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Introduction  CD44, a multistructural and multifunctional transmembrane glycoprotein, is a promising cancer stem cell (CSC) marker that regulates the properties of CSCs, including self-renewal, tumor initiation, and metastasis, and confers resistance to chemotherapy and radiotherapy. The aim of the present study was to evaluate the gene and protein expression of CD44 and explore its prognostic value in head and neck squamous cell carcinoma (HNSCC). Methodology  The present observational study employs computational tools for analysis. The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma dataset (520 primary HNSCC and 44 normal tissues) from the University of Alabama at Birmingham Cancer platform was used to study the association of CD44 mRNA transcript levels with various clinicopathological characteristics of HNSCC including age, gender, tumor grade, tumor stage, human papillomavirus (HPV) status, p53 mutation status, and overall survival. The CD44 protein expression in HNSCC and normal tissues was ascertained using the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium Head-and-Neck cancer dataset (108 primary HNSCC and 71 normal tissues). Results  CD44 mRNA transcript and protein expression levels were significantly higher in HNSCC tissues than in normal tissues, and high CD44 expression was correlated with poor survival. CD44 was upregulated in Stage 1 and Grade 2 HNSCC compared with other stages and grades. Overexpression of CD44 was observed in HPV-negative and TP53-positive mutant status in HNSCC. Conclusion  The pleiotropic roles of CD44 in tumorigenesis urge the need to explore its differential expression in HNSCC. The study concludes that CD44 can be a potential diagnostic and prognostic biomarker for HNSCC and offer new molecular targets for CD44-targeted therapy for cancer management., Competing Interests: Conflict of Interest This original research article is published as a part of the Ph.D. research program of Dr. L. Kavitha pursuing Ph.D. in the Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, India., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

The World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworm and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings., Competing Interests: The FECPAKG2 technology was produced and distributed by Techion Group Ltd, of which ET is an employee and GM is managing director. Both hold stocks in Techion Group Ltd. The Mini-FLOTAC device is a commercial product distributed by GC, LR and MPM through the University of Napoli Federico II. However, their affiliations did not play any role in the preparation and submission of this manuscript. All other authors declared that they have no competing interests.

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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

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.)

Background: Sudden cardiac arrest (SCA) requiring cardiopulmonary resuscitation (CPR) is one of the common emergencies encountered in the emergency department (ED) of any hospital. Although several studies have reported the predictors of CPR outcome in general, there are limited data from the EDs in India., Materials and Methods: This retrospective study included all patients above 18 years with SCA who were resuscitated in the ED of a tertiary care hospital with an annual census of 60,000 patients between August 2014 and July 2015. A modified Utstein template was used for data collection. Factors relating to a sustained return of spontaneous circulation and mortality were analyzed using descriptive analytic statistics and logistic regressions., Results: The study cohort contained 254 patients, with a male predominance (64.6%). Median age was 55 (interquartile range: 42-64) years. Majority were in-hospital cardiac arrests (73.6%). Only 7.4% (5/67) of the out-of-hospital cardiac arrests received bystander resuscitation before ED arrival. The initial documented rhythm was pulseless electrical activity (PEA)/asystole in the majority (76%) of cases while shockable rhythms pulseless ventricular tachycardia/ventricular fibrillation were noted in only 8% (21/254) of cases. Overall ED-SCA survival to hospital admission was 29.5% and survival to discharge was 9.9%. Multivariate logistic regression analysis showed age ≥65 years (odds ratio [OR]: 12.33; 95% confidence interval [CI]: 1.38-109.59; P = 0.02) and total duration of CPR >10 min (OR: 5.42; 95% CI: 1.15-25.5; P = 0.03) to be independent predictors of mortality., Conclusion: SCA in the ED is being increasingly seen in younger age groups. Despite advances in resuscitation medicine, survival rates of both in-hospital and out-of-hospital SCA remain poor. There exists a great need for improving prehospital care as well as control of risk factors to decrease the incidence and improve the outcome of SCA.

