We conducted a large surveillance study among members of an integrated healthcare delivery system in Pacific Northwest of the United States to estimate medical costs attributable to medically attended acute gastroenteritis (MAAGE) on the day care was sought and during 30-day follow-up. We used multivariable regression to compare costs of MAAGE and non-MAAGE cases matched on age, gender, and index time. Differences accounted for confounders, including race, ethnicity, and history of chronic underlying conditions. Analyses included 73,140 MAAGE episodes from adults and 18,617 from children who were Kaiser Permanente Northwest members during 2014-2016. Total costs were higher for MAAGE cases relative to non-MAAGE comparators as were costs on the day care was sought and costs during follow-up. Costs of MAAGE are substantial relative to the cost of usual-care medical services, and much of the burden accrues during short-term follow-up.

BACKGROUND: Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized. METHODS: We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing. RESULTS: In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001). CONCLUSIONS: Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.

BACKGROUND: The endemic coronaviruses OC43, HKU1, NL63 and 229E cause cold-like symptoms and are related to SARS-CoV-2, but their natural histories are poorly understood. In a cohort of children followed from birth to 4 years, we documented all coronavirus infections, including SARS-CoV-2, to understand protection against subsequent infections with the same virus (homotypic immunity) or a different coronavirus (heterotypic immunity). METHODS: Mother-child pairs were enrolled in metropolitan Cincinnati during the third trimester of pregnancy in 2017-18. Mothers reported their child's socio-demographics, risk factors, and weekly symptoms. Mid-turbinate nasal swabs were collected weekly. Blood was collected at 6 weeks, 6, 12, 18, 24 months and annually thereafter. Infections were detected by testing nasal swabs by an RT-PCR multi-pathogen panel and by serum IgG responses. Health care visits were documented from pediatric records. Analysis was limited to 116 children with high sample adherence. Re-consent for monitoring SARS-CoV-2 infections from June 2020 through November 2021 was obtained for 74 (64%) children. RESULTS: We detected 345 endemic coronavirus infections (1.1 infections/child-year) and 21 SARS-CoV-2 infections (0.3 infections/child-year). Endemic coronavirus and SARS-CoV-2 infections were asymptomatic or mild. Significant protective homotypic immunity occurred after a single infection with OC43 (77%) and HKU1 (84%), and after two infections with NL63 (73%). No heterotypic protection against endemic coronaviruses or SARS-CoV-2 was identified. CONCLUSIONS: Natural coronavirus infections were common and resulted in strong homotypic immunity but not heterotypic immunity against other coronaviruses, including SARS-CoV-2. Endemic coronavirus and SARS-CoV-2 infections in this US cohort were typically asymptomatic or mild.

BACKGROUND: Respiratory viral shedding is incompletely characterized by existing studies due to the lack of longitudinal nasal sampling and limited inclusion of healthy/asymptomatic children. We describe characteristics associated with prolonged virus detection by PCR in a community-based birth cohort. METHODS: Children were followed from birth to 2 years of age in the PREVAIL cohort. Weekly nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel. Weekly text surveys were administered to ascertain the presence of acute respiratory illnesses defined as fever and/or cough. Maternal reports and medical chart abstractions identified healthcare utilization. Prolonged virus detection was defined as a persistently positive test lasting >4 weeks. Factors associated with prolonged virus detection were assessed using mixed effects multivariable logistic regression. RESULTS: From a sub-cohort of 101 children with >70% weekly swabs collected, a total of 1489 viral infections were detected. Prolonged virus detection was found in 23.4% of viral infections overall, 39% of bocavirus infections, 33% of rhinovirus/enterovirus infections, 14% of RSV A infections, and 7% of RSV B infections. No prolonged detection was found for influenza A or B, coronavirus 229E or HKU1, and parainfluenza 2 or 4 virus infections. First lifetime infection with each virus, and co-detection of another respiratory virus were significantly associated with prolonged detection, while symptom status, child sex, and child age were not. CONCLUSIONS: Prolonged virus detection was observed in 1 in 4 viral infections in this cohort of healthy children and varied by pathogen, occurring most often for bocavirus and rhinovirus/enterovirus. Evaluating the immunological basis of how viral co-detections and recurrent viral infections impact duration of virus detection by PCR is needed to better understand the dynamics of prolonged viral shedding.

BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. DISCUSSION: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.

BACKGROUND: While enteric viruses are highly transmissible, household factors associated with transmission are less well documented. We identified individual- and household-level factors associated with viral acute gastroenteritis (AGE) transmission in a large health care network in the United States. METHODS: Patients presenting with AGE were enrolled from April 2014 to September 2016. Patients and symptomatic household members were interviewed, and stool specimens were collected and tested for viral pathogens. Within a household, primary cases were those with the earliest symptom onset and a positive viral test result; secondary cases were household contacts (HHCs) with symptom onset 1-7 days from the primary case onset. Transmission households had at least 1 secondary case. RESULTS: Our analysis included 570 primary cases with 1479 HHCs. The overall secondary attack rate was 23%. HHCs were likely to become secondary cases (n = 338) if they were <5 years old (adjusted odds ratio [aOR], 1.8; 95% CI, 1.2-2.6). Secondary transmission was likely to occur if the primary case was aged <5 years (aOR, 2.2; 95% CI, 1.4-3.6) or 5 to 17 years (aOR, 3.3; 95% CI, 1.9-5.7), was norovirus positive (aOR, 2.7; 95% CI, 1.9-3.7), had a diapered contact (aOR: 2.2, 95% CI: 1.6-3.2), or reported symptoms for >4 days (aOR, 1.5; 95% CI, 1.1-2.1). Households with ≥3 members (aOR, 2.1; 95% CI, 1.1-4.5) were more likely to experience transmission. DISCUSSION: Risk of AGE transmission within households increased if the primary case was younger, was norovirus positive, had a longer symptom duration, or had a diapered contact. Targeted prevention messaging around appropriate cleaning, disinfection, and isolation of persons with AGE should be encouraged.

BACKGROUND: In the United States, public health surveillance systems often underestimate the burden of acute gastroenteritis (AGE) because they only identify disease among those who interact with the healthcare system. OBJECTIVE: To identify factors associated with healthcare-seeking behavior among individuals experiencing community-acquired AGE. METHODS: From October 2016 -September 2017, we conducted a weekly, age-stratified, random sample of Kaiser Permanente Northwest members located in northwest Oregon and southwest Washington, United States. Individuals who completed the online survey and experienced AGE were included in the analysis. Univariate and multivariable logistic regressions were performed to identify predictors of healthcare-seeking behavior. RESULTS: Of the 3,894 survey respondents, 395 experienced an AGE episode and were eligible for analysis, of whom, 82 (21%) sought care for their AGE episode. In the final multivariable model, individuals with a concurrent fever (odds ratio [OR]: 4.76, 95% confidence interval [95% CI]: 2.48-9.13), increased diarrhea duration (≥6 days vs 1-4 days, OR: 4.22, 95% CI: 1.78-10.03), or increased vomiting duration (≥3 days vs 1 days, OR: 2.97, 95% CI: 1.22-7.26), were significantly more likely to seek healthcare. In the adjusted model, no sociodemographic or chronic disease variables were associated with healthcare-seeking behavior. CONCLUSION: These findings suggest that individuals with a short duration of AGE and those without concurrent fever are underrepresented in healthcare facility-based surveillance systems.

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant 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.YesData may be available upon reasonable request.

