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Background: Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling., Methods: To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures. We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member., Discussion: Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aguolu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Experiences in early childhood form the bedrock of future human potential. In impoverished settings, structured early childhood education (ECE) in preschool years can augment overall childhood and later human abilities. The current study evaluates preschool learning exposure and childhood cognition, using longitudinal follow-up of a community-based birth cohort in Vellore, south India. The birth cohort study site in Vellore recruited 251 newborns between 2010 and 2012 from dense urban settlements and further followed up into childhood. Preschool enrolment details were obtained from parents. Childhood cognition was assessed by Weschler's preschool primary scale of intelligence (WPPSI) and Malin's intelligence scale for Indian Children (MISIC) at 5 and 9 years of age respectively. Bivariate and multivariate regression analyses were performed with adjustments for socio-economic status (SES), maternal education, stunting status and home environment. Out of 251 new-borns recruited into the MAL-ED birth cohort, 212 (84.46%) and 205 (81.7%) children were available for the 5 year and 9 year follow-up respectively. At 5 years, structured ECE of 18 to 24 months duration was significantly associated with higher cognition scores, with the highest increase in processing speed [β: 19.55 (11.26-27.77)], followed by full-scale intelligence [β: 6.75 (2.96-10.550)], even after adjustments for SES, maternal cognition, home factors and early childhood stunting status. Similarly adjusted analysis at 9 years showed that children who attended 1.5-2 years of structured ECE persisted to have higher cognition, especially in the performance domain [β: 8.82 (2.60-15.03)], followed by the full-scale intelligence [β: 7.24 (2.52-11.90)]. Follow-up of an Indian birth cohort showed that structured ECE exposure was associated with better school entry cognition as well as mid-childhood cognition. Strengthening ECE through a multi-pronged approach could facilitate to maximize cognitive potential of human capital., (© 2024. The Author(s).)

Background: Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever., Methods: We developed standardized protocols for typhoid ES, including sampling site selection, validation, characterization; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG, and tviB) and a marker of human fecal contamination (HF183). ES was implemented over 12 months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022., Results: S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%; 95% confidence interval [CI], 4.4%-12.4%) vs 11/533 (2.1%; 95% CI, 1.1%-4.0%) in grab and 79/517 (15.3%; 95% CI, 9.8%-23.0%) vs 23/594 (3.9%; 95% CI, 1.9%-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES., Conclusions: ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines (TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting., Methods: The primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants' intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness., Discussion: The results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines., Trial Registration: Clinical Trials Registry of India (CTRI) CTRI/2022/03/041314. Prospectively registered on 23 March 2022 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62548&EncHid=&userName=vellore%20typhoid ). CTRI collects the full WHO Trial Registration Data Set., (© 2023. The Author(s).)

Background: Primary SARS-CoV-2 vaccination has been shown to wane with time and provide lower protection from disease with new viral variants, prompting the WHO to recommend the administration of booster doses. We determined the safety and immunogenicity of homologous or heterologous boosters with ChAdOx1 nCoV-19 (COVISHIELD™) or BBV152 (COVAXIN®), the two vaccines used widely for primary immunization in India, in participants who had already received two primary doses of these vaccines., Methods: Participants primed with two doses each of COVISHIELD™ or COVAXIN® 12-36 weeks previously, were randomised to receive either COVISHIELD™ or COVAXIN® booster in a 1:1 ratio. The primary outcome was day 28 post-booster anti-spike IgG seropositivity and secondary outcomes were anti-spike IgG levels and assessment of safety and reactogenicity. The results of 90 days intention-to-treat analysis are presented. This trial is registered with ISRCTN (CTRI/2021/08/035648)., Findings: In the COVISHIELD™ primed group with 200 participants, the seropositivity 28 days post booster in the heterologous COVAXIN® arm was 99% and non-inferior to the homologous COVISHIELD™ arm, which was also 99% (difference 0%; 95% CI: -2.8% to 2.7%). The geometric mean concentration (GMC) of anti-spike antibodies following heterologous COVAXIN® boost on day 28 was 36,190.78 AU/mL (95% CI: 30,526.64-42,905.88) while the GMC following homologous COVISHIELD™ boost was 97,445.09 AU/mL (82,626.97-114,920.7). In the COVAXIN® primed group with 204 participants, the seropositivity 28 days post booster in the heterologous COVISHIELD™ arm was 100% and non inferior to the homologous COVAXIN® arm which was 96% (difference 4%, 95% CI: 0.2%-7.8%). The GMC following heterologous COVISHIELD™ boost was 241,681.6 AU/mL (95% CI: 201,380.2-290,048.3) compared to homologous COVAXIN® boost, which was 48,473.94 AU/mL (95% CI: 38,529.56-60,984.95). The day 28 geometric mean ratio (GMR) of the anti-spike IgG between the heterologous and homologous boosted arms was 0.42 (95% CI: 0.34-0.52) in the COVISHIELD™ primed group and 5.11 (95% CI: 3.83-6.81) in the COVAXIN® primed group. There were no related serious adverse events reported in any group., Interpretation: Homologous and heterologous boosting with COVISHIELD™ or COVAXIN® in COVISHIELD™ or COVAXIN® primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD™ after COVAXIN® prime offers the best immune response among the four combinations evaluated., Funding: Azim Premji Foundation and Bill and Melinda Gates Foundation., Competing Interests: The study is funded by Azim Premji Foundation the 10.13039/100000865Bill and Melinda Gates Foundation. The funding is to the institution, Christian Medical College, Vellore. K.B.T. was an investigator in a study which received funding support from Bharath Biotech, manufacturer of Covaxin. The funding was given to his institute, Centre for Cellular and Molecular Biology, Hyderabad. None of the other authors have declared any competing interests., (© 2023 The Author(s).)

Objective: To recalibrate the Framingham Risk Score-cardiovascular diseases (FRS-CVD) using 10-year mortality data and baseline risk factor data for a rural cohort and assess the effect of recalibration on proportion categorised as high risk., Methods: Participants of a cardiovascular risk factor survey aged 30-64 years in 2011-12, from 9 villages of a rural block in Vellore, Tamil Nadu, were followed up for mortality till 2021, as part of an established demographic surveillance system. We calculated both lipid-based and Body Mass Index-based FRS-CVD risk scores, as well as recalibrated scores using risk factor data from the baseline survey and CVD mortality observed over 10 years., Results: Based on original lipid-based FRS-CVD scores, 8.48% (109) of 1285 males had a 10-year CVD risk ≥30%, compared to 11.60% (149) with recalibrated scores. Among 1737 females, 1.50% (26) had a 10-year CVD risk of ≥30%, using original FRS-CVD scores, and 3.22% (56) using recalibrated scores. Similarly, for BMI based FRS-CVD scores, overall, 3.63% (110/3028) had a 10-year risk of ≥30%, compared to 6.64% (201) using recalibrated scores. The median 10-year FRS-CVD original score in males was 7.57 (IQR: 3.67-15.83), and 2.53 (IQR: 1.28-5.32) in females, compared to 8.95 (IQR: 4.35-18.52) and 3.79 (IQR: 1.92-7.93) respectively, for the recalibrated FRS-CVD risk scores., Conclusion: The recalibrated Framingham models showed a greater proportion of the population at risk of CVDs compared to the original FRS scores, with males having 2-3 times greater CVD risk scores compared to females., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Human resilience is dynamic and generated through myriad interactions starting from early childhood. Resilience can improve quality of life and longevity., Objective: The current analysis evaluates childhood resilience at 9 years of age and its associations with concurrent cognition and early childhood factors, using longitudinal follow-up of a community birth cohort in Vellore, south India., Methods: Resilience was assessed using the Child and Youth Resilience Measure and cognition utilizing the Malin's Intelligence Scale for Indian Children. Early childhood variables included growth stunting, maternal depression scores, home environment scores, and socio-economic status (SES) at 2 years of age. Statistical evaluation included bivariate analysis with further multi-variate regression for each resilience domain and the total resilience score., Findings: Out of 251 newborns recruited into the original birth cohort, 205 (81.7%) children were available for the 9-year follow-up. Mean (SD) scores in individual, caregiving, and context domains of resilience were 26.34 (3.2), 19.52 (1.6), and 20 (1.8) respectively. Individual resilience domain was associated with verbal cognition scores at 9 years of age (0.07, p = 0.019) and total home environment scores (0.16, p = 0.027) at 2 years of age, when adjusted for stunting, maternal depression, and SES. The total resilience score was associated only with concurrent verbal intelligence (0.08, p = 0.026) after adjustment with early childhood factors. Analysis of individual home environment factors showed that daily stimulation was associated with the individual domain of resilience., Conclusions: Follow-up of an Indian birth cohort showed that in addition to concurrent cognitive abilities, childhood resilience was related to early childhood stimulating home environment. Promoting optimal stimulating home environments in low-resource settings to nurture holistic childhood development including mental health is essential.

