Detection of Rotavirus in Respiratory Specimens From Bangladeshi Children Aged <2 Years Hospitalized for Acute Gastroenteritis.

To examine the potential for respiratory transmission of rotavirus, we systematically assessed if rotavirus RNA is detectable by real-time quantitative reverse transcription-polymerase chain reaction from nasal and oropharyngeal swab specimens of Bangladeshi children with acute rotavirus gastroenteritis. Forehead swabs were collected to assess skin contamination. Among 399 children aged <2 years hospitalized for gastroenteritis during peak rotavirus season, rotavirus RNA was detected in stool, oral, nasal and forehead swab specimens of 354 (89%). A subset was genotyped; genotype was concordant within a child's specimen set and several different genotypes were detected across children. These findings support possible respiratory transmission of rotavirus and warrant further investigation.

Correlates of Rotavirus Vaccine Shedding and Seroconversion in a U.S. Cohort of Healthy Infants.

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.

Clinical severity of enteric viruses detected using a quantitative molecular assay compared to conventional assays in the Global Enteric Multicenter Study.

BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses. METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs. RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff. CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

Evaluation of Intussusception Following Pentavalent Rotavirus Vaccine (RotaTeq) Administration in 5 African Countries.

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.

Deaths Associated with Pediatric Hepatitis of Unknown Etiology, United States, October 2021-June 2023.

During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus.

Rotavirus genotypes in the post-vaccine era: A systematic review and meta-analysis of global, regional, and temporal trends in settings with and without rotavirus vaccine introduction.

BACKGROUND: Even moderate differences in rotavirus vaccine effectiveness against non-vaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. METHODS: We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and non-introducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. RESULTS: Crude pooling of genotype data from 361 studies indicated higher G2P[4], a non-vaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to non-introducing settings, G2P[4] detections were more likely in settings with recent introduction (e.g. 1-2 years post-introduction aOR: 4.39 (95% CI: 2.87-6.72)) but were similarly likely in settings with more time elapsed since introduction, (e.g. 7 or more years aOR (1.62 95% CI: 0.49-5.37)). CONCLUSIONS: When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction.

Epidemiology and Risk Factors of Norovirus Infections Among Diarrhea Patients Admitted to Tertiary Care Hospitals in Bangladesh.

BACKGROUND: Norovirus is a major cause of endemic acute gastroenteritis (AGE) worldwide. We described the epidemiology, risk factors, and genotypic distribution of noroviruses among hospitalized patients of all ages in Bangladesh. METHODS: From March 2018 to October 2021, 1250 AGE case patients and controls (age, sex, season, and site matched) were enrolled at 10 hospitals. Demographic and clinical information was collected; real-time reverse-transcriptase polymerase chain reaction (RT-PCR) used to test stool specimens, and positive samples were genotyped. RESULTS: Norovirus was detected in 9% of cases (111 of 1250) and 15% (182 of 1250) of controls. Eighty-two percent of norovirus-positive cases were in children <5 years old. Norovirus-positive AGE hospitalizations occurred year-round, with peaks in April and October. Risk factors for norovirus included age <5 years (adjusted odds ratio, 3.1 [95% confidence interval, 1.9-5.2]) and exposure to a patient with AGE in the 10 days before enrollment (3.8 [1.9-7.2]). GII.3[P16] and GII.4 Sydney[P16] were the predominant genotypes. CONCLUSIONS: We highlight the burden of norovirus in hospital settings. Young age and recent exposure to a patient with AGE were risk factors for norovirus. A high prevalence of norovirus among controls might represent asymptomatic reinfections or prolonged shedding from a previous infection; carefully designed longitudinal studies are needed to improve our understanding of norovirus infections in Bangladesh.

Histo-Blood Group Antigen Null Phenotypes Associated With a Decreased Risk of Clinical Rotavirus Vaccine Failure Among Children <2 Years of Age Participating in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in Kenya, Mali, and the Gambia.

BACKGROUND: Previously studied risk factors for rotavirus vaccine failure have not fully explained reduced rotavirus vaccine effectiveness in low-income settings. We assessed the relationship between histo-blood group antigen (HBGA) phenotypes and clinical rotavirus vaccine failure among children <2 years of age participating in the Vaccine Impact on Diarrhea in Africa Study in 3 sub-Saharan African countries. METHODS: Saliva was collected and tested for HBGA phenotype in children who received rotavirus vaccine. The association between secretor and Lewis phenotypes and rotavirus vaccine failure was examined overall and by infecting rotavirus genotype using conditional logistic regression in 218 rotavirus-positive cases with moderate-to-severe diarrhea and 297 matched healthy controls. RESULTS: Both nonsecretor and Lewis-negative phenotypes (null phenotypes) were associated with decreased rotavirus vaccine failure across all sites (matched odds ratio, 0.30 [95% confidence interval: 0.16-0.56] or 0.39 [0.25-0.62], respectively]. A similar decrease in risk against rotavirus vaccine failure among null HBGA phenotypes was observed for cases with P[8] and P[4] infection and their matched controls. While we found no statistically significant association between null HBGA phenotypes and vaccine failure among P[6] infections, the matched odds ratio point estimate for Lewis-negative individuals was >4. CONCLUSIONS: Our study demonstrated a significant relationship between null HBGA phenotypes and decreased rotavirus vaccine failure in a population with P[8] as the most common infecting genotype. Further studies are needed in populations with a large burden of P[6] rotavirus diarrhea to understand the role of host genetics in reduced rotavirus vaccine effectiveness.

