Enterovirus

Background

Microbiology

• A genus of small RNA viruses within the Picornaviridae family which includes rhinovirus, echovirus, coxsackievirus, and poliovirus
• Traditionally organized by subgenera (poliovirus, group A and B coxsackievirus, echovirus, and numbered enterovirus) and serotype
• Now organized by sequencing of VP1 gene into four species:
  • Enterovirus A
    • Coxsackieviruses: CV-A2 to CV-A8, CV-A10, CV-A12, CV-A14, and CV-A16
    • Enteroviruses: EV-A71, EV-A76, EV-A89, EV-A90 to EV-A92, EV-A114
  • Enterovirus B
    • Coxsackieviruses: CV-A9, CV-B1 to CV-B6
    • Echoviruses: E-1 to E-7, E-9, E-11 to E-21, E-24 to E-27, E-29 to E-33
    • Enteroviruses: EV-B69, EV-B73 to EV-B75, EV-B77 to EV-B88, EV-B93, EV-B97, EV-B98, EV-B100, EV-B101, EV-B106, EV-B107, EV-B110
  • Enterovirus C
    • Polioviruses: PV-1 to PV-3
    • Coxsackieviruses: CV-A1, CV-A11, CV-A13, CV-A17, CV-A19 to CV-A22, CV-A24
    • Enteroviruses: EV-C95, EV-C96, EC-C99, EV-C102, EV-C104, EV-C105, EV-C109, EV-C113, EV-C116
  • Enterovirus D
    • Enteroviruses: EV-D68, EV-D70, EV-D94, EV-D111

Pathophysiology

• Local replication in the GI tract followed by viremia that seeds to other sites including upper respiratory tract (including conjunctivae) and meninges
• Some are transmitted via droplet/contact via eyes, especially some of the exclusively respiratory viruses like EV-D68
• There is receptor tropism by genotype

Epidemiology

• Most common cause of aseptic meningitis

Risk Factors

• Hypogammaglobulinemia from a number of causes
• Neonates

Clinical Manifestations

• Clinical syndromes are myriad, including mild febrile illnesses, upper or lower respiratory infections, aseptic meningitis, encephalitis, paralysis, myocarditis, and neonatal enteroviral sepsis

Hand-Foot-Mouth Disease

• Typically caused by group A enteroviruses, especially coxsackie A16, enterovirus A71, and enterovirus A6
• Causes painful lesions in oral mucosa and palms and soles in young children

Neurologic Syndromes

• Most common identified cause of aseptic meningitis

Respiratory Disease

• Enteroviruses account for most upper respiratory infections in the summer, including undifferentiated febrile illness

Other Syndromes

• Most common cause of myopericarditis
• Myositis
• Coxsackievirus diseases in the newborn
• Non-specific exanthems
• Upper respiratory tract infection

Enterovirus A71

• Causes aseptic meningitis, gastroenteritis

Immunodeficiencies

• Agammaglobulinemia predisposes to the development of chronic meningoencephalitis, which can be severe and fatal
• Relevant diseases include X-linked agammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiency disease, and hyper-IgM syndrome, as well as acquired defects including hematopoietic stem cell transplantation, rituximab, and obinutuzumab

Pregnancy

• Enteroviral infection within the week before delivery has a high risk for severe neonatal sepsis

Differential Diagnosis

• Other causes of aseptic meningitis

Diagnosis

• Molecular diagnostics are the gold standard
  • Possible samples include CSF, nasopharyngeal swab, throat, stool, and conjunctiva
  • Stool is more sensitive but less specific than CSF, so should only be requested when CSF is negative but there is a high pretest probability
• Viral culture is not routinely done

Management

• Supportive