States from which enterovirus-positive or parechovirus-positive results were reported, by surveillance system — United States, 2014–2016
Infections caused by enteroviruses (EV) and parechoviruses (PeV), members of the Picornaviridae family, are associated with various clinical manifestations, including hand, foot, and mouth disease; respiratory illness; myocarditis; meningitis; and sepsis; and can result in death. The genus
NESS is a passive, laboratory-based surveillance system that has been used to track EV and PeV reports since the 1960s and is the most comprehensive database of these reports in the United States. During 2014–2016, 11 laboratories reported to NESS, including nine state health departments, one municipal health department, and the CDC Polio and Picornavirus Laboratory Branch (PPLB). The largest contributor of reports to NESS was PPLB (1,553), which serves as a reference laboratory for jurisdictions with no or limited EV and PeV typing capacity. Testing data for untyped EV are also collected through NREVSS, a passive, laboratory-based surveillance system that collects aggregate reports of tests for EV and the percentage positive by week.
During 2014–2016, a total of 2,967 EV and PeV cases were reported to NESS, including 2,758 (93.0%) for which the type was known. Reports that included virus type represented 2,734 individual patients, among whom one virus type was identified from 2,726 (99.7%) and two types were identified from eight (0.3%). Among 2,370 (86.7%) patients with known sex, 1,422 (60.0%) were male, and among 1,351 (90.1%) for whom age was known, the median age was 4 years (interquartile range = 1–10 years). State of residence was known for 2,727 (99.7%) patients; among these, California was the most frequently reported state (413, 15.1%), followed by New York (366, 13.4%). Residents from all 50 states and the District of Columbia were represented (
States from which enterovirus-positive or parechovirus-positive results were reported, by surveillance system — United States, 2014–2016
| 2014 (N = 2,051) | 2015 (N = 370) | 2016 (N = 337) | 2014–2016 (N = 2,758) | ||||
|---|---|---|---|---|---|---|---|
| Type | No. (%) | Type | No. (%) | Type | No. (%) | Type | No (%) |
| Enterovirus D68 | 1,395 (68.0) | Echovirus 30 | 100 (27.0) | Enterovirus D68 | 138 (40.9) | Enterovirus D68 | 1,542 (55.9) |
| Coxsackievirus B3 | 98 (4.8) | Echovirus 18 | 61 (16.5) | Coxsackievirus A6 | 39 (11.6) | Echovirus 30 | 159 (5.8) |
| Coxsackievirus A6 | 86 (4.2) | Coxsackievirus A6 | 27 (7.3) | Coxsackievirus B4 | 18 (5.3) | Coxsackievirus A6 | 152 (5.5) |
| Echovirus 11 | 52 (2.5) | Echovirus 3 | 21 (5.7) | Echovirus 6 | 15 (4.5) | Echovirus 18 | 116 (4.2) |
| Echovirus 18 | 52 (2.5) | Echovirus 9 | 21 (5.7) | Parechovirus A3 | 15 (4.5) | Coxsackievirus B3 | 109 (4.0) |
| Echovirus 30 | 49 (2.4) | Coxsackievirus A9 | 19 (5.1) | Coxsackievirus A9 | 14 (4.2) | Echovirus 9 | 65 (2.4) |
| Parechovirus A3 | 43 (2.1) | Coxsackievirus B4 | 15 (4.1) | Coxsackievirus B2 | 10 (3.0) | Echovirus 11 | 64 (2.3) |
| Echovirus 9 | 41 (2.0) | Coxsackievirus B5 | 15 (4.1) | Echovirus 30 | 10 (3.0) | Parechovirus A3 | 62 (2.3) |
| Coxsackievirus B2 | 36 (1.8) | Echovirus 6 | 11 (3.0) | Coxsackievirus B1 | 9 (2.7) | Coxsackievirus B4 | 55 (2.0) |
| Coxsackievirus B5 | 32 (1.6) | Echovirus 25 | 10 (2.7) | Parechovirus A1 | 9 (2.7) | Coxsackievirus B5 | 53 (1.9) |
| Coxsackievirus A21 | 27 (1.3) | Coxsackievirus B3 | 9 (2.4) | Echovirus 11 | 8 (2.4) | Coxsackievirus B2 | 50 (1.8) |
| Enterovirus A71 | 23 (1.1) | Enterovirus D68 | 9 (2.4) | Coxsackievirus A10 | 7 (2.1) | Coxsackievirus A9 | 40 (1.5) |
| Coxsackievirus B4 | 22 (1.1) | Coxsackievirus A16 | 8 (2.2) | Coxsackievirus B5 | 6 (1.8) | Echovirus 6 | 40 (1.5) |
| Coxsackievirus A16 | 14 (0.7) | Coxsackievirus A5 | 6 (1.6) | Coxsackievirus A16 | 5 (1.5) | Echovirus 3 | 33 (1.2) |
| Echovirus 6 | 14 (0.7) | Coxsackievirus A10 | 5 (1.4) | Coxsackievirus A2 | 5 (1.5) | Coxsackievirus A16 | 27 (1.0) |
| — | — | Parechovirus A1* | 5 (1.4) | — | — | Coxsackievirus A21* | 27 (1.0) |
* Additional types are shown where the least common type shown occurred with equal frequency.
