Based on sequence data and analysis of the VP1 region, the 66 or more human enterovirus (HEV) serotypes of the Picornaviridae family are classified into 5 species (HEV A-D and polioviruses).¹ HEV-B contains all the echoviruses.¹ Parechovirus, the most recently recognized genus of Picornaviridae, includes type 1 (formerly echovirus-22) and type 2 (formerly echovirus-23)² and is associated with diarrhea and less frequently with myocarditis, aseptic meningitis and encephalitis, involving perhaps 12% of patients with CNS symptoms² (cf. Coxsackie A and B Virus herein.)

Echoviruses cause nonspecific rashes, aseptic meningitis, encephalitis, hepatitis,³ chronic meningitis, meningoencephalitis, especially in young infants, and myositis, possibly including masticator myopathy.^4-6 Aseptic meningitis is due to viruses E13 (USA),⁷ E30 (Taiwan),^8,9 E16 (Cuba),¹⁰ and E11 (Israel)¹¹; Echovirus 30 in the West and echovirus 9 in the East have reappeared as major causes of aseptic meningitis in the US.¹²  E7 is manifest as hand-foot-mouth disease, which is endemic in some areas and can result in severe left ventricular dysfunction and extensive CNS damage due to encephalomyelitis.¹³ RNA from coxsackie B3 virus, another member of the HEV-B species, is found in ~ 40-50% of patients with dilated cardiomyopathy (cf. #14); HEV-Bs, including CVB3 and ECHO viruses, probably cause human myocarditis¹⁵ for which good diagnostic tools are only now becoming available. (See Adenoviruses)

In general, ECHO virus-specific EIAs are not available or are insufficiently sensitive,¹⁰ but sequencing is expected to yield common peptide sequences that will allow serology less tedious than neutralization.

Isolation from the CSF is diagnostic for meningitis; isolation of a virus from the nasopharynx or stool is only suggestive but corroboration of an etiologic role should be obtained by demonstrating a serologic response, including neutralization of tissue culture infections. Antibodies can be measured by HAI, neutralization or CF. In echovirus infection, homotypic and heterotypic antibody responses can occur.¹⁶ Antigenic cross-reactions with other enteroviruses such as coxsackievirus A and B is common. In addition, there are 30 serotypes of echovirus with great antigenic variations even within the same serotype;¹⁷ serology alone is usually unhelpful unless known serotypes are circulating in the community.

Development of cDNA probes for direct detection of viral RNA in skeletal muscle specimens¹⁸ and other techniques for detection of echoviruses¹⁹ show promise for rapid diagnosis of early or persistent disease. Direct sequencing of PCR products from specific regions of the viral genome shows sufficient diversity to enable future genotyping of different echovirus strains.²⁰

cDNA probes suggest involvement of echoviruses in adult-onset myositis.¹⁸ RT-PCR for detection promises specific, sensitive detection, including in blood, that will enhance diagnosis; RT-PCR for sequencing will provide common sites/targets for viral therapy. Already sequencing allows identification in serum and subsequent confirmation by detection of type-specific neutralizing antibodies.²⁰  Molecular typing, together with a serotype-specific E33 PCR improved and speeded the investigation of an outbreak of Echovirus 33 that could not be definitively typed by antibody neutralization.²¹