). http://
www.cdc.gov/rubella. Updated February 4, 2009. Accessed
November 11, 2014
3. Papania MJ et al: Elimination of endemic measles,
rubella, and congenital rubella syndrome from the
Western hemisphere: the US experience. JAMA Pediatr.
168(2):148-55, 2014
IMAGE GALLERY
(Left) CT in an infant with congenital rubella syndrome shows atrophy of the cerebral hemispheres. Overlap of the cranial sutures (due
to volume loss) and basal ganglia calcification
congenital rubella syndrome. (Courtesy L. Rorke-Adams, MD.) (Right) Necrosis is present in the caudate nucleus of an infant with congenital
rubella syndrome. (Courtesy L. Rorke-Adams, MD.)
are present. (From DI2: Brain.) (Center) Focal necrosis is present in the centrum ovale in
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