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Enterovirus Infections

Asif Noor, MD
Leonard R. Krilov, MD
Introduction
• Enterovirus (EV) is a member of the family picornaviridae (pico= small).
Parechoviruses (PV) and Saffold viruses (SV) are now grouped with EVs, as they share
certain morphological and functional properties.

• The virion is nonenveloped, spherical, and about 30 nm in diameter, and the genome is a
positive-sense RNA.

• EV is regarded as one of the most common causes of childhood infections and


community outbreaks. The incidence of EV infection increases during summer months
in the northern hemisphere.
Classification
• EVs were originally classified based on effects in tissue culture and pattern of diseases
in animal models.

• Human EVs were originally grouped as either polioviruses or non-polioviruses. The


non-polioviruses included: 1) other numbered EVs, 2) enteric cytopathogenic human
orphan (ECHO) viruses, and 3) coxsackieviruses (CV).

• The newer classification is based on molecular serotyping, which includes


determination of the nucleotide (RNA) sequence encoding the viral polypeptide capsid.
Traditional Versus Newer Classification
Traditional Classification Newer Classification
Host disease pattern and tissue culture Molecular serotyping
effects in infected animal models (RNA sequence)
Coxsackieviruses A Group A
Groups &
1–22, 24 Coxsackievirus A serotypes 2–8, 10, 12, 14, 16;
Serotypes A-23 was reclassified an Echovirus 9 Enterovirus serotypes 71, 76, 89–92
Coxsackieviruses B Group B
1–6 Coxsackievirus A serotype 9; B serotypes 1–6; Echovirus
Echoviruses serotypes 1–7, 9, 11–21, 24–27, 29–33; Enterovirus
1–9, 11–27, serotypes 69, 73–75, 77–88, 93, 97, 98, 100, 101, 106,
29–33 107
Polioviruses Group C
1–3 Poliovirus serotypes 1–3; Coxsackievirus A serotypes 1,
11, 13, 17, 19–22, 24
Enterovirus Group D
68–72 Enterovirus D68, D70, D94, D111
Epidemiology
• Transmission: EVs are spread from person to person via fecal-oral and respiratory
routes. EV 71, the cause of hemorrhagic conjunctivitis, is also spread via fingers,
fomites, and tears.

• Shedding: Most of the EVs are shed in respiratory secretions for 1-3 weeks and in feces
for 2-8 weeks.

• Incubation period: The period for brief EV febrile illnesses is 1-3 days and for polio
virus is 9-12 days.

• Seasonality: Most EV infections are seen in summer and fall in the temperate northern
hemisphere; the virus circulates throughout the year in the tropics.
Pathogenesis

Initial viral Primary Secondary Antibodies


Portal of entry
replication viremia viremia appear

Fecal-oral Symptoms from


Local mucosal involvement of Multiplication in
Viremia ceases
Polio and most tissue of secondary the secondary
non-polio pharynx (tonsil) infection site infection sites
Except in B-cell
or lower GI tract (CNS, heart, liver, and secondary
Respiratory skin, respiratory, disorders
(Peyer patches) seeding of CNS
GI)
CV-A21, EV-D68,
EV-D70 Initial infection in
Viral detection by Antibodies
congenital detectable
PCR
Fomites/ocular infections
Day 1 Day 2 Day 3-5 Day 7-14
EV-D70
Clinical Presentation
EVs are believed to account for 10-15 million symptomatic infections in the United States every
year. Symptomatic infections range from a minor illness to fulminant sepsis and meningitis.

Herpangina (coxsackievirus) Vesicular eruptions on hand (A), Eczema Coxsackium in a 6-month-old infant
lesions on the posterior palate of a foot (B), and mouth (C) of a 6- with underlying atopic dermatitis and acute
young adult male. year-old boy with coxsackievirus onset of vesicles and erosive rash
A6 infection. Several of his
fingernails shed (D) 2 months after Eczema Coxsackium in a 6-month-old infant with underlying
the initial pictures were taken. atopic dermatitis and acute onset of vesicles and erosive rash
Clinical Presentation
Common clinical syndromes due to a picornavirus infection
Clinical syndrome Viral type Clinical features
Nonspecific febrile All viral types Fevers for 3-4 days, can be biphasic. Minimal respiratory or gastrointestinal
illness symptoms. Normal white blood cell count on CBC.

Aseptic meningitis CV-B5; Echoviruses Fever with meningeal signs. CSF pleocytosis with normal glucose and protein.
4,6,9,13, and 30-33 Good prognosis in majority of the cases.
Acute hemorrhagic EV 70, CV A24 (rare) Sudden onset of eye pain with subconjunctival hemorrhage.
conjunctivitis
Herpangina CV A & B; PV 1 & 6; EV 71; Fevers with painful vesicles or ulcers over posterior palate and/or tonsils.
SV 2 & 3
Hand-foot-mouth CV A (6 & 16) & B; EV71; Fever with painful enanthem (vesicles/ulcers) in mouth and exanthem
disease Echoviruses (vesicles, papular rash), particularly on hands and feet.

Carditis CV B1-5 Myopericarditis presenting with heart failure or arrhythmia.


Nonspecific CV A16 (most common), Variable rash (vesicular, maculopapular, urticarial, petechial, purpuric) after
exanthem A6, A9, Echovirus 9 fevers (+/-) for 1-2 days.
Clinical Presentation
Newly described syndromes
Clinical syndrome Viral type Clinical features
Eczema Coxsackium CV A6 Acute onset of skin vesicles or erosions in a child with atopic dermatitis. Illness is
milder and shorter as compared to herpes simplex (HSV) superinfection.
Acute flaccid paralysis EV 71, CV A7 Paralysis but less severe illness and less bulbar involvement as compared to
poliovirus.
Acute respiratory EV D68 Acute onset of cough, dyspnea, wheezing, and hypoxemia in children with history
illness of asthma or wheezing. Recent association with acute flaccid paralysis.

Special Host infections


Neonatal infection Echovirus 6,9, 11; Acquired prenatally and most present within the first postnatal week. EV should be
CV B1-5; PV 3 considered in neonatal sepsis when neither bacteria nor HSV is isolated.

Immunocompromised Echovirus 11 Serious and persistent infection in children with defective congenital or acquired B-
hosts lymphocyte function

Poliovirus infection
Acute paralytic disease Poliovirus 1-3 Rapid onset of paralysis occurs after 1-3 days of febrile illness with sore throat,
headache, myalgias. Asymmetric paralysis primarily effects proximal muscles.
Management
• Laboratory diagnosis: EV is diagnosed via polymerase chain reaction (PCR), culture, or serology.
Test Method Sensitivity Specificity
Viral culture (3-8 days) Cell culture 0% to 80% 100%
PCR assay (1-2 hours) -CSF PCR 100% 97%
-Respiratory multiplex PCR Variable Variable
(some report as
rhinovirus/enterovirus)
Serology Microneutralization Limited use because it is relatively insensitive, poorly
standardized, and labor-intensive

• Treatment
o No specific treatment exists to date; supportive care is the mainstay.
o Some evidence supports use of IVIG in neonatal infection or infection in immunocompromised hosts.
o Pleconaril, an antiviral agent, is not licensed and is not available in the United States.

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