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: A low-level risk of intussusception following rotavirus vaccination has been observed in some settings and may vary by vaccine type. We examined the association between RotaTeq vaccination and intussusception in low-income settings in a pooled analysis from 5 African countries that introduced RotaTeq into their national immunization program. METHODS: Active surveillance was conducted at 20 hospitals to identify intussusception cases. A standard case report form was completed for each enrolled child, and vaccination status was determined by review of the child's vaccination card. The pseudo-likelihood adaptation of self-controlled case-series method was used to assess the association between RotaTeq administration and intussusception in the 1-7, 8-21, and 1-21 day periods after each vaccine dose in infants aged 28-245 days. RESULTS: Data from 318 infants with confirmed rotavirus vaccination status were analyzed. No clustering of cases occurred in any of the risk windows after any of the vaccine doses. Compared with the background risk of naturally occurring intussusception, no increased risk was observed after dose 1 in the 1-7 day (relative incidence = 2.71; 95% confidence interval [CI] = 0.47-8.03) or the 8-21 day window (relative incidence = 0.77; 95%CI = 0.0-2.69). Similarly, no increased risk of intussusception was observed in any risk window after dose 2 or 3. CONCLUSIONS: RotaTeq vaccination was not associated with increased risk of intussusception in this analysis from 5 African countries. This finding mirrors results from similar analyses with other rotavirus vaccines in low-income settings and highlights the need for vaccine-specific and setting-specific risk monitoring.

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: 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.

We thank Dr. Rogers for her interest in our article1. The question of whether rotavirus vaccination may affect the risk of type 1 diabetes (T1D) is certainly one that is worthwhile to investigate using a variety of epidemiologic methods. Although information from cohort studies can be analyzed in several different ways, we feel that MarketScan® data, which we used in our analysis, is best analyzed with person-time as the denominator1, as was done by Dr. Rogers and colleagues in their study on this topic2. While the timing of viral challenge with wild-type rotavirus may be unknown in our study population, the timing of vaccination is well documented due to the use of insurance claims data and the inclusion criterion of continuous enrollment since birth. In contrast, once a child is lost to follow-up, the timing and occurrence of T1D is unknown. Furthermore, loss to follow-up (caused by change in insurance status) may be different in children who are completely unvaccinated as compared to children who receive routine vaccinations—one reason for which we subset our main analysis population to those children who had received at least one dose of diphtheria-tetanus-pertussis (DTaP) vaccine by one year of age. Lastly, T1D risk in children is not static, and tends to increase with age3,4.

Côte d'Ivoire introduced rotavirus vaccine in March 2017. Rotavirus surveillance is conducted at Centre Hospitalier Universitaire de Yopougon in Abidjan, the capital city. Children <5 years of age are enrolled in rotavirus surveillance if admitted to the hospital with acute gastroenteritis. We used sentinel surveillance data from 2014 through mid-2019 to compare trends in rotavirus pediatric gastroenteritis hospitalizations before and after rotavirus vaccine introduction. We used Poisson regression to analyze changes in rotavirus prevalence, adjusting for calendar month and accounting for total monthly admissions; January 2014 - December 2016 was considered "pre-vaccine," and January 2017 - June 2019 was considered "post-vaccine." Age distribution and severity were compared between periods using the Mann-Whitney U test. Rotavirus-positive admissions declined 51% (95% CI: 28%-67%), from 31.5% pre-vaccine to 14.9% afterward. The median age of rotavirus-positive children increased from 7 months (interquartile range [IQR]: 5-11) in the pre-vaccine period to 11 months (IQR: 7-18, p = .005) in the post-vaccine period. The median severity score decreased from 11 to 9 (p = .008) among all children, and from 12 pre- to 10.5 post-vaccine (p = .35) among rotavirus-positive children. Our findings suggest that rotavirus vaccine introduction contributed to reduced rotavirus hospitalization in Abidjan and possibly more broadly.

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.

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.