Objectives: Geographical Information Surveillance (GIS) is an advanced digital technology tool that maps location-based data and helps in epidemiological modeling. We applied GIS to analyze patterns of spread and hotspots of COVID-19 cases in the Vellore district in South India., Methods: Laboratory-confirmed COVID-19 cases from the Vellore district and neighboring taluks from March 2020 to June 2021 were geocoded and spatial maps were generated. Time trends exploring urban-rural burden with an age-sex distribution of cases and other variables were correlated with outcomes., Results: A total of 45,401 cases of COVID-19 were detected, with 20,730 cases during the first wave and 24,671 cases during the second wave. The overall incidence rates of COVID-19 were 462.8 and 588.6 per 100,000 population during the first and second waves, respectively. The spread pattern revealed epicenters in densely populated urban areas with radial spread sparing rural areas in the first wave. The case fatality rate was 1.89% and 1.6% during the first and second waves, which increased with advancing age., Conclusions: Modern surveillance systems like GIS can accurately predict the trends and spread patterns during future pandemics. In addition, real-time mapping can help design risk mitigation strategies, thereby preventing the spread to rural areas., Competing Interests: Conflict of interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We report an outbreak of typhoid fever between April and June 2019 in the Surveillance for Enteric Fever in India cohort, a pediatric cohort from four contiguous semi-urban settlements of Vellore in South India. This cohort of children 6 months to 15 years of age was under surveillance from October 2017 to December 2019. A clustering of typhoid cases in the cohort was noted with reference to time, place, and person. The overall typhoid attack rate in the cohort was 0.9%, with the highest attack rate of 1.7% being documented in one of the four areas. The rate of hospitalization and complications in children who were typhoid positive during the outbreak was 28% and 2%, respectively. Given the background of suboptimal water, sanitation, and hygiene, and the risk of typhoid fever outbreaks in these settings, it is imperative that a typhoid vaccine be considered for introduction as a pragmatic preventive approach.

Stunting and extreme poverty are considered significant risk factors impacting child development in low-and-middle-income countries. We used two birth cohorts recruited 8-9 years apart in urban low-income (slum) settings in Vellore, south India and analyzed secular growth trends and their predictors. In the rotavirus cohort recruited between 2002 and 2003, 373 children completed the 3-year follow-up. "The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development" (MAL-ED) cohort recruited between 2010 and 2012 had 215 children completing follow-up. The MAL-ED cohort had better socio-economic status (SES) markers and mothers were better educated compared with the previous cohort. Children in the MAL-ED cohort had less stunting at 1, 2, and 3 years of age. The linear mixed effects model evaluating linear growth during the first 3 years of age showed that low birth weight and being a female child were associated with stunting in both cohorts. There was no association between SES and stunting in the rotavirus cohort, whereas SES was associated with linear growth in the MAL-ED cohort. Future studies could incorporate nutritional and nonnutritional interventions in vulnerable populations to evaluate their effect on birth weight as well as early childhood stunting.

Scrub typhus is a zoonotic rickettsial disease caused by the bacterium Orientia tsutsugamushi. The non-specificity of presentation, low index of suspicion and the poor availability of diagnostic tests often lead to delayed diagnosis and significant morbidity and mortality. Temperature, humidity, rainfall and Normalized Difference Vegetation Index (NDVI) on the spatio-temporal clustering of scrub typhus cases in children in three contiguous administrative districts in South India over 5 years were studied. A total of 419 children were diagnosed with scrub typhus during the study period. A surge of children with scrub typhus was noted when the NVDI ranged between 0.6 and 0.8 µm. Temperature, humidity and rainfall had a major role in the incidence of scrub typhus., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Millions of children worldwide especially in the Asian subcontinent are vulnerable to early childhood stunting. There are contradictory reports of the association between catch-up growth in childhood and school age cognition., Methods: A community-based birth cohort recruited between 2010 and 2012 from urban slums in Vellore, India was followed up until 9 years of age. From regular anthropometric measurements, stunting status for each individual child was calculated at 2, 5 and 9 years. Cognition was assessed at 9 years of age using the Malin's Intelligence Scale for Indian Children (MISIC). Children were divided into groups based on stunting at each time point as well as catch-up growth, and a regression model was utilised to evaluate their association with cognition at 9 years., Results: Among 203 children included in this analysis, 94/203 (46.31%) children were stunted at 2 years of age, of whom 39.36% had a catch-up growth at 5 years of age, and 38.30% at 9 years. Around 10% of the cohort remained stunted at all time points. In the multivariable analysis, children who were stunted at 2, 5 and 9 years had a significantly lower verbal and total intelligence quotient (IQ) scores by 4.6 points compared to those who were never stunted. Children with catch up growth following stunting at 2 years had higher cognition scores than those who were persistently stunted throughout the childhood., Conclusions: This study showed persistent stunting in childhood was associated with lowering of 4-5 IQ points in childhood cognition at 9 years of age. Recovery from early life stunting in children with catch up growth prevented further lowering of cognition scores in these children compared to persistently stunted children. Nutritional supplementation during late infancy and early toddlerhood in addition to continuing nutritional supplementation programmes for preschool and school children can improve childhood stunting and cognitive abilities in vulnerable populations., Competing Interests: No competing interests exist

Objectives: To study the household environmental risk factors and hazards associated with elevated blood lead levels (EBLLs) in preschool children in an urban setting of Vellore, South India., Methods: A case-control study within the MAL-ED (Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development) birth cohort was conducted between January 2014 and January 2015. The study included 153 pre-school children: 87 cases and 66 controls with elevated and normal BLLs, respectively. A structured questionnaire was used to assess the sociodemographic profile, household environment, breastfeeding practices, children's habits, and the use of cosmetics in them. Household environmental samples of wall and door paint, floor dust, drinking water, and cosmetics were estimated for lead levels using gas flame atomic absorption spectrometry (FAAS)., Results: Children born with low birth weight, those living in houses painted at least once in the last five years and those residing in houses older than ten years had a higher odds of EBLLs [OR (95% CI) = 3.79 (1.24-11.1); 4.84 (1.42-16.53); 5.07 (2.06-12.46), and 2.58 (0.99-6.69)], respectively. Drinking water samples from both cases (88%) and controls (95%) had lead levels more than the Environmental Protection Agency (EPA), USA recommendation of 0.015 ppm., Conclusions: Low birth weight and the household environment pose important risk factors/hazards for elevated blood lead levels in urban preschool children. Multipronged interventions that include government legislations, household environmental modification, safe water supply, and community education are pivotal in reducing lead exposure in young children., (© 2021. Dr. K C Chaudhuri Foundation.)

