Background The burden of dengue virus (DENV) infection across geographical regions of India is poorly quantified. We estimated the age-specific seroprevalence, force of infection, and number of infections in India. MethodsWe did a community-based survey in 240 clusters (118 rural, 122 urban), selected from 60 districts of 15 Indian states from five geographical regions. We enumerated each cluster, randomly selected (with an Andriod application developed specifically for the survey) 25 individuals from age groups of 5-8 years, 9-17 years, and 18-45 years, and sampled a minimum of 11 individuals from each age group (all the 25 randomly selected individuals in each age group were visited in their houses and individuals who consented for the survey were included in the study). Age was the only inclusion criterion; for the purpose of enumeration, individuals residing in the household for more than 6 months were included. Sera were tested centrally by a laboratory team of scientific and technical staff for IgG antibodies against the DENV with the use of indirect ELISA. We calculated age group specific seroprevalence and constructed catalytic models to estimate force of infection. FindingsFrom June 19, 2017, to April 12, 2018, we randomly selected 17 930 individuals from three age groups. Of these, blood samples were collected and tested for 12 300 individuals (5-8 years, n=4059; 9-17 years, n=4265; 18-45 years, n=3976). The overall seroprevalence of DENV infection in India was 48•7% (95% CI 43•5-54•0), increasing from 28•3% (21•5-36•2) among children aged 5-8 years to 41•0% (32•4-50•1) among children aged 9-17 years and 56•2% (49•0-63•1) among individuals aged between 18-45 years. The seroprevalence was high in the southern (76•9% [69•1-83•2]), western (62•3% [55•3-68•8]), and northern (60•3% [49•3-70•5]) regions. The estimated number of primary DENV infections with the constant force of infection model was 12 991 357 (12 825 128-13 130 258) and for the age-dependent force of infection model was 8 655 425 (7 243 630-9 545 052) among individuals aged 5-45 years from 30 Indian states in 2017.Interpretation The burden of dengue infection in India was heterogeneous, with evidence of high transmission in northern, western, and southern regions. The survey findings will be useful in making informed decisions about introduction of upcoming dengue vaccines in India.

BackgroundThere is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them.MethodsIn this prospective observational cohort study (2011–2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant.ResultsOf the total of 2588 neonates enrolled, culture positive sepsis and total sepsis–i.e. culture positive and/or culture negative sepsis–was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens–Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)–showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks’ gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth.ConclusionsIn this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.

SummaryBackgroundEvidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation.MethodsIn this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31–33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149.FindingsBetween March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: −1·6 (SD 1·2) in the 4 month group versus −1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI −0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0–3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group.InterpretationAlthough there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation.FundingIndian Council of Medical Research supported the study until Nov 14, 2015. Subsequently, Shuchita Gupta's salary was supported for 2 months by an institute fellowship from All India Institute Of Medical Sciences, and a grant by Wellcome Trust thereafter.

The aim of the present study was to evaluate the impact of a high-protein meal replacement (HPMR) on weight and metabolic, lipid and inflammatory parameters in overweight/obese Asian Indians. In this 12-week open-label, parallel-arm randomised controlled trial, 122 overweight/obese men and women were administered either a HPMR or a control diet after 2 weeks of diet and exercise run-in. Body weight, waist circumference (WC), percentage body fat (%BF), fasting blood glucose, post-oral glucose tolerance test (post-OGTT) blood glucose, fasting and post-OGTT serum insulin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), kidney function and hepatic aminotransferases were assessed before and after the intervention. Additional improvement in mean values for the following parameters in the HPMR group compared with the control group was observed: body weight, 4·9 % (95 % CI 3·8, 6·1; P<0·001); WC, 3·8 % (95 % CI 2·5, 5·1; P<0·001); %BF, 6·3 % (95 % CI 4·3, 8·2; P<0·001); systolic blood pressure, 2·8 % (95 % CI 0·4, 5·1; P=0·002); diastolic blood pressure, 3·5 % (95 % CI 0·7, 6·3; P= 0·01); post-OGTT blood glucose, 7·3 % (95 % CI 1·4, 13·1; P=0·02); total cholesterol, 2·5 % (95 % CI 1·6, 3·5; P<0·001); LDL-cholesterol, 7·3 % (95 % CI 1·7, 12·9; P<0·01); alanine aminotransferase, 22·0 % (95 % CI 2·1, 42; P=0·03) and aspartate aminotransferase, 15·2 % (95 % CI 0·9, 29·5; P=0·04). The absolute reduction in BMI was 0·9 units in the intervention arm compared with the control arm (-0·9 %, 95 % CI -1·4, -0·5; P<0·001) and in serum TAG was 11·9 mg/dl (-11·9 mg/dl, 95 % CI -21·1, -2·7; P<0·01). The reduction in fasting serum insulin in the intervention v. the control arm was 3·8 v. 0 % (P=0·002); post-OGTT serum insulin was 50·3 v. 77·3 mU/l (P=0·005); and hs-CRP, 16·7 % v. 0 % (P=0·002). These findings show that intervention with HPMR may lead to significant weight loss and improvement in obesity measures, metabolic, lipid and inflammatory parameters and hepatic transaminases in overweight/obese Asian Indians.