Seasonality, Clinical Characteristics, and Outcomes of Respiratory Syncytial Virus Disease by Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. METHODS: During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. RESULTS: Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. CONCLUSIONS: Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.

Medical Costs of Respiratory Syncytial Virus-Associated Hospitalizations and Emergency Department Visits in Children Aged Younger Than 5 Years: Observational Findings from the New Vaccine Surveillance Network, 2016-2019.

OBJECTIVE: To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network. STUDY DESIGN: We used accounting and prospective surveillance data from 6 pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n = 2007) and ED visits (n = 1267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices. We examined RSV-associated medical costs by care setting using descriptive and bivariate analyses. We assessed associations between known RSV risk factors and hospitalization costs and length of stay using χ2 tests of association. RESULTS: The median cost was $7100 (IQR $4006-$13 355) per hospitalized child and $503 (IQR $387-$930) per ED visit. Eighty percent (n = 2628) of our final sample were children aged younger than 2 years. Fewer weeks' gestational age was associated with greater median costs in hospitalized children (P < .001, ≥37 weeks of gestational age: $6840 [$3905-$12 450]; 29-36 weeks of gestational age: $7721 [$4362-$15 274]; <29 weeks of gestational age: $9131 [$4518-$19 924]). Infants born full term accounted for 70% of the total expenditures in our sample. Almost three quarters of the health care dollars spent originated in children younger than 12 months of age, the primary age group targeted by recommended RSV prophylactics. CONCLUSIONS: Reducing the cost burden for RSV-associated medical care in young children will require prevention of RSV in all young children, not just high-risk infants. Newly available maternal vaccine and immunoprophylaxis products could substantially reduce RSV-associated medical costs.

Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season - New Vaccine Surveillance Network, October 2023-February 2024.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8-19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%-96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19-76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.

Interim Estimates of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

Sustained Within-season Vaccine Effectiveness Against Influenza-associated Hospitalization in Children: Evidence From the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020.

BACKGROUND: Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited. METHODS: We conducted a prospective, test-negative study of children 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% × (1 - odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression. RESULTS: Of 8430 children, 4653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were vaccinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs 57%, P < .001); overall VE against hospitalization was 53% (95% confidence interval [CI]: 46, 60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%, 12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4000, P = .275). Odds of hospitalization increased 2.9% (95% CI: -5.4%, 11.8%) and 9.6% (95% CI: -7.0%, 29.1%) per month in children ≤8 years (n = 3084) and 9-17 years (n = 916), respectively. These findings were not statistically significant. CONCLUSIONS: We observed minimal, not statistically significant within-season declines in VE. Vaccination following current Advisory Committee on Immunization Practices (ACIP) guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.

SARS-CoV-2 Epidemiology and COVID-19 mRNA Vaccine Effectiveness Among Infants and Children Aged 6 Months-4 Years - New Vaccine Surveillance Network, United States, July 2022-September 2023.

SARS-CoV-2 infection in young children is often mild or asymptomatic; however, some children are at risk for severe disease. Data describing the protective effectiveness of COVID-19 mRNA vaccines against COVID-19-associated emergency department (ED) visits and hospitalization in this population are limited. Data from the New Vaccine Surveillance Network, a prospective population-based surveillance system, were used to estimate vaccine effectiveness using a test-negative, case-control design and describe the epidemiology of SARS-CoV-2 in infants and children aged 6 months-4 years during July 1, 2022-September 30, 2023. Among 7,434 children included, 5% received a positive SARS-CoV-2 test result, and 95% received a negative test result; 86% were unvaccinated, 4% had received 1 dose of any vaccine product, and 10% had received ≥2 doses. When compared with receipt of no vaccines among children, receipt of ≥2 COVID-19 mRNA vaccine doses was 40% effective (95% CI = 8%-60%) in preventing ED visits and hospitalization. These findings support existing recommendations for COVID-19 vaccination of young children to reduce COVID-19-associated ED visits and hospitalization.

Vaccine Effectiveness Against Influenza Hospitalization and Emergency Department Visits in 2 A(H3N2) Dominant Influenza Seasons Among Children <18 Years Old-New Vaccine Surveillance Network 2016-2017 and 2017-2018.

