What is Enterovirus?
Enteroviruses are members of the Picornaviridae virus family that commonly cause infections in humans, ranging from mild self-limiting febrile illnesses in children to severe and potentially fatal diseases including meningitis, encephalitis, acute flaccid myelitis, myocarditis, and respiratory disease. 1
Viral Classification and Structure
Enteroviruses are classified into four species (A-D) based on genetic divergence, distinct from human rhinoviruses which comprise three additional species (A-C) within the same Enterovirus genus 1. The most well-known member is poliovirus, classified within species C enteroviruses and the target of global eradication efforts 1.
These are small RNA viruses containing positive-sense single-stranded RNA [(+)ssRNA] 2. The genus encompasses numerous types, with over 60 identified in various mammals beyond the many human serotypes 3.
Clinical Disease Spectrum
Common Presentations
- Self-limiting febrile illnesses in infants and young children (most common presentation) 1
- Aseptic meningitis (enteroviruses are now recognized as the most common cause of meningitis) 1, 4
- Hand, foot and mouth disease (HFMD) - particularly associated with CV-A6, EV-A71, and CV-A16 1
- Herpangina 5
Severe Manifestations with Significant Morbidity/Mortality
- Meningoencephalitis and encephalitis 1, 5
- Acute flaccid myelitis (AFM) and acute flaccid paralysis (AFP) - both involve rapid limb weakness with low muscle tone, but AFM specifically shows gray matter changes in the spinal cord on MRI 1
- Myocarditis - particularly associated with coxsackievirus B types 1
- Severe respiratory disease - notably with EV-D68 1
- Sepsis-like syndrome 1
- Acute hepatitis 1
- Pneumonia 5
- Viral hemorrhagic conjunctivitis - caused by EV-D70 or CV-A24 1
High-Risk Populations
Certain enterovirus types pose outbreak risks with significant mortality, particularly:
- EV-A71: responsible for large HFMD outbreaks with rare but severe rhomboencephalitis cases in Asia and Europe 1
- EV-D68: associated with epidemics of severe respiratory disease and AFM 1
Immunocompromised patients warrant special attention as they can present with particularly non-specific and severe disease, and may shed enteroviruses in stool for years (especially those on IgG-depleting therapies like rituximab) 1.
Transmission and Epidemiology
Enteroviruses spread via fecal-oral and respiratory routes, causing seasonal outbreaks that strain healthcare systems 4. The viruses colonize the throat and gut for weeks to months, which complicates interpretation of positive tests from these sites 1.
Diagnostic Approach
Reverse transcriptase PCR (RT-PCR) targeting the 5' non-coding region (5'NCR) is the diagnostic method of choice due to superior sensitivity, specificity, and rapid turnaround time compared to viral culture 1.
Critical Sampling Considerations
For suspected neurological infections, collect multiple specimen types:
- Cerebrospinal fluid (CSF)
- Blood
- Respiratory specimens (nasopharyngeal aspirates/swabs) - essential because viruses like EV-D68 are rarely detectable in CSF or stool 1
- Stool samples - particularly for suspected poliovirus or when investigating AFM/AFP 1
This multi-site sampling is crucial because viral loads are often higher in stool, blood, and respiratory samples than CSF, and virus may remain undetectable in spinal fluid while present elsewhere 1.
Treatment Limitations
No specific antiviral agents are currently available for enterovirus infections 5, 2. Treatment remains supportive and symptomatic only, emphasizing the critical need for prevention strategies and vaccine development 5, 4. Vaccines currently exist only for selected serotypes (e.g., poliovirus, and EV-A71 in China) 1.
Key Clinical Pitfalls
- Do not rely solely on CSF testing for neurological presentations - acellular CSF is common, especially in children under 3 months, and EV-D68 is rarely detected in CSF 1
- Interpret positive throat/stool results cautiously - prolonged colonization means detection doesn't always indicate acute infection 1
- Maintain high suspicion in immunocompromised patients - presentations can be atypical and severe 1