Background: Globally, over 130 million babies are born every year, and almost 8 million die before their first birthday. Data on perinatal mortality (PM) and its various causes are lacking in many parts of the world including India., Objectives: This study aimed to estimate stillbirth (SB), early neonatal, and PM rates and its causes over the last decade in a rural development block, India., Materials and Methods: This is a nonconcurrent cohort study, analyzing the births, SBs, and early neonatal deaths between January 2008 and December 2017. The World Health Organization-PM classification was used to allocate causes of death as well as maternal risk factors. Birth weights were classified using standard growth charts., Results: There were 20,704 births after 28 weeks gestation and where the fetus weighed more than 1000 g of which 285 were SBs. There were 20,419 live births with 229 early neonatal deaths. There was a significant decline in PM rate from 32 per 1000 to 11 per 1000. There was a decrease in the small for gestational age fetuses from 20% to 12.5%. The main cause for SBs was antepartum hypoxia (34.4%) and fetal growth disorders (26.3%). Complications of intrapartum events contributed to 32.8% of the early neonatal deaths., Conclusion: Steady decline in PM rate and in the number of small for gestational age fetuses over 10 years was seen. Pregnancy registration and follow-up help in giving us a better understanding of the causes of PM., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Community Medicine.)

Background: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden., Methods: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting., Results: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure., Conclusions: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Typhoid fever causes substantial morbidity and mortality in low- and middle-income countries. We conducted a case-control study in Vellore, southern India, to understand risk factors for transmission of typhoid., Methods: From April 2018 to October 2019, households of blood culture-confirmed typhoid cases that occurred within a fever surveillance cohort aged 6 months-15 years, and controls matched for age, sex, geographic location, and socioeconomic status, were recruited. Information on risk factors was obtained using standard questionnaires. Household and environmental samples were collected for detection of Salmonella Typhi using real-time polymerase chain reaction. Multivariable analysis was used to evaluate associations between risk factors and typhoid., Results: One hundred pairs of cases and controls were recruited. On multivariable regression analysis, mothers eating food from street vendors during the previous week (odds ratio [OR] = 2.04; 95% confidence interval [CI], 1.03-4.12; P = .04) was independently associated with typhoid, whereas treatment of household drinking water (OR = 0.45; 95% CI, 0.25-0.80; P = .007) was protective. There was no significant difference in S Typhi detection between the environmental samples from case and control households., Conclusions: Street-vended food is a risk factor for typhoid in densely populated urban communities of Vellore. Improved sanitation facilities and awareness about point-of-use water treatment are likely to contribute to typhoid control., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Typhoid fever remains a major public health problem in India. Recently, the Surveillance for Enteric Fever in India program completed a multisite surveillance study. However, data on subnational variation in typhoid fever are needed to guide the introduction of the new typhoid conjugate vaccine in India., Methods: We applied a geospatial statistical model to estimate typhoid fever incidence across India, using data from 4 cohort studies and 6 hybrid surveillance sites from October 2017 to March 2020. We collected geocoded data from the Demographic and Health Survey in India as predictors of typhoid fever incidence. We used a log linear regression model to predict a primary outcome of typhoid incidence., Results: We estimated a national incidence of typhoid fever in India of 360 cases (95% confidence interval [CI], 297-494) per 100 000 person-years, with an annual estimate of 4.5 million cases (95% CI, 3.7-6.1 million) and 8930 deaths (95% CI, 7360-12 260), assuming a 0.2% case-fatality rate. We found substantial geographic variation of typhoid incidence across the country, with higher incidence in southwestern states and urban centers in the north., Conclusions: There is a large burden of typhoid fever in India with substantial heterogeneity across the country, with higher burden in urban centers., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Acute febrile illness in children is frequently treated with antibiotics. However, the inappropriate use of antibiotics has led to the emergence of multidrug-resistant pathogens., Methods: We measured use of antibiotics for fever in 4 pediatric cohorts that were part of the Surveillance for Enteric Fever in India (SEFI) network. In this network, 24 062 children were followed up weekly, capturing information on fever and other morbidity between October 2017 and December 2019., Results: An antibiotic was given in 27 183 of the 76 027 (35.8%) episodes of fever. The incidence of fever-related antibiotic use was 58.0 (95% confidence interval [CI], 57.2-58.6) per 100 child-years. The median time to initiation of antibiotics was 4 days, and in 65% of those who received an antibiotic it was initiated by the second day. Antibiotics were continued for <3 days in 24% of the episodes. Higher temperature, younger age, male sex, joint family, higher education, internet access, and availability of personal conveyance were associated with antibiotic treatment for fever., Conclusions: In developing countries where antibiotic use is not regulated, broad-spectrum antibiotics are initiated early, and often inappropriately, in febrile illness. Frequent and inappropriate use of antibiotics may increase risk of antimicrobial resistance., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Typhoid is known to be heterogenous in time and space, with documented spatiotemporal clustering and hotspots associated with environmental factors. This analysis evaluated spatial clustering of typhoid and modeled incidence rates of typhoid from active surveillance at 4 sites with child cohorts in India., Methods: Among approximately 24 000 children aged 0.5-15 years followed for 2 years, typhoid was confirmed by blood culture in all children with fever >3 days. Local hotspots for incident typhoid cases were assessed using SaTScan spatial cluster detection. Incidence of typhoid was modeled with sociodemographic and water, sanitation, and hygiene-related factors in smaller grids using nonspatial and spatial regression analyses., Results: Hotspot households for typhoid were identified at Vellore and Kolkata. There were 4 significant SaTScan clusters (P < .05) for typhoid in Vellore. Mean incidence of typhoid was 0.004 per child-year with the highest incidence (0.526 per child-year) in Kolkata. Unsafe water and poor sanitation were positively associated with typhoid in Kolkata and Delhi, whereas drinking untreated water was significantly associated in Vellore (P = .0342) and Delhi (P = .0188)., Conclusions: Despite decades of efforts to improve water and sanitation by the Indian government, environmental factors continue to influence the incidence of typhoid. Hence, administration of the conjugate vaccine may be essential even as efforts to improve water and sanitation continue., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Children suffer the highest burden of the typhoid fever, with a considerable proportion shedding Salmonella Typhi in stool, potentially resulting in transmission of S Typhi., Methods: We enrolled 70 children with blood culture-confirmed typhoid fever (index cases), from 63 households, during community-based fever surveillance in India. The index cases and their household contacts were followed up with stool samples at multiple time points over 3 weeks and 1 week, respectively. S Typhi was detected using quantitative real-time polymerase chain reaction., Results: Fifteen of 70 (21.4%) children with culture-confirmed typhoid fever shed S Typhi in stool after onset of fever. Ten of 15 children shed S Typhi for a median of 11.5 (range, 3-61) days from the day of completion of antibiotics. Of 172 household contacts from 56 of the 63 index case households, 12 (7%) contacts in 11 (19.6%) households had S Typhi in stool. Five of the 12 contacts who were shedding S Typhi were asymptomatic, whereas 7 reported recent fever., Conclusions: One in 5 children with typhoid fever shed S Typhi, with shedding persisting even after antibiotics. One in 5 households had at least 1 contact of the child shedding S Typhi, highlighting potential concurrent typhoid infections in households in settings with poor water and sanitation., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: In 2015, the Vellore district in southern India was selected for intensified routine immunization, targeting children from communities experiencing disadvantage such as migrant, tribal, and other hard-to-reach groups. This mixed-methods study was conducted to assess routine immunization coverage and the factors influencing childhood vaccination uptake among these communities in Vellore., Methods: We conducted a cross-sectional household survey (n = 100) and six focus group discussions (n = 43) among parents of children aged 12-23 months from the known communities experiencing disadvantage in Vellore during 2017 and 2018. Multivariate logistic regression was conducted to examine associations between the parental characteristics and children's vaccination status in the household survey data; the qualitative discussions were analyzed by using the (previously published) "5As" taxonomy for the determinants of vaccine uptake., Results: In the household survey, the proportions of fully vaccinated children were 65% (95% CI: 53-76%) and 77% (95% CI: 58-88%) based on information from vaccination cards or parental recall and vaccination cards alone, respectively. Children whose mothers were wage earners [Adjusted prevalence odds ratio (aPOR): 0.21, 95% CI = 0.07-0.64], or salaried/small business owners [aPOR: 0.18, 95% CI = 0.04-0.73] were less likely to be fully vaccinated than children who had homemakers mothers. In the focus group discussions, parents identified difficulties in accessing routine immunization when travelling for work and showed knowledge gaps regarding the benefits and risks of vaccination, and fears surrounding certain vaccines due to negative news reports and common side-effects following childhood vaccination., Conclusions: Vaccination coverage among children from the surveyed communities in Vellore was suboptimal. Our findings suggest the need to target children from Narikuravar families and conduct periodic community-based health education campaigns to improve parental awareness about and trust in childhood vaccines among the communities experiencing disadvantage in Vellore., (© 2021. The Author(s).)

