Publications by authors named "Gagandeep Kang"

346 Publications

Vaccination coverage and the factors influencing routine childhood vaccination uptake among communities experiencing disadvantage in Vellore, southern India: a mixed-methods study.

BMC Public Health 2021 Oct 7;21(1):1807. Epub 2021 Oct 7.

Department of Community Health, Christian Medical College, Vellore, Tamil Nadu, India.

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.
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http://dx.doi.org/10.1186/s12889-021-11881-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499461PMC
October 2021

Persistence of G10P[11] neonatal rotavirus infections in southern India.

J Clin Virol 2021 Sep 28;144:104989. Epub 2021 Sep 28.

The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India. Electronic address:

Background: Neonatal rotavirus infections are predominantly caused by distinct genotypes restricted to this age-group and are mostly asymptomatic.

Method: Stool samples from neonates admitted for >48 h in neonatal intensive care units (NICUs) in Vellore (2014-2015) and Chennai (2015-2016) in southern India, and from neonates born at hospitals in Vellore but not admitted to NICUs (2015-2016) were tested for rotavirus by ELISA and genotyped by hemi-nested RT-PCR.

Results: Of 791 neonates, 150 and 336 were recruited from Vellore and Chennai NICUs, and 305 were born in five hospitals in Vellore. Positivity rates in the three settings were 49.3% (74/150), 29.5% (99/336) and 54% (164/305), respectively. G10P[11] was the commonly identified genotype in 87.8% (65/74), 94.9% (94/99) and 98.2% (161/164) of the neonates in Vellore and Chennai NICUs, and those born at Vellore hospitals, respectively. Neonates delivered by lower segment cesarian section (LSCS) at Vellore hospitals, not admitted to NICUs, had a significantly higher odds of acquiring rotavirus infection compared to those delivered vaginally [p = 0.002, OR = 2.4 (1.4-4.3)].

Conclusions: This report demonstrates the persistence of G10P[11] strain in Vellore and Chennai, indicating widespread neonatal G10P[11] strain in southern India and their persistence over two decades, leading to interesting questions about strain stability.
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http://dx.doi.org/10.1016/j.jcv.2021.104989DOI Listing
September 2021

Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India.

Am J Trop Med Hyg 2021 Sep 27. Epub 2021 Sep 27.

The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India.

In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under age 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1-4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11-0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06-0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.
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http://dx.doi.org/10.4269/ajtmh.20-0617DOI Listing
September 2021

Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic.

EClinicalMedicine 2021 Sep 3;39:101053. Epub 2021 Aug 3.

Texas Children's Center for Vaccine Development, Baylor College of Medicine, Houston, TX, USA.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring harmonized through robust systems of global pharmacovigilance and surveillance. G requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.
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http://dx.doi.org/10.1016/j.eclinm.2021.101053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330385PMC
September 2021

Influences on catch-up growth using relative versus absolute metrics: evidence from the MAL-ED cohort study.

BMC Public Health 2021 06 29;21(1):1246. Epub 2021 Jun 29.

The Johns Hopkins University, 615 North Wolfe Street, Room W2041, Baltimore, MD, 21205, USA.

Background: Poor growth in early childhood has been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child's environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics.

Methods: Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression.

Results: At 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0-24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD.

Conclusions: The study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD).
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http://dx.doi.org/10.1186/s12889-021-11120-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240385PMC
June 2021

Global diarrhoea-associated mortality estimates and models in children: Recommendations for dataset and study selection.

Vaccine 2021 07 13;39(32):4391-4398. Epub 2021 Jun 13.

Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland. Electronic address:

Background: Multiple factors contribute to variation in disease burden, including the type and quality of data, and inherent properties of the models used. Understanding how these factors affect mortality estimates is crucial, especially in the context of public health decision making. We examine how the quality of the studies selected to provide mortality data, influence estimates of burden and provide recommendations about the inclusion of studies and datasets to calculate mortality estimates.

Methods: To determine how mortality estimates are affected by the data used to generate model outputs, we compared the studies used by The Institute of Health Metrics and Evaluation (IHME) and Maternal and Child Epidemiology Estimation (MCEE) modelling groups to generate enterotoxigenic Escherichia coli (ETEC) and Shigella-associated mortality estimates for 2016. Guided by an expert WHO Working Group, we applied a modified Newcastle-Ottawa Scale (NOS) to evaluate the quality of studies used by both modelling groups.