Studies have shown egg-adaptive mutations in influenza vaccine strains that might have impaired protection against circulating A(H3N2) influenza viruses during the 2016-2017 and 2017-2018 seasons. We used the test-negative design and multivariable models to assess vaccine effectiveness against influenza-associated hospitalization and emergency department visits among children (<18 years old) during the 2016-2017 and 2017-2018 seasons. Effectiveness was 71% (95% confidence interval, 59%-79%), 46% (35%-55%), and 45% (33%-55%) against A(H1N1)pdm09, A(H3N2), and B viruses respectively, across both seasons. During high-severity seasons with concerns for vaccine mismatch, vaccination offered substantial protection against severe influenza outcomes requiring hospitalization or emergency department visits among children.

Understanding Variation in Rotavirus Vaccine Effectiveness Estimates in the United States: The Role of Rotavirus Activity and Diagnostic Misclassification.

BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children's stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year-vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive-vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year-vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive-vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021.

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years† with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.

Rotavirus Genotype Trends and Gastrointestinal Pathogen Detection in the United States, 2014-2016: Results From the New Vaccine Surveillance Network.

BACKGROUND: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014-2016. METHODS: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. RESULTS: A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease was highest in children < 3 years of age. Four G types (G1, G2, G9, and G12) accounted for 94.6% of strains while 2 P types (P[4] and P[8]) accounted for 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all 3 seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty-four percent of RVA-positive specimens contained other AGE pathogens. CONCLUSIONS: G12P[8] predominated over 3 seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the postvaccine era.

Effect of Vaccination on Preventing Influenza-Associated Hospitalizations Among Children During a Severe Season Associated With B/Victoria Viruses, 2019-2020.

BACKGROUND: The 2019-2020 influenza season was characterized by early onset with B/Victoria followed by A(H1N1)pdm09 viruses. Emergence of new B/Victoria viruses raised concerns about possible vaccine mismatch. We estimated vaccine effectiveness (VE) against influenza-associated hospitalizations and emergency department (ED) visits among children in the United States. METHODS: We assessed VE among children aged 6 months-17 years with acute respiratory illness and ≤10 days of symptoms enrolled at 7 pediatric medical centers in the New Vaccine Surveillance Network. Combined midturbinate/throat swabs were tested for influenza virus using molecular assays. Vaccination history was collected from parental report, state immunization information systems, and/or provider records. We estimated VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive vs negative for influenza. RESULTS: Among 2029 inpatients, 335 (17%) were influenza positive: 37% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 52%-71%) for influenza-related hospitalizations, 54% (95% CI, 33%-69%) for B/Victoria viruses, and 64% (95% CI, 49%-75%) for A(H1N1)pdm09. Among 2102 ED patients, 671 (32%) were influenza positive: 47% with influenza B/Victoria alone and 42% with influenza A(H1N1)pdm09 alone. VE was 56% (95% CI, 46%-65%) for an influenza-related ED visit, 55% (95% CI, 40%-66%) for B/Victoria viruses, and 53% (95% CI, 37%-65%) for A(H1N1)pdm09. CONCLUSIONS: Influenza vaccination provided significant protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the 2 predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus subclade.

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020.

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via local (3) and passive national (4) surveillance. EV-D68 detections were limited in 2017, but substantial circulation was observed in 2018 (5). To assess recent levels of circulation, EV-D68 detections in respiratory specimens collected from patients aged <18 years* with ARI evaluated in emergency departments (EDs) or admitted to one of seven U.S. medical centers† within the New Vaccine Surveillance Network (NVSN) were summarized. This report provides a provisional description of EV-D68 detections during July-November in 2018, 2019 and 2020, and describes the demographic and clinical characteristics of these patients. In 2018, a total of 382 EV-D68 detections in respiratory specimens obtained from patients aged <18 years with ARI were reported by NVSN; the number decreased to six detections in 2019 and 30 in 2020. Among patients aged <18 years with EV-D68 in 2020, 22 (73%) were non-Hispanic Black (Black) persons. EV-D68 detections in 2020 were lower than anticipated based on the biennial circulation pattern observed since 2014. The circulation of EV-D68 in 2020 might have been limited by widespread COVID-19 mitigation measures; how these changes in behavior might influence the timing and levels of circulation in future years is unknown. Ongoing monitoring of EV-D68 detections is warranted for preparedness for EV-D68-associated ARI and AFM.

