Summary Background 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. Methods We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6–7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6–7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry–India (CTRI/2010/091/000102) and ClinicalTrials.gov ( NCT01305109 ). Findings 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; p=0·0013) and 56·4% (36·6–70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33–0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. Interpretation Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. Funding Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.
Summary Rotavirus is the most common cause of fatal and severe childhood diarrhoea worldwide. Two new rotavirus vaccines have shown efficacy against severe rotavirus disease in large clinical trials. ...Between 2006 and 2010, 27 countries introduced rotavirus vaccination into national immunisation programmes and, subsequently, the burden of severe rotavirus disease in these countries has decreased substantially in both vaccinated and unvaccinated children. Rotavirus vaccination has led to large, sustained declines in childhood deaths from diarrhoea in Brazil and Mexico, which supports estimates that rotavirus was the leading cause of diarrhoeal deaths in these countries. Studies after licensing have provided new insights into these vaccines, such as the duration of protection, relative effectiveness in poor populations, and strain evolution after vaccine introduction. The challenge for policy makers worldwide is to analyse the effect of vaccination in early adopter countries and to assess whether the benefits outweigh the costs and encourage wider dissemination of these vaccines.
The Fogarty International Center (FIC) of the US National Institutes of Health has supported long-term training and research for more than 3600 future leaders in science and public health from ...low-income and middle-income countries; tens of thousands more persons have received short-term training. More than 23 extramural training and research programs plus an intramural program are now operating. Newer FIC training programs are addressing chronic, noncommunicable diseases and strengthening the quality of medical schools and health care provider training. Most FIC trainees return to their countries of origin, where they mentor and train thousands of individuals in their home countries.
Summary Background Concerns exist about whether monovalent (RV1) and pentavalent (RV5) rotavirus vaccines provide adequate protection against diverse strains and whether vaccine introduction will ...lead to selective pressure. We aimed to investigate the distribution of rotavirus strains and strain-specific rotavirus vaccine effectiveness after vaccine introduction. Methods We did a systematic review of published work to assess the strain-specific effectiveness of RV1 and RV5 rotavirus vaccines. We classified strains as homotypic, partly heterotypic, and fully heterotypic based on the amount of antigen-matching between strain and vaccine. When studies reported vaccine effectiveness against single antigens (G-type or P-type), we categorised them as either single-antigen vaccine type or single-antigen non-vaccine type. Our primary outcome was strain-specific vaccine effectiveness, comparing effectiveness of homotypic strains with fully or partly heterotypic strains. A secondary outcome was the prevalence of rotavirus strains after vaccine introduction. We estimated pooled odds ratios using random-effect regression models, stratified by country income level and vaccine type, and tested for differences in strain-specific vaccine effectiveness. We assessed strain distribution trends from surveillance reports. Findings In high-income countries, RV1 pooled vaccine effectiveness was 94% (95% CI 80–98) against homotypic strains, 71% (39–86) against partly heterotypic strains, and 87% (76–93) against fully heterotypic strains. In middle-income settings, respective pooled data were 59% (36–73), 72% (58–81), and 47% (28–61). In high-income countries, RV5 vaccine effectiveness was 83% (78–87) against homotypic strains, 82% (70–89) against single-antigen vaccine type strains, 82% (70–89) against partly heterotypic strains, and 75% (47–88) against single-antigen non-vaccine type strains. In middle-income settings, RV5 vaccine effectiveness was 70% (58–78) against single-antigen vaccine type strains, 37% (10–56) against partly heterotypic strains, and 87% (38–97) against single-antigen non-vaccine type strains. No difference was noted in vaccine effectiveness for either RV1 or RV5 in any setting (all p>0·05). Prevalent strains in countries using RV1 were G2P4 (2198 of 4428, 50%) and G1P8 (953, 22%), and those in countries using RV5 were G1P8 (1280 of 3875, 33%) and G2P4 (1169, 30%). Sustained predominance of a single strain was not recorded. Interpretation RV1 and RV5 exert similar effectiveness against homotypic and heterotypic rotavirus strains. Persistence of specific strains was not recorded, suggesting vaccine-induced selective pressure did not occur. Expansion of rotavirus surveillance efforts to low-income countries and ongoing surveillance are crucial to identify emergence of new strains and to assess strain-specific vaccine effectiveness in various settings. Funding None.
By working directly as a team and recruiting members with new skills as the vaccine development process evolved, many of the risks and expenses for research and development that would have been ...almost insurmountable for a local manufacturer were buffeted with financial help from the public-private partnership between the Indian Government, the manufacturer (Bharat Biotech International), PATH (a non-profit organisation supported by the Bill & Melinda Gates Foundation), and other academic institutions at different phases of the development programme, and with technical support from various members of the team.
During the past decade, the programme has encountered a number of unanticipated obstacles,1-3 which have led to renewed discussions about whether eradication of poliomyelitis is feasible and, if so, ...what is the best way to achieve it.4-6 To address these issues, we engaged more than 100 scientists from 18 countries-virologists, epidemiologists, publichealth workers, policy makers, and representatives from the pharmaceutical industry-to review current progress and propose directions for the future. Unknown risk factors include the prevalence of chronic excreters, the long length of time that wild or vaccine-derived poliovirus can circulate without causing detectable disease, and the force of spread of virus and the severity of disease in immunologically naive communities.5 Leaving populations in poor countries unprotected would create the possibility for pathogenic viruses to spread and reignite new epidemics, and would be unacceptable for a number of ethical and political reasons.
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