Background Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms.Methods We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted ‘immunity’), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data.Results Recreating the low attack rates observed in daycare and school outbreaks required a model with immunity. However, immunity alone resulted in shorter duration outbreaks than what was observed. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data.Conclusions The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. Interventions should leverage population immunity and encourage more rigorous individual exclusion to improve venue-level control measures.Competing Interest StatementDr. Lopman reports personal fees from Takeda Pharmaceuticals, CDC Foundation, and Hall Booth Smith, P.C. outside the submitted work.Funding StatementThis Study was funded by the Joint Initiative for Vaccine Economics, Phase 5, a cooperative agreement between the University of Michigan and the Centers for Disease Control and Prevention (U01IP000965). Additionally, this study was funded by the National Institute of General Medical Sciences (U01GM110712). Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant 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.YesThe surveillance datasets are available from the Centers for Disease Control and Prevention upon request and application. Computing code available from the corresponding author upon reasonable request.

BACKGROUND: Respiratory viral infections are a major cause of morbidity and hospitalization in young children. Nevertheless, the population burden of respiratory viral infections, especially asymptomatic cases, is not known due to the lack of prospective community-based cohort studies with intensive monitoring. METHODS: To address this gap, we enacted the PREVAIL cohort, a CDC-sponsored birth cohort in Cincinnati, Ohio where children were followed from birth to 2 years of age. Weekly text surveys were administered to mothers to record acute respiratory illnesses (ARIs), which were defined as the presence of cough or fever (≥38oC). Weekly mid-turbinate nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel, which detected 16 viral pathogens. Viral infection was defined as one or more positive tests from the same virus or viral subtype within 30 days of previous positive. Maternal report and medical chart abstractions identified health care utilization. RESULTS: From 4/2017 to 7/2020, 245 mother-infant pairs were recruited and followed. From the 13,781 nasal swabs tested, a total of 2,211 viral infections were detected, of which, 821 (37%) were symptomatic. Children experienced 9.4 respiratory viral infections/child-year; half were rhinovirus/enterovirus. Viral ARI incidence was 3.3 episodes/child-year. Emergency department visits or hospitalization occurred with only 15% of respiratory syncytial virus infections, 10% of influenza infections, and only 4% of all viral infections. Regardless of pathogen, most infections were asymptomatic or mild. CONCLUSIONS: Respiratory viral infections are common in children 0-2 years. Most viral infections are asymptomatic or non-medically attended, underscoring the importance of community-based cohort studies.

Knowledge of the epidemiology of sporadic acute gastroenteritis (AGE) in the United States is limited. During September 2016-September 2017, we surveyed Kaiser Permanente Northwest members in Oregon and Washington, USA, to collect data on the 30-day prevalence of dually defined AGE and diarrhea disease and related health-seeking behavior; from a subset of participants, we obtained a stool specimen. Using the iterative proportional fitting algorithm with raked weights, we generated AGE prevalence and annualized rate estimates. We detected norovirus, rotavirus, astrovirus, and sapovirus from submitted stool specimens through real-time quantitative reverse transcription PCR (qRT-PCR). We estimated a 30-day prevalence of 10.4% for AGE and 7.6% for diarrhea only; annual rates were 1.27 cases/person/year for AGE and 0.92 cases/person/year for diarrhea only. Of those with AGE, 19% sought medical care. Almost one quarter (22.4%) of stool specimens from those reporting AGE tested positive for ≥1 viral pathogen, compared with 8.2% from those without AGE.

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.

We assessed rotavirus vaccine impact using data on acute gastroenteritis (AGE) encounters within an integrated healthcare delivery system during 2000 - 2018. Following rotavirus vaccine introduction, all-cause AGE rates among children <5 years declined by 36% (95% CI: 32-40%) for outpatient and 54% (95% CI: 46-60%) for inpatient encounters.

