Rotavirus is the leading cause of gastroenteritis in children worldwide. In this report, the efficacy of the rotavirus vaccine among 4417 children in Malawi and South Africa was studied in a ...randomized trial. Severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group as compared with 1.9% of the infants in the pooled vaccine group; the vaccine efficacy was 61.2%.
In this trial of rotavirus vaccine in Malawi and South Africa, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group as compared with 1.9% of the infants in the pooled vaccine group; the vaccine efficacy was 61.2%.
Rotavirus is the most important cause of severe gastroenteritis among children worldwide. The World Health Organization (WHO) estimates that globally 527,000 deaths occur each year among children as a result of rotavirus infection
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; more than 230,000 of the deaths occur in sub-Saharan Africa. Six of the seven countries with the highest mortality due to rotavirus diarrhea are located in Africa.
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Similarly, data generated from global rotavirus surveillance networks highlight the burden of hospitalizations for rotavirus
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; among young children hospitalized for acute diarrhea, the median detection rate for rotavirus was 40% globally and 41% in Africa. Therefore, measures to . . .
Highlights ► Prevalence data on ∼110,000 rotavirus strains identified from 100 countries worldwide during a 12-year period preceding introduction of rotavirus vaccines were collected and presented in ...this systematic review ► The paper summarizes (i) baseline strain prevalence data for the pre-vaccine era, (ii) analyzes spatiotemporal trends in distribution of circulating strains, and (iii) provides a weighted model to describe a more reliable estimate on the medical importance of individual rotavirus strains.
Rotavirus is a leading cause of diarrhoeal mortality in children but there is considerable disagreement about how many deaths occur each year.
We compared CHERG, GBD and WHO/CDC estimates of age ...under 5 years (U5) rotavirus deaths at the global, regional and national level using a standard year (2013) and standard list of 186 countries. The global estimates were 157,398 (CHERG), 122,322 (GBD) and 215,757 (WHO/CDC). The three groups used different methods: (i) to select data points for rotavirus-positive proportions; (ii) to extrapolate data points to individual countries; (iii) to account for rotavirus vaccine coverage; (iv) to convert rotavirus-positive proportions to rotavirus attributable fractions; and (v) to calculate uncertainty ranges. We conducted new analyses to inform future estimates. We found that acute watery diarrhoea was associated with 87% (95% CI 83-90%) of U5 diarrhoea hospitalisations based on data from 84 hospital sites in 9 countries, and 65% (95% CI 57-74%) of U5 diarrhoea deaths based on verbal autopsy reports from 9 country sites. We reanalysed data from the Global Enteric Multicenter Study (GEMS) and found 44% (55% in Asia, and 32% in Africa) rotavirus-positivity among U5 acute watery diarrhoea hospitalisations, and 28% rotavirus-positivity among U5 acute watery diarrhoea deaths. 97% (95% CI 95-98%) of the U5 diarrhoea hospitalisations that tested positive for rotavirus were entirely attributable to rotavirus. For all clinical syndromes combined the rotavirus attributable fraction was 34% (95% CI 31-36%). This increased by a factor of 1.08 (95% CI 1.02-1.14) when the GEMS results were reanalysed using a more sensitive molecular test.
We developed consensus on seven proposals for improving the quality and transparency of future rotavirus mortality estimates.
Introduction of rotavirus vaccines into national immunization programs (NIPs) could result in strain selection due to vaccine-induced selective pressure. This study describes the distribution and ...diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP. State-based vaccine selection facilitated a unique comparison of diversity in RotaTeq and Rotarix vaccine states.
From 1995 to 2015, the Australian Rotavirus Surveillance Program conducted genotypic analysis on 13051 rotavirus-positive samples from children <5 years of age, hospitalized with acute gastroenteritis. Rotavirus G and P genotypes were determined using serological and heminested multiplex reverse-transcription polymerase chain reaction assays.
