Deepthi Kattula

Seasonality of Rotavirus in South Asia: A Meta-Analysis Approach Assessing Associations with Temperature, Precipitation, and Vegetation Index

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 first 1000 days of life: prenatal and postnatal risk factors for morbidity and growth in a birth cohort in southern India

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.

Risk Factors for Cryptosporidiosis among Children in a Semi Urban Slum in Southern India: A Nested Case-Control Study

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.

Prevalence and clustering of soil‐transmitted helminth infections in a tribal area in southern India

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.

Environmental Factors Associated with High Fly Densities and Diarrhea in Vellore, India

ABSTRACT 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.

Longitudinal Analysis of the Intestinal Microbiota in Persistently Stunted Young Children in South India

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.

Molecular Identification of Hookworm Isolates in Humans, Dogs and Soil in a Tribal Area in Tamil Nadu, India

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.

The Effect of Early Life Antibiotic Exposures on Diarrheal Rates Among Young Children in Vellore, India

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.

Antibiotic treatment of diarrhoea is associated with decreased time to the next diarrhoea episode among young children in Vellore, India

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 childs 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.

Seasonality of water quality and diarrheal disease counts in urban and rural settings in south India.

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.