Background: Neighbourhood socio-economic environment (SEE) is associated with obesity in older children and adults, but little is known about this relationship in younger children. Breastfeeding is an important preventative of adiposity in childhood, but its relationship with neighbourhood SEE is unknown. Aims: We assessed differences in adiposity and obesity in children before age two by neighbourhood SEE, controlling for family socio-demographics and breastfeeding duration. Materials and Methods: Family socio-demographics, child body mass index z scores (BMIz), and breastfeeding duration were collected at periodic study visits from participants in PREVAIL (n = 245), a birth cohort in Cincinnati, OH. Addresses were assigned a Deprivation Index score, a validated measure of SEE, and dichotomized into highest SEE (least deprived quartile of scores) and not highest SEE (remaining quartiles). Longitudinal and Poisson models assessed differences in BMIz by SEE over the second year of life and obesity risk at age two, respectively (highest SEE, reference), while attenuation of obesity risk by breastfeeding duration was tested in mediation models. Results: Residing outside of the highest SEE neighbourhoods was associated with an increased BMIz of 0.04 (95%CI 0.02, 0.06) per month of life and increased obesity risk at age two (aRR: 3.7, 95%CI 1.2, 16.2), controlling for family socio-demographics. Breastfeeding duration attenuated >9% of the obesity risk attributable to SEE (mediated RR: 3.4, 95%CI 1.1, 14.8). Discussion: In the PREVAIL Cohort, residing outside of the highest SEE neighbourhoods predicted a significant increase in BMIz and obesity risk in children before age two, a relationship that was partially mediated by breastfeeding duration. Conclusion: Breastfeeding support may play an important role in reducing obesity rates in children in lower SEE neighbourhoods. © 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

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: 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.

OBJECTIVE: Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination. METHODS: We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature. RESULTS: A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold. CONCLUSION: Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.

BACKGROUND: Norovirus outbreaks are notoriously explosive, with dramatic symptomology and rapid disease spread. Children are particularly vulnerable to infection and drive norovirus transmission due to their high contact rates with each other and the environment. Despite the explosive nature of norovirus outbreaks, attack rates in schools and daycares remain low with the majority of students not reporting symptoms. METHODS: We explore immunologic and epidemiologic mechanisms that may underlie epidemic norovirus transmission dynamics using a disease transmission model. Towards this end, we compared different model scenarios, including innate resistance and acquired immunity (collectively denoted 'immunity'), stochastic extinction, and an individual exclusion intervention. We calibrated our model to daycare and school outbreaks from national surveillance data. RESULTS: Including immunity in the model led to attack rates that were consistent with the data. However, immunity alone resulted in the majority of outbreak durations being relatively short. The addition of individual exclusion (to the immunity model) extended outbreak durations by reducing the amount of time that symptomatic people contribute to transmission. Including both immunity and individual exclusion mechanisms resulted in simulations where both attack rates and outbreak durations were consistent with surveillance data. CONCLUSIONS: The epidemiology of norovirus outbreaks in daycare and school settings cannot be well described by a simple transmission model in which all individuals start as fully susceptible. More studies on how best to design interventions which leverage population immunity and encourage more rigorous individual exclusion may improve venue-level control measures.

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.

BACKGROUND: Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. METHODS: Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014 - June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into one episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting-specific incidence estimates were calculated using age-stratified bootstrapping. RESULTS: The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged <5 years (20.4 episodes per 1000 PY), followed by adults aged 65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY, astrovirus: 1.3 per 1000 PY, rotavirus: 0.5 per 1000 PY). CONCLUSIONS: Viral enteropathogens, particularly norovirus, are an important contributor to MAAGE, especially among children <5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.

