BACKGROUND: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). METHODS: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. RESULTS: Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. CONCLUSIONS: Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

A modified Vesikari severity score (MVSS) is a useful research tool for assessing severity of acute gastroenteritis. We present a MVSS for studies in which a follow-up assessment of symptoms cannot be obtained. The MVSS significantly correlated with other markers of severity, including illness duration and work and school absenteeism.

BACKGROUND: Most U.S. acute gastroenteritis (AGE) episodes in children are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children. METHODS: We tested and typed stool specimens collected between December 2011 to June 2016 from one NVSN site in Kansas City for the three viruses, and calculated hospitalization and emergency department (ED) detection rate. RESULTS: Of 3,205 collected specimens, 2,453 (76.5%) were from AGE patients (339 inpatients and 2,114 ED patients) and 752 (23.5%) were from healthy controls (HC). In AGE patients, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%) and AdV40/41 in 101 (4.5%) of 2249 patients. In HC, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent.Hospitalization rates were 5 (AdV40/41), 4 (astrovirus) and 8 (sapovirus) per 100,000 children <11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus) and 5.3 (sapovirus) per 1000 children <5 years old. CONCLUSIONS: Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.

OBJECTIVE: Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. METHODS: From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. RESULTS: Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. CONCLUSIONS: Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.

INTRODUCTION: From April 1 to May 31, 2022, Grand Canyon National Park received increased acute gastroenteritis reports. Pooled portable toilet specimens identified norovirus genogroups I and II. We sought to determine outbreak transmission contributors and individual risk factors while rafting or backpacking in the park. METHODS: Grand Canyon rafters and backpackers were surveyed online from June 13-July 8, 2022, and a Cox proportional hazards model was used to identify predictors associated with illness and adjusted for potential confounding factors. RESULTS: Among 762 surveys, 119 cases and 505 well persons submitted complete survey data. Illness among rafters was associated with interaction with ill persons during the trip (adjusted hazard ratio [adjHR] = 3.4 [95%CI 2.3-5.0]) and lack of any hand hygiene (1.2 [0.7-1.9]) or use of only sanitizer or water (1.6 [1.04-2.6]) before snacks. Younger rafters had higher illness rates compared to those ≥60 y (1.5 [1.2-1.8] for ages 40-59 and 2.2 [1.4-3.5] for ages <40 y). CONCLUSIONS: Person-to-person transmission likely accounted for the widespread outbreak. Future outbreak mitigation efforts on river trips could focus on symptom screening before the trip starts, prompt separation of ill and well passengers, strict adherence to hand hygiene with soap and water, minimizing social interactions among rafting groups, and widespread outbreak notices and education to all park users.