Prevalence, Clinical Severity, and Seasonality of Adenovirus 40/41, Astrovirus, Sapovirus, and Rotavirus Among Young Children With Moderate-to-Severe Diarrhea: Results From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: While rotavirus causes severe diarrheal disease in children aged <5 years, data on other viral causes in sub-Saharan Africa are limited. METHODS: In the Vaccine Impact on Diarrhea in Africa study (2015-2018), we analyzed stool from children aged 0-59 months with moderate-to-severe diarrhea (MSD) and without diarrhea (controls) in Kenya, Mali, and The Gambia using quantitative polymerase chain reaction. We derived the attributable fraction (AFe) based on the association between MSD and the pathogen, accounting for other pathogens, site, and age. A pathogen was attributable if the AFe was ≥0.5.The severity of attributable MSD was defined by a modified Vesikari score (mVS). Monthly cases were plotted against temperature and rainfall to assess seasonality. RESULTS: Among 4840 MSD cases, proportions attributed to rotavirus, adenovirus 40/41, astrovirus, and sapovirus were 12.6%, 2.7%, 2.9%, and 1.9%, respectively. Attributable rotavirus, adenovirus 40/41, and astrovirus MSD cases occurred at all sites, with mVS of 11, 10, and 7, respectively. MSD cases attributable to sapovirus occurred in Kenya, with mVS of 9. Astrovirus and adenovirus 40/41 peaked during the rainy season in The Gambia, while rotavirus peaked during the dry season in Mali and The Gambia. CONCLUSIONS: In sub-Saharan Africa, rotavirus was the most common cause of MSD; adenovirus 40/41, astrovirus, and sapovirus contributed to a lesser extent among children aged <5 years. Rotavirus- and adenovirus 40/41-attributable MSD were most severe. Seasonality varied by pathogen and location. Efforts to increase the coverage of rotavirus vaccines and to improve prevention and treatment for childhood diarrhea should continue.

Norovirus Disease Among Children <5 Years in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: To address a paucity of data from sub-Saharan Africa, we examined the prevalence, severity, and seasonality of norovirus genogroup II (NVII) among children <5 years old in The Gambia, Kenya, and Mali following rotavirus vaccine introduction. METHODS: Population-based surveillance was conducted to capture medically-attended moderate-to-severe diarrhea (MSD) cases, defined as a child 0-59 months old passing ≥3 loose stools in a 24-hour period with ≥1 of the following: sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization within 7 days of diarrhea onset. Diarrhea-free matched controls randomly selected from a censused population were enrolled at home. Stools from cases and controls were tested for enteropathogens, including norovirus and rotavirus, by TaqMan quantitative polymerase chain reaction (PCR) and conventional reverse transcription PCR. We used multiple logistic regression to derive adjusted attributable fractions (AFe) for each pathogen causing MSD, which takes into consideration the prevalence in both cases and controls, for each site and age. A pathogen was considered etiologic if AFe was ≥0.5. In further analyses focusing on the predominant NVII strains, we compared rotavirus and NVII severity using a 20-point modified Vesikari score and examined seasonal fluctuations. RESULTS: From May 2015 to July 2018, we enrolled 4840 MSD cases and 6213 controls. NVI was attributed to only 1 MSD episode. NVII was attributed to 185 (3.8%) of all MSD episodes and was the sole attributable pathogen in 139 (2.9%); peaking (36.0%) at age 6-8 months with majority (61.2%) aged 6-11 months. MSD cases whose episodes were attributed to NVII alone compared with rotavirus alone were younger (median age, 8 vs 12 months, P < .0001) and had less severe illness (median Vesikari severity score, 9 vs 11, P = .0003) but equally likely to be dehydrated. NVII occurred year-round at all study sites. CONCLUSIONS: Infants aged 6-11 months bear the greatest burden of norovirus disease, with NVII predominating. An early infant vaccine schedule and rigorous adherence to guidelines recommended for management of dehydrating diarrhea may offer substantial benefit in these African settings.

