Viral Etiology of Acute Gastroenteritis in <2-Year-Old US Children in the Post-Rotavirus Vaccine Era.

BACKGROUND: The rotavirus disease burden has declined substantially since rotavirus vaccine was introduced in the United States in 2006. The aim of this study was to determine the viral etiology of acute gastroenteritis (AGE) in US children aged <2 years. METHODS: The New Vaccine Surveillance Network (NVSN) of geographically diverse US sites conducts active pediatric population-based surveillance in hospitals and emergency departments. Stool samples were collected from children aged <2 years with symptoms of AGE (n = 330) and age-matched healthy controls (HCs) (n = 272) between January and December 2012. Samples were tested by real-time reverse-transcriptase polymerase chain reaction assays {adenovirus (type 40 and 41), norovirus, parechovirus A, enterovirus, sapovirus, and astrovirus} and an enzyme immunoassay (rotavirus). All samples that tested positive were genotyped. RESULTS: Detection rates of pathogens in children with AGE versus those of HCs were, respectively, 23.0% versus 6.6% for norovirus (P < .01), 23.0% versus 16.0% for adenovirus (P = .08), 11.0% versus 16.0% for parechovirus A (P = .09), 11.0% versus 9.0% for enterovirus (P = .34), 7.0% versus 3.0% for sapovirus (P = .07), 3.0% versus 0.3% for astrovirus (P = .01), and 3.0% versus 0.4% for rotavirus (P = .01). A high prevalence of adenovirus was detected at 1 surveillance site (49.0% for children with AGE and 43.0% for HCs). Norovirus GII.4 New Orleans was the most frequently detected (33.0%) norovirus genotype. Codetection of >1 virus was more common in children with AGE (16.0%) than in HCs (10.0%) (P = .03). CONCLUSIONS: Norovirus, astrovirus, sapovirus, and rotavirus were detected significantly more in children with AGE than in HCs, and norovirus was the leading AGE-causing pathogen in US children aged <2 years during the year 2012.

Molecular identification of 13 new enterovirus types, EV79-88, EV97, and EV100-101, members of the species Human Enterovirus B.

Molecular methods have enabled the rapid identification of new enterovirus (EV) serotypes that are untypeable using existing neutralizing antisera. As a result, sequencing of the VP1 capsid gene has been developed as a surrogate for antigenic typing to distinguish enterovirus types. In this study, 17 enterovirus isolates from four countries were identified as members of 13 new types within the species Human Enterovirus B (HEV-B) by complete genome sequencing. Members of each of these new types are at least 75% identical to one another (91% amino acid identity) in VP1, but members of different types differ from one another and from other enteroviruses by at least 27% in nucleotide sequence (26% amino acid sequence difference). The complete P1 (capsid) sequences of the new types are at least 17% different from those of all other enterovirus serotypes (14.5% amino acid sequence difference), but they are highly conserved within a type (<8% amino acid sequence difference). For both VP1 and P1, the 17 isolates are monophyletic by type with respect to all other EV serotypes. The P2 and P3 sequences are closely related to those of other HEV-B viruses (>93% amino acid identity), confirming that the 17 new strains belong to HEV-B. We propose that these 17 isolates be classified as members of 13 new human enterovirus types, enteroviruses 79-88, 97, and 100-101.

Emergence of echovirus type 13 as a prominent enterovirus.

In 2001, increased activity of the rarely detected enterovirus echovirus type 13 (E13) was observed in the United States. This article describes the epidemiologic, clinical, and genetic characteristics of E13 activity in the United States in 2001, compared with E13 activity abroad in 2000-2002. In the United States, E13 accounted for 376 (24%) of the 1584 enterovirus isolates reported in 2001 (29% of the reported isolates had a known serotype), compared with 74 isolates reported during 1970-2000. Five states reported aseptic meningitis outbreaks associated with E13, for a total of 521 cases. All characterized E13 isolates from the United States, Europe, Asia, and Oceania recovered in 2000-2002 were at least 95% identical to each other in VP1 capsid gene sequence, but they were genetically distinct from E13 isolates recovered before 2000. Continued surveillance of enteroviruses is important to alert physicians and public health officials to changes in disease trends and to improve efficiencies of clinical intervention.

Molecular epidemiology and type-specific detection of echovirus 11 isolates from the Americas, Europe, Africa, Australia, southern Asia and the Middle East.

Echovirus 11 (E11) is among the most commonly isolated human enteroviruses. To examine the range of genetic variation within the E11 serotype, we determined the complete VP1 sequences for 53 geographically dispersed E11 strains isolated in 16 countries from 1953 to 2001. E11 sequences were monophyletic with respect to all other enterovirus serotypes. The sequences clustered into four monophyletic genogroups, A-D; members of each genogroup differed from one another by <20%. Isolates in different genogroups differed from one another by 19-28%. The E11 prototype strain, USA/CA53-Gregory, was the sole member of genogroup B. All recent US isolates were members of one of two discrete lineages within genogroup D. The well-characterized E11 antigenic variant, USA/CA63-Silva, was also a member of genogroup D. Members of genogroups A and C were antigenically similar to USA/CA53-Gregory, as measured by neutralization with anti-Gregory and anti-Silva antisera. Only USA/CA63-Silva was neutralized more efficiently by the anti-Silva antiserum; other genogroup D viruses were Gregory-like or intermediate in their neutralization phenotype. Recent non-US isolates were distributed in genogroups A, C and D. Sequence similarities among genogroup D isolates from North America, Europe, Asia, Australia and North Africa demonstrate that an E11 strain can spread rapidly over a wide geographic area. The aligned sequences were used to develop an E11-specific RT-PCR assay, using degenerate, inosine-containing primers, to amplify all members of all genogroups.

Prospective study of enteroviral infections and development of beta-cell autoimmunity. Diabetes autoimmunity study in the young (DAISY).

OBJECTIVE: To determine whether there is association between infection with enteroviruses and beta-cell autoimmunity in children at elevated risk of developing type 1 diabetes. BACKGROUND: Recent prospective and case-control studies of children who are at high risk of developing type 1 diabetes have suggested that enterovirus (EV) infections are a risk factor for beta-cell autoimmunity and type 1 diabetes. METHODS: A nested matched case-control study of incident cases of beta-cell autoimmunity within two prospective cohorts of genetically high-risk children (cases=26, controls=39). EV infection was detected by PCR of serum, saliva and rectal swab samples. RESULTS: Prior to autoimmunity conversion (or the equivalent age in controls), 11.5% of cases and 17.9% of controls were positive for EV infection. EV was detected in 19.5% of cases and 25.6% of controls over the whole follow-up period. Conditional logistic regression gave no evidence that the frequency of EV infection was associated with beta-cell autoimmunity. There was a trend for the mean number of EV infections found in EV-positive cases (2.2/case) to be higher than in EV-positive controls (1.2/control, P=0.08). However, there were no multiple infections prior to conversion in either cases or controls. CONCLUSIONS: There is no evidence from this study that EV infection is a risk factor for development of beta-cell autoimmunity. Further study is needed to assess whether persistent or repeated EV infections occur frequently in individuals with beta-cell autoimmunity.