Population effectiveness of the pentavalent and monovalent rotavirus vaccines: a systematic review and meta-analysis of observational studies.
ABSTRACT: Rotavirus was the leading cause of acute gastroenteritis (AGE) in infants and young children prior to the introduction of routine vaccination. Since 2006 there have been two licensed vaccines available; with successful clinical trials leading the World Health Organization to recommend rotavirus vaccination for all children worldwide. In order to inform immunisation policy we have conducted a systematic review and meta-analysis of observation studies to assess population effectiveness against acute gastroenteritis.We systematically searched PubMed, Medline, Web of Science, Cinhal and Academic Search Premier and grey literature sources for studies published between January 2006 and April 2014. Studies were eligible for inclusion if they were observational measuring population effectiveness of rotavirus vaccination against health care attendances for rotavirus gastroenteritis or AGE. To evaluate study quality we use used the Newcastle-Ottawa Scale for non-randomised studies, categorising studies by risk of bias. Publication bias was assessed using funnel plots. If two or more studies reported a measure of vaccine effectiveness (VE), we conducted a random effects meta-analysis. We stratified analyses by World Bank country income level and used study quality in sensitivity analyses.We identified 30 studies, 19 were from high-income countries and 11 from middle-income countries. Vaccine effectiveness against hospitalization for laboratory confirmed rotavirus gastroenteritis was highest in high-income countries (89% VE; 95% CI 84-92%) compared to middle-income countries (74% VE; 95% CI 67-80%). Vaccine effectiveness was higher for those receiving the complete vaccine schedule (81% VE; 95% CI 75-86%) compared to partial schedule (62% VE; 95% CI 55-69%). Two studies from high-income countries measured VE against community consultations for AGE with a pooled estimate of 40% (95% CI 13-58%; 2 studies).We found strong evidence to further support the continued use of rotavirus vaccines. Vaccine effectiveness was similar to that reported in clinical trials for both high and middle-income countries. There is limited data from Low income settings at present. There was lower effectiveness against milder disease. Further studies, should continue to report effectiveness against AGE and less-severe rotavirus disease because as evidenced by pre-vaccine introduction studies this is likely to contribute the greatest burden on healthcare resources, particularly in high-income countries.
Project description:Background:Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus vaccine Rotarix, as measured by laboratory-confirmed rotavirus infection after referral to hospital and/or emergency departments in children aged <5 years with gastroenteritis. Methods:We performed a systematic search for peer-reviewed studies conducted in real-life settings published between 2006 and 2016 and a meta-analysis to calculate the overall Rotarix VE, which was further discriminated through stratified analyses. Results:The overall VE estimate was 69% (95% confidence interval [CI], 62% to 75%); stratified analyses revealed a non-negligible impact of factors such as study design and socioeconomic status. Depending on the control group, VE ranged from 63% (95% CI, 52% to 72%) to 81% (95% CI, 69% to 88%) for unmatched and matched rotavirus test-negative controls. VE varied with socioeconomic status: 81% (95% CI, 74% to 86%) in high-income countries, 54% (95% CI, 39% to 65%) in upper-middle-income countries, and 63% (95% CI, 50% to 72%) in lower-middle-income countries. Age, rotavirus strain, and disease severity were also shown to impact VE, but to a lesser extent. Conclusions:This meta-analysis of real-world studies showed that Rotarix is effective in helping to prevent hospitalizations and/or emergency department visits due to rotavirus infection.
Project description:Two rotavirus vaccines, RotaTeq and Rotarix, are licensed for global use; however, the protection they confer to unvaccinated individuals through indirect effects remains unknown. We systematically reviewed the literature and quantified indirect rotavirus vaccine effectiveness (VE) for preventing rotavirus hospitalization in children aged less than 5 years. From 148 identified abstracts, 14 studies met our eligibility criteria. In our main analysis using a random-effects model, indirect rotavirus VE was 48% (95% confidence interval [CI]: 39-55%). In a subgroup analysis by country income level, indirect VE was greater in high-income countries (52%; 95% CI: 43-60%) than in low- and middle-income countries (LMICs) (25%; 95% CI: 5-41%). In a sensitivity analysis using a quality-effects model, the indirect VE in LMICs was not statistically significant (25%; 95% CI: 0-44%). Our findings highlight the importance of increasing rotavirus vaccine coverage, particularly in LMICs where evidence for indirect VE is limited and rotavirus burden is high.
Project description:<b>Background: </b>Using a multicenter, active surveillance network from 2 rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata.<br><br><b>Methods: </b>We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the vaccine effectiveness (VE) for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity.<br><br><b>Results: </b>RV5-specific VE analyses included 2961 subjects, 402 rotavirus cases (14%) and 2559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%), and 804 rotavirus-negative AGE controls. Over the 2 rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (confidence interval [CI], 74%-84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI, 68%-88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains.<br><br><b>Conclusions: </b>In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting and broadly heterologous protection against rotavirus gastroenteritis.