Objective: To identify predictors of recovery in children with uncomplicated severe acute malnutrition (SAM)., Design: This is a secondary data analysis from an individual randomised controlled trial, where children with uncomplicated SAM were randomised to three feeding regimens, namely ready-to-use therapeutic food (RUTF) sourced from Compact India, locally prepared RUTF or augmented home-prepared foods, under two age strata (6-17 months and 18-59 months) for 16 weeks or until recovery. Three sets of predictors that could influence recovery, namely child, family and nutritional predictors, were analysed., Setting: Rural and urban slum areas of three states of India, namely Rajasthan, Delhi and Tamil Nadu., Participants: In total, 906 children (age: 6-59 months) were analysed to estimate the adjusted hazard ratio (AHR) using the Cox proportional hazard ratio model to identify various predictors., Results: Being a female child (AHR: 1·269 (1·016, 1·584)), better employment status of the child's father (AHR: 1·53 (1·197, 1·95)) and residence in a rental house (AHR: 1·485 (1·137, 1·94)) increased the chances of recovery. No hospitalisation (AHR: 1·778 (1·055, 2·997)), no fever, (AHR: 2·748 (2·161, 3·494)) and ≤ 2 episodes of diarrhoea (AHR: 1·579 (1·035, 2·412)) during the treatment phase; availability of community-based peer support to mothers for feeding (AHR: 1·61 (1·237, 2·097)) and a better weight-for-height Z-score (WHZ) at enrolment (AHR: 1·811 (1·297, 2·529)) predicted higher chances of recovery from SAM., Conclusion: The probability of recovery increases in children with better WHZ and with the initiation of treatment for acute illnesses to avoid hospitalisation, availability of peer support and better employment status of the father.

Background: Children 0-14 years constitute about 31.4% of Indian population, among whom the magnitude and risk factors of childhood injuries have not been adequately studied., Objective: To study the prevalence of and assess the factors associated with unintentional injuries among children aged 6 month - 18 years in various regions., Methodology: This multi-centric, cross-sectional, community-based study was conducted at 11 sites across India. States included were Gujarat, Karnataka, Madhya Pradesh, Punjab, Sikkim, Tamil Nadu, Uttarakhand, and West Bengal between March, 2018 and September, 2020. A total of 2341 urban and rural households from each site were selected based on probability proportionate to size. The World Health Organization (WHO) child injury questionnaire adapted to the Indian settings was used after validation. Information on injuries was collected for previous 12 months. Definitions for types (road traffic accidents, falls, burns, poisoning, drowning, animal-related injuries) and severity of injuries was adapted from the WHO study. Information was elicited from parents/primary caregivers. Data were collected electronically, and handled with a management information system., Results: In the 25751 households studied, there were 31020 children aged 6 months-18 years. A total of 1452 children (66.1% males) had 1535 unintentional injuries (excluding minor injuries) had occurred in the preceding one year. The overall prevalence of unintentional injuries excluding minor injuries was 4.7% (95% CI: 4.4-4.9). The commonest type of injury was fall-related (842, 54.8%) and the least common was drowning (3, 0.2%). Injuries in the home environment accounted for more than 50% of cases., Conclusions: The findings of the study provide inputs for developing a comprehensive child injury prevention policy in the country. Child safe school with age-appropriate measures, a safe home environment, and road safety measures for children should be a three-pronged approach in minimizing the number and the severity of child injuries both in urban and rural areas.

Background: Early childhood developmental pattern analyses not only project future cognition potential, but also identify potential risks for possible intervention. The current study evaluates developmental trends in the first 3 years of life and their predictors in a low and middle income country setting., Methods: Trends of early childhood development at 6, 15, 24 and 36 months of age and their predictors were explored in a longitudinal community-based birth cohort study in an urban slum in Vellore, South India. Development was assessed using the Bayley Scales of Infant and Toddler Development-III (BSID-III)., Results: The birth cohort enrolled 251 children with 94, 91, 91 and 87% follow-up at 6, 15, 24 and 36 months respectively. Child development domains of cognition, language, motor and social skills showed a significant decline in scores between 6 and 36 months of age. Higher socioeconomic position (SEP) and nurturing home environment contributed to increase in cognition scores by 1.9 and 0.9 units respectively. However, stunting caused a decline in cognition scores by 1.7 units. Higher maternal cognition, higher SEP, and caregiver responsivity positively contributed to language change over time, while higher maternal depression contributed negatively. An enriching home environment, growth parameters and blood iron status had positive association with change in motor skills., Conclusions: A triple intervention plan to enhance home environment and nurturance, early childhood nutrient supplementation, and maternal education and well-being might prevent child developmental decline in high risk settings.

Background: India attributes to about 15% of the maternal mortality globally. Many a time poor maternal and neonatal outcomes occur unanticipated during intrapartum and postpartum period. An efficient referral system identifies the indications necessitating prompt referrals besides ensuring patient friendliness and continuity of care., Methodology: The descriptive, retrospective study was done in a secondary care hospital of a teaching institution in South India, run by primary care physicians, obstetricians and pediatricians. It describes the referrals from labour room in a year, identifying the referral rate, indications, maternal and neonatal outcomes., Results: The referral rate was found to be 3 per cent. The most common indication for the referrals was hypertensive disorders of pregnancy (54.5 percent). Among the women referred, there were no maternal deaths and majority had uncomplicated postpartum period. Eleven women developed postpartum hemorrhage. Neonatal outcome reflected a good trend as 83 per cent had an uneventful hospital stay. There were eight early neonatal deaths., Conclusion: The hospital could reduce the referral load to its tertiary care due to adequate training of primary care post graduates in basic obstetrics and anaesthesia skills, establishing standardized referral protocol and monitoring with regular clinical audits. Patient experience could be improved with inter referral unit communication and linking the health information system., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Background: Early childhood home environment is intricately linked to child development and later cognitive and academic skills. There is limited literature evaluating home environmental trends and predictors in the low- and middle-income country settings., Aims: Determine the trends of early childhood home environment changes between 6 and 36 months of age, and the factors associated with these changes., Study Design: Longitudinal community-based birth cohort follow-up study in a semi-urban slum in Vellore, South India., Subjects: Consecutive sampling of a birth cohort between March 2010 and February 2012., Outcome Measures: Home environment was objectively assessed using the 'Home Observation for the Measurement of the Environment' (HOME) scale. Predictors of change in the home environment over time also were analyzed. Multivariable linear regression models and linear mixed effect models were used to identify the factors associated with HOME score at individual time points and over-a-time period, respectively., Results: The birth cohort enrolled 251 children with a follow-up of 235, 228 and 218 children at 6, 24 and 36 months, respectively. The socio-economic status (SES) was the single biggest predictor for the HOME score at each time point, with increasing strength over time. Maternal education predicted home environment at 24 months, while maternal depression was negatively associated at 6 and 24 months of age. SES and maternal factors contributed to the overall change in the HOME score. Maternal factors predicted relational home environmental change over time., Conclusion: SES and maternal factors consistently predicted early childhood home environment at 6, 24 and 36 months of age and its change over time. It is important to support maternal education and wellbeing along with socio-economic measures to optimize early childhood environment., (© 2020 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd..)

