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I. DEFINITION

Enteroviruses (EVs) and parechoviruses (HPeVs) are a large group of viral pathogens represented by 2 different genera of the family Picornaviridae. They are all made of a single strand of RNA in a capsid of individually distinct polypeptides. The capsid proteins impart antigenicity and facilitate transfer of RNA into the cells of newly infected hosts.

  1. Enteroviruses. The genus of EVs traditionally consisted of 5 groups, each with a well-known human pathogenicity: coxsackie A viruses, coxsackie B virus, echoviruses, EVs 68 to 71, and poliovirus. The new classification (based on viral genomic structure) groups nonpolio EVs into 4 species: human EV types A, B, C, and D. Although they were reclassified, many authorities continue to use their original names.

  2. Parechoviruses. The genus of HPeVs is made up of at least 16 types. HPeV1 and HPeV2 previously were classified as echoviruses 22 and 23, respectively. HPeVs (especially HPeV3) have been implicated in severe neonatal diseases including sepsis, hepatitis and coagulopathy, and/or meningoencephalitis with long-term sequelae. Interestingly, severe central nervous system (CNS) disease is associated with normal inflammatory markers and little or no cerebrospinal fluid (CSF) pleocytosis in the majority of cases.

II. INCIDENCE

  1. Enteroviruses. EVs have worldwide distribution and produce human illness of varying severity, from mild coryza to life-threatening multisystem disease. The diseases have some seasonal variation with increased incidence during summer and fall in temperate zones, but there is little seasonal variation in tropical areas.

    Enteroviral infections are spread by fecal–oral and respiratory routes and in neonates transplacentally, perinatally, and possibly via breast feeding. Incubation periods are typically 3 to 6 days. All subgroups of EVs are linked to nursery and neonatal intensive care unit (NICU) outbreaks. Enteroviral infections are not reportable nationally, and the current incidence of EV illness among neonates is unknown. However, there is a National Enterovirus Surveillance System (NESS), which is a passive surveillance system that has been collecting laboratory data on types of EV and HPeV in the United States since the 1960s. During 2009 to 2013, 2724 specimens representing 2532 patients tested positive for EV and HPeV were reported to NESS; 39% were from children <1 year of age, and coxsackie A6 virus (CVA6) was the most reported type overall. The most common serotypes associated with neonatal infections are EV6, EV9, and EV11 and CVB2, CVB4, and CVB5. In 2014, EVD68 caused a nationwide outbreak, with many patients admitted to intensive care units for respiratory symptoms.

  2. Parechoviruses. During NESS 2009 to 2013 surveillance, HPeV3 was the most common isolate of that genus (12.3%) and was identified as an important cause of neonatal sepsis. A report from Edinburgh, Scotland, for EV surveillance from 2006 to 2010 revealed an incidence of 2.8% for HPeV, but for infants <3 months of age, HPeV3 was also the predominant isolate (22%–25%). A recent study from Ireland found an HPeV infection rate of 13% in infants being tested for late-onset neonatal sepsis.

III. PATHOPHYSIOLOGY

  1. Enteroviruses. EVs manifest disease in nearly all body systems. Paradoxically, signs of disease can range from mild to life threatening within the same serotype. Host susceptibility (including absence of serotype-specific maternal neutralizing antibody) seems to be the most important predisposing factor. For the great majority of children and adults, enteroviral illnesses are mild, but for the neonate, EVs can cause serious multiorgan dysfunction and death (sepsis-like illness, meningoencephalitis myocarditis, hepatitis, coagulopathy, and ...

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