G1P8 was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P8 dominant in states using RotaTeq, and equine-like G3P8 and G2P4 dominant in states and territories using Rotarix.
The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P8), and in states and territories using Rotarix (equine-like G3P8 and G2P4), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.
Background. Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection ...beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. Methods. We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)–exposed and stunted children. Results. Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997–2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval CI, 32.8–68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%–87.0%) and 31.7% (95% CI, −140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P8 than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% 95% CI, 5.6%–94.9% in 257 well-nourished and 27.8% 95% CI, −99.5% to 73.9% in 205 stunted children; P = .12), or by HIV exposure (60.5% 95% CI, 13.3%–82.0% in 745 HIV-unexposed and 42.2% 95% CI, −106.9% to 83.8% in 174 exposed children; P = .91). Conclusions. Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting.
Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. ...We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
To analyze the epidemiological characteristics of group A rotavirus (RVA) diarrhea in Beijing between 2019 and 2022 and evaluate the effectiveness of the RV5 vaccine. Stool specimens were collected ...from patients with acute diarrhea, and RVA was detected and genotyped. The whole genome of RVA was sequenced by fragment amplification and Sanger sequencing. Phylogenetic trees were constructed using Bayesian and maximum likelihood methods. Descriptive epidemiological methods were used to analyze the characteristics of RVA diarrhea. Test‐negative design was used to evaluate the vaccine effectiveness (VE) of the RV5. Compared with 2011–2018, RVA‐positive rates in patients with acute diarrhea under 5 years of age and adults decreased significantly between 2019 and 2022, to 9.45% (249/634) and 3.66% (220/6016), respectively. The predominant genotype of RVA had changed from G9‐VIP8‐III between 2019 and 2021 to G8‐VP8‐III in 2022, and P8 sequences from G8‐VP8‐III strains formed a new branch called P8‐IIIb. The complete genotype of G8‐VP8‐III was G8‐P8‐I2‐R2‐C2‐M2‐A2‐N2‐T2‐E2‐H2. The VE of 3 doses of RV5 was 90.4% (95% CI: 28.8%–98.7%) against RVA diarrhea. The prevalence of RVA decreased in Beijing between 2019 and 2022, and the predominant genotype changed to G8P8, which may be related to RV5 vaccination. Continuous surveillance is necessary to evaluate vaccine effectiveness and improve vaccine design.
Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we ...measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.
Even moderate differences in rotavirus vaccine effectiveness against nonvaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal ...fluctuations underlie observed changes in genotype distributions is unclear.
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 nonintroducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction.
Crude pooling of genotype data from 361 studies indicated higher G2P4, a nonvaccine 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 nonintroducing settings, G2P4 detections were more likely in settings with recent introduction (eg, 1-2 years postintroduction adjusted odds ratio aOR, 4.39; 95% confidence interval CI, 2.87-6.72) but were similarly likely in settings with more time elapsed since introduction, (eg, 7 or more years aOR, 1.62; 95% CI, .49-5.37).
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 G2P4 may be transient after rotavirus vaccine introduction.
In 2006, 2 rotavirus vaccines were licensed. We summarize the impact of rotavirus vaccination on hospitalizations and deaths from rotavirus and all-cause acute gastroenteritis (AGE) during the first ...10 years since vaccine licensure, including recent evidence from countries with high child mortality. We used standardized guidelines (PRISMA) to identify observational evaluations of rotavirus vaccine impact among children <5 years of age that presented at least 12 months of pre– and post–vaccine introduction surveillance data. We identified 57 articles from 27 countries. Among children <5 years of age, the median percentage reduction in AGE hospitalizations was 38% overall and 41%, 30%, and 46% in countries with low, medium, and high child mortality, respectively. Hospitalizations and emergency department visits due to rotavirus AGE were reduced by a median of 67% overall and 71%, 59%, and 60% in countries with low, medium, and high child mortality, respectively. Implementation of rotavirus vaccines has substantially decreased hospitalizations from rotavirus and all-cause AGE.
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