Background: Head circumference (HC) measurement is routinely not performed in early childhood and there is conflicting information about its utility in literature. The current study analyses the association between HC at two years of age and cognition at two and five years of age., Methods: A community based birth-cohort recruited between 2010 and 2012 was followed up till five years of age in an urban slum in Vellore, India. Children were recruited at birth after informed parental consent by consecutive sampling using eligibility criteria of healthy new-born, singleton pregnancy and family's availability in the study area during follow-up. HC measured at two years of age was used as the exposure variable to calculate association with cognition at both two and five years of age. Cognitive domain of Bayley scale of infant development was used at two years of age and Wechsler Preschool Primary Scales of Intelligence at five years., Results: Of the 251 enrolled children, 138 (55%) were girls and 71 (30%) belonged to lower socioeconomic status. At 2 years, 8.81% of children had HC < - 3SD. Compared to children with HC z-scores ≥ - 2 SD, those with measurements < - 3 SD had a lower cognition scores by - 2.21 [95% CI: - 3.87 - -0.56] at 2 years. Also, children with HC < - 3 SD at two years scored significantly lower scores in cognitive domains of verbal, - 7.35 [95% CI: - 11.78 - -2.92] and performance, - 7.07 [95% CI: - 11.77 - -2.36] intelligence at five years., Conclusions: This study showed that smaller HC at 2 years of age was negatively associated with cognition at both 2 and 5 years of age. Early childhood HC measurements can be utilised as a cheaper screening tool to identify children at risk in LMIC settings. Further studies can confirm these findings in diverse settings.

Objective: Early childhood factors can have persisting effects on development and cognition in children. We propose to explore the trends of Fe deficiency and Pb toxicity in early childhood and their association with child development at 2 years of age and cognition at 5 years., Design: Longitudinal birth cohort study., Setting: Urban slum, Vellore, India., Participants: Children enrolled at birth were followed up regularly in the first 2 years with developmental and cognitive assessments at 2 and 5 years of age, respectively., Results: The birth cohort enrolled 251 children with 228 children followed up at 2 years and 212 at 5 years of age. Fe deficiency (ID) was highest at 15 months of age and improved subsequently at 24 months. Blood Pb levels (BLL) remained high at all age groups with an increasing trend with age; 97 % at 36 months having high BLL. Persistent high mean BLL at 15 and 24 months had negative association with both cognition and expressive language raw scores of 24 months, while high mean BLL at 15, 24 and 36 months had no significant association with any of the domains of cognition at 5 years of age. Early childhood cumulative body Fe status at 7, 15 and 24 months did not show any association with child development at 2 years, but was associated with verbal, performance and processing speed components of cognition at 5 years., Conclusions: Optimising body Fe status and limiting Pb exposure in early childhood can augment child development and school entry cognition.

We investigated an outbreak of hepatitis A infection among children in an urban settlement of Vellore, South India. A total of 58 cases of jaundice were reported between April and August 2019. Sera from children who presented with jaundice were tested for hepatitis A virus (HAV) IgM. HAV IgM was positive in 18 (94.7%) of the 19 cases tested. These children also received a blood culture at the same time, as a part of the ongoing Surveillance for Enteric Fever in India (SEFI). Blood cultures from three children with confirmed hepatitis A infection grew Salmonella sp . : two with Salmonella Typhi and one with Salmonella Poona. Salmonella Poona is being reported for the first time from India. The overall hospitalization rate during the outbreak was 21%. Outbreaks of hepatitis A continue to occur with substantial morbidity in children from endemic settings, with notable emergence of other concurrent enteric infections, thereby warranting continued surveillance.

Background: Cohort studies are pivotal in understanding the natural history, and to thereby determine the incidence of a disease. The conduct of large-scale community-based cohort studies is challenging with reference to money, manpower and time. Further, attrition inherent to cohort studies can affect the power, and thereby the study's validity. Our objective was to estimate the percentage of participant withdrawal and to subsequently understand reasons for the same in the Vellore Typhoid Surveillance (VTS) cohort., Methods: VTS study, a prospective community-based pediatric cohort, was established in a semi-urban settlement of Vellore to estimate the incidence rate of typhoid fever. An active weekly surveillance identified children with fever, and blood cultures were performed for fevers of ≥3 days. Reasons for participant drop-out in the cohort were documented. Nine focus group discussions (FGD), each with 5 to 7 parents/primary caregivers of former as well current participants were conducted separately, to understand reasons for consent withdrawal as well as the good aspects of the study that the current participants perceived. A descriptive, as well as an interpretative account of the themes that emerged from the FGDs were done., Results: Of the 5639 children in the VTS cohort, 404 (7.2%) withdrew consent during the 12-month surveillance. Of these, 50% dropped out due to migration from study area; 18.1% as their parents were unhappy with the blood draws for blood culture; and 14.4% did not clearly put forth the reason for consent withdrawal. Being from an orthodox background, high socio-economic status and joint family were associated with a decision to drop-out. Frequent and voluminous blood draws, male field research assistants (FRA) making weekly home-visits, the perception that inquiring about fever made their child fall sick, and that the study clinic did not initiate antibiotics immediately, were the important themes that emerged from the FGDs conducted among drop-outs., Conclusion: Our study showed that specific beliefs and behaviours within the community influenced the drop-out rate of the VTS cohort. Background characteristics and perceptions that exist, along with attrition data from previous cohort studies in the specific community are important to be considered while implementing large-scale cohort studies.

Context: Domestic violence in Indian setting has five major components: emotional abuse; physical violence; sexual violence; honor killing; dowry-related abuse; and death., Aims: The aim of the study was to estimate the prevalence of domestic violence and 3 of its components - emotional abuse, physical violence, and sexual violence among women in the age group of 15-49 years in Kaniyambadi block, rural Vellore, Tamil Nadu and to determine the risk factors of domestic violence., Settings and Design: A community-based cross-sectional study among women between the ages 15 and 49 years at the rural setting of Kaniyambadi block, Tamil Nadu., Results: Prevalence of all forms of domestic violence among women was 77.5%, and forty percent women were classified as having ever been subjected to severe domestic violence. Prevalence of physical violence was 65.8%, sexual abuse was 17.5%, and emotional abuse was 54.2%. Alcohol consumption by husband (adjusted odds ratio [AOR] 4.37; 1.35, 14.18), controlling behavior by family member (AOR 8.07; 2.47, 26.37), and woman's employment (AOR 4.33; 1.27, 14.77) were statistically significant determinants of domestic violence. Three-fourth (73.1%) of the women felt that being subjected to domestic violence has affected their physical and mental health., Conclusions: The high prevalence of domestic violence in our community needs to be addressed as it has tacit implications on socioeconomic well-being, physical and mental health of a woman, her family, and thereby, society as a whole., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Community Medicine.)

