Evaluation of opportunities to implement community-wide mass drug administration for interrupting transmission of soil-transmitted helminths infections in India.

BACKGROUND: The World Health Organization Neglected Tropical Disease (NTD) guidelines recommend control of soil transmitted helminth (STH)-associated morbidity with targeted deworming of preschool and school-aged children who are disproportionately affected by STH-associated morbidity. However, this strategy leaves many adults untreated and reinfection within communities perpetuates transmission even when mass drug administration (MDA) coverage of children is high. Evidence suggests that it may be possible to interrupt STH transmission by expanding MDA to a community-wide MDA (cMDA). METHODS: This multi-methods study of organizational readiness survey, key informant interviews, and program mapping, were conducted with government stakeholders in three Indian states, Goa, Sikkim, and Odisha, to assess readiness of the states for transitioning from school-based MDA to cMDA and identify opportunities to leverage existing infrastructure from other NTD programs like lymphatic filariasis (LF) for STH cMDA. PRINCIPAL FINDINGS: Overall, all three states indicated a highly favorable policy environment, effective leadership structure, adequate material resources, demonstrated technical capacity, and adequate community infrastructure needed to launch a STH cMDA program. The findings indicated a high-level of health system readiness to implement provided human resources and financial resources to deliver cMDA is strengthened. Areas with a significant overlap between LF and STH MDA platforms, particularly at the community-level, may be best primed for transitioning. Immunization, maternal child health, and non-communicable disease control programs were the other programs for possible integration of cMDA. States indicated having effective leadership structures in place at the state-level, however, engaging local leaders and community groups were considered crucial for successful implementation of cMDA. In-migration was a perceived challenge for estimating drug requirement and preventing possible stockouts. CONCLUSIONS: Findings from this study are intended to proactively support government decision making, prioritization, and program planning across heterogenous implementation contexts in India to speed the translation of research findings into practice. CLINICAL TRIAL REGISTRATION: NCT03014167; ClinicalTrials.gov.

Omicron infection increases IgG binding to spike protein of predecessor variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1 and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Residual archival sera (N = 81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N = 18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). We found an approximately two-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared with the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of the weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36%-49%) was observed to Omicron spike protein. Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants.

Early Childhood Stimulating Environment Predicts Later Childhood Resilience in an Indian Longitudinal Birth Cohort Study.

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.

Impact of the COVID-19 National Lockdown on a Rural and Tribal Population of Tamil Nadu, Southern India: A Mixed-Methods Survey.

We assessed the impact of the national lockdown on a rural and tribal population in Tamil Nadu, southern India. A mixed-methods approach with a pilot-tested, semi-structured questionnaire and focus group discussions were used. The impact of the lockdown on health, finances, and livelihood was studied using descriptive statistics. Multivariable logistic regression was carried out to identify factors associated with households that borrowed loans or sold assets during the lockdown, and unemployment during the lockdown. Of the 607 rural and tribal households surveyed, households from comparatively higher socioeconomic quintiles (adjusted odds ratio [aOR], 1.84; 95% CI, 1.01-3.34), with no financial savings (aOR, 2.91; 95% CI, 1.17-7.22), and with larger families (aOR, 1.76; 95% CI, 1.22-2.53), took loans or sold assets during the lockdown. Previously employed individuals from rural households (aOR, 5.07; 95% CI, 3.30-7.78), lower socioeconomic households (aOR, 3.08; 95% CI, 1.74, 5.45), and households with no savings (aOR, 1.78; 95% CI, 1.30-2.44) became predominantly unemployed during the lockdown. Existing government schemes for the elderly, differently abled, and widows were shown to be accessible to 89% of the individuals requiring these schemes in our survey. During the focus group discussions, the limited reach of online classes for schoolchildren was noted and attributed to the lack of smartphones and poor Internet connectivity. Although the sudden, unannounced national lockdown was imposed to flatten the COVID-19 curve, aspects related to livelihood and financial security were affected for both the rural and tribal populations.

Are early childhood stunting and catch-up growth associated with school age cognition?-Evidence from an Indian birth cohort.

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.

Soil-transmitted helminth infections after mass drug administration for lymphatic filariasis in rural southern India.

OBJECTIVES: Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. METHODS: Children aged 2 to 15 years and adults (defined as ≥15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. RESULTS: Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. CONCLUSION: Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.

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

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.

The Diagnostic Value of Congenital and Nevoid Cutaneous Lesions Associated with Autism Spectrum Disorders in Indian Children- A Case-Control Study.