BACKGROUND: Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. METHODS: Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014 - June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into one episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting-specific incidence estimates were calculated using age-stratified bootstrapping. RESULTS: The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged <5 years (20.4 episodes per 1000 PY), followed by adults aged ≥65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY, astrovirus: 1.3 per 1000 PY, rotavirus: 0.5 per 1000 PY). CONCLUSIONS: Viral enteropathogens, particularly norovirus, are an important contributor to MAAGE, especially among children <5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).(†) These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is ongoing in many communities throughout the United States. Although case-based and syndromic surveillance are critical for monitoring the pandemic, these systems rely on persons obtaining testing or reporting a COVID-19-like illness. Using serologic tests to detect the presence of SARS-CoV-2 antibodies is an adjunctive strategy that estimates the prevalence of past infection in a population. During April 28-May 3, 2020, coinciding with the end of a statewide shelter-in-place order, CDC and the Georgia Department of Public Health conducted a serologic survey in DeKalb and Fulton counties in metropolitan Atlanta to estimate SARS-CoV-2 seroprevalence in the population. A two-stage cluster sampling design was used to randomly select 30 census blocks in each county, with a target of seven participating households per census block. Weighted estimates were calculated to account for the probability of selection and adjusted for age group, sex, and race/ethnicity. A total of 394 households and 696 persons participated and had a serology result; 19 (2.7%) of 696 persons had SARS-CoV-2 antibodies detected. The estimated weighted seroprevalence across these two metropolitan Atlanta counties was 2.5% (95% confidence interval [CI] = 1.4-4.5). Non-Hispanic black participants more commonly had SARS-CoV-2 antibodies than did participants of other racial/ethnic groups (p<0.01). Among persons with SARS-CoV-2 antibodies, 13 (weighted % = 49.9; 95% CI = 24.4-75.5) reported a COVID-19-compatible illness,* six (weighted % = 28.2; 95% CI = 11.9-53.3) sought medical care for a COVID-19-compatible illness, and five (weighted % = 15.7; 95% CI = 5.1-39.4) had been tested for SARS-CoV-2 infection, demonstrating that many of these infections would not have been identified through case-based or syndromic surveillance. The relatively low seroprevalence estimate in this report indicates that most persons in the catchment area had not been infected with SARS-CoV-2 at the time of the survey. Continued preventive measures, including social distancing, consistent and correct use of face coverings, and hand hygiene, remain critical in controlling community spread of SARS-CoV-2.

BACKGROUND: Rotavirus is a common cause of severe pediatric acute gastroenteritis (AGE). Two vaccines are licensed in the United States and have demonstrated high effectiveness against moderate to severe disease. However, fewer data are available on rotavirus vaccine effectiveness (VE) against milder disease. METHODS: We leveraged active surveillance data from Kaiser Permanente Northwest (KPNW) to calculate rotavirus VE against medically attended rotavirus illness among age-eligible children. We utilized a test-negative case-control design and applied 4 distinct case definitions based on reverse-transcription-quantitative real-time PCR (qRT-PCR) assay and enzyme immunoassay (EIA) test results. VE was calculated as 100*(1 - Odds Ratio), and models were adjusted for age group. RESULTS: The VE analysis population comprised 842 children, 799 (95%) of which had mild disease requiring at most a clinic visit, and 698 (83%) of whom were fully vaccinated against rotavirus. Age-adjusted VE was 70% (95% confidence interval [CI]: 37 - 86%) against disease defined solely by qRT-PCR results, 72% (95% CI: 31 - 89%) against disease as defined by qRT-PCR with a quantification cycle (Cq) value <27, 73% (95% CI: 32 - 90%) against disease that was qRT-PCR positive but EIA negative, and 62% (95% CI: -20 - 88%) against disease defined solely by EIA. Results were similar when restricting to disease resulting in at most an ambulatory clinic or emergency department visit. CONCLUSIONS: These results support the effectiveness of rotavirus vaccination in protecting U.S. children from mild to moderate as well as severe disease. Our findings are also useful to show the effectiveness of rotavirus vaccination against qRT-PCR-defined illness.