Importance The impact of non-pharmaceutical interventions (NPIs) in response to the SARS-CoV-2 pandemic on incidence of other infectious diseases is still being assessed.Objective To determine if the observed change in reported norovirus outbreaks in the United States was best explained by underreporting, seasonal trends, or reduced exposure due to NPIs. We also aimed to assess if the change in reported norovirus outbreaks varied by setting.Design An ecologic, interrupted time series analysis of norovirus outbreaks from nine states reported to the National Outbreak Reporting System (NORS) from July 2012–July 2020.Setting Surveillance data from Massachusetts, Michigan, Minnesota, Ohio, Oregon, South Carolina, Tennessee, Virginia, and Wisconsin were included in the analysis.Participants 9,226 reports of acute gastroenteritis outbreaks with norovirus as an epidemiologically suspected or laboratory-confirmed etiology were included in the analysis, resulting in more than 8 years of follow up. Outbreak reports from states that participated in NoroSTAT for at least 4 years were included in the analysis (range: 4–8 years).Exposure The main exposure of interest was time period: before (July 2012–February 2020) or after (April 2020–July 2020) the start of NPIs in the United StatesMain outcome The main outcome of interest was monthly rate of reported norovirus outbreaks. As a secondary outcome, we also examined the average outbreak size.Results We found that the decline in norovirus outbreak reports was significant for all 9 states considered (pooled incidence rate ratio (IRR) comparing April 2020-July 2020 vs. all pre-COVID months for each state= 0.14, 95% CI: 0.098, 0.21; P=&lt;0.0001), even after accounting for typical seasonal decline in incidence during the summer months. These patterns were similar across a variety of settings, including nursing homes, child daycares, healthcare settings, and schools. The average outbreak size was also reduced by 61% (95% CI: 56%, 42.7%; P=&lt;0.0001), suggesting that the decline does not reflect a tendency to report only more severe outbreaks due to strained surveillance systems, but instead reflects a decline in incidence.Conclusions and relevance While NPIs implemented during the spring and summer of 2020 were intended to reduce transmission of SARS-CoV-2, these changes also appear to have impacted the incidence of norovirus, a non-respiratory pathogen. These results suggest that NPIs may provide benefit for preventing transmission of other human pathogens, reducing strain to health systems during the continued SARS-CoV-2 pandemic.Disclaimer The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention (CDC).Competing Interest StatementBAL reports grants and personal fees from Takeda Pharmaceuticals and personal fees from World Health Organization outside the submitted work.Funding StatementBAL and ANMK were supported by NIH/NIGMS (R01 GM124280, R01 GM 12480-03S1) and NSF (2032084).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval to use the data for the present work was provided by the Norovirus Outbreak Reporting System team upon submitting a formal data request. For the present analysis, data were only provided at the outbreak level and no personally identifiable data were used such that the released data meets federal guidelines for ethical compliance in release of surveillance data, as described in the Public Health Service Act. The original data collection is from public health surveillance and is covered by section 301 of the Public Health Service Act (42 USC 241). As a surveillance activity, the initial data collection is considered not to be research with human subjects based on these guidelines.All necessary patient/participa t consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesNorostat data are publicly available at https://www.cdc.gov/norovirus/reporting/norostat/data-table.html. More detailed Norostat data can be obtained by sending a formal data request to the Centers for Disease Control and Prevention at NORSDashboard@cdc.gov. https://www.cdc.gov/norovirus/reporting/norostat/data-table.html

OBJECTIVE: To describe demographics, pathogen distribution/seasonality, and risk factors in children seeking care for acute gastroenteritis (AGE) at a midwestern US emergency department during 5 postrotavirus vaccine years (2011-2016), and further, to compare the same data with matched healthy controls (HC). STUDY DESIGN: AGE and HC participants <11 years old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016 were included. AGE was defined as ≥3 diarrhea episodes or ≥1 vomiting episode. Each HC's age was similar to an AGE participant's age. Pathogens were analyzed for seasonality effects. Participant risk factors for AGE illness and pathogen detections were compared between HC and a matched subset of AGE cases. RESULTS: One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%). Norovirus was detected most frequently among AGE (n = 568 [22.7%]) and second-most frequently in HC (n = 39 [6.8%]). Rotavirus was the second most frequently detected pathogen among AGE (n = 196 [7.8%]). Children with AGE were significantly more likely to have reported a sick contact compared with HC, both outside the home (15.6% vs 1.4%; P < .001) and inside the home (18.6% vs 2.1%; P < .001). Daycare attendance was higher among children with AGE (41.4%) compared with HC (29.5%; P < .001). The Clostridium difficile detection rate was slightly higher among HC (7.0%) than AGE (5.3%). CONCLUSIONS: Norovirus was the most prevalent pathogen among children with AGE. Norovirus was detected in some HC, suggesting potential asymptomatic shedding among HC. The proportion of AGE participants with a sick contact was approximately 10 times greater than that of HC.

