Enterovirus C

Abstract: Sixty-six human enterovirus serotypes have been identified by serum neutralization, but the molecular determinants of the serotypes are unknown. Since the picornavirus VP1 protein contains a number of neutralization domains, we hypothesized that the VP1 sequence should correspond with neutralization (serotype) and, hence, with phylogenetic lineage. To test this hypothesis and to analyze the phylogenetic relationships among the human enteroviruses, we determined the complete VP1 sequences of the prototype strains of 47 human enterovirus serotypes and 10 antigenic variants. Our sequences, together with those available from GenBank, comprise a database of complete VP1 sequences for all 66 human enterovirus serotypes plus additional strains of seven serotypes. Phylogenetic trees constructed from complete VP1 sequences produced the same four major clusters as published trees based on partial VP2 sequences; in contrast to the VP2 trees, however, in the VP1 trees strains of the same serotype were always monophyletic. In pairwise comparisons of complete VP1 sequences, enteroviruses of the same serotype were clearly distinguished from those of heterologous serotypes, and the limits of intraserotypic divergence appeared to be about 25% nucleotide sequence difference or 12% amino acid sequence difference. Pairwise comparisons suggested that coxsackie A11 and A15 viruses should be classified as strains of the same serotype, as should coxsackie A13 and A18 viruses. Pairwise identity scores also distinguished between enteroviruses of different clusters and enteroviruses from picornaviruses of different genera. The data suggest that VP1 sequence comparisons may be valuable in enterovirus typing and in picornavirus taxonomy by assisting in the genus assignment of unclassified picornaviruses.

Abstract: Problem Enteroviruses are common human viruses associated with various clinical syndromes, from minor febrile illness to severe, potentially fatal conditions (e.g., aseptic meningitis, paralysis, myocarditis, and neonatal enteroviral sepsis). Multiple enterovirus serotypes exist. Individual serotypes have different temporal patterns of circulation and often are associated with different clinical manifestations. Changes in circulating serotypes might be accompanied by large-scale outbreaks. Reporting period covered 1970-2005. DESCRIPTION OF SURVEILLANCE SYSTEM: The National Enterovirus Surveillance System (NESS) is a voluntary, passive surveillance system that has monitored trends in circulating enteroviruses since 1961. Enterovirus detections by serotype with specimen type, collection date, and demographic information are reported monthly by participating laboratories to CDC, which summarizes the data and disseminates the results. For this analysis, the available data set for 1970-1982 included only information on serotype and state for each report; complete records were available for 1983-2005. Results During 1970-2005, a total of 52,812 enterovirus detections were reported to NESS (29,772 of them during 1983-2005). Laboratory participation and the numbers of reports declined throughout the 1990s, but they increased again after 2000. The 15 most commonly reported enteroviruses accounted for 83.5% of reports with known serotype, and the five most commonly reported serotypes (echoviruses [E] 9, 11, 30, and 6, and coxsackievirus B5) accounted for 48.1%. Predominant serotypes and ranking of individual enteroviruses changed over time. Long-term circulation patterns for individual serotypes varied but were consistent with epidemic (e.g., E9, E13, E30, and coxsackievirus B5) or endemic patterns (e.g., coxsackieviruses A9, B2, B4, and enterovirus 71). Children aged /=20 years (male/female ratio: 1.4 and 0.9, respectively). Enterovirus detections had prominent summer-fall seasonality, with June-October accounting for 77.9% of reports with known month of specimen collection. Cerebrospinal fluid was the most common specimen type, followed by respiratory and fecal specimens (49.8%, 26.9%, and 13.6%, respectively). Death was reported for 3.3% of detections with known outcome. Infections with coxsackievirus B4 (odds ratio [OR] = 3.3; 95% confidence interval [CI] = 1.7-6.0), and human parechovirus 1 (formerly E22) (OR = 3.7; CI = 1.7-7.6) were associated with higher risk for death, and infections with E9 were associated with lower risk for death (OR = 0.1; CI = 0-0.4) than infections with other enteroviruses. Interpretation NESS data allowed identification and description of a core group of consistently circulating enteroviruses that probably determine the disease burden associated with enterovirus infections. These data also are helpful in guiding outbreak investigations and identifying targets for development of diagnostic assays and antivirals. Efforts to update the reporting system initiated in the early 2000s (i.e., simplification of reporting forms and transition to electronic reporting) resulted in a substantial increase in reporting compared with the late 1990s. Public health action Efforts to increase laboratory participation in NESS should continue to allow for more complete and accurate surveillance for enteroviruses. Further improvement in the timeliness of feedback through the development of a NESS website to allow access to historic data and to the information on circulating serotypes can provide additional incentives to public health laboratories to participate in NESS.

Abstract: An outbreak of paralytic poliomyelitis occurred in the Dominican Republic (13 confirmed cases) and Haiti (8 confirmed cases, including 2 fatal cases) during 2000-2001. All but one of the patients were either unvaccinated or incompletely vaccinated children, and cases occurred in communities with very low (7 to 40%) rates of coverage with oral poliovirus vaccine (OPV). The outbreak was associated with the circulation of a derivative of the type 1 OPV strain, probably originating from a single OPV dose given in 1998-1999. The vaccine-derived poliovirus associated with the outbreak had biological properties indistinguishable from those of wild poliovirus.

Abstract: Human enteroviruses (family Picornaviridae) are the major cause of aseptic meningitis and also cause a wide range of other acute illnesses, including neonatal sepsis-like disease, acute flaccid paralysis, and acute hemorrhagic conjunctivitis. The neutralization assay is usually used for enterovirus typing, but it is labor-intensive and time-consuming and standardized antisera are in limited supply. We have developed a molecular typing system based on reverse transcription-PCR and nucleotide sequencing of the 3′ half of the genomic region encoding VP1. The standard PCR primers amplify approximately 450 bp of VP1 for most known human enterovirus serotypes. The serotype of an “unknown” may be inferred by comparison of the partial VP1 sequence to those in a database containing VP1 sequences for the prototype strains of all 66 human enterovirus serotypes. Fifty-one clinical isolates of known serotypes from the years 1991 to 1998 were amplified and sequenced, and the antigenic and molecular typing results agreed for all isolates. With one exception, the nucleotide sequences of homologous strains were at least 75% identical to one another (>88% amino acid identity). Strains with homologous serotypes were easily discriminated from those with heterologous serotypes by using these criteria for identification. This method can greatly reduce the time required to type an enterovirus isolate and can be used to type isolates that are difficult or impossible to type with standard immunological reagents. The technique may also be useful for the rapid determination of whether viruses isolated during an outbreak are epidemiologically related.