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Concern has grown that children vaccinated against rotavirus in developing countries may be vulnerable to rotavirus diarrhea in the second year of life due to waning immunity. Adding a booster dose of rotavirus vaccine at 9 or 12 months of age with measles vaccine has been suggested as a strategy to address this. We evaluated the hypothetical potential benefits of a booster dose on reduction of rotavirus mortality. The projected number of deaths averted were calculated using national level full series vaccination coverage, estimated national rotavirus deaths by week of age, and VE at <12 months of age and ≥12 months of age derived from the published literature. We assumed three functional forms of waning based on the VE estimates: stepwise, linear, and logarithmic. We modeled three potential boosting scenarios: (a) reduced VE waning in the second year of life by 50%, (b) reestablished second year of life VE to the levels in the first year of life, and (c) boosted first year VE by 50% of the difference between VE in the first and second years. To express uncertainty resulting from the parameters, each of the nine models were run 1000 times using a random sample of input values. Across all WHO regions, with the stepwise models we estimated a median of 9800 (95%CI: 9400, 10,200), 19,600 (95%CI: 18,800, 20,400), and 29,400 (95%CI: 28,200, 30,700) additional rotavirus deaths averted in the reduced VE waning, reestablished VE, and boosted VE scenarios. These estimates were highly sensitive to the assumed functional form of waning with approximately 65–80% fewer deaths averted if immunity waned in a linear or logarithmic fashion compared to the stepwise model. While these projections will benefit from improved input data points, our results inform consideration of booster doses of rotavirus vaccine. [ABSTRACT FROM AUTHOR]

Serum antibodies play an important role in natural protection from rotavirus infection and disease, but conflicting estimates of association have emerged from epidemiological studies in different geographical settings. In this study, we aim to assess the relationship between pre-existing serum immunoglobulin (Ig)G and IgA titers with protection against rotavirus infection and disease in a birth cohort of Indian children. Children were recruited at birth and followed up for 36 months. Stool samples were collected every 2 weeks and during episodes of diarrhea and serum samples were obtained at least every 6 months. The incidence rate of rotavirus infection and diarrhea was 0.9 (95% CI: 0.88, 0.99) and 0.2 (95% CI: 0.19, 0.25) episodes per child year, respectively. The risk of rotavirus infection and diarrhea decreased with age, while antibody titers (IgG and IgA) increased with age. After adjusting for age and number of previous infections, higher levels of IgG and IgA were independently associated with reduced risk of rotavirus infection. However, we did not find a clear association of IgG or IgA with rotavirus diarrhea risk or a threshold level of protection. The study supports a correlation of serum antibodies in reducing the risk of rotavirus infections, however the potential of serum antibody titer as a correlate of protection is not clear for children in lower income settings. [ABSTRACT FROM AUTHOR]

Abstract: Two rotavirus vaccines are currently recommended for inclusion in routine childhood immunization programmes. We developed a deterministic age-structured model of rotavirus transmission and disease to investigate the population-level effects of vaccination in England and Wales. The model explicitly captures the natural history of infection and uses realistic population mixing patterns. The model accurately reproduces the strong seasonal pattern and age distribution of rotavirus disease observed in England and Wales. We predict vaccination will provide both direct and indirect protection within the population. If coverage levels comparable to other childhood vaccines are achieved, we predict that vaccination will reduce rotavirus disease incidence by 61% resulting in a potential fall in burden on health-care services. [Copyright &y& Elsevier]

The authors explore the importance of birth cohorts in understanding norovirus infection, epidemiology and immunity. They note on the importance of birth cohort studies in understanding the acquisition of protective immunity against a pathogen. They mention a birth cohort study in Mexico which showed that severe disease is restricted to the first 2 infections, that each infection reduces future disease risk.

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

Background Vaccines may play a role in controlling the spread of antibiotic resistance. However, it is unknown if rotavirus vaccination affects antibiotic use in the United States (US). Methods Using data from the IBM MarketScan Commercial Database, we conducted a retrospective cohort of US children born between 2007 and 2018 who were continuously enrolled for the first 8 months of life (N = 2 136 136). We followed children through 5 years of age and compared children who completed a full rotavirus vaccination series by 8 months of age to children who had not received any doses of rotavirus vaccination. We evaluated antibiotic prescriptions associated with an acute gastroenteritis (AGE) diagnosis and defined the switching of antibiotics as the prescription of a second, different antibiotic within 28 days. Using a stratified Kaplan-Meier approach, we estimated the cumulative incidence for each study group, adjusted for receipt of pneumococcal conjugate vaccine, provider type, and urban/rural status. Results Overall, 0.8% (n = 17 318) of participants received an antibiotic prescription following an AGE diagnosis. The 5-year adjusted relative cumulative incidence of antibiotic prescription following an AGE diagnosis was 0.793 (95% confidence interval [CI],.761–.827) among children with complete rotavirus vaccination compared to children without rotavirus vaccination. Additionally, children with complete vaccination were less likely to switch antibiotics (0.808 [95% CI,.743–.887]). Rotavirus vaccination has averted an estimated 67 045 (95% CI, 53 729–80 664) antibiotic prescriptions nationally among children born between 2007 and 2018. Conclusions These results demonstrate that rotavirus vaccines reduce antibiotic prescribing for AGE, which could help reduce the growth of antibiotic resistance. [ABSTRACT FROM AUTHOR]