BACKGROUND: To reduce the burden from the COVID-19 pandemic in the United States, federal and state local governments implemented restrictions such as limitations on gatherings, restaurant dining, and travel, and recommended non-pharmaceutical interventions including physical distancing, mask-wearing, surface disinfection, and increased hand hygiene. Resulting behavioral changes impacted other infectious diseases including enteropathogens such as norovirus and rotavirus, which had fairly regular seasonal patterns prior to the COVID-19 pandemic. The study objective was to project future incidence of norovirus and rotavirus gastroenteritis as contacts resumed and other NPIs are relaxed. METHODS: We fitted compartmental mathematical models to pre-pandemic U.S. surveillance data (2012-2019) for norovirus and rotavirus using maximum likelihood estimation. Then, we projected incidence for 2022-2030 under scenarios where the number of contacts a person has per day varies from70%, 80%, 90%, and full resumption (100%) of pre-pandemic levels. RESULTS: We found that the population susceptibility to both viruses increased between March 2020 and November 2021. The 70-90% contact resumption scenarios led to lower incidence than observed pre-pandemic for both viruses. However, we found a greater than two-fold increase in community incidence relative to the pre-pandemic period under the 100% contact scenarios for both viruses. With rotavirus, for which population immunity is driven partially by vaccination, patterns settled into a new steady state quickly in 2022 under the 70-90% scenarios. For norovirus, for which immunity is relatively short-lasting and only acquired through infection, surged under the 100% contact scenario projection. CONCLUSIONS: These results, which quantify the consequences of population susceptibility build-up, can help public health agencies prepare for potential resurgence of enteric viruses.

OBJECTIVES: Acute gastroenteritis (AGE) outbreaks commonly occur in congregate settings, including schools and childcare facilities. These outbreaks disrupt institutions, causing absences and temporary facility closures. This study analyzed the epidemiology of school and childcare AGE outbreaks in the United States. METHODS: We analyzed AGE outbreaks occurring in kindergarten to grade 12 schools and childcare facilities reported via the National Outbreak Reporting System in the United States from 2009 to 2019 and compared this information to 2020 data. Outbreak and case characteristics were compared using the Kruskal-Wallis rank sum test, 2 goodness-of-fit test, and Fisher exact test. RESULTS: From 2009 to 2019, there were 2623 school, 1972 childcare, and 38 school and childcare outbreaks. School outbreaks were larger (median, 29 cases) than childcare outbreaks (median, 10 cases). Childcare outbreaks were longer (median, 15 days) than school outbreaks (median, 9 days). Norovirus (2383 outbreaks; 110190 illnesses) and Shigella spp. (756 outbreaks; 9123 illnesses) were the most reported etiologies. Norovirus was the leading etiology in schools; norovirus and Shigella spp. were dominant etiologies in childcare centers. Most (85.7%) outbreaks were spread via person-to-person contact. In 2020, 123 outbreaks were reported, 85% in the first quarter. CONCLUSIONS: Schools and childcare centers are common AGE outbreak settings in the United States. Most outbreaks were caused by norovirus and Shigella spp. and spread via person-to-person transmission. Fewer outbreaks were reported in 2020 from the COVID-19 pandemic. Prevention and control efforts should focus on interrupting transmission, including environmental disinfection, proper handwashing, safe diapering, and exclusion of ill persons.

On May 11, 2022, the National Park Service (NPS) Office of Public Health (OPH) and Coconino County Health and Human Services (CCHHS) in Flagstaff, Arizona contacted CDC about a rising number of acute gastroenteritis cases among backcountry visitors to Grand Canyon National Park (Grand Canyon). The agencies reviewed illness report forms, assessed infection prevention and control (IPC) practices, and distributed a detailed survey to river rafters and hikers with backcountry permits (backpackers) who visited the Grand Canyon backcountry. During April 1-June 17, a total of 191 rafters and 31 backpackers reported symptoms consistent with acute gastroenteritis. Specimens from portable toilets used by nine river rafting trip groups were tested using real-time reverse transcription-polymerase chain reaction and test results were positive for norovirus. Norovirus-associated acute gastroenteritis is highly transmissible in settings with close person-to-person contact and decreased access to hand hygiene, such as backpacking or rafting. IPC assessments led to recommendations for regular disinfection of potable water spigots throughout the backcountry, promotion of proper handwashing with soap and water when possible, and separation of ill persons from those who are not ill. Prevention and control of acute gastroenteritis outbreaks in the backcountry requires rapid reporting of illnesses, implementing IPC guidelines for commercial outfitters and river rafting launch points, and minimizing interactions among rafting groups.

