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The trillions of microorganisms residing in the human body display varying degrees of compositional and functional diversities within and between individuals and contribute significantly to host physiology and susceptibility to disease. Microbial species present in the vaginal milieu of reproductive age women showed a large personal component and varies widely in different ethnic groups at the taxonomic, genomic, and functional levels. Lactobacillus iners, L. crispatus, L. gasseri, L. jensenii, and L. johnsonii are most frequently detected bacterial species in the vaginal milieu of reproductive age women. However, we currently lack (i) an understanding of the baseline vaginal microbiota of reproductive age Indian women, (ii) the extent of taxonomic and functional variations of vaginal microbiota between individuals and (iii) the genomic repertoires of the dominant vaginal microbiota associated with the Indian subjects. In our study, we analyzed the metagenome of high vaginal swab (HVS) samples collected from 40 pregnant Indian women enrolled in the GARBH-Ini cohort. Composition and abundance of bacterial species was characterized by pyrosequencing 16S rRNA gene. We identified 3067 OTUs with ≥ 10 reads from four different bacterial phyla. Several species of lactobacilli were clustered into three community state types (CSTs). L. iners, L. crispatus, L. gasseri, and L. jensenii are the most frequently detected Lactobacillus species in the vaginal environment of Indian women. Other than Lactobacillus, several species of Halomonas were also identified in the vaginal environment of most of the women sampled. To gain genomic and functional insights, we isolated several Lactobacillus species from the HVS samples and explored their whole genome sequences by shotgun sequencing. We analyzed the genome of dominant Lactobacillus species, L. iners, L. crispatus, L. gasseri, and L. paragesseri to represent the CSTs and identify functions that may influence the composition of complex vaginal microbial ecology. This study reports for the first time the vaginal microbial ecology of Indian women and genomic insights into L. iners, L. crispatus, L. gasseri, and L. paragesseri commonly found in the genital tract of reproductive age women.

BACKGROUND "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

BackgroundThe incidence of preterm birth (PTB) in India is around 13%. Specific bacterial communities or individual taxon living in the vaginal milieu of pregnant women is a potential risk factor for PTB and may play an important role in its pathophysiology. Besides, bacterial taxa associated with PTB vary across populations.ObjectiveConduct a comparative analysis of vaginal microbiome composition and microbial genomic repertoires of women who enrolled in the Interdisciplinary Group for Advanced Research on Birth Outcomes – A DBT India Initiative (GARBH-Ini) pregnancy cohort to identify bacterial taxa associated with term birth (TB) and PTB in Indian women.MethodsVaginal swabs were collected during all three trimesters from 38 pregnant Indian women who delivered spontaneous term (n=20) and preterm (n=18) neonates. Paired-end sequencing of V3-V4 region of 16S rRNA gene was performed using the metagenomic DNA isolated from vaginal swabs (n=115). Whole genome sequencing of bacterial species associated with birth outcomes was carried out by shotgun method. Lactobacillus species were grown anaerobically in the De Man, Rogosa and Sharpe (MRS) agar culture medium for isolation of genomic DNA and whole genome sequencing.ResultsVaginal microbiome of both term and preterm samples reveals similar alpha diversity indices. However, significantly higher abundance of Lactobacillus iners (p-value All_TrimestersMegasphaera sp (p-value1st_Trimester <0.05), Gardnerella vaginalis (p-value2nd_Trimester= 0.01) and Sneathia sanguinegens (p-value2nd_Trimester <0.0001) were identified in preterm samples whereas higher abundance of L. gasseri (p-value3rd_Trimester =0.010) was observed in term samples by Wilcoxon rank-sum test. The relative abundance of L. iners, and Megasphaera sp. were found to be significantly different over time between term and preterm mothers. Analyses of the representative genomes of L. crispatus and L. gasseri indicate presence of secretory transcriptional regulator and several ribosomally synthesized antimicrobial peptides correlated with anti-inflammatory condition in the vagina. These findings indicate protective role of L. crispatus and L. gasseri in reducing the risk of PTB.ConclusionOur findings indicate that the dominance of specific Lactobacillus species and few other facultative anaerobes are associated with birth outcomes.