Results: IHME and MCEE used different sets of ETEC and Shigella studies in their models and the majority of studies were high quality. The distribution of the NOS scores was similar between the two modelling groups. We observed an overrepresentation of studies from some countries in SEAR, AFR and WPR compared to other WHO regions.

Conclusion: We identified key differences in study inclusion and exclusion criteria used by IHME and MCEE and discuss their impact on datasets used to generate diarrhoea-associated mortality estimates. Based on these observations, we provide a set of recommendations for future estimates of mortality associated with enteric diseases.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.086DOI Listing
July 2021

Cost effectiveness of typhoid vaccination in India.

Vaccine 2021 07 10;39(30):4089-4098. Epub 2021 Jun 10.

Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:

Introduction: World Health Organization has prequalified the use of typhoid conjugate vaccine (TCV) in children over six months of age in typhoid endemic countries. We assessed the cost-effectiveness of introducing TCV separately for urban and rural areas of India.

Methods: A decision analytic model was developed, using a societal perspective, to compare long-term costs and outcomes (3% discount rate) in a new-born cohort of 100,000 children immunized with or without TCV. Three vaccination scenarios were modelled, assuming the protective efficacy of TCV to last for 5, 10 and 15 years following immunization. Incidence of typhoid infection estimated under 'National Surveillance System for Enteric Fever' (NSSEFI)' was used. The prices of vaccine and cost of service delivery were included for vaccination arm. Both health system cost and out-of-pocket expenditures for treatment of typhoid illness and its complications was included.

Results: TCV introduction in urban areas would result in prevention of 17% to 36% typhoid cases and deaths. With exclusion of indirect costs, the incremental cost per QALY gained was ₹ 151,346 (54,730-307,975), ₹ 61,710 (-5250 to 163,283) and ₹ 45,188 (-17,069 to 141,093) for scenario 1, 2 and 3 respectively. While, with inclusion of indirect costs, all 3 scenarios were cost saving. Further, in rural areas, TCV is estimated to reduce the typhoid cases and deaths by 19% to 36%, with ICER (incremental cost per QALY gained) ranging from ₹ 2340 (1316-4370) to ₹ 3574 (2057 - 6691) thousand (inclusive of indirect costs) among the 3 vaccination scenarios.

Conclusion: From a societal perspective, introduction of TCV is a cost saving strategy in urban India. Further, due to low incidence of typhoid infection, introduction of TCV is not cost-effective in rural settings of India.
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http://dx.doi.org/10.1016/j.vaccine.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256879PMC
July 2021

Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization.

Vaccine 2021 07 1;39(30):4013-4024. Epub 2021 Jun 1.

World Health Organization, 20 Avenue Appia, Geneva 1211, Switzerland.

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166525PMC
July 2021

Developmental trends in early childhood and their predictors from an Indian birth cohort.

BMC Public Health 2021 06 6;21(1):1083. Epub 2021 Jun 6.

Wellcome research Unit, Christian Medical College, Vellore, 632004, India.

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.
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http://dx.doi.org/10.1186/s12889-021-11147-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180095PMC
June 2021

Risk Factors and Hazards in the Household Environment for Elevated Blood Lead Levels in Urban Preschool Children of Vellore: A Case-Control Approach in the MAL-ED Birth Cohort.

Indian J Pediatr 2021 May 20. Epub 2021 May 20.

Department of Community Health, Christian Medical College, Vellore, Tamil Nadu, 632 002, India.

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.
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http://dx.doi.org/10.1007/s12098-021-03738-0DOI Listing
May 2021

Longitudinal Serology of SARS-CoV-2-Infected Individuals in India: A Prospective Cohort Study.

Am J Trop Med Hyg 2021 May 18. Epub 2021 May 18.

1Translational Health Science and Technology Institute, Faridabad, Haryana, India.

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.
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http://dx.doi.org/10.4269/ajtmh.21-0164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274753PMC
May 2021

Salmonella Typhi acquires diverse plasmids from other Enterobacteriaceae to develop cephalosporin resistance.

Genomics 2021 Jul 12;113(4):2171-2176. Epub 2021 May 12.

Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Background: Recent reports have established the emergence and dissemination of extensively drug resistant (XDR) H58 Salmonella Typhi clone in Pakistan. In India where typhoid fever is endemic, only sporadic cases of ceftriaxone resistant S. Typhi are reported. This study aimed at elucidating the phylogenetic evolutionary framework of ceftriaxone resistant S. Typhi isolates from India to predict their potential dissemination.