INTRODUCTION: Since August 2009, the Democratic Republic of Congo (DRC) has implemented sentinel site surveillance for rotavirus gastroenteritis. Limited hospital studies have been carried out, in DRC, describing the epidemiology of rotavirus diarrhea before rotavirus vaccine introduction in October 2019. This analysis describes the epidemiology of rotavirus gastroenteritis and characteristics of circulating viral strains from 2009 to 2019. MATERIALS AND METHODS: We analyzed demographic and clinic data collected from children < 5 years old enrolled at three rotavirus sentinel surveillance sites in DRC during 2009-2019, prior to rotavirus vaccine introduction in 2019. Data have been described and presented as mean ± standard deviation for quantitative variables with normal distribution, or as median with an interquartile range [Q1-Q3] for quantitative variables with non-normal distribution, or as absolute value with percentage for qualitative variables. RESULTS: Between August 2009 and December 2019, 4,928 children < 5 years old were admitted to sentinel surveillance sites for gastroenteritis in the DRC; the rotavirus positivity rate was 60 %. There was a slight male gender predominance (56 %), and the majority of children (79 %) were 0-11 months of age. Every year, the incidence was highest between May and September corresponding to the dry and cool season. Genotyping was performed for 50 % of confirmed rotavirus cases. The most common G genotypes were G1 (39 %) and G2 (24 %) and most common P genotypes were P[6] (49 %) and P[8] (37 %). The most common G-P genotype combinations were G1P[8] (22 %), G2P[6] (16 %) and G1P[6] (14 %). Genotype distribution varied by site, age group, and year. CONCLUSION: From 2009 to 2019, rotavirus-associated gastroenteritis represented a significant burden among DRC children under 5 who were admitted to sentinel sites. G1P[8] was the most commonly identified genotype. Continued monitoring after the introduction of rotavirus vaccine will be essential to monitor any changes in epidemiology.

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.

On April 21, 2022, CDC issued a health advisory(†) encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.(§) A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.(¶) Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases(†) of hepatitis of unknown etiology to public health authorities. In the United States and Europe, many of these patients have also received positive adenovirus test results (1,3). Typed specimens have indicated adenovirus type 41, which typically causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus is not a recognized cause of hepatitis in healthy children (4). Because neither acute hepatitis of unknown etiology nor adenovirus type 41 is reportable in the United States, it is unclear whether either has recently increased above historical levels. Data from four sources were analyzed to assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in the United States. Because of potential changes in health care-seeking behavior during 2020-2021, data from October 2021-March 2022 were compared with a pre-COVID-19 pandemic baseline. These data do not suggest an increase in pediatric hepatitis or adenovirus types 40/41 above baseline levels. Pediatric hepatitis is rare, and the relatively low weekly and monthly counts of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will help contextualize reported cases of acute hepatitis of unknown etiology in U.S. children.

BACKGROUND: In 2015, Tajikistan became the second country in Central Asia to introduce rotavirus vaccine into its national immunization program. Before vaccine introduction, rotavirus was estimated to cause > 40% of pediatric diarrhea hospitalizations in Tajikistan. We aimed to assess the impact of rotavirus vaccine introduction on rotavirus disease burden and estimate rotavirus vaccine effectiveness (VE). METHODS: Using surveillance data from 2013 through 2019, we examined trends in monthly hospital admissions among children < 5 years old, before and after rotavirus vaccine introduction. Poisson regression was used to quantify decreases. VE was estimated using a test-negative case control design, with data from admissions during 2017 - 2019. Immunization records were obtained from clinics. RESULTS: Among enrolled children, rotavirus positivity declined from 42% to 25% in the post-vaccine introduction period, a decrease of 41% (95% Confidence Interval [CI]: 36 - 45%). Declines were greatest in children < 12 months of age. Estimated VE of a complete course of rotavirus vaccine was 55% (95% CI: 21 - 73%) among children 5 - 59 months of age and 64% (95% CI: 36 - 80%) among children 5 - 23 months of age. VE point estimates were higher among children receiving both doses of rotavirus vaccine non-concurrently with OPV and among children receiving their first dose of rotavirus vaccine at 4 - 11 months of age, but CIs were wide and overlapping. CONCLUSIONS: Our data demonstrate that rotavirus vaccine introduction was associated with a substantial reduction in pediatric rotavirus hospitalization burden in Tajikistan, and that rotavirus vaccination is effective in Tajik children.

Mozambique introduced monovalent rotavirus vaccine (Rotarix(®)) in September 2015. We evaluated the effectiveness of Rotarix(®) under conditions of routine use in Mozambican children hospitalized with acute gastroenteritis (AGE). A test negative case-control analysis was performed on data collected during 2017-2019 from children &lt;5 years old, admitted with AGE in seven sentinel hospital sites in Mozambique. Adjusted VE was calculated for ≥1 dose of vaccine vs. zero doses using unconditional logistic regression, where VE = (1 - aOR) × 100%. VE estimates were stratified by age group, AGE severity, malnutrition, and genotype. Among 689 children eligible for analysis, 23.7% were rotavirus positive (cases) and 76.3% were negative (controls). The adjusted VE of ≥1 dose in children aged 6-11 months was 52.0% (95% CI, -11, 79), and -24.0% (95% CI, -459, 62) among children aged 12-23 months. Estimated VE was lower in stunted than non-stunted children (14% (95% CI, -138, 66) vs. 59% (95% CI, -125, 91)). Rotavirus vaccination appeared moderately effective against rotavirus gastroenteritis hospitalization in young Mozambican children. VE point estimates were lower in older and stunted children, although confidence intervals were wide and overlapped across strata. These findings provide additional evidence for other high-mortality countries considering rotavirus vaccine introduction.