Norovirus is the leading cause of acute gastroenteritis in the United States (1). In April 2020, the incidence of norovirus outbreaks in the United States declined substantially, likely because of implementation of COVID-19–related nonpharmaceutical interventions, such as facility closures, social distancing, and increased hand hygiene (2). Similar declines were observed in other countries (3,4). Norovirus outbreaks in the United States increased rapidly starting in January 2022, approaching prepandemic (i.e., 2012–2019) levels. Norovirus transmission can be prevented by thorough handwashing and proper cleaning and disinfection of contaminated surfaces © 2022, MMWR Recommendations and Reports.All Rights Reserved.

In June 2021, Kansas state and county public health officials identified and investigated three cases of shigellosis (a bacterial diarrheal illness caused by Shigella spp.) associated with visiting a wildlife park. The park has animal exhibits and a splash pad. Two affected persons visited animal exhibits, and all three entered the splash pad. Nonhuman primates are the only known animal reservoir of Shigella. The splash pad, which sprays water on users and is designed so that water does not collect in the user area, was closed on June 19. The state and county public health codes do not include regulations for splash pads. Thus, these venues are not typically inspected, and environmental health expertise is limited. A case-control study identified two distinct outbreaks associated with the park (a shigellosis outbreak involving 21 cases and a subsequent norovirus infection outbreak involving six cases). Shigella and norovirus can be transmitted by contaminated water; in both outbreaks, illness was associated with getting splash pad water in the mouth (multiply imputed adjusted odds ratio [aOR(MI)] = 6.4, p = 0.036; and 28.6, p = 0.006, respectively). Maintaining adequate water disinfection and environmental health expertise and targeting prevention efforts to caregivers of splash pad users help prevent splash pad-associated outbreaks. Outbreak incidence might be further reduced when U.S. jurisdicitons voluntarily adopt CDC's Model Aquatic Health Code (MAHC) recommendations and through the prevention messages: "Don't get in the water if sick with diarrhea," "Don't stand or sit above the jets," and "Don't swallow the water."(†).

BACKGROUND: Globally, noroviruses cause infections year-round but have recognized winter seasonality in the northern hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact. METHODS: We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred from August 2009-July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions. RESULTS: During August 2009-July 2019, 24,995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, median norovirus season duration was 24 weeks, with onset occurring between October-December and offset occurring between April-May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions. CONCLUSIONS: Timing and duration of the US norovirus season varied annually, but generally occurred during October-May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors promoting virus transmission and help guide future interventions.

BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the U.S. 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 U.S. surveillance sites on 8-59-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 (CDC). We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with CDC 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 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.

BACKGROUND: Despite vaccine-induced decreases in US rotavirus (RV) disease, acute gastroenteritis (AGE) remains relatively common. We evaluated AGE pathogen distribution in hospitalized US children in the post-RV vaccine era. METHODS: From December 2011 to June 2016, the New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based surveillance in hospitalized children with AGE. We tested stools from 2 NVSN sites (Kansas City, Houston) with Luminex x-TAG Gastrointestinal Pathogen Panels (Luminex GPP) and analyzed selected signs and symptoms. RESULTS: For 660 pediatric AGE inpatients and 624 age-matched healthy controls (HCs), overall organism detection was 51.2% and 20.6%, respectively (P < .001). Among AGE subjects, GPP polymerase chain reaction detected >1 virus in 39% and >1 bacterium in 14% of specimens. Detection frequencies for AGE subjects vs HCs were norovirus (NoV) 18.5% vs 6.6%, RV 16.1% vs 9.8%, adenovirus 7.7% vs 1.4%, Shigella 4.8% vs 1.0%, Salmonella 3.1% vs 0.1%, and Clostridioides difficile in ≥2-year-olds 4.4% vs 2.4%. More co-detections occurred among AGE patients (37/660, 5.6%) than HCs (14/624, 2.2%; P = .0024). Per logistic regression analysis, ill contacts increased risk for NoV, RV, and Shigella (P < .001). More vomiting episodes occurred with NoV and RV, and more diarrheal episodes with Shigella and Salmonella. Modified Vesikari scores were highest for Shigella and lowest for C. difficile. CONCLUSIONS: NoV detection was most frequent; however, RV remained important in hospitalized AGE in the post-RV vaccine era. Continued active surveillance is important to document ongoing vaccine effects, pathogen emergence, and baseline disease burden for new vaccines.