Background: Welders in the unorganized occupational sector in the economically developing world are exposed to respiratory, skin, eye, ear, and neurological problems exacerbated by non-usage of personal protective equipment (PPE)., Objective: To study the frequency of health problems and the usage of PPE among welders in unorganized welding units in Vellore, India., Methods: A cross-sectional survey was conducted among 150 welders to determine the frequency of skin, ear, eye, and respiratory morbidity and the usage of PPE. A group of 150 non-welders were chosen for comparison., Results: Significant differences in the frequency of skin burns, redness, hyper pigmentation, itching, eye injuries, and sensorineural deafness were observed among the welders and non-welders (P < 0.001). Hypertension was noted in 12.6% of the welders as compared to 0.7% among the non-welders. None of the welders used appropriate PPE. For welders, low educational attainment was associated with an increased risk of eye injury (P < 0.05, OR = 0.29). There was also a significant difference between sensorineural deafness and a welder having less than 10 years of welding work experience (P < 0.001, OR = 18.18) which could probably be accounted for by the healthy worker effect., Conclusion: Welders in this sample experienced a significant skin, eye, and ear morbidity accentuated by the non-usage of PPE. All worked without formal training and were unaware of the safe working guidelines that exist, but are not implemented for the welders in India.

Introduction: Socioeconomic status (SES) scales measure poverty, wealth and economic inequality in a population to guide appropriate economic and public health policies. Measurement of poverty and comparison of material deprivation across nations is a challenge. This study compared four SES scales which have been used locally and internationally and evaluated them against childhood stunting, used as an indicator of chronic deprivation, in urban southern India., Methods: A door-to-door survey collected information on socio-demographic indicators such as education, occupation, assets, income and living conditions in a semi-urban slum area in Vellore, Tamil Nadu in southern India. A total of 7925 households were categorized by four SES scales-Kuppuswamy scale, Below Poverty Line scale (BPL), the modified Kuppuswamy scale, and the multidimensional poverty index (MDPI) and the level of agreement compared between scales. Logistic regression was used to test the association of SES scales with stunting., Findings: The Kuppuswamy, BPL, MDPI and modified Kuppuswamy scales classified 7.1%, 1%, 5.5%, and 55.3% of families as low SES respectively, indicating conservative estimation of low SES by the BPL and MDPI scales in comparison with the modified Kuppuswamy scale, which had the highest sensitivity (89%). Children from low SES classified by all scales had higher odds of stunting, but the level of agreement between scales was very poor ranging from 1%-15%., Conclusion: There is great non-uniformity between existing SES scales and cautious interpretation of SES scales is needed in the context of social, cultural, and economic realities.

Background: Hookworms (Necator americanus and Ancylostoma duodenale) remain a major public health problem worldwide. Infections with hookworms (e.g., A. caninum, A. ceylanicum and A. braziliense) are also prevalent in dogs, but the role of dogs as a reservoir for zoonotic hookworm infections in humans needs to be further explored., Methodology/principal Findings: As part of an open-label community based cluster-randomized trial in a tribal area in Tamil Nadu (India; 2013-2015), a total of 143 isolates of hookworm eggs from human stool were speciated based on a previously described PCR-RFLP methodology. The presence of hookworm DNA was confirmed in 119 of 143 human samples. N. americanus (100%) was the most prevalent species, followed by A. caninum (16.8%) and A. duodenale (8.4%). Because of the high prevalence of A. caninum in humans, dog samples were also collected to assess the prevalence of A. caninum in dogs. In 68 out of 77 canine stool samples the presence of hookworms was confirmed using PCR-RFLP. In dogs, both A. caninum (76.4%) and A. ceylanicum (27.9%) were identified. Additionally, to determine the contamination of soil with zoonotic hookworm larvae, topsoil was collected from defecating areas. Hookworm DNA was detected in 72 out of 78 soil samples that revealed presence of hookworm-like nematode larvae. In soil, different hookworm species were identified, with animal hookworms being more prevalent (A. ceylanicum: 60.2%, A. caninum: 29.4%, A. duodenale: 16.6%, N. americanus: 1.4%, A. braziliense: 1.4%)., Conclusions/significance: In our study we regularly detected the presence of A. caninum DNA in the stool of humans. Whether this is the result of infection is currently unknown but it does warrant a closer look at dogs as a potential reservoir.