BACKGROUND AND AIMS: Cutaneous lesions are the defining features of several neurocutaneous syndromes like neurofibromatosis1(NF1), tuberous sclerosis complex (TSC), and Sturge Weber syndrome to name a few. With this background, we explored the possibility of identifying congenital and nevoid cutaneous markers that may help in the early recognition of autism spectrum disorders (ASD) in Indian children. The objective of this study was to measure the strength of association between congenital and nevoid cutaneous lesions and ASD among Indian children. METHODS: A case-control study was conducted from January 2018 to June 2018. 132 children (18 months-16 years of age) with ASD and equal number of age and sex-matched children without autism were studied. Diagnosis of ASD was based on DSM-5 criteria. All the children were examined for cutaneous lesions with special attention to nevoid and congenital conditions. The strength of association was measured using the diagnostic odds ratio (OR). RESULTS: The prevalence of congenital and nevoid lesions were higher in ASD group (OR = 3.12, P = 0.0001). Among them, pigmentary mosaicism of hyperpigmented type (OR = 2.76, P = 0.02) and café-au-lait macules (CALMs) (OR = 2.40, P = 0.001) were the most prevalent with hyperpigmented pigmentary mosaicism showing a higher association with autism. Atypical CALMs (OR = 2, P = 0.09) were also more prevalent in the ASD group though not statistically significant. CONCLUSION: The presence of hyperpigmented pigmentary mosaicism and CALMs warrant closer surveillance by the caregivers and physicians for evolving features of autism. Larger multicentric studies are required to validate these findings.

A Systematic Study of the Prevalence and Risk Factors of CKD in Uddanam, India.

INTRODUCTION: Despite reports of a high prevalence of chronic kidney disease (CKD) from the coastal Uddanam region of Andhra Pradesh, India, there are no accurate data on the distribution of kidney function abnormalities and CKD risk factors in this region. METHODS: A total of 2419 participants were recruited through multistage cluster random sampling from 67 villages. Serum creatinine and urine protein creatinine ratio were measured using validated methodologies. All abnormal estimated glomerular filtration rate (eGFR) and urine protein creatinine ratio values were reconfirmed after 3 months. A range of sociodemographic factors were evaluated for their association with CKD using Poisson regression. RESULTS: Of 2402 eligible subjects (mean ± SD age, 45.67 ± 13.29 years; 51% female), 506 (21.07%) had CKD (mean ± SD age, 51.79 ± 13.12 years; 41.3% female). A total of 246 (10.24%) had eGFR <60 ml/min/1.73 m2, whereas 371 (15.45%) had an elevated urine protein creatinine ratio (>0.15 g/g). The poststratified estimates, adjusted for age and sex distribution of the region for CKD prevalence, are 18.7% (range, 16.4%-21.0%) overall and 21.3% (range, 18.2%-24.4% ) and 16.2% (range, 13.7%-18.8%) in men and women, respectively. Older age, male sex, tobacco use, hypertension, and family history of CKD were independently associated with CKD. Compared with those with higher eGFR, those with eGFR <60 ml/min/1.73m2 were older, were more likely to be uneducated, manual laborers/farmers, or tobacco users, and were more likely to have hypertension, a family history of CKD, a diagnosis of heart disease, and a lower body mass index. Among those with low eGFR, there was no difference between those with urine protein creatinine ratio <0.15 or >0.15, except a lower frequency of males in the former. CONCLUSION: We confirmed the high prevalence of CKD in the adult population of Uddanam. The cause was not apparent in a majority. Subjects with a low eGFR with or without elevated proteinuria were phenotypically distinct from those with proteinuria and preserved eGFR. Our data suggest the need to apply a population-based approach to screening and prevention and studies to understand the causes of CKD in this region.

Cerebral Venous Thrombosis, Seasonal Trends, and Climatic Influence: A Region-SpecificStudy.