For over a decade, the New Vaccine Surveillance Network (NVSN) has conducted active rotavirus (RVA) strain surveillance in the USA. The evolution of RVA in the post-vaccine introduction era and the possible effects of vaccine pressure on contemporary circulating strains in the USA are still under investigation. Here, we report the whole-gene characterization (eleven ORFs) for 157 RVA strains collected at seven NVSN sites during the 2014 through 2016 seasons. The sequenced strains included 52 G1P[8], 47 G12P[8], 18 G9P[8], 24 G2P[4], 5 G3P[6], as well as 7 vaccine strains, a single mixed strain (G9G12P[8]), and 3 less common strains. The majority of the single and mixed strains possessed a Wa-like backbone with consensus genotype constellation of G1/G3/G9/G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, while the G2P[4], G3P[6], and G2P[8] strains displayed a DS-1-like genetic backbone with consensus constellation of G2/G3-P[4]/P[6]/P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Two intergenogroup reassortant G1P[8] strains were detected that appear to be progenies of reassortment events between Wa-like G1P[8] and DS-1-like G2P[4] strains. Two Rotarix(®) vaccine (RV1) and two RV5 derived (vd) reassortant strains were detected. Phylogenetic and similarity matrices analysis revealed 2-11 sub-genotypic allelic clusters among the genes of Wa- and DS-1-like strains. Most study strains clustered into previously defined alleles. Amino acid (AA) substitutions occurring in the neutralization epitopes of the VP7 and VP4 proteins characterized in this study were mostly neutral in nature, suggesting that these RVA proteins were possibly under strong negative or purifying selection in order to maintain competent and actual functionality, but fourteen radical (AA changes that occur between groups) AA substitutions were noted that may allow RVA strains to gain a selective advantage through immune escape. The tracking of RVA strains at the sub-genotypic allele constellation level will enhance our understanding of RVA evolution under vaccine pressure, help identify possible mechanisms of immune escape, and provide valuable information for formulation of future RVA vaccines.

BACKGROUND: In the US, norovirus is the leading cause of healthcare-associated gastroenteritis outbreaks. To inform prevention efforts, we describe the epidemiology of norovirus outbreaks in long-term care facilities (LTCFs). METHODS: CDC collects epidemiologic and laboratory data on norovirus outbreaks from U.S. health departments through the National Outbreak Reporting System (NORS) and CaliciNet. Reports from both systems were merged, and norovirus outbreaks in nursing homes, assisted living, and other LTCFs occurring in 2009-2018 were analyzed. Data from the Centers for Medicare and Medicaid Services and the National Center for Health Statistics were used to estimate state LTCF counts. RESULTS: During 2009-2018, 50 states, Washington D.C., and Puerto Rico reported 13,092 norovirus outbreaks and 416,284 outbreak-associated cases in LTCFs. Participation in NORS and CaliciNet increased from 2009-2014 and median reporting of LTCF norovirus outbreaks stabilized at 4.1 outbreaks per 100 LTCFs (IQR: 1.0-7.1) annually since 2014. Most outbreaks were spread via person-to-person transmission (90.4%) and 75% occurred during December-March. Genogroup was reported for 7,292 outbreaks with 862 (11.8%) positive for GI and 6,370 (87.3%) for GII. Among 4,425 GII outbreaks with typing data, 3,618 (81.8%) were GII.4. LTCF residents had higher attack rates than staff (median 29.0% versus 10.9%; p<0.001). For every 1,000 cases, there were 21.6 hospitalizations and 2.3 deaths. CONCLUSIONS: LTCFs have a high burden of norovirus outbreaks. Most LTCF norovirus outbreaks occurred during winter months and were spread person-to-person. Outbreak surveillance can inform development of interventions for this vulnerable population, such as vaccines targeting GII.4 norovirus strains.