We compared acute gastroenteritis (AGE)-related hospitalization rates among children <5 years of age during the pre–rotavirus vaccine (2000–2006) and post–rotavirus vaccine (2008–2013) periods to estimate national reductions in AGE-related hospitalizations and associated costs. We estimate that between 2008 and 2013, AGE-related hospitalizations declined by 382000, and $1.228 billion in medical costs were averted. [ABSTRACT FROM AUTHOR]

Background. The Republic of Moldova was the first low- to middle-income country in theWorld Health Organization European Region to introduce rotavirus vaccine (July 2012). We aimed to assess the impact of the rotavirus vaccine program and estimate vaccine effectiveness (VE). Methods. Surveillance for rotavirus gastroenteritis was conducted in 2 hospitals in the capital city of Chisinau starting in September 2009. Monthly rotavirus admissions by age were examined before and after introduction of rotavirus vaccination using interrupted timeseries analyses. We performed a case-control study of VE by comparing rotavirus case patients with test-negative controls. Results. Coverage with at least 1 dose of vaccine increased from 35% in year 1 to 55% in year 2 for children <1 year of age. The percentage of hospital admissions positive for rotavirus fell from 45% in the prevaccine period to 25% (rate reduction, 36%; 95% confidence interval [CI], 26%–44%) and 14% (rate reduction, 67%; 95% CI, 48%–88%) in the first and second years after vaccine introduction, respectively, among children aged <5 years. Reductions were most pronounced among those aged <1 year. Significant reductions among cohorts too old to be vaccinated suggest indirect benefits. Two-dose VE was 79% (95% CI, 62%–88%) against rotavirus hospitalization and 84% (95% CI, 64%–93%) against moderate to severe rotavirus. Conclusions. These results consistently point to profound direct and herd immunity impacts of the rotavirus vaccine program in young children in the Republic of Moldova. Vaccine coverage was modest in these early years following introduction, so there remains potential for further disease reductions. [ABSTRACT FROM AUTHOR]

Background. Ghana was among the first African nations to introduce monovalent rotavirus vaccine (RV1) into its childhood immunization schedule in April 2012. We aimed to assess the impact of vaccine introduction on rotavirus and acute gastroenteritis (AGE) hospitalizations and to estimate vaccine effectiveness (VE). Methods. Using data from 2 teaching hospitals, monthly AGE and rotavirus admissions by age were examined 40 months before and 31 months after RV1 introduction using interrupted time-series analyses. From January 2013, we enrolled children <2 years of age who were eligible for RV1 from a total of 7 sentinel sites across the country. To estimate VE, we fit unconditional logistic regression models to calculate odds ratios of vaccination by rotavirus case-patient status, controlling for potential confounders. Results. Vaccine coverage ranged from 95% to 100% for dose 1 and 93% to 100% for dose 2. In the first 3 years after vaccine introduction, the percentage of hospital admissions positive for rotavirus fell from 48% in the prevaccine period to 28% (49% adjusted rate reduction; 95% confidence interval [CI], 32%–63%) postvaccination among <5-year-olds. With high vaccine coverage, it was not possible to arrive at robust VE estimates; any-dose VE against rotavirus hospitalization was estimated at 60% (95% CI, −2% to 84%; P = .056). Conclusions. Results from the first 3 years following RV1 introduction suggest substantial reductions of pediatric diarrheal disease as a result of vaccination. Our VE estimate is consistent with the observed rotavirus decrease and with efficacy estimates from elsewhere in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background. Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines.Methods. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers.Findings. We observed an inverse correlation between u5MR and IgA titers for RV1 (r2 = 0.72; P < .001 and RV5 (r2 = 0.66; P < .001) and between efficacy and IgA titers for both vaccines (r2 = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC <90 were associated with decline in vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC < 90 (44%; 95% confidence interval [CI], 30–55) compared to countries with GMC > 90 (85%; 95% CI, 82–88).Interpretation. We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination. [ABSTRACT FROM AUTHOR]