BackgroundDifferent formulae have been developed globally to estimate gestational age (GA) by ultrasonography in the first trimester of pregnancy. In this study, we develop an Indian population-specific dating formula and compare its performance with published formulae. Finally, we evaluate the implications of the choice of dating method on preterm birth (PTB) rate. This study’s data was from GARBH-Ini, an ongoing pregnancy cohort of North Indian women to study PTB.MethodsComparisons between ultrasonography-Hadlock and last menstrual period (LMP) based dating methods were made by studying the distribution of their differences by Bland-Altman analysis. Using data-driven approaches, we removed data outliers more efficiently than by applying clinical parameters. We applied advanced machine learning algorithms to identify relevant features for GA estimation and developed an Indian population-specific formula (Garbhini-GA1) for the first trimester. PTB rates of Garbhini-GA1 and other formulae were compared by estimating sensitivity and accuracy.ResultsPerformance of Garbhini-GA1 formula, a non-linear function of crown-rump length (CRL), was equivalent to published formulae for estimation of first trimester GA (LoA, - 0.46,0.96 weeks). We found that CRL was the most crucial parameter in estimating GA and no other clinical or socioeconomic covariates contributed to GA estimation. The estimated PTB rate across all the formulae including LMP ranged 11.27 – 16.50% with Garbhini-GA1 estimating the least rate with highest sensitivity and accuracy. While the LMP-based method overestimated GA by three days compared to USG-Hadlock formula; at an individual level, these methods had less than 50% agreement in the classification of PTB.ConclusionsAn accurate estimation of GA is crucial for the management of PTB. Garbhini-GA1, the first such formula developed in an Indian setting, estimates PTB rates with higher accuracy, especially when compared to commonly used Hadlock formula. Our results reinforce the need to develop population-specific gestational age formulae.

BackgroundBacterial infections account for a significant proportion of neonatal and infant mortality globally. We aimed to identify predictors of death in infants with probable serious bacterial infection (PSBI) defined as signs/symptoms of possible serious bacterial infection along with baseline C-reactive protein (CRP) ≥12 mg/l.MethodsWe did a secondary analysis using the data collected from 700 infants with PSBI who participated in a randomized controlled trial in India in which zinc or placebo was given in addition to the standard antibiotics. Logistic regression was used to estimate the associations between relevant variables and death within 21 days.ResultsThose infants who were fed cow's milk or formula before the illness episode had 3.7-fold (95% confidence interval (CI) 1.5-9.3) and 5.3-fold (95% CI 2.0-13.6) higher odds of death, respectively. Lethargy (odds ratio (OR) 2.4, 95% CI 1.1-5.4) and CRP (OR 1.9, 95% CI 1.1-3.3) were also independent predictors of death. In the model including only clinical features, female gender (OR 2.25, 95% CI 1.0-5.0), abdominal distention (3.7, 95% CI 1.1-12.3), and bulging fontanelle (5.8, 95% CI 1.1-30.5) were also independent predictors for death.ConclusionFormula or cow milk feeding prior to the illness, lethargy at the time of presentation, and high serum CRP levels predicted death in infants with PSBI.

Background & objectives: Healthcare associated infections (HAIs) increase the length of stay in the hospital and consequently costs as reported from studies done in developed countries. The current study was undertaken to evaluate the impact of HAIs on length of stay and costs of health care in children admitted to Paediatric Intensive Care Unit (PICU) of a tertiary care hospital in north India.Methods: This prospective study was done in the seven bedded PICU of a large multi-specialty tertiary care hospital in New Delhi, India. A total of 20 children with HAI (cases) and 35 children without HAI (controls), admitted to the PICU during the study period (January 2012 to June 2012), were matched for gender, age, and average severity of illness score. Each patient's length of stay was obtained prospectively. Costs of healthcare were estimated according to traditional and time driven activity based costing methods approach. Results: The median extra length of PICU stay for children with HAI (cases), compared with children with no HAI (controls), was seven days (IQR 3-16). The mean total costs of patients with and without HAI were ' 2,04,787 (US$ 3,413) and ' 56,587 (US$ 943), respectively and the mean difference in the total cost between cases and controls was ' 1,48,200 (95% CI 55,716 to 2,40,685, p