EV-D68 was the most frequently reported type during 2014–2016, accounting for 1,542 (55.9%) reports for this period, including 1,395 (68.0%) in 2014, when a large nationwide outbreak of respiratory disease associated with EV-D68 occurred. In 2015, EV-D68 accounted for only nine (2.4%) reports that included virus type. EV-D68 again constituted a large percentage (40.9%) of reported types in 2016, but the 138 reports represented <10% of the EV-D68 reports in 2014. Overall, 1,351 (86.7%) EV-D68 detections were from respiratory specimens; 154 (9.9%) were from specimens whose source was unknown.
After EV-D68, the most frequently reported types during 2014–2016 were echovirus 30 (159; 13.1% of 1,216 reports of non–EV-D68 types), coxsackievirus (CV)-A6 (152; 12.5%), echovirus 18 (116; 9.5%), and CV-B3 (109; 9.0%). Among reports in which a type other than EV-D68 was detected (1,466), the most frequently reported specimen source was cerebrospinal fluid (493; 38.0% of 1,298 specimens with known source), followed by throat/nasopharyngeal swab (487; 37.5%).
Data reported to NREVSS were used to evaluate trends in the percentage of tests positive for EV over time. Among 62,210 specimens from which virus isolation was attempted in 47 laboratories, 0.6% (347) tested positive for untyped EV; among 70,915 specimens tested in 72 laboratories by reverse transcription–polymerase chain reaction, 5,555 (7.8%) tested positive. The percentage of specimens testing positive peaked in summer or early fall for all years (
Percentage of specimens tested that were enterovirus-positive, by week and testing method used — National Respiratory and Enteric Virus Surveillance System, United States, 2014–2016
EV and PeV type surveillance in the United States was affected by the 2014 EV-D68 outbreak (
The objectives of type-based EV and PeV surveillance in the United States are to 1) help public health practitioners determine long-term patterns of circulation for individual types, 2) interpret trends in picornavirus-associated illnesses by associating them with circulating types, 3) support recognition of disease outbreaks associated with circulating types, 4) guide the development of new diagnostic tests and therapies, and 5) monitor detections of poliovirus, which is nationally notifiable in the United States.
Reports to NESS continue to be affected by changes in diagnostic practices. For example, qualitative pan-EV molecular testing has largely replaced traditional cell culture virus isolation techniques in clinical settings because it produces results in a clinically relevant time frame and is more analytically sensitive (
The findings in this report are subject to at least four limitations. First, NESS is a passive surveillance system that relies on voluntary reports from laboratories, and EV and PeV infections, except for polio, are not nationally notifiable in the United States. Second, to minimize the reporting burden for participating laboratories, patient-level clinical information is not routinely collected, so it is not possible to associate reported types with specific clinical manifestations or severity of illness. Third, typing tends to occur primarily during summer months, which might lead to underreporting of EV and PeV during other times of the year. Finally, although participating laboratories are encouraged to report monthly, reports are often delayed, making the timely compilation of data difficult.
Recent outbreaks, such as those of EV-D68–associated respiratory illness, CV-A6–associated severe hand, foot, and mouth disease, and a cluster of severe PeV-A3 infections among infants (
Enterovirus (EV) and parechovirus (PeV) infections can cause a variety of illnesses, ranging from asymptomatic infection to severe illness and death, and are divided into types.
During 2014–2016, reports of EV and PeV peaked in summer and early fall. Enterovirus D68 was the most frequently reported type (56%); echovirus 30, coxsackievirus A6, echovirus 18, and coxsackievirus B3 were also frequently reported.
Improved type-based surveillance can inform disease prevention strategies by supporting outbreak detection and guiding the development of new tests and interventions. Improving surveillance would require increasing the number and capacity of participating laboratories and timely reporting.