Methods: Five ceftriaxone resistant S. Typhi isolates from three tertiary care hospitals in India were sequenced on an Ion Torrent Personal Genome Machine (PGM). A core genome single-nucleotide-polymorphism (SNP) based phylogeny of the isolates in comparison to the global collection of MDR and XDR S. Typhi isolates was built. Two of five isolates were additionally sequenced using Oxford Nanopore MinION to completely characterize the plasmid and understand its transmission dynamics within Enterobacteriaceae.

Results: Comparative genomic analysis and detailed plasmid characterization indicate that while in Pakistan (4.3.1 lineage I) the XDR trait is associated with bla gene on IncY plasmid, in India (4.3.1 lineage II), the ceftriaxone resistance is due to short term persistence of resistance plasmids such as IncX3 (bla) or IncN (bla + bla).

Conclusion: Considering the selection pressure exerted by the extensive use of ceftriaxone in India, there are potential risks for the occurrence of plasmid transmission events in the predominant H58 lineages. Therefore, continuous monitoring of S. Typhi lineages carrying plasmid-mediated cephalosporin resistant genes is vital not just for India but also globally.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276774PMC
July 2021

Enterotoxigenic Escherichia coli (ETEC) vaccines: Priority activities to enable product development, licensure, and global access.

Vaccine 2021 07 6;39(31):4266-4277. Epub 2021 May 6.

PATH, USA.

Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interventions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the association between ETEC infection and physical and cognitive stunting as well as delayed educational attainment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further elucidation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of addressing globally unmet data needs in the areas of research, product development, and policy, as well as commercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently needed.
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http://dx.doi.org/10.1016/j.vaccine.2021.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273896PMC
July 2021

Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India.

PLoS Negl Trop Dis 2021 04 30;15(4):e0009338. Epub 2021 Apr 30.

The DeWorm3 Project, University of Washington, Seattle, Washington, United States of America.

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project-a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia-allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0-17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3-37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2-0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3-0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4-0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities. Trial Registration: NCT03014167.
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http://dx.doi.org/10.1371/journal.pntd.0009338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184002PMC
April 2021

Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India.

Pathogens 2021 Apr 1;10(4). Epub 2021 Apr 1.

The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore 632004, India.

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56-29.4% in pre-vaccine years to 34-12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.
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http://dx.doi.org/10.3390/pathogens10040416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066972PMC
April 2021

Association between head circumference at two years and second and fifth year cognition.

BMC Pediatr 2021 02 11;21(1):74. Epub 2021 Feb 11.

Wellcome research Unit, Christian Medical College, Vellore, 632004, India.

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.
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http://dx.doi.org/10.1186/s12887-021-02543-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876785PMC
February 2021

Information for Action: The Power of Surveillance.

Indian J Pediatr 2021 03 4;88(Suppl 1):1-3. Epub 2021 Feb 4.

Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, PO box #04, Faridabad, Haryana, 121001, India.

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http://dx.doi.org/10.1007/s12098-020-03634-zDOI Listing
March 2021

Tracking SARS-CoV-2 infection in India with serology.

Lancet Glob Health 2021 03 27;9(3):e219-e220. Epub 2021 Jan 27.

Christian Medical College, Vellore 632002, India. Electronic address:

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http://dx.doi.org/10.1016/S2214-109X(20)30546-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906663PMC
March 2021

Home environment: Short-term trends and predictors in early childhood from an Indian community birth cohort.

Child Care Health Dev 2021 05 20;47(3):336-348. Epub 2021 Jan 20.

Wellcome research Unit, Christian Medical College, Vellore, India.

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.
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http://dx.doi.org/10.1111/cch.12846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048661PMC
May 2021

Key criteria for the ethical acceptability of COVID-19 human challenge studies: Report of a WHO Working Group.

Vaccine 2021 01 28;39(4):633-640. Epub 2020 Oct 28.

Monash Bioethics Centre, Monash University, Clayton, Victoria, Australia.

This report of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19 outlines ethical standards for COVID-19 challenge studies. It includes eight Key Criteria related to scientific justification, risk-benefit assessment, consultation and engagement, co-ordination of research, site selection, participant selection, expert review, and informed consent. The document aims to provide comprehensive guidance to scientists, research ethics committees, funders, policymakers, and regulators in deliberations regarding SARS-CoV-2 challenge studies by outlining criteria that would need to be satisfied in order for such studies to be ethically acceptable.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598752PMC
January 2021

Reimagining India's health system: a Lancet Citizens' Commission.

Lancet 2021 04 10;397(10283):1427-1430. Epub 2020 Dec 10.

Harvard Business School and Lakshmi Mittal and Family South Asia Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)32174-7DOI Listing
April 2021
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