Concept: Rotavirus vaccine
Background Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. Methods We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. Results Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. Conclusions Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).
Rotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR.
In January 2006, the Journal published two landmark articles reporting the safety and efficacy of two different vaccines - RotaTeq (Merck), a pentavalent vaccine (RV5)(1) and Rotarix (GlaxoSmithKline), a monovalent vaccine (RV1)(2) - to prevent rotavirus, the most common cause of severe childhood diarrhea worldwide and of deaths from diarrhea in low-income countries. Each trial enrolled more than 60,000 infants to determine whether these live oral vaccines caused intussusception, the rare complication that in 1999 forced the withdrawal of the first licensed rotavirus vaccine, RotaShield (Wyeth Lederle), less than a year after it was recommended for routine immunization of U.S. . . .
A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine.
Rotavirus is a leading cause of severe pediatric diarrhea globally, estimated to have caused 120,000 deaths among children aged <5 years in sub-Saharan Africa in 2013 (1). In 2009, the World Health Organization (WHO) recommended rotavirus vaccination for all infants worldwide (2). Two rotavirus vaccines are currently licensed globally: the monovalent Rotarix vaccine (RV1, GlaxoSmithKline; 2-dose series) and the pentavalent RotaTeq vaccine (RV5, Merck; 3-dose series). This report describes progress of rotavirus vaccine introduction (3), coverage (using estimates from WHO and the United Nations Children's Fund [UNICEF]) (4), and impact on pediatric diarrhea hospitalizations in the WHO African Region. By December 2016, 31 (66%) of 47 countries in the WHO African Region had introduced rotavirus vaccine, including 26 that introduced RV1 and five that introduced RV5. Among these countries, rotavirus vaccination coverage (completed series) was 77%, according to WHO/UNICEF population-weighted estimates. In 12 countries with surveillance data available before and after vaccine introduction, the proportion of pediatric diarrhea hospitalizations that were rotavirus-positive declined 33%, from 39% preintroduction to 26% following rotavirus vaccine introduction. These results support introduction of rotavirus vaccine in the remaining countries in the region and continuation of rotavirus surveillance to monitor impact.
Oral rotavirus vaccines have consistently proven to be less immunogenic among infants in developing countries. Discrepancies in the intestinal microbiota, including a greater burden of enteropathogens and an altered commensal community composition, may contribute to this trend by inhibiting the replication of vaccine viruses. To test this possibility, we performed a nested case-control study in Vellore, India, in which we compared the intestinal microbiota of infants who responded serologically or not after two doses of Rotarix delivered at 6 and 10 weeks of age as part of a clinical trial (CTRI/2012/05/002677). The prevalence of 40 bacterial, viral, and eukaryotic pathogen targets was assessed in pre-vaccination stool samples from 325 infants using singleplex real-time PCR on a Taqman array card (TAC). In a subset of 170 infants, we assessed bacterial microbiota composition by sequencing the 16S rRNA gene V4 region. Contrary to expectations, responders were more likely than non-responders to harbor ≥1 bacterial enteropathogen at dose 1 (26% [40/156] vs 13% [21/157] of infants with TAC results who completed the study per protocol; χ2, P = .006), although this was not apparent at dose 2 (24% [38/158] vs 23% [36/158]; P = .790). Rotavirus shedding after dose 1 was negatively correlated with the replication of co-administered oral poliovirus vaccine (OPV). We observed no consistent differences in composition or diversity of the 16S bacterial microbiota according to serological response, although rotavirus shedding was associated with slightly more bacterial taxa pre-vaccination. Overall, our findings demonstrate an inhibitory effect of co-administered OPV on the first dose of Rotarix, consistent with previous studies, but in the context of OPV co-administration we did not find a strong association between other components of the intestinal microbiota at the time of vaccination and Rotarix immunogenicity.
Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO’s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia.
Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India.
Transmission of rotavirus vaccine or vaccine-reassortant strains to unvaccinated contacts has been reported. Therefore, it is essential to evaluate and characterize the nature of vaccine-virus shedding among rotavirus vaccine recipients. Two groups of healthy infants who received a complete course of RotaTeq (RV5) or Rotarix (RV2) were enrolled (between March 2010 and June 2011) to compare fecal shedding for one month after each vaccine dose. Shedding was assessed using both enzyme immunoassay (EIA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Eighty-seven infants (34 girls and 53 boys) were enrolled in the study. After the first vaccine dose, the peak time of virus shedding occurred between day 4 and day 7, with positive detection rates of 80-90% by real-time RT-PCR and 20-30% by EIA. In both groups, vaccine shedding occurred as early as one day and as late as 25-28 days. Mixed effects logistic regression analysis of real-time RT-PCR data showed no significant differences between two groups when shedding rates were compared after the first vaccine dose (odds ratio [OR] 1.26; P=0.71) or after the second vaccine dose (odds ratio [OR] 1.26; P=0.99). However, infants receiving RV2 shed significantly higher viral loads than those receiving RV5 when compared after the first vaccine dose (P=0.001) and after the second dose (P=0.039). In terms of shedding rates detected by real-time RT-PCR, vaccine uptake of RV5 or RV2 among infants in Taiwan was comparable. Clinical significance of higher shedding viral loads in RV2 should be further observed.