Background: Open drains are common methods of transporting solid waste and excreta in low-income urban neighborhoods. Open drains can overflow due to blockages with solid waste and during rainfall, posing exposure risks. The goal of this study was to evaluate whether pediatric enteric infection was associated with open drains and flooding in a dense, low-income, urban neighborhood., Methods: As part of the MAL-ED study in Vellore, India, a cohort of 230 children provided stool specimens at 14-17 scheduled home visits and during diarrheal episodes in the first two years of life. All specimens were analyzed for enteric pathogens. Caregivers in 100 households reported on flooding of drains and households and monthly frequency of contact with open drains and flood water. Household GPS points were collected. Monthly rainfall totals for the Vellore district were collected from the Indian Meteorological Department. Clustering of reported drain and house flooding were identified by Kulldorff's Bernoulli Spatial Scan. Differences in enteric infection were assessed for household responses and spatial clusters, with interactions between reported flooding and rainfall to approximate monthly drain flooding retrospectively, using multivariable, mixed-effects logistic regression models., Results: Coverage of household toilets was low (33%), and most toilets (82%) discharged directly into open drains, suggesting poor neighborhood fecal sludge management. Odds of enteric infection increased significantly with total monthly rainfall for children who lived in households that reported that the nearby drain flooded (4% increase per cm of rain: OR: 1.04, 95% CI: 1.00-1.08) and for children in households in a downstream spatial cluster of reported drain flooding (5% increase per cm of rain: OR: 1.05, 95% CI: 1.01-1.09). There was no association between odds of enteric infection and frequency of reported contact with drain or floodwater., Conclusions: Children in areas susceptible to open drain flooding had increased odds of enteric infection as rainfall increased. Results suggested that infection increased with rainfall due to neighborhood infrastructure (including poor fecal sludge management) and not frequency of contact. Thus, these exposures may not be mitigated by changes in personal behaviors alone. These results underscore the importance of improving the neighborhood environment to improve children's health in low-income, urban settings.

Background: Exclusive breastfeeding is recommended in the first six months of life. Observing breastfeeding practices and further the introduction of complementary food using a birth cohort can provide a better understanding with reference to the child's growth and nutrition. We aim to describe the exclusive breastfeeding practices in the Indian MAL-ED birth cohort., Methods: The Indian MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort comprises of eight contiguous urban slums in Vellore. Of the 251 children enrolled in the cohort at birth, a 24 month follow-up was completed for 228 children and data collection was from March 2010 through February 2012. Trained field research assistants collected data on exclusive breastfeeding and complementary feeding practices from birth using a structured questionnaire through a biweekly surveillance. Survival and Cox proportional hazard regression analyses were used to estimate the duration of exclusive breastfeeding and factors influencing the same., Results: Breastfeeding was initiated within the first hour of birth in 148 (59%) infants. Colostrum was given in 225 (89.6%) infants whilst 32 (12.7%) infants received prelacteal feeds. Exclusive breastfeeding up to four months was observed in 55 (22.1%, 95% Confidence Interval [CI] 17.1%, 27.5%) infants with only three (1.1%, 95% CI 0.2%, 3.5%) of the cohort mothers continuing to exclusively breastfeed up to six months. Cox proportional hazard regression analysis revealed no gender differences to being exclusive breastfed (Adjusted Hazard Ratio [AHR] 0.97; 95% CI 0.74, 1.27). Children from families of low socioeconomic status had a lower risk of early cessation of exclusive breastfeeding compared to children from middle or higher socioeconomic status (AHR 0.52; 95% CI 0.38, 0.71)., Conclusions: Early initiation of exclusive breastfeeding is important and improving rates suggest continuation of efforts in this direction energetically. Continuation of exclusive breastfeeding practice is significantly low in these urban slums with introduction of animal milk and complementary foods even before six months of age. This highlights the urgent need to evaluate pragmatic interventions to raise awareness on the importance of exclusive breastfeeding and its practice., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Stunting in developing countries continues to be a major public health problem. Measuring head circumference (HC) during clinical anthropometric assessment can help predict stunting. The aim of this study was to assess burden and determine the predictors of low HC (<- 2 SD) at birth and during first 2 years of life in a semi- urban settlement of Vellore., Methods: The study uses baseline data and serial HC measurements from the birth cohort of MAL-ED study, where 228 children from Vellore completed follow-up between March 2010 to February 2014. Analysis of baseline, maternal and paternal characteristics, micro-nutrient status and cognition with HC measurements was performed using STATA version 13.0 software., Results: The mean HC (±SD) at 1st, 12th and 24th month were 33.37 (1.29) cm, 42.76 (1.23) cm and 44.9 (1.22) cm respectively. A third of the infants (75/228) had HC less than - 2 SD at first month of life, and on follow-up, 50% of the cohort had HC ≤ -2 SD both at 12th and 24th month. Low HC measurements at all three time-points were observed for 21.6% (46/222) infants. Low HC was significantly associated with stunting in 37.3% (OR = 10.8), 57.3% (OR = 3.1) and 44.4% (OR = 2.6) children at 1st, 12th and 24th month respectively. Bivariate analysis of low HC (<- 2 SD) at 12th month showed a statistically significant association with lower socioeconomic status, low paternal and maternal HC and low maternal IQ. Multivariable logistic regression analysis showed maternal (AOR = 0.759, 95% CI = 0.604 to 0.954) and paternal (AOR = 0.734, 95% CI = 0.581 to 0.930) HC to be significantly associated with HC attained by the infant at the end of 12 months., Conclusions: One-third of the children in our cohort had low head circumference (HC) at birth, with one-fifth recording low HC at all time-points until 2 years of age. Low HC was significantly associated with stunting. Paternal and maternal HC predicted HC in children. HC measurement, often less used, can be a simple tool that can be additionally used by clinicians as well as parents/caregivers to monitor child growth.

Background: Vellore district in southern India was selected for intensified immunization efforts through India's Mission Indradhanush campaign based on 74% coverage in the National Family Health Survey in 2015. As rural households rely almost entirely on the Universal Immunization Program (UIP), we assessed routine immunization coverage and factors associated with vaccination status of children in rural Vellore., Methods: We conducted a cross-sectional household survey among parents or primary caretakers of children aged 12-23 months during August-September 2017 using two-stage, EPI cluster sampling. We verified vaccination histories from vaccination cards and collected data on sociodemographic and non-socio-demographic characteristics by using mobile data capture. Associations with vaccination status were examined with univariate and multivariate logistic regression models., Results: A total of 643 children were included. Coverage of BCG, third dose pentavalent/DPT, measles/MR vaccines and full vaccination (BCG, three doses of polio and pentavalent/DPT and measles/MR vaccines) among children with vaccination cards (n = 606) was 94%, 96%, 93% and 84%, respectively. Of children with vaccination cards, 70.8% had received all recommended doses according to the UIP schedule. No socio-demographic differences were identified, but parents' familiarity with the schedule (Adjusted Prevalence Odds Ratio (aPOR): 2.06, 95%CI = 1.26-3.38) and receiving information on recommended vaccinations during antenatal visits (aPOR: 2.16, 95% CI = 1.13-4.12) were significantly associated with full vaccination status of the children., Conclusions: We found higher UIP antigen coverage and proportion of fully vaccinated children than previously reported from rural Vellore. However, adherence to the recommended schedule was still not optimal. Our study highlights the potential of improving parental awareness of vaccination schedule and targeting health education interventions at pregnant women during antenatal visits to sustain and improve routine immunization coverage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Rotavirus infection accounts for 39% of under-five diarrhoeal deaths globally and 22% of these deaths occur in India. Introduction of rotavirus vaccine in a national immunisation programme is considered to be the most effective intervention in preventing severe rotavirus disease. In 2016, India introduced an indigenous rotavirus vaccine (Rotavac) into the Universal Immunisation Programme in a phased manner. This paper describes the protocol for surveillance to monitor the performance of rotavirus vaccine following its introduction into the routine childhood immunisation programme., Methods: An active surveillance system was established to identify acute gastroenteritis cases among children less than 5 years of age. For all children enrolled at sentinel sites, case reporting forms are completed and a copy of vaccination record and a stool specimen obtained. The forms and specimens are sent to the referral laboratory for data entry, analysis, testing and storage. Data from sentinel sites in states that have introduced rotavirus vaccine into their routine immunisation schedule will be used to determine rotavirus vaccine impact and effectiveness., Ethics and Dissemination: The Institutional Review Board of Christian Medical College, Vellore, and all the site institutional ethics committees approved the project. Results will be disseminated in peer-reviewed journals and with stakeholders of the universal immunisation programme in India., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background and Objectives: Gestational Diabetes Mellitus (GDM) has been well documented to be associated with significant mortality and morbidity among both mother and their offspring. Prevalence of GDM in India varies between regions and has been documented to be on the rise over the last two decades which is a public health concern and reflects an increase in the frequency of type 2 diabetes mellitus in these populations. This study aimed at estimating the prevalence of GDM among antenatal women attending a rural secondary care hospital in southern India and attempts to study associations between anthropometry, parental history, physical activity of pregnant women and GDM., Methods: A hospital based cross sectional study was done among 630 pregnant women who were screened with oral glucose tolerance test between 24 and 28 weeks of gestation based on IADPSG criteria. Risk factors for developing GDM were assessed by conducting home visits to 75 women diagnosed to have GDM and 150 randomly selected women without GDM., Results: Hospital based prevalence of GDM was 14% (95 % CI: 11.3% to 16.7%) and a significant rise in prevalence levels was noted with age. Women with family history of diabetes mellitus, women with body fat of more than 23% had 2.65 and 2.89 times significantly higher odds of developing GDM. Interpretation and conclusion: Family history of diabetes and excess body fat are risk factors associated with GDM. Among them excess body fat could be an independent risk factor without the influence of foetal weight and preventive measures could be directed towards it., (© Journal of the Association of Physicians of India 2011.)