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Trends in Rotavirus Laboratory Detections and Internet Search Volume Before and After Rotavirus Vaccine Introduction and in the Context of the Coronavirus Disease 2019 Pandemic-United States, 2000-2021.

BACKGROUND: Since rotavirus vaccines became available in the United States in 2006, there have been reductions in rotavirus hospitalizations, changes in seasonality, and the emergence of a biennial trend of rotavirus activity. Reductions in other pathogens have been associated with coronavirus disease 2019 (COVID-19) mitigation measures. We assessed ongoing rotavirus disease trends during the COVID-19 pandemic. METHODS: We report a 3-week moving average of the number of rotavirus tests, positive tests, and the percent positivity from laboratories reporting to the National Respiratory and Enteric Virus Surveillance System (NREVSS) from July 2000 through June 2021. To complement NREVSS data, we analyzed Google internet search interest in "rotavirus" from July 2004 to June 2021. RESULTS: Declines in rotavirus activity following vaccine introduction and the biennial trend are evident through the 2018-2019 surveillance year. In 2019-2021, rotavirus test positivity was below the historic ranges during the months of typically high rotavirus activity, and precipitous declines were noted in March 2020. CONCLUSIONS: In the 15 years since rotavirus vaccine was introduced, the number of laboratory-detected rotavirus infections has been consistently lower than during the prevaccine era. During the COVID-19 pandemic, rotavirus activity was suppressed. There may be many rotavirus-susceptible children during the 2021-2022 rotavirus season.

Rotavirus Genotypes in Hospitalized Children With Acute Gastroenteritis Before and After Rotavirus Vaccine Introduction in Blantyre, Malawi, 1997-2019.

BACKGROUND: Rotavirus vaccine (Rotarix [RV1]) has reduced diarrhea-associated hospitalizations and deaths in Malawi. We examined the trends in circulating rotavirus genotypes in Malawi over a 22-year period to assess the impact of RV1 introduction on strain distribution. METHODS: Data on rotavirus-positive stool specimens among children aged <5 years hospitalized with diarrhea in Blantyre, Malawi before (July 1997-October 2012, n = 1765) and after (November 2012-October 2019, n = 934) RV1 introduction were analyzed. Rotavirus G and P genotypes were assigned using reverse-transcription polymerase chain reaction. RESULTS: A rich rotavirus strain diversity circulated throughout the 22-year period; Shannon (H') and Simpson diversity (D') indices did not differ between the pre- and postvaccine periods (H' P < .149; D' P < .287). Overall, G1 (n = 268/924 [28.7%]), G2 (n = 308/924 [33.0%]), G3 (n = 72/924 [7.7%]), and G12 (n = 109/924 [11.8%]) were the most prevalent genotypes identified following RV1 introduction. The prevalence of G1P[8] and G2P[4] genotypes declined each successive year following RV1 introduction, and were not detected after 2018. Genotype G3 reemerged and became the predominant genotype from 2017 onward. No evidence of genotype selection was observed 7 years post-RV1 introduction. CONCLUSIONS: Rotavirus strain diversity and genotype variation in Malawi are likely driven by natural mechanisms rather than vaccine pressure.

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

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

Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged <10 Years - United States, October 2021-June 2022.

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.

Acute Hepatitis and Adenovirus Infection Among Children - Alabama, October 2021-February 2022.

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.

Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children - United States, 2017-2022.

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.

Global Experience With Rotavirus Vaccines.

Rotavirus is a major cause of severe pediatric diarrhea worldwide. In 2006, 2 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 successful trials in low-income settings, the World Health Organization (WHO) recommended rotavirus vaccination for all infants globally in 2009. In 2018, 2 new rotavirus vaccines, Rotasiil and Rotavac, were prequalified by WHO, expanding global availability. As of March 2021, rotavirus vaccines have been introduced nationally in 106 countries. Since, Rotavirus vaccines have demonstrated effectiveness against severe disease and mortality, even among age groups in eligible for vaccination. Cross-genotypic protection has been demonstrated, and the favorable benefit-risk profile of these vaccines continues to be confirmed. Ongoing research seeks to better understand reasons for the geographic disparities in effectiveness observed, in order to optimize vaccine strategies worldwide.

Persistence of Maternal Anti-Rotavirus Immunoglobulin G in the Post-Rotavirus Vaccine Era.

To assess whether titers of anti-rotavirus immunoglobulin G persist during the post-rotavirus vaccine era, the Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) Cohort analyzed serum samples collected from Cincinnati-area mothers and young infants in 2017-2018. Rotavirus-specific antibodies continue to be transferred from US mothers to their offspring in the post-rotavirus vaccine era, despite dramatic decreases in childhood rotavirus gastroenteritis.

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

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