Project description:Background:The monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. Methods:We used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. Results:VE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40-84%) for one dose and 77% (95%CI: 66-85%) for two doses. Two-dose VE in children aged <12?months and ?12?months was 85% (95%CI: 74-91%) and 54% (95%CI: 15-75%), respectively. In contrast, we found no evidence that the vaccine was effective against all-cause AGE (VE?=?-20%, 95%CI: -36% to -5%), or against AGE hospitalisations (VE?=?35%, 95% CI: -86% to 77%). Conclusions:In this first detailed assessment of VE of the Rotarix® vaccine in the English national programme, we show that Rotarix® was highly effective in preventing laboratory-confirmed rotavirus infection in young children. This provides reassurance about the vaccine's performance in real-life settings and gives key information for future cost-effectiveness analyses. The high VE against rotavirus-specific AGE, and the exceptionally successful implementation of the national rotavirus vaccine programme (with >90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios.
Project description:BACKGROUND:The direct effectiveness of infant rotavirus vaccination implemented in 2006 in the United States has been evaluated extensively, however, understanding of population-level vaccine effectiveness (VE) is still incomplete. METHODS:We analyzed time series data on rotavirus gastroenteritis (RVGE) and all-cause acute gastroenteritis (AGE) hospitalization rates in the United States from the MarketScan® Research Databases for July 2001-June 2016. Individuals were grouped into ages 0-4, 5-9, 10-14, 15-24, 25-44, and 45-64 years. Negative binomial regression models were fitted to monthly RVGE and AGE data to estimate the direct, indirect, overall, and total VE. RESULTS:A total of 9211 RVGE and 726,528 AGE hospitalizations were analyzed. Children 0-4 years of age had the largest declines in RVGE hospitalizations with direct VE of 87% (95% CI: 83, 90%). Substantial indirect effects were observed across age groups and generally declined in each older group. Overall VE against RVGE hospitalizations for all ages combined was 69% (95% CI: 62, 76%). Total VE was highest among young children; a vaccinated child in the post-vaccine era has a 95% reduced risk of RVGE hospitalization compared to a child in the pre-vaccine era. We observed higher direct VE in odd post-vaccine years and an opposite pattern for indirect VE. CONCLUSIONS:Vaccine benefits extended to unvaccinated individuals in all age groups, suggesting infants are important drivers of disease transmission across the population. Imperfect disease classification and changing disease incidence may lead to bias in observed direct VE. TRIAL REGISTRATION:Not applicable.
Project description:BACKGROUND:Studies have demonstrated reduced rotavirus vaccine effectiveness (VE) in resource-limited settings. Enteropathogen coinfections in rotavirus cases have been hypothesized to contribute to the lower VE in such settings. We sought to determine if coinfections affect rotavirus VE in Botswana. METHODS:Between June 2013 and April 2015, children <60 months old, presenting with severe gastroenteritis at 4 hospitals as part of a national rotavirus surveillance were enrolled. Rotavirus enzyme immunoassay (EIA)-positive samples were tested with an in-house real-time polymerase chain reaction (PCR) panel that detected 9 pathogens and a commercial 15 multiplex PCR gastrointestinal pathogen panel. Coinfection was defined as detection of rotavirus plus 1 of the 5 pathogens with the highest attributable fractions for diarrhea. Vaccine status was compared between rotavirus case patients and non-rotavirus "test-negative" controls. VE was also calculated restricting cases to those with rotavirus as the only pathogen detected. RESULTS:Two hundred and forty-two children tested rotavirus EIA positive, and 368 children were negative. Of the 182 rotavirus EIA-positive samples tested with the gastrointestinal pathogen panel assay, coinfections were detected in 60 (33%). The overall adjusted 2-dose VE was 59% (95% confidence interval [CI]: 27-77) in the rotavirus coinfection group and 51% (95% CI: -14 to 79) in the rotavirus monoinfection subgroup. Using in-house multiplex PCR panel, of 213 rotavirus EIA-positive subjects, coinfections were detected in 98 samples (46%). The overall adjusted VEs for 2 doses were 48% (95% CI: -2 to 74) and 62% (95% CI: 25-80) in rotavirus monoinfection subgroup. CONCLUSIONS:We could not find evidence of an effect of enteric coinfections on the effectiveness of rotavirus vaccine.