BACKGROUND AND PURPOSE: Studies looking at seasonal variation on cerebral venous thrombosis (CVT) are few with conflicting conclusions. In this region-specific study, we looked for climatic influence and seasonal trends on the incidence of CVT. METHODS: Imaging proven adult CVT cases treated over a period of 18 years from a specific geographical location with similar seasons and climatic conditions were studied. Metrological parameters prepared using 30 years of data was used. Quantum geographical information system (QGIS software) and SPSS v 22 were used for patient plotting and analysis. RESULTS: Total of 970 cases were studied. The incidence was significantly higher in summer 411 (42.3%) compared with autumn 317 (32.7%) and winter 242 (25.05); P = 0.038. This trend was consistent across all the 18 years in time series analysis. Mean age was 33.5 years (range 18-88 years). A significant majority 673 (69.4%) were below 40 years of age; P = 0.012. Females constituted 394 (40.6%) of cases. Postpartum CVT cases constituted 237 (30%). Interaction analysis showed younger age (<40 years) were more vulnerable for CVT in summer; P = 0.009. There was no seasonal influence on postpartum CVT. Apart for a weak positive correlation between rain fall (r = 0.18, P < 0.01); humidity and cloud cover was not influencing the incidence. CONCLUSIONS: Higher ambient temperatures were consistently associated with higher incidence of CVT. This is the largest region-specific study on CVT in the world. These results may be applicable to other regions with similar climatic conditions.

Body iron and lead status in early childhood and its effects on development and cognition: a longitudinal study from urban Vellore.

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.

Regular Low-Dose Oral Metronidazole Is Associated With Fewer Vesicovaginal and Rectovaginal Fistulae in Recurrent Cervical Cancer: Results From a 10-Year Retrospective Cohort.

PURPOSE: Anaerobic necrosis in cervical cancer can lead to malodor, fistulae, and treatment abandonment. In this retrospective cohort study, we examined the association between maintenance metronidazole and the incidence of malignant fistulae in recurrent cervical cancer. METHODS: We screened all cervical cancer records registered between 2007 and 2016 in the local palliative care database at Christian Medical College, Vellore, India. There were 208 eligible patients with post-treatment residual/recurrent pelvic disease. Among them, 76 had received oral maintenance metronidazole 200 mg once per day for 2 to 86 weeks (interquartile range, 4-16 weeks). RESULTS: Seventy-two patients developed at least one fistula. Forty-nine had vesicovaginal fistulae, 10 had rectovaginal fistuale, and 13 developed both types of fistulae. Patients on maintenance metronidazole had fewer fistulae (22.4% v 41.7%; P = .005), a longer median fistula-free survival (42.9 months v 14.1 months; P < .001), and a postrecurrence survival of 11.5 months versus 8.7 months (P = .112). We performed Cox multivariable proportional hazards regression analysis on the data from the subset of 146 patients observed until death. Bladder/rectal infiltration had a higher risk of fistula (HR, 5.24; P = .011), whereas distant metastases (HR, 2.46; P = .012) and Eastern Cooperative Oncology Group performance status greater than 1 (HR, 1.64; P = .008) were associated with a higher risk of death. Maintenance metronidazole was associated with a lower risk of fistula (hazard ratio [HR], 0.33; 95% CI, 0.16 to 0.67; P = .002) and a lower risk of death (HR, 0.56; 95% CI, 0.39 to 0.81; P = .002). CONCLUSION: Our data indicate that there is a significant inverse association between oral maintenance metronidazole and malignant fistulae in locally recurrent cervical cancer. The impact of this simple intervention on pelvic symptoms, fistulae, and survival should be evaluated in prospective studies.

Risk factors for acquisition of scrub typhus in children admitted to a tertiary centre and its surrounding districts in South India: a case control study.

BACKGROUND: Scrub typhus is a mite borne zoonosis common in the tropics with no good preventive strategy. Children are also affected leading to considerable morbidity and mortality. We conducted a case control study and a vector survey to determine the risk factors for acquisition of scrub typhus. METHODS: A case control study with a 1:2 case control ratio was conducted over a 2 year period at a tertiary care centre and its surrounding districts in South India. Cases were children < 15 years with confirmed scrub typhus. Controls were age and locality matched community controls without fever. Demographic, environmental and behavioural risk factors were obtained in cases and controls by an interview and an environmental survey. A vector survey was also undertaken in the immediate vicinity of the cases. RESULTS: Case Control study: 101 cases and 167 controls were analysed. On multivariate analysis, significant association was observed with environmental factors such as the presence of a water body within 100 m of the house (OR 3.56(1.36,9.75); p 0.011), cooking outside the house (OR 5.61 (1.51,23.01); p 0.011), owning pets (OR 3.33(1.16,9.09); p 0.031), and the presence of bushes within 5 m of the house (OR 2.78 (1.11,7.69); p 0.033). Of the behavioural factors, the child going to school by a vehicle (OR 3.12 (2.29,8.37); p 0.006) was associated with an increased risk. Drying clothes on a clothesline showed a trend towards protection from acquiring scrub typhus (OR 0.31 (0.08, 1.08); p 0.077). Vector survey:26 rodents were trapped in as many houses. Trombiculid mites were isolated in 24 houses with 9(34.6%) being able to transmit scrub typhus. 254 trombiculid mites belonging to four species and two genera were collected. Leptotrombidium deliense, (33.5%). Schoengastiella ligula, (11.0%) of the total mite specimens collected. S. ligula always co-existed with L. deliense. The estimated Chigger index for Leptotrombidium deliense and Schoengastiella ligula was 3.27and 1.08 per animal respectively. CONCLUSIONS: Our study highlights risk factors for scrub typhus, some of which may be modifiable. A clean peri-domestic environment free of vegetation, drying clothes on a clothesline and cooking indoors may decrease the risk of scrub typhus.

