Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed for developing countries. Methods In a double-blind placebo controlled multicentre trial, 6799 infants aged 6 to 7 weeks were randomised to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. Primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. Findings At analyses, the median age was 17·2 months; over 96% subjects received all three doses of the vaccine/placebo and ~1% were lost to follow up. 4532 and 2267 subjects were randomly assigned to receive vaccine and placebo, respectively. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. 71 events of severe rotavirus gastroenteritis were reported in 4752 person years among the vaccinees compared to 76 events in 2360 person years in the placebo recipients; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; P<0·001) and 56·4% (95% CI 36·6–70·1; P <0·001) in the first year of life. The number of infants needed to be immunized to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37–97). The incidence of severe rotavirus gastroenteritis/100 person years was 1·5 in vaccine and 3·2 in placebo group and an incidence rate ratio of 0·46 (95% CI 0·33–0·65). The absolute rate reduction for severe rotavirus gastroenteritis was 1·7 (95% CI 2·5–0·9). Efficacy against severe gastroenteritis of any aetiology was 18·6% (95% CI 1·9–32·3); it was 24·1% (95% CI 5·8–38·7) in the first year of life. The prevalence of immediate, solicited, and serious adverse events were similar in both groups. There were six cases of intussusception amongst 4532 vaccinees and two amongst 2267 placebo recipients (P=0·73). All intussusception cases occurred after the third dose. Among vaccine and placebo recipients, the minimum interval between dosing and intussusception was 112 and 36 days, respectively. Interpretation The monovalent human-bovine (116E) rotavirus vaccine is effective and well-tolerated in Indian infants.

Background Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middleincome countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.Methods We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and populationbased childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.Findings In 2018, among children under 5 years globally, there were an estimated 109•5 million influenza virus episodes (uncertainty range [UR] 63•1-190•6), 10•1 million influenza-virus-associated ALRI cases (6•8-15•1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middleincome countries.Funding WHO; Bill & Melinda Gates Foundation.

Summaryobjective To compare the results obtained from 26 proxy indicators of domestic hand-washing practices with those obtained from direct, 'structured' observation of hand-washing in a sample of 387 households and to assess the potential of these indicators for use in the evaluation of hygiene promotion campaigns.methods Fieldwork in rural India between February 2005 and April 2006. Household-level data on hand-washing practices and the availability of soap and water were collected by structured observation, questionnaire survey, pocket voting, hand-wash demonstration and environmental check.Between them these techniques produced 27 binary indicators of hand-washing practices, each of which was used to classify households as 'hand-washing' or 'non-hand-washing. To assess the extent to which household classification based on each of 26 proxy indicators concurred with classification based on observation, we used the kappa statistic. The prevalence of households defined as 'handwashing' according to each indicator was compared statistically with the prevalence according to structured observations by testing for a significant difference between two proportions.results Agreement between all the proxy indicators and the observation data was poor and all but two of the indicators produced estimates of hand-washing prevalence that were significantly different from that resulting from observation.conclusion Although some interventions may be able to use proxy indicators as a guide to the magnitude and direction of their impact, these indicators do not provide an accurate guide to the actual practice or prevalence of hand-washing. Structured observation remains the best indicator of those tested.

The gut microbiome has varied impact on the wellbeing of humans. It is influenced by different factors such as age, dietary habits, socio-economic status, geographic location, and genetic makeup of individuals. For devising microbiome-based therapies, it is crucial to identify population specific features of the gut microbiome. Indian population is one of the most ethnically, culturally, and geographically diverse, but the gut microbiome features remain largely unknown. The present study describes gut microbial communities of healthy Indian subjects and compares it with the microbiota from other populations. Based on large differences in alpha diversity indices, abundance of 11 bacterial phyla and individual specific OTUs, we report inter-individual variations in gut microbial communities of these subjects. While the gut microbiome of Indians is different from that of Americans, it shared high similarity to individuals from the Indian subcontinent i.e., Bangladeshi. Distinctive feature of Indian gut microbiota is the predominance of genus Prevotella and Megasphaera. Further, when compared with other non-human primates, it appears that Indians share more OTUs with omnivorous mammals. Our metagenomic imputation indicates higher potential for glycan biosynthesis and xenobiotic metabolism in these subjects. Our study indicates urgent need of identification of population specific microbiome biomarkers of Indian subpopulations to have more holistic view of the Indian gut microbiome and its health implications.

BackgroundGlobally, ageing impacts all countries, with a majority of older persons residing in lower- and middle-income countries now and into the future. An understanding of the health and well-being of these ageing populations is important for policy and planning; however, research on ageing and adult health that informs policy predominantly comes from higher-income countries. A collaboration between the WHO Study on global AGEing and adult health (SAGE) and International Network for the Demographic Evaluation of Populations and Their Health in developing countries (INDEPTH), with support from the US National Institute on Aging (NIA) and the Swedish Council for Working Life and Social Research (FAS), has resulted in valuable health, disability and well-being information through a first wave of data collection in 2006–2007 from field sites in South Africa, Tanzania, Kenya, Ghana, Viet Nam, Bangladesh, Indonesia and India.ObjectiveTo provide an overview of the demographic and health characteristics of participating countries, describe the research collaboration and introduce the first dataset and outputs.MethodsData from two SAGE survey modules implemented in eight Health and Demographic Surveillance Systems (HDSS) were merged with core HDSS data to produce a summary dataset for the site-specific and cross-site analyses described in this supplement. Each participating HDSS site used standardised training materials and survey instruments. Face-to-face interviews were conducted. Ethical clearance was obtained from WHO and the local ethical authority for each participating HDSS site.ResultsPeople aged 50 years and over in the eight participating countries represent over 15% of the current global older population, and is projected to reach 23% by 2030. The Asian HDSS sites have a larger proportion of burden of disease from non-communicable diseases and injuries relative to their African counterparts. A pooled sample of over 46,000 persons aged 50 and over from these eight HDSS sites was produced. The SAGE modules resulted in self-reported health, health status, functioning (from the WHO Disability Assessment Scale (WHODAS-II)) and well-being (from the WHO Quality of Life instrument (WHOQoL) variables). The HDSS databases contributed age, sex, marital status, education, socio-economic status and household size variables.ConclusionThe INDEPTH WHO–SAGE collaboration demonstrates the value and future possibilities for this type of research in informing policy and planning for a number of countries. This INDEPTH WHO–SAGE dataset will be placed in the public domain together with this open-access supplement and will be available through the GHA website (www.globalhealthaction.net) and other repositories. An improved dataset is being developed containing supplementary HDSS variables and vignette-adjusted health variables. This living collaboration is now preparing for a next wave of data collection.