In 2006, two rotavirus vaccines were licensed in Taiwan but were not added to the national immunization schedule. National Health Insurance data from 2003 through 2017 were used to compare rotavirus-associated pediatric hospitalizations before and after vaccine introduction. Rotavirus hospitalization rates among children < 5 years of age significantly declined by 24% (95% confidence interval [CI] 23 - 25%) in post-vaccine compared to pre-vaccine rotavirus seasons. Rotavirus hospitalization rates declined by 42% (95% CI 39 - 44%) among infants < 12 months of age, and by 38% (95% CI 36 - 40%) among children 12 - 23 months of age. These findings suggest that, despite not being included in the national immunization schedule, rotavirus vaccines had a measurable impact on reducing rotavirus hospitalization burden among Taiwanese children.

BACKGROUND: In the USA, COVID-19 vaccines became available in mid-December, 2020, with adults aged 65 years and older among the first groups prioritised for vaccination. We estimated the national-level impact of the initial phases of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older. METHODS: We analysed population-based data reported to US federal agencies on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 50 years and older during the period Nov 1, 2020, to April 10, 2021. We calculated the relative change in incidence among older age groups compared with a younger reference group for pre-vaccination and post-vaccination periods, defined by the week when vaccination coverage in a given age group first exceeded coverage in the reference age group by at least 1%; time lags for immune response and time to outcome were incorporated. We assessed whether the ratio of these relative changes differed when comparing the pre-vaccination and post-vaccination periods. FINDINGS: The ratio of relative changes comparing the change in the COVID-19 case incidence ratio over the post-vaccine versus pre-vaccine periods showed relative decreases of 53% (95% CI 50 to 55) and 62% (59 to 64) among adults aged 65 to 74 years and 75 years and older, respectively, compared with those aged 50 to 64 years. We found similar results for emergency department visits with relative decreases of 61% (52 to 68) for adults aged 65 to 74 years and 77% (71 to 78) for those aged 75 years and older compared with adults aged 50 to 64 years. Hospital admissions declined by 39% (29 to 48) among those aged 60 to 69 years, 60% (54 to 66) among those aged 70 to 79 years, and 68% (62 to 73), among those aged 80 years and older, compared with adults aged 50 to 59 years. COVID-19 deaths also declined (by 41%, 95% CI -14 to 69 among adults aged 65-74 years and by 30%, -47 to 66 among those aged ≥75 years, compared with adults aged 50 to 64 years), but the magnitude of the impact of vaccination roll-out on deaths was unclear. INTERPRETATION: The initial roll-out of the US COVID-19 vaccination programme was associated with reductions in COVID-19 cases, emergency department visits, and hospital admissions among older adults. FUNDING: None.

We characterized common exposures reported by a convenience sample of 202 US patients with coronavirus disease during January-April 2020 and identified factors associated with presumed household transmission. The most commonly reported settings of known exposure were households and healthcare facilities; among case-patients who had known contact with a confirmed case-patient compared with those who did not, healthcare occupations were more common. Among case-patients without known contact, use of public transportation was more common. Within the household, presumed transmission was highest from older (>65 years) index case-patients and from children to parents, independent of index case-patient age. These findings may inform guidance for limiting transmission and emphasize the value of testing to identify community-acquired infections.

Rotavirus is a major cause of severe pediatric diarrhea worldwide. In 2006, two live, oral rotavirus vaccines, Rotarix and RotaTeq, were licensed for use in infants and were rapidly adopted in many high- and middle-income settings where efficacy had been demonstrated in clinical trials. Following completion of additional successful trials in low-income settings, the World Health Organization (WHO) recommended rotavirus vaccination for all infants globally in 2009. In 2018, two new rotavirus vaccines, Rotasiil and Rotavac, were prequalified by WHO, further expanding global availability. As of March 2021, rotavirus vaccines have been introduced nationally in 106 countries. Since introduction, rotavirus vaccines have demonstrated effectiveness against severe disease and mortality, even among age groups not eligible for vaccination. Cross-genotypic protection has also been demonstrated, and the favorable benefit-risk profile of these vaccines continues to be confirmed via post-marketing surveillance. Ongoing research seeks to better understand reasons for the lower effectiveness observed in lower-resource settings, and to use these findings to optimize vaccine strategies worldwide.