Background: Globally, 5.82 million deaths occurred among children under the age of five years in 2015 and injury specific mortality rate was 73 per 100,000 population. In India, injury specific mortality rate is around 2.1 per 1000 live births contributing to 4% of the total under 5 mortality rate. This study aims to estimate the burden and understand factors associated with unintentional injuries among children aged 1-5 years residing in urban slums of Vellore, southern India. We also attempted to assess the hazards posed by the living environment of these children and study their association with unintentional injury patterns., Methods: This cross-sectional study was conducted in eight urban slums of Vellore, southern India and primary caregivers of children aged 1-5 years were interviewed with a questionnaire to obtain the details of injuries sustained in the past three months. Environmental hazard risk assessment was conducted at places frequented by these children and their scores calculated. Baseline prevalence and incidence rates of unintentional injuries were estimated. Multivariate logistic regression and poisson regression analysis were performed to examine factors associated with unintentional injuries and repeated injuries respectively. Association between environmental hazard risk and unintentional injuries was estimated., Results: Prevalence of unintentional injuries was 39.1% (95% CI 35.4-42.9%) and incidence rate was 16.5 (95% CI 14.7-18.3) per 100 child months (N = 662). Bivariate analysis revealed that children of working mothers (OR 1.48; 1.01-2.18) and children from overcrowded families (OR 1.78; 1.22-2.60) had increased odds of sustaining unintentional injuries. Multivariate regression analysis revealed that children from overcrowded families had increased odds of sustaining unintentional injuries (AOR 1.66, 95% CI 1.14-2.41). Boys (IRR 1.33, 95% CI 1.07-1.66) and children from overcrowded families (IRR 1.50; 1.14-1.98) were at increased risk of having repeated injuries. There is an increase in incidence rate of injuries with an increased environmental hazard risk, although not statistically significant., Conclusions: The burden of unintentional injuries was very high among study children when compared to studies in other urban slums in India. Environment plays an important role in the epidemiology of unintentional injuries; providing safe play environment and adequate supervision of children is important to reduce its burden.

Background: Despite almost three decades of the Universal Immunization Program in India, a little more than half the children aged 12-23months receive the full schedule of routine vaccinations. We examined socio-demographic factors associated with partial-vaccination and non-vaccination and the reasons for non-vaccination among Indian children during 1998 and 2008., Methods: Data from three consecutive, nationally-representative, District Level Household and Facility Surveys (1998-99, 2002-04 and 2007-08) were pooled. Multinomial logistic regression was used to identify individual and household level socio-demographic variables associated with the child's vaccination status. The mother's reported reasons for non-vaccination were analyzed qualitatively, adapting from a previously published framework., Results: The pooled dataset contained information on 178,473 children 12-23months of age; 53%, 32% and 15% were fully vaccinated, partially vaccinated and unvaccinated respectively. Compared with the 1998-1999 survey, children in the 2007-2008 survey were less likely to be unvaccinated (Adjusted Prevalence Odds Ratio (aPOR): 0.92, 95%CI=0.86-0.98) but more likely to be partially vaccinated (aPOR: 1.58, 95%CI=1.52-1.65). Vaccination status was inversely associated with female gender, Muslim religion, lower caste, urban residence and maternal characteristics such as lower educational attainment, non-institutional delivery, fewer antenatal care visits and non-receipt of maternal tetanus vaccination. The mother's reported reasons for non-vaccination indicated gaps in awareness, acceptance and affordability (financial and non-financial costs) related to routine vaccinations., Conclusions: Persisting socio-demographic disparities related to partial-vaccination and non-vaccination were associated with important childhood, maternal and household characteristics. Further research investigating the causal pathways through which maternal and social characteristics influence decision-making for childhood vaccinations is needed to improve uptake of routine vaccination in India. Also, efforts to increase uptake should address parental fears related to vaccination to improve trust in government health services as part of ongoing social mobilization and communication strategies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: ROTAVAC, an indigenous rotavirus vaccine, was introduced in the universal immunization program of India in four states in 2016 and expanded to five more states in 2017. The clinical trial on efficacy of ROTAVAC did not detect an increased risk of intussusception, but the trial was not large enough to detect a small risk. This protocol paper describes the establishment and implementation of a surveillance system to monitor the safety of rotavirus vaccine and investigate the potential infectious etiologies of intussusception., Methods: This is a multi-centric hospital-based active surveillance being conducted at 28 hospitals in nine states of India. Data gathered from surveillance will be used to assess the risk of intussusception after ROTAVAC administration and to determine the infectious etiologies of intussusception. For safety assessment of ROTAVAC vaccine, children aged less than two years with intussusception admitted at the sentinel hospitals are enrolled into surveillance, a case report form completed, and a copy of the vaccination card obtained. The risk of intussusception following rotavirus vaccination will be assessed using a self-controlled case-series design. The investigation for potential infectious etiologies of intussusception is through a matched case-control design. Children enrolled for the safety assessment serve as cases and for each case, an age, gender and location matched control is enrolled within 30 days of case enrollment. Stool specimens are obtained from cases and controls. All forms and specimens are sent to the referral laboratory for data entry, analysis, multiplexed molecular testing, and storage., Discussion: Anticipated public health benefits of this surveillance include the generation of information useful to national government on safety of vaccine and to make future decisions on vaccine use through risk-benefit analysis. Investigating infectious agents may help to determine the potential infectious etiologies of intussusception.

This health utilization survey of 720 children (age <2 y) from 5 rural blocks in Vellore district identified that 80% used government facilities for preventive care while >80% used private facilities for curative services. Only 0.7% were home deliveries, 46% reported illness in the two-week recall, and 83% sought care for these illness.

