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Enterovirus PCR

Enteroviruses belong to the RNA picornavirus family, which also includes rhinovirus and hepatitis A. The enterovirus group includes polio, echo and group A & B coxsackieviruses. There are 67 distinct enterovirus serotypes, which are responsible for a broad spectrum of disease. The nonpolio enteroviruses include 23 group A coxsackieviruses, 6 goup B coxsackieviruses and 29 echoviruses.

Enteroviruses are transmitted by the fecal-oral or respiratory routes and from mother to infant in the peripartum period. Enterovirus implants and replicates in susceptible tissues of the pharynx or intestine. After multiplying in the submucosal lymphatics, the virus spreads to regional lymph nodes, followed by dissemination to target organs such as the central nervous system, heart and skin.

Enteroviruses are found worldwide and throughout the year, although in temperate climates infections are more prevalent in summer and fall. An estimated 50 to 80% of nonpolio-enteroviral infections are completely asymptomatic. Seventy five percent of reported enteroviral infections occur in children younger than 15 years. In the United States, attack rates are highest in infants younger than 1 year and infants in diapers are the most efficient disseminators of infection. The most common presentation of infection in infants and children is nonspecific febrile illness. However, many other symptoms may also occur including:

  • Respiratory symptoms ranging from pharyngitis to pneumonia
  • Skin exanthems
  • GI symptoms including vomiting & diarrhea
  • Hepatitis
  • Acute hemorrhagic conjunctivitis
  • Myopericarditis
  • Neurologic manifestations including meningitis, encephalitis, and paralysis.

Viral cultures are useful in diagnosis of enteroviral infection. With suspected respiratory or gastrointestinal infection, virus is best isolated from throat, stool or rectal swab specimens and recovery is optimized by submission of samples from multiple sites. Cultures from these sites generally become positive within 3 to 7 days. Although it is possible to subgroup enterovirus isolates from culture, this information generally has no clinical relevance. Enteroviral infections may also be diagnosed retrospectively by serology.

Enterovirus is a leading cause of aseptic meningitis in adults and children that occurs seasonally in the Midwest United States, generally in summer and fall. The sensitivity of viral culture of cerebrospinal fluid (CSF) for enterovirus is 30 to 75% and an average of 7 days is required for isolation. Thus, viral culture is not an optimal test in the evaluation of meningitis. Alternatively, enterovirus PCR has become standard practice due to its much-improved sensitivity and turnaround time. Several studies have demonstrated the positive impact of PCR in the management of patients hospitalized for meningitis. For example, one study demonstrated that pediatric inpatients who had PCR done prior to discharge had significantly fewer ancillary tests ordered, less antibiotic use, and shorter hospital stays.

A survey of aseptic meningitis cases admitted to the Emergency Department in Kansas City over the last three years showed an average length of stay of 2.8 days with average hospital charges of $14,050. Typically, patients were admitted to await results of bacterial cerebrospinal fluid (CSF) cultures and viral CSF PCR studies, as well as receiving IV antibiotics. A pilot study was undertaken in 2004 to evaluate the effectiveness of performing CSF Enterovirus PCR on a STAT basis. Results were provided within 3-4 hours, so that patients with a typical aseptic meningitis presentation based on clinical findings and other CSF results, and a positive Enterovirus PCR could be discharged from the ED. There were 28 STAT PCR’s performed for the ED during the pilot study. Eight specimens tested positive (29%), and the majority of those patients avoided admission to the hospital. Some were discharged from the ED within minutes of the physician receiving the result. Because of the significant impact of the pilot study on patient outcomes, STAT Enterovirus PCR testing is recommended during peak season.

Specimen requirement is 1 mL CSF submitted in a sterile, screw-capped tube. The specimen should be refrigerated if transportation will be delayed. Specimens grossly contaminated with blood may inhibit PCR and cause false-negative results.

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