Prevalence and Risk Factors of Vitamin A Deficiency in Children and Women of Childbearing Age in a Southern Indian Tribal Population: A Cross-Sectional Study.

BACKGROUND: Night blindness and keratomalacia continue to be a problem among the tribal children and pregnant women residing in Jawadhi hills. OBJECTIVES: The objective of the study is to determine the prevalence and risk factors of Vitamin A deficiency (VAD) among children aged 1-8 years and women of reproductive age in a southern Indian tribal population. MATERIALS AND METHODS: A cross-sectional study was done among children aged 1-8 years and women aged 15-45 years residing in Jawadhi hills. Participants were randomly selected by cluster sampling. Their sociodemographic characteristics and frequency of consumption of Vitamin A rich food were collected through a structured questionnaire. Anthropometric measures and serum retinol levels, using high-performance liquid chromatography, were estimated for all participants. RESULTS: A total of 166 children and 211 women participated in this study. The prevalence of VAD among the children (1-8 years) was 10.2% (95% confidence interval [CI] 5.5%-14.9%) and among women of the reproductive age group was 3.8% (95% CI: 1.2%-6.4%). Dietary intake was not associated with serum retinol levels. Low educational status of the head of the household (adjusted odds ratio [aOR] = 8.9) and pregnancy (aOR = 11.6) was significantly associated with an increased risk of VAD among children and women, respectively. CONCLUSIONS: The prevalence of VAD among children is a moderate public health problem. Strategies must focus on pregnant women and children from families with more than four children.

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677).

Prevalence of Refractive Errors and Number Needed to Screen among Rural High School Children in Southern India: A Cross-sectional Study.

INTRODUCTION: Avoidable blindness is mainly due to uncorrected refractive errors (URE). School Eye Screening (SES) can be used as an initiative to address this issue. AIM: To determine prevalence of URE and Number Needed to Screen (NNS) to find one child with low vision or blindness from URE among rural school children. MATERIALS AND METHODS: A cross-sectional study was performed in 22 government schools with sixth to ninth grades in Kaniyambadi block of Vellore District of Tamil Nadu, India. There were 4739 children on the rolls. Among children present, all those identified to have a visual deficit in either eye, using a single line 20/40 Snellen's optotype E chart at 6 m, were referred to the hospital for confirmatory evaluation. Blindness (uncorrected) was defined as inability to see 20/200 in the better eye. In two of these schools, visual deficits were validated through a second school based examination by a clinician. RESULTS: Of the 4739 children on rolls, 601 were absent; all 4138 (87.3%) who were present underwent screening; 2.3% (98) {95% Confidence Interval (CI) 1.8 to 2.8} failed the screening test in at least one eye and were referred for examination. Only 28 (28.6%) of 98 children who were referred came for examination to the hospital. In the 2 of the 22 schools where the visual deficit was validated, there were no false positives. The prevalence of refractive error in these two schools was 2.2% (95% CI 1.7 - 2.7). NNS to detect one child with low vision or blindness from URE was 147. CONCLUSION: Magnitude of refractive error, low NNS, low response to referral necessitates complete care at school and hence a relook at the current SES program.

Study design and baseline results of an open-label cluster randomized community-intervention trial to assess the effectiveness of a modified mass deworming program in reducing hookworm infection in a tribal population in southern India.