BACKGROUND: The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. The aim of this study is to describe enteric illness outbreaks reported during 11 years of surveillance. METHODS: We extracted finalized reports from NORS for outbreaks occurring during 2009-2019. Outbreaks were included if they were caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis. RESULTS: A total of 38,395 outbreaks met inclusion criteria, increasing from 1,932 in 2009 to 3,889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n=23,812, 62%) and contaminated food (n=9,234, 24%). Norovirus was the most commonly reported etiology, reported in 22,820 (59%) outbreaks, followed by Salmonella (n=2,449, 6%) and Shigella (n=1,171, 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (p<0.0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and E. coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). The case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%). CONCLUSIONS: Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions.

BACKGROUND: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in USA (US) children. We report the RVA genotype prevalence as well as co-infection data from seven US New Vaccine Surveillance Network (NVSN) sites during three consecutive RVA seasons, 2014-2016. METHODS: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay (EIA) were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing. RESULTS: A total of 795 (76%) contained detectable RVA at 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 two P types (P[4] and P[8]) accounted 94.7% of the strains. Overall, G12P[8] was the most common genotype detected in all three seasons. Stepwise conditional logistic analysis found year and study site were significant predictors of genotype. Twenty four percent (24%) of RVA-positive specimens contained other AGE pathogens. CONCLUSIONS: G12P[8] predominated over three seasons, but strain predominance varied by year and study site. Ongoing surveillance provides continuous tracking and monitoring of US genotypes during the post vaccine era.

In April 2020, the incidence of norovirus outbreaks reported to the National Outbreak Reporting System (NORS) dramatically declined. We used regression models to determine if this decline was best explained by underreporting, seasonal trends, or reduced exposure due to non-pharmaceutical interventions (NPIs) implemented for SARS-CoV-2 using data from 9 states from July 2012-July 2020. The decline in norovirus outbreaks was significant for all 9 states and underreporting or seasonality are unlikely to be the primary explanations for these findings. These patterns were similar across a variety of settings. NPIs appear to have reduced incidence of norovirus, a non-respiratory pathogen.

During 2009-2018, four adenovirus, 10 astrovirus, 123 rotavirus, and 107 sapovirus gastroenteritis outbreaks were reported to the US National Outbreak Reporting System (annual median 30 outbreaks). Most were attributable to person-to-person transmission in long-term care facilities, daycares, and schools. Investigations of norovirus-negative gastroenteritis outbreaks should include testing for these viruses.

Norovirus is the leading cause of acute gastroenteritis outbreaks in the United States. We estimated the basic (R(0)) and effective (R(e)) reproduction numbers for 7,094 norovirus outbreaks reported to the National Outbreak Reporting System (NORS) during 2009-2017 and used regression models to assess whether transmission varied by outbreak setting. The median R(0) was 2.75 (interquartile range [IQR] 2.38-3.65), and median R(e) was 1.29 (IQR 1.12-1.74). Long-term care and assisted living facilities had an R(0) of 3.35 (95% CI 3.26-3.45), but R(0) did not differ substantially for outbreaks in other settings, except for outbreaks in schools, colleges, and universities, which had an R(0) of 2.92 (95% CI 2.82-3.03). Seasonally, R(0) was lowest (3.11 [95% CI 2.97-3.25]) in summer and peaked in fall and winter. Overall, we saw little variability in transmission across different outbreaks settings in the United States.

BACKGROUND: Norovirus is a leading cause of epidemic acute gastroenteritis (AGE) in the U.S, with most outbreaks occurring during winter. The majority of outbreaks are caused by GII.4 noroviruses, but data supporting whether this is true for sporadic medically-attended AGE are limited. Therefore, we sought to compare the clinical characteristics and seasonality of GII.4 vs. non-GII.4 viruses in children presenting with vomiting and/or diarrhea. METHODS: Children from 15 days to 17 years with AGE symptoms were recruited from the outpatient, emergency department, and inpatient settings at Vanderbilt Children's Hospital, Davidson County, Nashville, TN from 12/2012-11/2015. Stool specimens were tested by RT-qPCR for GI and GII noroviruses and subsequently genotyped by sequencing a partial region of the capsid gene. RESULTS: A total of 3705 subjects were enrolled and stool specimens were collected and tested from 2885 (78%) of enrollees. Overall, 636 (22%) samples were norovirus-positive, of which 567 (89%) were GII. Of the 460 (81%) genotyped GII-positive samples, 233 (51%) were typed as GII.4 and 227 (49%) as non-GII.4. Compared to children with non-GII.4 infections, children with GII.4 infections were younger, more likely to have diarrhea and receive oral rehydration fluids. Norovirus was detected year-round but peaked during winter. CONCLUSION: Approximately half of sporadic pediatric norovirus AGE cases were caused by GII.4 norovirus. Children infected with GII.4 had more severe symptoms requiring more medical care. Seasonal variations were noticed among different genotypes. These data highlight the importance of continuous norovirus surveillance and provide important information on which strains pediatric norovirus vaccines should protect against.