Project description:BACKGROUND:Altering rotavirus vaccine schedules may improve vaccine performance in low- and middle-income countries. We analyzed data from clinical trials of the monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in low- and middle-income countries to understand the association between vaccine dose timing and severe rotavirus gastroenteritis incidence. METHODS:We assessed the association between variations in rotavirus vaccine administration schedules and severe rotavirus gastroenteritis risk. We used the complement of the Kaplan-Meier survival estimator to estimate risk differences for different schedules. To adjust risk differences (RDs) for confounding, we calibrated estimates in the vaccinated arm using estimates from the placebo arm. RESULTS:There were 3,114 and 7,341 children included from the RV1 and RV5 trials, respectively. The 18-month adjusted severe rotavirus gastroenteritis risk was 4.0% (95% confidence interval [CI] = 1.1, 7.1) higher for those receiving their first RV5 dose at <6 versus ?6 weeks. For RV1, there was a 4.0% (95% CI = 0.0, 8.2) increase in 12-month adjusted risk for a 4- versus 6-week interval between doses. Further analysis revealed those receiving their first RV5 dose at 3-4 and 5-7 weeks had 2.9% (95% CI = 0.8, 5.3) and 1.3% (95% CI = -0.3, 3.0), respectively, higher risk compared with those at 9-12 weeks. Those receiving their first dose at 8 weeks had the lowest risk (RD: -2.6% [95% CI = -5.4, -0.1]) compared with those at 9-12 weeks. CONCLUSIONS:A modest delay in rotavirus vaccination start and increase in interval between doses may be associated with lower severe rotavirus gastroenteritis risk in low- and middle-income countries.
Project description:Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care.Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ?10 days' duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS.Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ?8 months. The RV1 VE against G2P disease was high (94%, CI 78 to 98), as was that against G1P disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls.RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P (heterotypic) disease.
Project description:Background: Randomized controlled trials of licensed oral rotavirus group A (RVA) vaccines, indicated lower efficacy in developing countries compared to developed countries. We investigated the pooled effectiveness of Rotarix ® in Africa in 2019, a decade since progressive introduction began in 2009. Methods: A systematic search was conducted in PubMed to identify studies that investigated the effectiveness of routine RVA vaccination in an African country between 2009 and 2019. A meta-analysis was undertaken to estimate pooled effectiveness of the full-dose versus partial-dose of Rotarix ® (RV1) vaccine and in different age groups. Pooled odds ratios were estimated using random effects model and the risk of bias assessed using Newcastle-Ottawa scale. The quality of the evidence was assessed using GRADE. Results: By December 2019, 39 (72%) countries in Africa had introduced RVA vaccination, of which 34 were using RV1. Thirteen eligible studies from eight countries were included in meta-analysis for vaccine effectiveness (VE) of RVA by vaccine dosage (full or partial) and age categories. Pooled RV1 VE against RVA associated hospitalizations was 44% (95% confidence interval (CI) 28-57%) for partial dose versus 58% (95% CI 50-65%) for full dose. VE was 61% (95% CI 50-69%), 55% (95% CI 32-71%), 56% (95% CI 43-67%), and 61% (95% CI 42-73%) for children aged <12 months, 12-23 months, <24 months and 12-59 months, respectively. Conclusion: RV1 vaccine use has resulted in a significant reduction in severe diarrhoea in African children and its VE is close to the efficacy findings observed in clinical trials. RV1 VE point estimate was higher for children who received full dose than those who received partial dose, and its protection lasted beyond the first year of life.
Project description:Rotavirus vaccination has substantially reduced the incidence of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but vaccine impact and estimated effectiveness are lower in low-income countries for reasons that are poorly understood. We used mathematical modeling to quantify rotavirus vaccine impact and investigate reduced vaccine effectiveness, particularly during the second year of life, in Malawi, where vaccination was introduced in October 2012 with doses at 6 and 10 weeks. We fitted models to 12 years of prevaccination data and validated the models against postvaccination data to evaluate the magnitude and duration of vaccine protection. The observed rollout of vaccination in Malawi was predicted to lead to a 26 to 77% decrease in the overall incidence of moderate-to-severe RVGE in 2016, depending on assumptions about waning of vaccine-induced immunity and heterogeneity in vaccine response. Vaccine effectiveness estimates were predicted to be higher among 4- to 11-month-olds than 12- to 23-month-olds, even when vaccine-induced immunity did not wane, due to differences in the rate at which vaccinated and unvaccinated individuals acquire immunity from natural infection. We found that vaccine effectiveness during the first and second years of life could potentially be improved by increasing the proportion of infants who respond to vaccination or by lowering the rotavirus transmission rate. An additional dose of rotavirus vaccine at 9 months of age was predicted to lead to higher estimated vaccine effectiveness but to only modest (5 to 16%) reductions in RVGE incidence over the first 3 years after introduction, regardless of assumptions about waning of vaccine-induced immunity.