Objective: This study examined associations between household sanitation and enteric infection - including diarrhoeal-specific outcomes - in children 0-2 years of age in a low-income, dense urban neighbourhood., Methods: As part of the MAL-ED study, 230 children in a low-income, urban, Indian neighbourhood provided stool specimens at 14-17 scheduled time points and during diarrhoeal episodes in the first 2 years of life that were analysed for bacterial, parasitic (protozoa and helminths) and viral pathogens. From interviews with caregivers in 100 households, the relationship between the presence (and discharge) of household sanitation facilities and any, pathogen-specific, and diarrhoea-specific enteric infection was tested through mixed-effects Poisson regression models., Results: Few study households (33%) reported having toilets, most of which (82%) discharged into open drains. Controlling for season and household socio-economic status, the presence of a household toilet was associated with lower risks of enteric infection (RR: 0.91, 95% CI: 0.79-1.06), bacterial infection (RR: 0.87, 95% CI: 0.75-1.02) and protozoal infection (RR: 0.64, 95% CI: 0.39-1.04), although not statistically significant, but had no association with diarrhoea (RR: 1.00, 95% CI: 0.68-1.45) or viral infections (RR: 1.12, 95% CI: 0.79-1.60). Models also suggested that the relationship between household toilets discharging to drains and enteric infection risk may vary by season., Conclusions: The presence of a household toilet was associated with lower risk of bacterial and protozoal enteric infections, but not diarrhoea or viral infections, suggesting the health effects of sanitation may be more accurately estimated using outcome measures that account for aetiologic agents., (© 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: In a multicountry birth cohort study, we describe rotavirus infection in the first 2 years of life in sites with and without rotavirus vaccination programs., Methods: Children were recruited by 17 days of age and followed to 24 months with collection of monthly surveillance and diarrheal stools. Data on sociodemographics, feeding, and illness were collected at defined intervals. Stools were tested for rotavirus and sera for antirotavirus immunoglobulins by enzyme immunoassays., Results: A total of 1737 children contributed 22646 surveillance and 7440 diarrheal specimens. Overall, rotavirus was detected in 5.5% (408/7440) of diarrheal stools, and 344 (19.8%) children ever had rotavirus gastroenteritis. Household overcrowding and a high pathogen load were consistent risk factors for infection and disease. Three prior infections conferred 74% (P < .001) protection against subsequent infection in sites not using vaccine. In Peru, incidence of rotavirus disease was relatively higher during the second year of life despite high vaccination coverage., Conclusions: Rotavirus infection and disease were common, but with significant heterogeneity by site. Protection by vaccination may not be sustained in the second year of life in settings with high burdens of transmission and poor response to oral vaccines., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

AbstractUrban sanitation necessitates management of fecal sludge inside and outside the household. This study examined associations between household sanitation, fecal contamination, and enteric infection in two low-income neighborhoods in Vellore, India. Surveys and spatial analysis assessed the presence and clustering of toilets and fecal sludge management (FSM) practices in 200 households. Fecal contamination was measured in environmental samples from 50 households and household drains. Enteric infection was assessed from stool specimens from children under 5 years of age in these households. The two neighborhoods differed significantly in toilet coverage (78% versus 33%) and spatial clustering. Overall, 49% of toilets discharged directly into open drains ("poor FSM"). Children in households with poor FSM had 3.78 times higher prevalence of enteric infection when compared with children in other households, even those without toilets. In the neighborhood with high coverage of household toilets, children in households with poor FSM had 10 times higher prevalence of enteric infection than other children in the neighborhood and drains in poor FSM clusters who had significantly higher concentrations of genogroup II norovirus. Conversely, children in households with a toilet that contained excreta in a tank onsite had 55% lower prevalence of enteric infection compared with the rest of the study area. Notably, households with a toilet in the neighborhood with low toilet coverage had more fecal contamination on floors where children played compared with those without a toilet. Overall, both toilet coverage levels and FSM were associated with environmental fecal contamination and, subsequently, enteric infection prevalence in this urban setting.

Background: Providing treatment to patients with diabetes mellitus in rural areas at a cost they can afford is a public health challenge., Aims: This study aims to measure the rate of compliance to oral hypoglycemic agents among patients with type 2 diabetes mellitus attending peripheral mobile clinics in rural South India. To study factors that impact glycemic control., Setting and Design: A cross-sectional study was done among patients attending peripheral mobile clinics in a rural block in Southern India., Materials and Methods: Pill counts were done to assess compliance. Participants' dietary intake was measured using a 24 h diet recall and their level of physical activity was measured using the WHO Global Physical Activity Questionnaire. Glycated hemoglobin (HbA1c) was measured for all participants., Statistical Analyses Used: Data were entered on EpiData and analyzed using SPSS. The prevalence of good glycemic control and good compliance was measured. A multiple linear regression was done to study factors affecting glycemic control., Results: Overall 52% of the participants were compliant to at least one drug and 50% had achieved good glycemic control. Compliance increased by 2.1% with every passing year since the diagnosis of diabetes. HbA1c reduced by 0.09% for every 10% increase in overall compliance., Conclusions: Levels of compliance and glycemic control achieved through this primary care team is comparable to those achieved through other systems., Competing Interests: There are no conflicts of interest.

Background: Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings., Methods: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered., Results: Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87-100%, whereas measles vaccination rates ranged widely, 73-100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific., Conclusions: Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Municipal water sources in India have been found to be highly contaminated, with further water quality deterioration occurring during household storage. Quantifying water quality deterioration requires knowledge about the exact source tap and length of water storage at the household, which is not usually known. This study presents a methodology to link source and household stored water, and explores the effects of spatial assumptions on the association between tap-to-household water quality deterioration and enteric infections in two semi-urban slums of Vellore, India. To determine a possible water source for each household sample, we paired household and tap samples collected on the same day using three spatial approaches implemented in GIS: minimum Euclidean distance; minimum network distance; and inverse network-distance weighted average. Logistic and Poisson regression models were used to determine associations between water quality deterioration and household-level characteristics, and between diarrheal cases and water quality deterioration. On average, 60% of households had higher fecal coliform concentrations in household samples than at source taps. Only the weighted average approach detected a higher risk of water quality deterioration for households that do not purify water and that have animals in the home (RR=1.50 [1.03, 2.18], p=0.033); and showed that households with water quality deterioration were more likely to report diarrheal cases (OR=3.08 [1.21, 8.18], p=0.02). Studies to assess contamination between source and household are rare due to methodological challenges and high costs associated with collecting paired samples. Our study demonstrated it is possible to derive useful spatial links between samples post hoc; and that the pairing approach affects the conclusions related to associations between enteric infections and water quality deterioration., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Since point-of-use methods of water filtration have shown limited acceptance in Vellore, southern India, this study evaluated the effectiveness of decentralized membrane filtration 1) with safe storage, 2) without safe storage, versus 3) no intervention, consisting of central chlorination as per government guidelines, in improving the microbiological quality of drinking water and preventing childhood diarrhea. Periodic testing of water sources, pre-/postfiltration samples, and household water, and a biweekly follow up of children less than 2 years of age was done for 1 year. The membrane filters achieved a log reduction of 0.86 (0.69-1.06), 1.14 (0.99-1.30), and 0.79 (0.67-0.94) for total coliforms, fecal coliforms, and Escherichia coli, respectively, in field conditions. A 24% (incidence rate ratio, IRR [95% confidence interval, CI] = 0.76 [0.51-1.13]; P = 0.178) reduction in diarrheal incidence in the intervention village with safe storage and a 14% (IRR [95% CI] = 1.14 [0.75-1.77]; P = 0.530) increase in incidence for the intervention village without safe storage versus no intervention village was observed, although not statistically significant. Microbiologically, the membrane filters decreased fecal contamination; however, provision of decentralized membrane-filtered water with or without safe storage was not protective against childhood diarrhea., (© The American Society of Tropical Medicine and Hygiene.)