Enterovirus

Diagnosis

Indications for Testing

  • Mild to moderate disease (eg, upper respiratory symptoms) – diagnostic testing usually not indicated
  • Disseminated or organ-specific syndromes – laboratory testing indicated

Laboratory Testing

  • CDC - testing recommendations
  • Nucleic acid amplification testing (eg, RT-PCR) recommended for CSF and blood specimens
    • Much more sensitive than culture
    • Rapid turnaround time aids in clinical management of patient
  • Culture – respiratory specimens, stool
    • Up to 1 week required for growth
  • Serologic antibody titers
    • Requires acute and convalescent titers
    • Serum neutralization is considered the gold standard
    • Complement fixation is a less widely accepted method and not generally recommended if serum neutralization is available
  • Specific testing – use for epidemiological studies

Clinical Background

Enteroviral disease is a common, under-recognized childhood illness.

Epidemiology

  • Prevalence – non-polio enteroviruses cause 10-15 million symptomatic cases annually in the U.S.
  • Age – affects all ages; most severe disease in infants and older adults
  • Occurrence
    • Infections occur throughout the year but peak during July-October
  • Transmission – fecal-oral route
  • Wild-type poliovirus 1-3 no longer in Western hemisphere due to effective vaccine strategies

Organism

  • Enteroviruses are single-stranded RNA viruses in the Picornaviridae family
  • >70 recognized serotypes
  • Most common non-polio enteroviruses
    • Coxsackieviruses A1-22 and 24
    • Coxsackieviruses B1-6
    • Echoviruses 1-9, 11-27 and 29-31
    • Enteroviruses 68-71

Clinical Presentation

  • Nonspecific febrile illness with or without rash (coxsackieviruses A4, 5, 9, 10, 16, and B1-5)
  • Acute hemorrhagic conjunctivitis (coxsackievirus A24, echovirus 70)
  • Hand-foot-mouth disease (coxsackievirus A16, B1-5; echovirus 4-6)
  • Neonatal disease
    • May cause severe morbidity and mortality
    • Related to sepsis, coxsackievirus B2-5, meningitis/encephalitis, myocarditis or hepatitis
    • Complications associated with poor outcome generally occur 1-2 days after birth
      • Suggests prenatal origin of infection
    • Sudden onset of fever, irritability and poor feeding characterize infection
    • Diarrhea, vomiting and rash (macular or maculopapular) in 25% of patients
    • Meningeal involvement in febrile disease 70% of time
  • Myocarditis (coxsackievirus B1-5 most common)
  • Herpangina (coxsackievirus A1-10)
  • Hepatitis
  • Pneumonia, bronchiolitis (coxsackievirus A9, 16, B1-5)
  • Central nervous system infections
    • Aseptic meningitis (meningeal inflammation in absence of bacterial pathogen)
      • Enteroviruses are the most common cause (80-92% of all cases)
      • Serotype of enterovirus varies (commonly coxsackievirus A2, 4, 7, 9, 10, B1-5; echovirus 6, 7, 9, 10; enterovirus 70, 71)
      • Clinical manifestations depend upon host
    • Enteroviral encephalitis is less common but more severe than aseptic meningitis
      • Coxsackievirus A9, B1-5; enterovirus 71
      • Global neurologic depression
      • Evidence of focal encephalitis, similar to herpes simplex encephalitis (enterovirus found on brain biopsy)
      • Immunocompromised adults and children with agammaglobulinemia are susceptible to chronic meningitis or meningoencephalitis
    • Paralytic syndrome
      • Classically associated with poliovirus
      • Typically flaccid paralysis
      • Enteroviruses 70 and 71, and coxsackievirus A7 can cause similar syndrome
  • Meningitis beyond neonatal period characterized by sudden onset of fever (38°-40°C)
    • Meningeal irritation (>6 weeks) occurs in >50% of patients
    • Headache and photophobia are almost universally reported
    • Neurologic abnormalities rare
    • Both short- and long-term outcomes generally good for immunocompetent hosts

Treatment

  • Supportive

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Enterovirus Detection by RT-PCR 0050249
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Rapid diagnostic test

Use when enteroviral infection suspected, especially for neurologic infections

Standard of care for diagnosing viral infection from CSF specimen

Negative result does not rule out PCR inhibitors or enterovirus nucleic acid in concentrations below level assay can detect

  
Viral Culture, Non-Respiratory 2006498
Method: Cell Culture

Use to identify agent in adenovirus, cytomegalovirus, enterovirus, herpes simplex virus, and varicella-zoster virus

Slow growth; not ideal for acute identification

  
Enterovirus Typing 0065058
Method: Immunofluorescence

Identify enterovirus type from culture

  • Echoviruses 4, 6, 9, 11, 30
  • Coxsackievirus A9, A16, A24
  • Coxsackievirus B1-B6
  • Poliovirus 1-3
  • Enterovirus 70, 71
    
Enterovirus Antibody Panel 2003259
Method: Serum Neutralization/Complement Fixation

Use to confirm disease occurrence

Panel includes coxsackie A9 and B1-6 antibodies, echovirus antibodies, and poliovirus antibodies

Presence of neutralizing antibodies against poliovirus implies immunity

Serum neutralization test is serotype specific; presence of antibodies against one type does not indicate immunity against other types

  
Echovirus Antibodies 0060053
Method: Semi-Quantitative Serum Neutralization

May be used to confirm disease occurrence if PCR or culture is not a viable option; includes echovirus 6, 7, 9, 11, 30

Mark specimens plainly as acute or convalescent

    
Poliovirus Antibodies 0060054
Method: Semi-Quantitative Serum Neutralization

May be used to confirm disease occurrence if PCR or culture is not a viable option; includes poliovirus 1-3

Mark specimens plainly as acute or convalescent

Presence of neutralizing antibodies against poliovirus implies immunity

Serum neutralization test is serotype specific; presence of antibodies against one type does not indicate immunity against other types

  
Coxsackie B Virus Antibodies 0060055
Method: Semi-Quantitative Serum Neutralization

May be used to confirm disease occurrence if PCR or culture is not a viable option; includes coxsackievirus B1-B6

Mark specimens plainly as acute or convalescent

    
Enterovirus and Parechovirus Detection by RT-PCR 2005730
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Use to confirm disease occurrence

    
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Coxsackie A9 Virus Antibodies by CF 0050503
Method: Semi-Quantitative Complement Fixation

May be used to confirm disease occurrence if PCR or culture is not a viable option
Viral Culture, Non-Respiratory, and Cytomegalovirus Rapid Culture 2006496
Method: Cell Culture/Immunofluorescence
Viral Culture, Respiratory, and Cytomegalovirus Rapid Culture 2006497
Method: Cell Culture/Immunofluorescence