INTRODUCTION: Hookworm infection is a leading cause of iron deficiency anemia and malnutrition in resource-poor settings. Periodic mass deworming with anthelminthic drugs remains the cornerstone of hookworm control efforts worldwide. Reinfection following treatment occurs, reflecting the human host's inability to acquire immunity following exposure to an untreated reservoir of infection. This cluster randomized trial will evaluate the effectiveness of a modified, population-based, mass deworming strategy in reducing hookworm infection in an endemic southern Indian population. METHODS: Forty five tribal villages were randomized into three groups: one received annual treatment; the second received two rounds of treatment at 1-month intervals; and the third received four rounds of treatment - two rounds 1 month apart at the beginning, followed by another two after 6 months. Stool samples collected through cross-sectional parasitological surveys pre- and post-intervention, and at 3-monthly intervals for a period of 1 year were tested for presence of hookworm ova. Long-term effectiveness of treatment will be assessed through another survey conducted 2 years after the last treatment cycle. RESULTS: From a population of 11,857 individuals, 8681 (73.2%) were found to be eligible and consented to participate, out-migration being the primary reason for non-participation. Baseline stool samples were obtained from 2082 participants, with 18.5% having hookworm infection, although majority were low intensity infections (<2000 eggs per gram of feces). DISCUSSION: This study will help identify the optimal mass deworming strategy that can achieve the greatest impact in the shortest period of time, particularly in settings where long-term program sustainability is a challenge.

Natural History of Cryptosporidiosis in a Birth Cohort in Southern India.

BACKGROUND: Cryptosporidium is a leading cause of moderate to severe childhood diarrhea in resource-poor settings. Understanding the natural history of cryptosporidiosis and the correlates of protection are essential to develop effective and sustainable approaches to disease control and prevention. METHODS: Children (N = 497) were recruited at birth in semiurban slums in Vellore, India, and followed for 3 years with twice-weekly home visits. Stool samples were collected every 2 weeks and during diarrheal episodes were tested for Cryptosporidium species by polymerase chain reaction (PCR). Serum samples obtained every 6 months were evaluated for seroconversion, defined as a 4-fold increase in immunoglobulin G directed against Cryptosporidium gp15 and/or Cp23 antigens between consecutive sera. RESULTS: Of 410 children completing follow-up, 397 (97%) acquired cryptosporidiosis by 3 years of age. PCR identified 1053 episodes of cryptosporidiosis, with an overall incidence of 0.86 infections per child-year by stool and serology. The median age for the first infection was 9 (interquartile range, 4-17) months, indicating early exposure. Although infections were mainly asymptomatic (693 [66%]), Cryptosporidium was identified in 9.4% of diarrheal episodes. The proportion of reinfected children was high (81%) and there was clustering of asymptomatic and symptomatic infections (P < .0001 for both). Protection against infection increased with the order of infection but was only 69% after 4 infections. Cryptosporidium hominis (73.3%) was the predominant Cryptosporidium species, and there was no species-specific protection. CONCLUSIONS: There is a high burden of endemic cryptosporidiosis in southern India. Clustering of infection is suggestive of host susceptibility. Multiple reinfections conferred some protection against subsequent infection.

Epidemiology & risk factors of scrub typhus in south India.

BACKGROUND & OBJECTIVES: Scrub typhus is a major public health threat in South and Southeastern Asian countries including India. Understanding local patterns of disease and factors that place individuals at risk is pivotal to future preventive measures against scrub typhus. The primary aim of this study was to identify specific epidemiological and geographical factors associated with an increased risk of developing scrub typhus in this region. METHODS: We mapped 709 patients from Tamil Nadu, Andhra Pradesh and Telangana who were admitted to the Christian Medical College (CMC) Hospital, Vellore, Tamil Nadu, India, for the period 2006-2011, assessed seasonality using monthly counts of scrub typhus cases, and conducted a case-control study among a subset of patients residing in Vellore. RESULTS: The geographic distribution of cases at CMC Hospital clusters around the Tamil Nadu-Andhra Pradesh border. However, distinct hotspots clearly exist distal to this area, near Madurai and the coast in Tamil Nadu, and in the Northeast of Andhra Pradesh. Seasonally, the highest numbers of cases were observed in the cooler months of the year, i.e. September to January. In the case-control analysis, cases were more likely to be agricultural laborers (OR 1.79, 95% CI 1.01 - 3.15), not wear a shirt at home (OR 4.23, 95% CI 1.12 - 16.3), live in houses adjacent to bushes or shrubs (OR 1.95, 95% CI 1.08 - 3.53), and live in a single room home (OR 1.75, 95% CI 1.02 - 3.01). On binary logistic regression, the first three of these variables were statistically significant. INTERPRETATION & CONCLUSIONS: With the growing number of cases detected in India, scrub typhus is fast emerging as a public health threat and further research to protect the population from this deadly infection is essential. Health education campaigns focusing on the agricultural workers of Southern India, especially during the cooler months of the year, can serve as an important public health measure to control infection.