BACKGROUND: Up-to-date estimates of the burden of norovirus, a leading cause of acute gastroenteritis (AGE) in the United States, are needed to assess the potential value of norovirus vaccines in development. We aimed to estimate the rates, annual counts, and healthcare charges of norovirus-associated ambulatory clinic encounters, Emergency Department (ED) visits, hospitalizations, and deaths in the United States. METHODS: We analyzed administrative data on AGE outcomes from July 1, 2001 through June 30, 2015. Data were sourced from IBM(R) MarketScan(R) Commercial and Medicare Supplemental Databases (ambulatory clinic and ED visits), the Healthcare Utilization Project National Inpatient Sample (NIS; hospitalizations), and the National Center for Health Statistics multiple-cause-of-mortality (MCM) data (deaths). Outcome data (ambulatory clinic and ED visits, hospitalizations, or deaths) were summarized by month, age group, and setting. Healthcare charges were estimated based on insurance claims. Monthly counts of cause-unspecified gastroenteritis-associated outcomes were modeled as functions of cause-specified outcomes, and model residuals were analyzed to estimate norovirus-associated outcomes. Healthcare charges were estimated by applying average charges per cause-unspecified gastroenteritis encounter to the estimated number of norovirus encounters. RESULTS: We estimate 900 deaths (95% Confidence Interval [CI]: 650 - 1100), 110,000 hospitalizations (95%CI: 80,000 - 145,000), 470,000 ED visits (95% CI: 348,000 - 610,000), and 2.3 million ambulatory clinic encounters (95% CI: 1.7 - 2.9 million) annually due to norovirus, with an associated $430 - 740 million in healthcare charges. CONCLUSIONS: Norovirus causes a substantial health burden in the United States each year, and an effective vaccine could have important public health impact.

INTRODUCTION: Noroviruses are the leading cause of foodborne illness worldwide, account for approximately one-fifth of acute gastroenteritis cases globally and cause a substantial economic burden. Candidate norovirus vaccines are in development, but there is currently no licensed vaccine. Areas covered: Noroviruses cause approximately 684 million cases and 212,000 deaths per year across all age groups, though burden estimates vary by study and region. Challenges to vaccine research include substantial and rapidly evolving genetic diversity, short-term and homotypic immunity to infection, and the absence of a single, well-established correlate of protection. Nonetheless, several norovirus vaccine candidates are currently in development, utilizing virus-like particles (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine (Phase I) are in clinical trials. Expert Commentary: A norovirus vaccine should target high risk populations, including the young and the elderly and protect against the most common circulating norovirus strains. A norovirus vaccine would be a powerful tool in the prevention and control of norovirus while lessening the burden of AGE worldwide. However, more robust burden and cost estimates are needed to justify investments in and guide norovirus vaccine development.

The U.S. Food and Drug Administration (FDA) and other federal agencies partner to ensure that medical countermeasures (e.g., drug therapies and vaccines) are available for public health emergencies (FDA, 2014). Despite continuing progress, providing medical countermeasures and treatment guidelines for certain populations (e.g., pregnant women) is challenging due to the lack of clinical and/or animal data. Thus, a workshop was convened to discuss animal models of pregnancy for the evaluation of disease progression and medical countermeasures.

The field of public health services and systems research (PHSSR) has emerged over the past decade to produce the evidence needed to address critical uncertainties about how best to organize, finance, and deliver effective public health strategies to all Americans. To advance these efforts, a national PHSSR research agenda-setting process was used to identify a broad inventory of information needs and uncertainties that public health stakeholders face in the domains of public health workforce, public health system structure and performance, public health financing, and public health information and technology. This paper presents the results of an expert review process used to transform the identified information needs into a concise set of research questions that can be pursued through new scientific inquiry in PHSSR. Established research frameworks were used to specify the contexts, mechanisms of action, and outcomes within the public health system that require further study. A total of 72 research questions were developed from the 113 original items in the PHSSR inventory of information needs. The questions include both persistent problems and newly emerging needs in public health practice and policy. The resulting research agenda provides a starting point for mobilizing the public health scientific enterprise around contemporary, high-priority uncertainties identified by broad cross sections of public health stakeholders. Regular updates to this agenda will be required to achieve continuous improvements in both the science and practice of public health.