Stunting or reduced linear growth is very prevalent in low-income countries. Recent studies have demonstrated a causal relationship between alterations in the gut microbiome and moderate or severe acute malnutrition in children in these countries. However, there have been no primary longitudinal studies comparing the intestinal microbiota of persistently stunted children to that of non-stunted children in the same community. In this pilot study, we characterized gut microbial community composition and diversity of the fecal microbiota of 10 children with low birth weight and persistent stunting (cases) and 10 children with normal birth weight and no stunting (controls) from a birth cohort every 3 months up to 2 years of age in a slum community in south India. There was an increase in diversity indices (P <0.0001) with increasing age in all children. However, there were no differences in diversity indices or in the rates of their increase with increasing age between cases and controls. The percent relative abundance of the Bacteroidetes phylum was higher in stunted compared to control children at 12 months of age (P = 0.043). There was an increase in the relative abundance of this phylum with increasing age in all children (P = 0.0380) with no difference in the rate of increase between cases and controls. There was a decrease in the relative abundance of Proteobacteria (P = 0.0004) and Actinobacteria (P = 0.0489) with increasing age in cases. The microbiota of control children was enriched in probiotic species Bifidobacterium longum and Lactobacillus mucosae, whereas that of stunted children was enriched in inflammogenic taxa including those in the Desulfovibrio genus and Campylobacterales order. Larger, longitudinal studies on the compositional and functional maturation of the microbiome in children are needed.

Background: Antibiotic treatment early in life is often not needed and has been associated with increased rates of subsequent diarrhoea. We estimated the impact of realistic interventions, which would prevent unnecessary antibiotic exposures before 6 months of age, on reducing childhood diarrhoeal rates., Methods: In data from a prospective observational cohort study conducted in Vellore, India, we used the parametric g-formula to model diarrhoeal incidence rate differences contrasting the observed incidence of diarrhoea to the incidence expected under hypothetical interventions. The interventions prevented unnecessary antibiotic treatments for non-bloody diarrhoea, vomiting and upper respiratory infections before 6 months of age. We also modelled targeted interventions, in which unnecessary antibiotic use was prevented only among children who had already stopped exclusive breast feeding., Results: More than half of all antibiotic exposures before 6 months (58.9%) were likely unnecessary. The incidence rate difference associated with removing unnecessary antibiotic use before 6 months of age was -0.28 (95% CI -0.46 to -0.08) episodes per 30 child-months. This implies that preventing unnecessary antibiotic exposures in just 4 children would reduce the incidence of diarrhoea by 1 from 6 months to 3 years of age., Conclusions: Interventions to reduce unnecessary antibiotic use among young children could result in an important reduction in diarrhoeal rates. This work provides an example application of statistical methods which can further the aim of presenting epidemiological findings that are relevant to public health practice., Competing Interests: Sylvia Becker-Dreps has held investigator-initiated research grants with Pfizer, Inc and Merck for research studies completely unrelated to the submitted work. Daniel Westreich engages in occasional, ad hoc consulting on epidemiologic methods for NIH/NICHD – there is no overlap with the present work. The other authors have no conflicts of interest to disclose., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The study examined relationships among meteorological parameters, water quality and diarrheal disease counts in two urban and three rural sites in Tamil Nadu, India. Disease surveillance was conducted between August 2010 and March 2012; concurrently water samples from street-level taps in piped distribution systems and from household storage containers were tested for pH, nitrate, total dissolved solids, and total and fecal coliforms. Methodological advances in data collection (concurrent prospective disease surveillance and environmental monitoring) and analysis (preserving temporality within the data through time series analysis) were used to quantify independent effects of meteorological conditions and water quality on diarrheal risk. The utility of a local calendar in communicating seasonality is also presented. Piped distribution systems in the study area showed high seasonal fluctuations in water quality. Higher ambient temperature decreased and higher rainfall increased diarrheal risk with temperature being the predominant factor in urban and rainfall in rural sites. Associations with microbial contamination were inconsistent; however, disease risk in the urban sites increased with higher median household total coliform concentrations. Understanding seasonal patterns in health outcomes and their temporal links to environmental exposures may lead to improvements in prospective environmental and disease surveillance tailored to addressing public health problems.