Continued Evidence of the Impact of Rotavirus Vaccine in Children Less Than 3 Years of Age From the United States New Vaccine Surveillance Network: A Multisite Active Surveillance Program, 2006-2016.

BACKGROUND: Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. METHODS: Children < 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006-2007 defined as the prevaccine period and 2008-2016 as the postvaccine period. Rotavirus genotype trends were compared over time. RESULTS: Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (P < .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. CONCLUSIONS: The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children < 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes.

Validation of Acute Gastroenteritis-related International Classification of Diseases, Clinical Modification Codes in Pediatric and Adult US Populations.

International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes.

Enterovirus D68-Associated Acute Respiratory Illness - New Vaccine Surveillance Network, United States, July-October, 2017 and 2018.

In the fall of 2014, an outbreak of enterovirus D68 (EV-D68)-associated acute respiratory illness (ARI) occurred in the United States (1,2); before 2014, EV-D68 was rarely reported to CDC (2,3). In the United States, reported EV-D68 detections typically peak during late summer and early fall (3). EV-D68 epidemiology is not fully understood because testing in clinical settings seldom has been available and detections are not notifiable to CDC. To better understand EV-D68 epidemiology, CDC recently established active, prospective EV-D68 surveillance among pediatric patients at seven U.S. medical centers through the New Vaccine Surveillance Network (NVSN) (4). This report details a preliminary characterization of EV-D68 testing and detections among emergency department (ED) and hospitalized patients with ARI at all NVSN sites during July 1-October 31, 2017, and the same period in 2018. Among patients with ARI who were tested, EV-D68 was detected in two patients (0.8%) in 2017 and 358 (13.9%) in 2018. Continued active, prospective surveillance of EV-D68-associated ARI is needed to better understand EV-D68 epidemiology in the United States.

Idiopathic T cell lymphopenia identified in New York State Newborn Screening.

Quantification of T-cell receptor excision circles (TRECs) for newborn screening for SCID has advanced the diagnosis of severe combined immune deficiency (SCID). However, it has led to the identification of infants with T cell lymphopenia without known cause. The clinical characteristics, appropriate laboratory monitoring, and outcomes of patients remain unclear. We performed a retrospective review of clinical and laboratory studies for 26 infants collected from 7 New York State referral centers from 2010 to 2016 with low TRECs (mean, 70copies/µl) and subnormal CD3 counts (mean, 1150/cubicmm). Over time absolute CD3 counts increased in 17 and decreased in 9; 22 (85%) have done well clinically regardless of absolute T cell values. Additional infants with TCL will continue to be identified in newborn screening panels. While most patients seem to do well clinically, parameters for diagnosis and monitoring have yet to be formalized, and additional information needs to be collected, causes and outcomes reported.

Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.

BACKGROUND: Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3-7 geographically diverse sites in the United States since 2006. METHODS: Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. RESULTS: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%-3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSIONS: Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure.

Full genome characterization of the first G3P[24] rotavirus strain detected in humans provides evidence of interspecies reassortment and mutational saturation in the VP7 gene.

During the 2008-2009 rotavirus season of the Centers for Disease Control and Prevention New Vaccine Surveillance Network, one case of paediatric acute gastroenteritis associated with a rotavirus G14P[24] strain was identified. This was the first detection of the genotype G14 and P[24] in humans, and the first detection of the G14P[24] combination. To gain an insight into the origins and the evolution of this strain, we determined the complete ORF sequences of all 11 genes. A majority of the genes identified were similar to the simian strain TUCH, except for the VP1 and VP7 genes that clustered only distantly with the bovine and equine strains, respectively. In addition, this strain carried AU-1-like NSP2 and NSP4 genes. Using codon-partitioning and protein-based phylogenetic approaches, we determined that the VP7 genotype of strain 2009727118 was actually G3; therefore, the proposed full genomic classification of the 2009727118 strain is G3-P[24]-I9-R2-C3-M3-A9-N3-T3-E3-H6. These findings indicate the possibility that the 2009727118 strain originated by interspecies transmission and multiple reassortment events involving human, bovine and equine rotaviruses, resulting in the introduction of some genes into the genome of simian rotaviruses. Additionally, we found evidence of mutational saturation in the third codon position of the VP7 ORF which presented an issue with homoplasy in phylogenetic analyses.