The Hopi Tribe is a sovereign nation home to ~7500 Hopi persons living primarily in 12 remote villages. The Hopi Tribe, like many other American Indian nations, has been disproportionately affected by COVID-19. On 18 May 2020, a team from the US Centers for Disease Control and Prevention (CDC) was deployed on the request of the tribe in response to increases in COVID-19 cases. Collaborating with Hopi Health Care Center (the reservation's federally run Indian Health Service health facility) and CDC, the Hopi strengthened public health systems and response capacity from May to August including: (1) implementing routine COVID-19 surveillance reporting; (2) establishing the Hopi Incident Management Authority for rapid coordination and implementation of response activities across partners; (3) implementing a community surveillance programme to facilitate early case detection and educate communities on COVID-19 prevention; and (4) applying innovative communication strategies to encourage mask wearing, hand hygiene and physical distancing. These efforts, as well as community adherence to mitigation measures, helped to drive down cases in August. As cases increased in September-November, the improved capacity gained during the first wave of the pandemic enabled the Hopi leadership to have real-time awareness of the changing epidemiological landscape. This prompted rapid response coordination, swift scale up of health communications and redeployment of the community surveillance programme. The Hopi experience in strengthening their public health systems to better confront COVID-19 may be informative to other indigenous peoples as they also respond to COVID-19 within the context of disproportionate burden.

BACKGROUND: Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. OBJECTIVE: The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. METHODS: Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. RESULTS: Of the 245 enrolled mother-child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother-child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. CONCLUSIONS: The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22222.

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.

To assess whether titers of anti-rotavirus IgG persist during the post-rotavirus vaccine era, the PREVAIL Cohort analyzed sera collected from Cincinnati-area mothers and young infants in 2017-18. Rotavirus-specific antibodies continue to be transferred from US mothers to offspring in the post-rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis.

The Hopi Tribe, a sovereign nation in northeastern Arizona, includes approximately 7,500 persons within 12 rural villages (1). During April 11–June 15, 2020, the Hopi Health Care Center (HHCC, an Indian Health Services facility) reported 136 cases of coronavirus disease 2019 (COVID-19) among Hopi residents; 27 (20%) patients required hospitalization (J Hirschman, MD, CDC, personal communication, June 2020). Contact tracing of Hopi COVID-19 cases identified delayed seeking of care and testing by persons experiencing COVID-19–compatible signs and symptoms*; inconsistent adherence to recommended mitigation measures,† such as mask-wearing and social distancing; and limited knowledge of the roles of testing, isolation, and quarantine procedures§ (2). Based on these findings, the Hopi Tribe Department of Health and Human Services (DHHS) collaborated with HHCC to develop a community-focused program to enhance COVID-19 surveillance and deliver systematic health communications to the communities. This report describes the surveillance program and findings from two field tests.¶

On June 3, 2020, a woman aged 73 years (patient A) with symptoms consistent with coronavirus disease 2019 (COVID-19) (1) was evaluated at the emergency department of the Hopi Health Care Center (HHCC, an Indian Health Services facility) and received a positive test result for SARS-CoV-2, the virus that causes COVID-19. The patient's symptoms commenced on May 27, and a sibling (patient B) of the patient experienced symptom onset the following day. On May 23, both patients had driven together and spent time in a retail store in Flagstaff, Arizona. Because of their similar exposures, symptom onset dates, and overlapping close contacts, these patients are referred to as co-index patients. The co-index patients had a total of 58 primary (i.e., direct) and secondary contacts (i.e., contacts of a primary contact); among these, 27 (47%) received positive SARS-CoV-2 test results. Four (15%) of the 27 contacts who became ill were household members of co-index patient B, 14 (52%) had attended family gatherings, one was a child who might have transmitted SARS-CoV-2 to six contacts, and eight (30%) were community members. Findings from the outbreak investigation prompted the HHCC and Hopi Tribe leadership to strengthen community education through community health representatives, public health nurses, and radio campaigns. In communities with similar extended family interaction, emphasizing safe ways to stay in touch, along with wearing a mask, frequent hand washing, and physical distancing might help limit the spread of disease.

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.