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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., Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.

Background From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. Methods A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005–2009, 3 sites from 2009 to 2012, and 28 sites during 2012–2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. Results Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0–11 months. Conclusions This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children

There is limited data on celiac disease in patients with cryptogenic cirrhosis or idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH). Our objective was to evaluate for celiac disease in patients with portal hypertension in India. Consecutive patients with portal hypertension having cryptogenic chronic liver disease (cases) and hepatitis B- or C-related cirrhosis (controls) were prospectively enrolled. We studied tissue transglutaminase (tTG) antibody and duodenal histology in study patients. Sixty-one cases (including 14 NCIPH patients) and 59 controls were enrolled. Celiac disease was noted in six cases (including two NCIPH patients) as compared to none in controls. In a significant proportion of the remaining study subjects, duodenal biopsy showed villous atrophy, crypt hyperplasia, and lamina propria inflammation, not accompanied by raised intraepithelial lymphocytes (IELs); this was seen more commonly in cases as compared to controls. An unexpectedly high rate of tTG antibody positivity was seen in study subjects (66 %) of cases as compared to 29 % in controls (p-value