Objectives: To estimate the effects of antibiotic exposures in the first 6 months of life on short- and long-term growth., Study Design: In a prospective observational cohort study of 497 children from Vellore, India, we estimated short-term effects of antibiotics during the first 6 months using longitudinal general linear regression to model weight-for-age, height-for-age, and weight-for-height z-scores in monthly intervals. To estimate long-term effects, we modeled growth from 6 months to 3 years as a function of antibiotic use in the first 6 months. We also estimated the effects of antibiotics on the monthly relative risks of underweight, stunting, and wasting in the first 6 months and to 3 years., Results: Underweight, stunting, and wasting were common in this population: 31%, 32%, and 15% on average after 6 months of age, respectively. There was no association between antibiotic exposures before 6 months and growth during that period. From 6 months to 3 years, adjusted absolute differences in weight and height were small (approximately -100 g and no more than -2 mm overall, respectively) and not statistically significant., Conclusions: Antibiotic exposures early in life were not associated with increased or decreased growth. The combination of malnutrition and recurrent illness likely complicate the relationship between antibiotic exposures and growth among children in low and middle-income countries., Competing Interests: The other authors declare no conflicts of interest., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Diarrhea causes significant morbidity and mortality in Indian children under 5 years of age. Flies carry enteric pathogens and may mediate foodborne infections. In this study, we characterized fly densities as a determinant of infectious diarrhea in a longitudinal cohort of 160 urban and 80 rural households with 1,274 individuals (27% under 5 years of age) in Vellore, India. Household questionnaires on living conditions were completed at enrollment. Fly abundance was measured during the wet and dry seasons using fly ribbons placed in kitchens. PCRs for enteric bacteria, viruses, and protozoa were performed on 60 fly samples. Forty-three (72%) fly samples were positive for the following pathogens: norovirus (50%), Salmonella spp. (46.7%), rotavirus (6.7%), and Escherichia coli (6.7%). Ninety-one episodes of diarrhea occurred (89% in children under 5 years of age). Stool pathogens isolated in 24 of 77 (31%) samples included E. coli, Shigella spp., Vibrio spp., Giardia, Cryptosporidium, and rotavirus. Multivariate log-linear models were used to explore the relationships between diarrhea and fly densities, controlling for demographics, hygiene, and human-animal interactions. Fly abundance was 6 times higher in rural than urban sites (P < 0.0001). Disposal of garbage close to homes and rural living were significant risk factors for high fly densities. The presence of latrines was protective against high fly densities and diarrhea. The adjusted relative risks of diarrheal episodes and duration of diarrhea, associated with fly density at the 75th percentile, were 1.18 (95% confidence interval [CI], 1.03 to 1.34) and 1.15 (95% CI, 1.02 to 1.29), respectively. Flies harbored enteric pathogens, including norovirus, a poorly documented pathogen on flies., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Antibiotic treatment of childhood illnesses is common in India. In addition to contributing to antimicrobial resistance, antibiotics might result in increased susceptibility to diarrhea through interactions with the gastrointestinal microbiota. Breast milk, which enriches the microbiota early in life, may increase the resilience of the microbiota against perturbations by antibiotics., Methods: In a prospective observational cohort study, we assessed whether antibiotic exposures from birth to 6 months affected rates of diarrhea up to age 3 years among 465 children from Vellore, India. Adjusting for treatment indicators, we modeled diarrheal rates among children exposed and unexposed to antibiotics using negative binomial regression. We further assessed whether the effect of antibiotics on diarrheal rates was modified by exclusive breastfeeding at 6 months., Results: More than half of the children (n = 267, 57.4%) were given at least one course of antibiotics in the first 6 months of life. The adjusted relative incidence rate of diarrhea was 33% higher among children who received antibiotics under 6 months of age compared with those who did not (incidence rate ratio: 1.33, 95% confidence interval: 1.12, 1.57). Children who were exclusively breastfed until 6 months of age did not have increased diarrheal rates following antibiotic use., Conclusions: Antibiotic exposures early in life were associated with increased rates of diarrhea in early childhood. Exclusive breastfeeding might protect against this negative impact.

