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.

The trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109).

Interference from transplacental and breast milk antibodies may impede the performance of oral live vaccines. The effect of breastfeeding on the immunogenicity of Rotarix, a two-dose oral monovalent rotavirus vaccine, was examined in a community-based trial in New Delhi, India. Four hundred mother-infant pairs were randomized into two equal groups. Infants were aged 6-7 weeks at enrollment. Mothers were encouraged to either breastfeed or to withhold breastfeeding during the 30 min prior to and after each vaccine dose was administered. We collected blood specimens from infants at enrollment and 4 weeks after the second vaccine dose. Blood and breast milk specimens were obtained from mothers at baseline and breast milk specimens were collected at the time of the second vaccine dose. Seroconversion was defined as infant serum anti-VP6 IgA antibody level of ≥20 IU/mL 4 weeks after the second vaccine dose and a ≥4-fold rise from baseline. There was no difference in the proportion who seroconverted between the two groups (26% vs 27%; p=0.92). The levels of infant serum IgA, maternal serum and breast milk IgA and IgG anti-rotavirus antibodies predicted the anti-rotavirus IgA level in infants at end-study and explained approximately 10% of the variability of the immune response (r(2)=0.10, p<0.001). In this population, the immune response to Rotarix was not enhanced by withholding breastfeeding around the time of vaccination. Maternal anti-rotavirus antibodies explained little of the variability in the immune response to the vaccine. Factors other than maternal anti-rotavirus antibodies probably explain why infants in low-and middle-income settings respond poorly to live oral rotavirus vaccines.

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Three administrations of vaccine doses of 1 X 10(4) ffu and 1 X 10(5) ffu were safe. The 1 X 10(5)-ffu dose of 116E demonstrated a robust immune response after 3 administrations. These favorable results warrant further development of the vaccine candidate and provide optimism that vaccinating infants in the developing world will prevent serious sequelae of rotavirus infection. Clinical trials registration. NCT00439660 and ISRCTN57452882 .

BackgroundSalmonella Typhi is responsible for about 20 million episodes of illness and over 140,000 deaths annually globally. South Asia has the highest documented burden of typhoid and is home to the multi-drug resistant H58 strain that makes treatment more challenging. The WHO recommends the use of Typhoid Conjugate Vaccines in typhoid endemic countries. Decisions on the preferred immunization strategy should be based on an analysis of disease burden, availability, affordability, and operational feasibility. Typhoid vaccines have so far remained unimplemented as public health measures because of a perceived decline in typhoid burden in recent years. The apparent decline, based on hospital reports, may be a result of rampant antimicrobial use in the community and therefore estimation of disease incidence at the community is necessary to better measure disease incidence and transmission.MethodsAge-specific incidence of typhoid fever in children between 6 months and 15 years will be estimated in four community based cohorts in varied settings across India using standardized protocols for active fever surveillance in the community. Data will be collected on secured cloud infrastructure using a combination of android and web-based real-time data collection tools. Blood cultures will be done for children with fever lasting 3 or more consecutive days using automated blood culture systems. Those with blood-culture confirmed typhoid fever will be followed up till 90 days to estimate costs and clinical outcomes of the illness episodes. Environmental factors, access to safe water, sanitation, hygiene, food hygiene, demography, population density and socioeconomic status will be assessed periodically to characterise risk factors and permit extrapolation of burden to similar risk settings.DiscussionWith the availability of licensed typhoid conjugated vaccines in India, it is important to consider whether the burden of disease is present and sufficient to require the use of vaccine in addition to other interventions. Active case finding in the community permits the detection of cases that would be missed in facility-based surveillance systems. Understanding the age distribution, burden, cost-of-illness and transmission of disease is essential to plan interventions and predict their potential impact.Trial registrationThe surveillance has been prospectively registered in the Clinical Trial Registry of India (CTRI/2017/09/009719) on 12 September 2017.

The bacterial species living in the gut mediate many aspects of biological processes such as nutrition and activation of adaptive immunity. In addition, commensal fungi residing in the intestine also influence host health. Although the interaction of bacterium and fungus has been shown, its precise mechanism during colonization of the human intestine remains largely unknown. Here, we show interaction between bacterial and fungal species for utilization of dietary components driving their efficient growth in the intestine. Next generation sequencing of fecal samples from Japanese and Indian adults revealed differential patterns of bacterial and fungal composition. In particular, Indians, who consume more plant polysaccharides than Japanese, harbored increased numbers of Prevotella and Candida. Candida spp. showed strong growth responses to the plant polysaccharide arabinoxylan in vitro. Furthermore, the culture supernatants of Candida spp. grown with arabinoxylan promoted rapid proliferation of Prevotella copri. Arabinose was identified as a potential growth-inducing factor in the Candida culture supernatants. Candida spp. exhibited a growth response to xylose, but not to arabinose, whereas P. copri proliferated in response to both xylose and arabinose. Candida spp., but not P. copri, colonized the intestine of germ-free mice. However, P. copri successfully colonized mouse intestine already harboring Candida. These findings demonstrate a proof of concept that fungal members of gut microbiota can facilitate a colonization of the intestine by their bacterial counterparts, potentially mediated by a dietary metabolite.

Low‐birthweight (LBW) infants are at an increased risk of stunting and poor linear growth. The risk might be additionally higher in these infants when born to short mothers. However, this hypothesis has been less explored. The objective of this secondary data analysis was to determine the risk of linear growth faltering and difference in linear growth velocity in LBW infants born to short mothers (<150 cm) compared to those born to mothers with height ≥150 cm during the first year of life. This analysis uses data from a community‐based randomized controlled trial of 2,052 hospital‐born term infants with birthweight ≤2,500g from urban low–middle socioeconomic neighbourhoods in Delhi, India. Data on maternal height and infant birth length were available from 1,858 (90.5%) of the infants. Infant anthropometry outcomes were measured at birth, 3, 6, 9, and 12 months of age. We found that infants born to short mothers had around twofold higher odds of stunting and lower attained length‐for‐age Z scores compared to infants of mothers with height ≥150 cm, at all ages of assessment. Linear growth velocity was significantly lower in infants of short mothers particularly in the first 6 months of life. We conclude that LBW infants born to short mothers are at a higher risk of stunting and have slower postnatal growth velocity resulting in lower attained length‐for‐age Z scores in infancy. Evidence‐based strategies need to be tested to optimize growth velocity in LBW infants especially those born to short mothers.