Background An estimated 2.7 of the 5.9 million deaths in children under 5 years of age occur in the neonatal period. Severe infections contribute to almost a quarter of these deaths. Mortality due to severe infections in developing country settings is substantial despite antibiotic therapy. Effective interventions that can be added to standard therapy for severe infections are required to reduce case fatality. Methods/Design This is a double-blind randomized placebo-controlled parallel group superiority trial to investigate the effect of zinc administered orally as an adjunct to standard therapy to infants aged 3 days up to 2 months (59 days) hospitalized with clinical severe infection, that will be undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1 ratio, we will randomly assign young infants to receive 10 mg of elemental zinc or placebo orally in addition to the standard therapy for a total of 14 days. The primary outcomes hospital case fatality, which is death due to any cause and at any time after enrolment while hospitalized for the illness episode, and extended case fatality, which encompasses the period until 12 weeks after enrolment. Discussion A previous study showed a beneficial effect of zinc in reducing the risk of treatment failure, as well as a non-significant effect on case fatality. This study was not powered to detect an effect on case fatality, which this current study is. If the results are consistent with this earlier trial, we would have provided strong evidence for recommending zinc as an adjunct to standard therapy for clinical severe infection in young infants. Trial registration Universal Trial Number: U1111-1187-6479, Clinical Trials Registry – India: CTRI/2017/02/007966 : Registered on February 27, 2017.

Background While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation. Methods In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself. Results An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance. Conclusions These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.

Objective Some of the conventional serological tests for coeliac disease (CD) are expensive, time-consuming and not readily available in developing countries, leading to a delay in diagnosis. Recently, point-of-care tests (POCT) have been manufactured and tested in Europe but have not been validated in our setting. We therefore aimed to study the diagnostic accuracy of the POCT ‘Biocard’ test in diagnosing CD in Indian children. Design Cross-sectional study. Setting Tertiary care centre in north India. Patients Children, aged 2–18 years, with chronic diarrhoea, short stature or refractory anaemia underwent serological testing for CD with antiendomysial antibodies (AEA), antitissue transglutaminase (tTG) antibodies and Biocard test followed by duodenal biopsy irrespective of serological results. CD was diagnosed with positive AEA and duodenal biopsy showing >grade 2 changes using modified Marsh criteria. Those who were both AEA negative and had normal histology were considered CD negative. Results Of 319 children who underwent the serological testing, 170 agreed for biopsy. Of these, 110 were diagnosed with CD and 30 were found to be CD negative. Remaining 30 had discordant AEA and histology results and were not included in analysis. Biocard test agreed with 92/110 positive and 27/30 negative diagnoses based on reference tests (83.6% sensitivity and 90% specificity). tTG was found to be 93.8% sensitive and 96.4% specific. Conclusions We successfully validated the POCT for CD in our setting. It could be used to increase case detection rates in developing countries with a large undiagnosed CD burden.

Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance.Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per μl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens.A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P0.001 and P= 0.05, respectively).Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.

Background: Pneumonia is a leading cause of death; in India, an estimated 370,000 children die of pneumonia each year. Zinc has multiple influences on the immune response to infections. Zinc supplementation has been shown to prevent diarrhea and pneumonia in children. However, zinc’s therapeutic effect on respiratory infections is less clear. Objective: We evaluated the role of zinc as an adjunct to antibiotics in the treatment of children hospitalized for severe or very severe pneumonia. Design: In this randomized, double-blind, placebo-controlled trial, we enrolled 550 children aged 2‐24 mo with severe or very severe pneumonia. Within each hospital and pneumonia-severity stratum, children were randomly assigned to receive zinc (20 mg elemental zinc/d) or a placebo in addition to antibiotics and supportive care. Results: The time to recovery from severe or very severe pneumonia was similar in both groups (HR: 0.98; 95% CI: 0.82, 1.17). In the stratified analysis, zinc was shown to be efficacious in reducing the time to recovery in children with very severe pneumonia (HR: 1.52; 95% CI: 1.03, 2.23); however, the effect was no longer statistically significant after adjustment for differences in severely underweight children in the 2 groups. Conclusions: This study showed no overall benefit of the addition of zinc to antibiotics in reducing the time to recovery from pneumonia but showed a possible benefit of zinc supplementation in a subgroup of children with very severe pneumonia. Additional research is needed in specific subgroups such as children with very severe pneumonia. This trial was registered at http://www.controlled-trials. com as ISRCTN48954234. Am J Clin Nutr 2013;97:1387‐ 94.

BACKGROUND AND AIM: The World Health Organization recommends oral zinc (tablets or syrups) as adjunct therapy with oral rehydration solution (ORS) for acute childhood diarrhea. Mixing zinc with ORS can be an attractive approach for simultaneous provision of these 2 effective interventions. This double-masked randomized controlled trial evaluated the efficacy of ORS containing 40 mg/L elemental zinc per liter (zinc-ORS) in reducing stool weight and duration of diarrhea. PATIENTS AND METHODS: Five hundred northern Indian children ages 1 to 35 months with diarrhea