Background: Antibiotics are commonly given for the treatment of childhood diarrhoea, but are not indicated in most cases. Antibiotics modify the gastrointestinal microbiota, which may have unanticipated effects on the risk of subsequent diarrhoea., Methods: In a prospective observational cohort study, we assessed the effect of caregiver-reported antibiotic treatment for diarrhoea on the timing of a child's next episode among 434 children followed from birth to 3 years of age in Vellore, India. We estimated median time differences and time ratios from inverse probability of exposure-weighted Kaplan-Meier curves for the time to next diarrhoea episode, comparing children who did and did not receive antibiotics for the previous episode., Results: Study children had more than five diarrhoea episodes on average in the first 3 years of life, and more than a quarter of all episodes were treated with antibiotics. Children who received antibiotics for their first diarrhoea episode had their second episode on average 8 weeks earlier (median time difference: -8, 95% confidence interval: -10, -3) than children who did not receive antibiotics. The effects of antibiotics on subsequent diarrhoea were greatest at earlier episodes and younger ages, and cefixime had a slightly larger effect compared with cotrimoxazole., Conclusions: Antibiotic treatment of diarrhoea was associated with reduced time to a subsequent diarrhoea episode, especially among younger infants. Whereas rational use of antibiotics has been advocated to reduce antimicrobial resistance in populations, we show that overuse of antibiotics may also have a direct adverse effect on individual patients., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: It is generally assumed that hookworm infections in humans are caused by Necator americanus and Ancylostoma duodenale. However, previous studies have also reported the presence of the animal hookworm A. ceylanicum in human stools., Methods: We determined hookworm infections in children in a tribal community in Tamil Nadu, India, using a semi-nested PCR-RFLP approach., Results: The results indicate that human species account for a majority of the hookworm infections (N. americanus 39/41 [95%]; A. duodenale 6/41 [15%]), whereas the animal hookworm A. ceylanicum only accounts for a minority of the infections (5%; 2/41)., Conclusions: The results emphasize the need to consider zoonotic ancylostomiasis while developing strategies to control hookworm infections., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cohort studies conducted in low-income countries generally use trained fieldworkers for collecting data on home visits. In industrialised countries, researchers use less resource intensive methods, such as self-administered structured questionnaires or symptom diaries. This study compared and assessed the reliability of the data on diarrhoea, fever and cough/cold in children as obtained by a pictorial diary maintained by the mother and collected separately by a fieldworker., Methods: A sample of 205 children was randomly selected from an ongoing birth cohort study. Pictorial diaries were distributed weekly to mothers of study children who were asked to maintain a record of morbidity for four weeks. We compared the reliability and completeness of the data on diarrhoea, fever and cough/cold obtained by the two methods., Results: Of 205 participants, 186 (91%) ever made a record in the diary and 62 (30%) mothers maintained the diary for all 28 days. The prevalence-adjusted bias-adjusted kappa statistics for diarrhoea, fever, cough/cold and for a healthy child were 92%, 79%, 35% and 35% respectively., Conclusion: Diary recording was incomplete in the majority of households. When recorded, the morbidity data by the pictorial diary method for acute illnesses were reliable. Strategies are needed to address behavioural factors affecting maternal recording such that field studies can obtain accurate morbidity measurements with limited resources.

The risk factors for acquisition of cryptosporidial infection in resource-poor settings are poorly understood. A nested case-control study was conducted to assess factors associated with childhood cryptosporidiosis (detected by stool polymerase chain reaction) in an endemic, Indian slum community using data from two community-based studies with 580 children followed prospectively until their second birthday. Factors were assessed for overall cryptosporidiosis (N = 406), and for multiple (N = 208), asymptomatic (N = 243), and symptomatic (N = 163) infections, respectively. Presence of older siblings (odds ratio [OR] = 1.88, P = 0.002) and stunting at 6 months of age (OR = 1.74, P = 0.019) were important risk factors for childhood cryptosporidiosis. Always boiling drinking water before consumption, the use of a toilet by all members of the family, and maternal age ≥ 23 years were protective. These results provide insights into acquisition of childhood cryptosporidiosis in settings with poor environmental sanitation, contaminated public water supply systems, and close human-animal contact. Disease control strategies will require a multifaceted approach., (© The American Society of Tropical Medicine and Hygiene.)

Background: Cryptosporidium spp. is a common, but under-reported cause of childhood diarrhea throughout the world, especially in developing countries. A comprehensive estimate of the burden of cryptosporidiosis in resource-poor settings is not available., Methodology/principal Findings: We used published and unpublished studies to estimate the burden of diarrhea, hospitalization and mortality due to cryptosporidial infections in Indian children. Our estimates suggest that annually, one in every 6-11 children <2 years of age will have an episode of cryptosporidial diarrhea, 1 in every 169-633 children will be hospitalized and 1 in every 2890-7247 children will die due to cryptosporidiosis. Since there are approximately 42 million children <2 years of age in India, it is estimated that Cryptosporidium results in 3.9-7.1 million diarrheal episodes, 66.4-249.0 thousand hospitalizations, and 5.8-14.6 thousand deaths each year., Conclusions/significance: The findings of this study suggest a high burden of cryptosporidiosis among children <2 years of age in India and makes a compelling case for further research on transmission and prevention modalities of Cryptosporidium spp. in India and other developing countries.

