• Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

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

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


  • 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


  • 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
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.

Enterovirus by PCR 0050249
Method: Qualitative Reverse Transcription Polymerase Chain Reaction


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


Slow growth; not ideal for acute identification

Enterovirus Typing 0065058
Method: Immunofluorescence

Enterovirus Antibody Panel 2003259
Method: Serum Neutralization/Complement Fixation


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

Poliovirus Antibodies 0060054
Method: Semi-Quantitative Serum Neutralization


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

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

General References

Ihekwaba UK, Kudesia G, McKendrick MW. Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections. Clin Infect Dis. 2008; 47(6): 783-9. PubMed

Nasri D, Bouslama L, Pillet S, Bourlet T, Aouni M, Pozzetto B. Basic rationale, current methods and future directions for molecular typing of human enterovirus. Expert Rev Mol Diagn. 2007; 7(4): 419-34. PubMed

Rhoades RE, Tabor-Godwin JM, Tsueng G, Feuer R. Enterovirus infections of the central nervous system. Virology. 2011; 411(2): 288-305. PubMed

Tyler KL. Emerging viral infections of the central nervous system: part 1. Arch Neurol. 2009; 66(8): 939-48. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Fisher MA, Stamper PD, Hujer KM, Love Z, Croft A, Cohen S, Bonomo RA, Carroll KC, Petti CA. Performance of the Phoenix bacterial identification system compared with disc diffusion methods for identifying extended-spectrum beta-lactamase, AmpC and KPC producers. J Med Microbiol. 2009; 58(Pt 6): 774-8. PubMed

Hymas WC, Aldous WK, Taggart EW, Stevenson JB, Hillyard DR. Description and validation of a novel real-time RT-PCR enterovirus assay. Clin Chem. 2008; 54(2): 406-13. PubMed

Polage CR, Petti CA. Assessment of the utility of viral culture of cerebrospinal fluid. Clin Infect Dis. 2006; 43(12): 1578-9. PubMed

Rittichier KR, Bryan PA, Bassett KE, Taggart W, Enriquez R, Hillyard DR, Byington CL. Diagnosis and outcomes of enterovirus infections in young infants. Pediatr Infect Dis J. 2005; 24(6): 546-50. PubMed

She RC, Crist G, Billetdeaux E, Langer J, Petti CA. Comparison of multiple shell vial cell lines for isolation of enteroviruses: a national perspective. J Clin Virol. 2006; 37(3): 151-5. PubMed

She RC, Preobrazhensky SN, Taggart EW, Petti CA, Bahler DW. Flow cytometric detection and serotyping of enterovirus for the clinical laboratory. J Virol Methods. 2009; 162(1-2): 245-50. PubMed

Taggart EW, Carroll KC, Byington CL, Crist GA, Hillyard DR. Use of heat labile UNG in an RT-PCR assay for enterovirus detection. J Virol Methods. 2002; 105(1): 57-65. PubMed

Medical Reviewers

Last Update: October 2016