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Enterovirus Surveillance --- United States, 2000--2001
Enteroviruses are common viruses associated with diverse clinical manifestations ranging from mild febrile illness to severe and potentially fatal syndromes including aseptic meningitis, encephalitis, neonatal systemic enteroviral disease, and paralytic poliomyelitis (1). A total of 64 enterovirus serotypes are recognized, including 61 nonpolio enteroviruses (2)*. Individual serotypes have different temporal patterns of circulation and often are associated with different clinical manifestations (1,4). This report describes temporal trends in reported enterovirus infections in the United States during 2000--2001, including widespread activity of two serotypes (echoviruses 13 and 18) that previously were detected rarely. Monitoring of circulating enterovirus serotypes helped identify these two agents as the primary causes of aseptic meningitis outbreaks in the United States in 2001. Further improvements in timeliness of reporting and geographic representation of the system are needed to allow more complete surveillance for enteroviruses.
Other than paralytic polio, diseases associated with enterovirus infections, including aseptic meningitis, are not nationally notifiable in the United States. The National Enterovirus Surveillance System (NESS) collects information on enterovirus serotypes and monitors temporal and geographic trends to help public health officials recognize and control outbreaks of enteroviral disease. Enterovirus detections from human specimens that are submitted for testing to participating laboratories are reported voluntarily to NESS along with basic demographic information, specimen type, and date of collection.
The number of laboratories participating in NESS increased from eight in 1999 to 21 in 2000 and 25 in 2001. During 2000--2001, a total of 27 laboratories participated in NESS, including 24 state public health laboratories, two private laboratories, and CDC's Enterovirus Laboratory, which receive specimens from multiple states. Enterovirus detections were reported in 36 states in 2000 and in 30 states in 2001. During 2000--2001, a total of 40 states reported enterovirus detections; of 2,319 reports, 1,925 (83.0%) were submitted by public health laboratories, 318 (13.7%) by private laboratories, and 76 (3.3%) by CDC. Of the 27 laboratories, three used genomic sequencing for enterovirus typing, and 24 used traditional antigenic typing methods. Serotypes were identified for 1,863 (80.3%) reports (Table 1). Consistent with the trend observed throughout the 1990s, the proportion of reported enteroviruses with unknown serotype increased from 13.1% during 1997--1999 to 19.7% during 2000--2001. Because the high proportion of unknown serotypes could lead to underestimating the number of individual enteroviruses, reports with unknown serotypes were excluded from the analysis of serotype distribution.
During 2000--2001, echovirus 18 and echovirus 13 were the predominant serotypes, accounting for 22.0% and 20.8% respectively of the reports with an identified serotype, followed by coxsackievirus B5 (11.9%), coxsackievirus B2 (6.3%), and echovirus 6 (6.1%) (Table 2). The serotype detected most commonly for 2000 was coxsackievirus B5 (34.4%). The predominant enteroviruses in 2001 were echoviruses 18 and 13, which accounted for 30.8% and 29.3%, respectively; echovirus 13 was reported in 24 states and echovirus 18 in 19 states. Illinois, Michigan, Tennessee, and Wisconsin reported the most echovirus 13 detections, and Illinois, Minnesota, New York, and Texas reported the most echovirus 18 detections. One vaccine-related type 3 poliovirus was reported in 2000.
The most common source for enterovirus detection was cerebrospinal fluid (980 [51.2%] of 1,915 reports indicating the source specimen), followed by stool or rectal swab (338 [17.7%]). Children aged <1 year accounted for 859 (44.0%) of 1,951 reports for which age data were available.
Reported by: State virology laboratory directors. Diagnostic Virology Laboratory, Associated Regional and Univ Pathologists Laboratories, Salt Lake City, Utah. Diagnostic Virology Laboratory, Texas Children's Hospital, Houston, Texas. S Oberste, PhD, A LaMonte, MPH, N Khetsuriani, MD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; V Hsu, MD, J Mullins, DVM, EIS officers, CDC.
Serotype-based enterovirus surveillance in the United States has five objectives. First, NESS data help to determine long-term patterns of circulation for individual serotypes (4). Second, the data are used to associate trends in enteroviral diseases with circulating serotypes such as viral meningitis--associated hospitalizations during periods of high activity of echoviruses 9 and 30 and lower numbers of these cases for years when group B coxsackieviruses predominate (CDC, unpublished data, 1988--1999). Third, the data are used to guide outbreak investigations. Fourth, because different serotypes have differential sensitivity to at least one candidate antienterovirus drug (5), information on circulating serotypes helps guide the development of new diagnostic tests and therapies. Finally, NESS monitors circulation of poliovirus strains to supplement poliovirus surveillance; this aspect of enterovirus surveillance will remain important until successful global poliovirus eradication ends the need for polio surveillance.
The findings in this report are consistent with previous observations on temporal variability of predominant serotypes. Of the 15 serotypes reported most commonly during 2000--2001, seven (coxsackieviruses A9, B2, and B4 and echoviruses 6, 9, 11, and 30) have appeared consistently among the 15 most common serotypes each year during 1993--1999 (6,7). Two enteroviruses (echovirus 18 and echovirus 13) that previously were rarely reported emerged as the predominant serotypes in 2001. Timely identification of increased activity by these serotypes helped guide investigation of outbreaks of aseptic meningitis reported to CDC in 2001 from six states (Alaska, Louisiana, Maryland, Mississippi, Montana, and Tennessee); all of these outbreaks were linked subsequently to one or both of these serotypes (8). For echovirus 13, this was the first report of widespread circulation in the United States and probably reflected the worldwide activity of this serotype that has been observed since 2000 (8).
Multiple factors might explain the increase in unknown serotypes, including limited availability of the appropriate typing antisera, high cost of reagents, and labor intensity of testing. The use of enterovirus typing based on genomic sequencing (9) could increase the proportion of identified serotypes, including those for which reagents are not readily available. The virtual absence of vaccine-related poliovirus isolates after 2000 is associated with the discontinuation of the use of oral polio vaccine in the United States beginning in 2000 (10).
The findings in this report are subject to at least two limitations. First, because of the voluntary and passive nature of NESS, the small number of reports for some states, and the lack of reporting or testing by others, these results might not be fully representative of the entire United States. Second, because many serotypes were not identified, the number of individual enteroviruses might be underestimated.
As laboratory participation in NESS increases, the data will become more representative geographically. More timely reporting from laboratories would allow NESS to provide frequent feedback in the form of an online enterovirus surveillance summary, which would increase the public health utility of this surveillance system.
* Echoviruses 22 and 23 have been reclassified recently as human parechoviruses 1 and 2, respectively, members of genus Parechovirus, which is related to (but distinct from) the genus Enterovirus. Epidemiologic and clinical features of these viruses are similar to those of the enteroviruses (3), and detection of these viruses continues to be reported to the National Enterovirus Surveillance System.
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