Objective: To estimate the burden and assess prenatal and postnatal determinants of illnesses experienced by children residing in a semiurban slum, during the first 1000 days of life., Design: Community-based birth cohort, Setting: Southern India, Participants: Four hundred and ninety-seven children of 561 pregnant women recruited and followed for 2 years with surveillance and anthropometry., Main Outcome Measure: Incidence rates of illness; rates of clinic visits and hospitalisations; factors associated with low birth weight, various illnesses and growth., Results: Data on 10 377.7 child-months of follow-up estimated an average rate of 14.8 illnesses/child-year. Gastrointestinal and respiratory illnesses were 20.6% and 47.8% of the total disease burden, respectively. The hospitalisation rate reduced from 46/100 child-years during infancy to 19/100 child-years in the second year. Anaemia during pregnancy (OR=2.3, 95% CI=1.08 to 5.18), less than four antenatal visits (OR=6.8, 95% CI=2.1 to 22.5) and preterm birth (OR=3.3, 95% CI=1.1 to 9.7) were independent prenatal risk factors for low birth weight. Female gender (HR=0.88, 95% CI=0.79 to 0.99) and 6 months of exclusive breast feeding (HR=0.76, 95% CI=0.66 to 0.88) offered protection against all morbidity. Average monthly height and weight gain were lower in female child and children exclusively breast fed for 6 months., Conclusions: The high morbidity in Indian slum children in the first 1000 days of life was mainly due to prenatal factors and gastrointestinal and respiratory illness. Policymakers need disease prevalence and pathways to target high-risk groups with appropriate interventions in the community., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

A single dose of live attenuated tetravalent (G1-G4) bovine human reassortant rotavirus vaccine (BRV-TV) was administered to healthy Indian adult volunteers, who were assessed for safety and immunogenicity of the vaccine with 3:1 randomization to vaccine or placebo. All 20 adult male volunteers in the study had rotavirus specific serum IgA at baseline. There were no side effects or adverse events reported. Administration of BRV-TV was not associated with fever, diarrhea, or altered liver transaminases. Rotavirus IgA seroconversion post single dose administration was 27%. This study shows that BRV-TV is non-reactogenic, safe and immunogenic in adults. The IgA units estimated for the same sample using human G1P[8] rotavirus strain as the antigen were consistently higher than with the bovine G6P[5] WC3 strain and the human G2P[4] DS-1 strain antigen. The use of different human and bovine rotavirus strains as antigens in a quantitative rotavirus specific serum IgA assay resulted in different estimations of IgA antibody in the same sample., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background & Objectives: Soil-transmitted helminths (STH) are a major public health problem in tropical and sub-tropical countries, affecting the physical growth and cognitive development in school-age children. This study was aimed to assess the prevalence and risk factors of STH infection among school children aged 6 -14 yr in Vellore and Thiruvanamalai districts in south India., Methods: Children aged 6-14 yr, going to government and government aided schools (n=33, randomly selected) in Vellore and Thiruvanamalai districts were screened to estimate the prevalence of STH, and a case control study was done on a subset to assess the risk factors for the infection., Results: The prevalence of STH was 7.8 per cent, varying widely in schools from 0 to 20.4 per cent, in 3706 screened children. Hookworm (8.4%) rates were high in rural areas, while Ascaris (3.3%) and Trichuris (2.2%) were more prevalent among urban children. Consumption of deworming tablets (OR=0.25, P < 0.01) offered protection, while residing in a field hut (OR=6.73, P=0.02) and unhygienic practices like open air defaecation (OR=5.37, P < 0.01), keeping untrimmed nails (OR=2.53, P=0.01) or eating food fallen on the ground (OR=2.52, P=0.01) were important risk factors for STH infection., Interpretation & Conclusions: Our study indicated that school children with specific risk factors in the studied area were vulnerable subpopulation with elevated risk of STH infection. Identifying risk factors and dynamics of transmission in vulnerable groups can help to plan for effective prevention strategies.