Previous reports of COVID-19 among US children have been based on health jurisdiction reporting. We performed SARS-CoV-2 testing on children enrolled in active, prospective, multi-center surveillance during January-March, 2020. Among 3187 children, only 4 (0.1%) SARS-CoV-2-positive cases were identified March 20-31 despite evidence of rising community circulation.

Outbreaks associated with fresh or marine (i.e., untreated) recreational water can be caused by pathogens or chemicals, including toxins. Voluntary reporting of these outbreaks to CDC's National Outbreak Reporting System (NORS) began in 2009. NORS data for 2009-2017 are finalized, and data for 2018-2019 are provisional. During 2009-2019 (as of May 13, 2020), public health officials from 31 states voluntarily reported 119 untreated recreational water-associated outbreaks, resulting at least 5,240 cases; 103 of the outbreaks (87%) started during June-August. Among the 119 outbreaks, 88 (74%) had confirmed etiologies. The leading etiologies were enteric pathogens: norovirus (19 [22%] outbreaks; 1,858 cases); Shiga toxin-producing Escherichia coli (STEC) (19 [22%]; 240), Cryptosporidium (17 [19%]; 237), and Shigella (14 [16%]; 713). This report highlights three examples of outbreaks that occurred during 2018-2019, were caused by leading etiologies (Shigella, norovirus, or STEC), and demonstrate the wide geographic distribution of such outbreaks across the United States. Detection and investigation of untreated recreational water-associated outbreaks are challenging, and the sources of these outbreaks often are not identified. Tools for controlling and preventing transmission of enteric pathogens through untreated recreational water include epidemiologic investigations, regular monitoring of water quality (i.e., testing for fecal indicator bacteria), microbial source tracking, and health policy and communications (e.g., observing beach closure signs and not swimming while ill with diarrhea).

OBJECTIVES: Diagnosing Clostridioides difficile infections in young children with high asymptomatic colonization is challenging. We compared the frequency of C difficile detection by polymerase chain reaction (PCR) in healthy control (HC) children with those with acute gastroenteritis (AGE) and evaluated fecal-lactoferrin and organism load as possible indicators of true C difficile infection disease. METHODS: Stool was collected from children <2 years old with AGE and from HCs. C difficile was detected by real-time PCR, and lactoferrin was measured by enzyme-linked immunosorbent assay. Clinical data were obtained via interviews and chart review. Mann-Whitney U test and chi(2) tests were used for group comparisons. RESULTS: Of 524 stools collected from 524 children (250 with AGE, 274 HCs), C difficile was detected less in children with AGE (14%, 36 of 250) than in HCs (28%, 76 of 274) stools (P < .0001). Among infants <1 year old (n = 297), C difficile was detected in 18% of children with AGE versus 32% of HCs (P < .005), and among children 1 to 2 years old (n = 227), C difficile was detected in 10% of children with AGE versus 21% of HCs (P < .02). There was no significant difference in C difficile PCR cycle threshold values between children with AGE and HCs or lactoferrin levels in C difficile PCR-positive versus -negative stools. CONCLUSIONS: HC children <2 years of age had higher rates of C difficile detection by PCR than children with AGE; C difficile detection by real-time PCR alone is not a reliable means to diagnose C difficile disease in children <2 years old.

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 three US counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006-2016. METHODS: Children <3 years of age hospitalized or visiting the ED with AGE, were enrolled from January 2006-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 pre-vaccine and 2008-2016 as post-vaccine periods. 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 post-vaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the post-vaccine 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 pre-vaccine period with a significantly lower proportion (7%) in the post-vaccine period (p<.001). G2P[4] remained stable (8% to 14%) in both periods, while G3P[8] and G12P[8] increased in proportion from pre-to post-vaccine 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.

BACKGROUND: Acute gastroenteritis(AGE) is a common reason for children to seek medical care. However, the viral etiology of AGE illness is not well described in the post-rotavirus vaccine era, particularly in the outpatient(OP) setting. METHODS: Between 2012 and 2015, children 15 days through 17 years old presenting to Vanderbilt Children's Hospital, Nashville, TN with AGE were enrolled prospectively from the inpatient, emergency department, and OP settings and stool specimens were collected. Healthy controls(HCs) were enrolled and frequency-matched for period, age group, race, and ethnicity. Stool specimens were tested by reverse-transcription real-time quantitative polymerase chain reaction for norovirus, sapovirus, and astrovirus RNA and by Rotaclone enzyme immunoassay for rotavirus antigen, followed by PCR verification of antigen detection. RESULTS: A total of 3705 AGE cases and 1563 HC were enrolled, among whom 2885 cases(78%) and 1110 HCs(71%) provided stool specimens that were tested. All four viruses were more frequently detected in AGE cases vs. HC: norovirus, 22% vs. 8%; rotavirus, 10% vs. 1%; sapovirus, 10% vs. 5%; and astrovirus, 5% vs. 2%(p<0.001 for each virus, respectively). AGE rates in the OP setting due to norovirus were highest compared to the other three viruses. Children under five years old had higher OP AGE rates compared to older children for all viruses. CONCLUSIONS: Norovirus remains the most common virus detected in all settings, occurring nearly twice as frequently as the next most common pathogens, sapovirus and rotavirus. Combined, these four viruses were associated with almost half of all AGE visits and therefore are an important reason for children to seek medical care.

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.

Importance: Rotavirus vaccines have been recommended for universal US infant immunization for more than 10 years, and understanding their effectiveness is key to the continued success of the US rotavirus vaccine immunization program. Objective: To assess the association of RotaTeq (RV5) and Rotarix (RV1) with inpatient and emergency department (ED) visits for rotavirus infection. Design, Setting, and Participants: This case-control vaccine effectiveness study was performed at inpatient and ED clinical settings in 7 US pediatric medical institutions from November 1, 2009, through June 30, 2016. Children younger than 5 years seeking medical care for acute gastroenteritis were enrolled. Clinical and epidemiologic data, vaccination verification, and results of stool sample tests for laboratory-confirmed rotavirus were collected. Data were analyzed from November 1, 2009, through June 30, 2016. Main Outcomes and Measures: Rotavirus vaccine effectiveness for preventing rotavirus-associated inpatient and ED visits over time for each licensed vaccine, stratified by clinical severity and age. Results: Among the 10 813 children included (5927 boys [54.8%] and 4886 girls [45.2%]; median [range] age, 21 [8-59] months), RV5 and RV1 analyses found that compared with controls, rotavirus-positive cases were more often white (RV5, 535 [62.2%] vs 3310 [57.7%]; RV1, 163 [43.1%] vs 864 [35.1%]), privately insured (RV5, 620 [72.1%] vs 4388 [76.5%]; RV1, 305 [80.7%] vs 2140 [87.0%]), and older (median [range] age for RV5, 26 [8-59] months vs 21 [8-59] months; median [range] age for RV1, 22 [8-59] months vs 19 [8-59] months) but did not differ by sex. Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. No statistically significant difference during this 7-year period was observed for either rotavirus vaccine. Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. A mixed course of both vaccines provided 86% (95% CI, 74%-93%) protection. Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. Conclusions and Relevance: Evidence from this large postlicensure study of rotavirus vaccine performance in the United States from 2010 to 2016 suggests that RV5 and RV1 rotavirus vaccines continue to perform well, particularly in preventing inpatient visits and severe infections and among younger children.