Objectives: To estimate the prevalence, spatial patterns and clustering in the distribution of soil-transmitted helminth (STH) infections, and factors associated with hookworm infections in a tribal population in Tamil Nadu, India., Methods: Cross-sectional study with one-stage cluster sampling of 22 clusters. Demographic and risk factor data and stool samples for microscopic ova/cysts examination were collected from 1237 participants. Geographical information systems mapping assessed spatial patterns of infection., Results: The overall prevalence of STH was 39% (95% CI 36%–42%), with hookworm 38% (95% CI 35–41%) and Ascaris lumbricoides 1.5% (95% CI 0.8–2.2%). No Trichuris trichiura infection was detected. People involved in farming had higher odds of hookworm infection (1.68, 95% CI 1.31–2.17, P < 0.001). In the multiple logistic regression, adults (2.31, 95% CI 1.80–2.96, P < 0.001), people with pet cats (1.55, 95% CI 1.10–2.18, P = 0.011) and people who did not wash their hands with soap after defecation (1.84, 95% CI 1.27–2.67, P = 0.001) had higher odds of hookworm infection, but gender and poor usage of foot wear did not significantly increase risk. Cluster analysis, based on design effect calculation, did not show any clustering of cases among the study population; however, spatial scan statistic detected a significant cluster for hookworm infections in one village., Conclusion: Multiple approaches including health education, improving the existing sanitary practices and regular preventive chemotherapy are needed to control the burden of STH in similar endemic areas.

Background: Rotavirus infection causes a significant proportion of diarrhea in infants and young children worldwide leading to dehydration, hospitalization, and in some cases death. Rotavirus infection represents a significant burden of disease in developing countries, such as those in South Asia., Methods: We conducted a meta-analysis to examine how patterns of rotavirus infection relate to temperature and precipitation in South Asia. Monthly rotavirus data were abstracted from 39 published epidemiological studies and related to monthly aggregated ambient temperature and cumulative precipitation for each study location using linear mixed-effects models. We also considered associations with vegetation index, gathered from remote sensing data. Finally, we assessed whether the relationship varied in tropical climates and humid mid-latitude climates., Results: Overall, as well as in tropical and humid mid-latitude climates, low temperature and precipitation levels are significant predictors of an increased rate of rotaviral diarrhea. A 1°C decrease in monthly ambient temperature and a decrease of 10 mm in precipitation are associated with 1.3% and 0.3% increase above the annual level in rotavirus infections, respectively. When assessing lagged relationships, temperature and precipitation in the previous month remained significant predictors and the association with temperature was stronger in the tropical climate. The same association was seen for vegetation index; a seasonal decline of 0.1 units results in a 3.8% increase in rate of rotavirus., Conclusions: In South Asia the highest rate of rotavirus was seen in the colder, drier months. Meteorological characteristics can be used to better focus and target public health prevention programs.

The common species and subgenotypes causing cryptosporidiosis were studied in 394 children and 627 animals with diarrhea in Vellore in southern India. Although no zoonotic strains were identified in 13 infected children, 1 of 12 infected animals had C. hominis, indicating the potential for cross-species transmission. This study also reports C. xiaoi for the first time in India.

Background: The three major soil-transmitted helminths (STH) Ascaris lumbricoides, Trichuris trichiura and Necator americanus/Ancylostoma duodenale are among the most widespread parasites worldwide. Despite the global expansion of preventive anthelmintic treatment, standard operating procedures to monitor anthelmintic drug efficacy are lacking. The objective of this study, therefore, was to define the efficacy of a single 400 milligram dose of albendazole (ALB) against these three STH using a standardized protocol., Methodology/principal Findings: Seven trials were undertaken among school children in Brazil, Cameroon, Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the McMaster egg counting technique to determine fecal egg counts (FEC). Overall, the highest CRs were observed for A. lumbricoides (98.2%) followed by hookworms (87.8%) and T. trichiura (46.6%). There was considerable variation in the CR for the three parasites across trials (country), by age or the pre-intervention FEC (pre-treatment). The latter is probably the most important as it had a considerable effect on the CR of all three STH. Therapeutic efficacies, as reflected by the FECRs, were very high for A. lumbricoides (99.5%) and hookworms (94.8%) but significantly lower for T. trichiura (50.8%), and were affected to different extents among the 3 species by the pre-intervention FEC counts and trial (country), but not by sex or age., Conclusions/significance: Our findings suggest that a FECR (based on arithmetic means) of >95% for A. lumbricoides and >90% for hookworms should be the expected minimum in all future surveys, and that therapeutic efficacy below this level following a single dose of ALB should be viewed with concern in light of potential drug resistance. A standard threshold for efficacy against T. trichiura has yet to be established, as a single-dose of ALB is unlikely to be satisfactory for this parasite., Trial Registration: ClinicalTrials.gov NCT01087099.