Natural History of Cryptosporidial Infection in a Birth Cohort in a South Indian Semi-Urban Slum

Infectious diseases are a leading cause of childhood mortality. Five of the top 10 causes of death among children living in middle and low income countries are attributed to diseases of infectious origin. Although during the past few decades (between 1970 and 2013), the number of deaths among under-five children worldwide has reduced by more than 64%, an estimated 6.3 million children under the age of five were reported to have died in 2013 and 64% of all childhood deaths have been attributed to infectious causes. In order to reach United Nations Millennium Development Goal (MDG) 4 of decreasing childhood mortality by two thirds by 2015, there is a drive to control and prevent deaths from preventable infectious diseases by prioritizing them in various child health programmes . Several aspects of cryptosporidial infections, and host factors that modify the infection amongst children in this birth cohort have been explored. The impact of the findings on public health issues, particularly relevant to control of cryptosporidial infections are highlighted here. Cryptosporidium spp. is a common cause of parasitic diarrhoea throughout the world and is one of top five pathogens causing moderate to severe diarrhoea among children in developing countries. Despite this, the epidemiology of cryptosporidiosis in endemic settings is poorly understood. This study is innovative because it is the largest birth cohort study on the natural history of childhood cryptosporidiosis. The integration of molecular and serological methods for the diagnosis of cryptosporidial infection, coupled with the intensive bi-weekly follow-up helped capture the true burden of childhood cryptosporidiosis, and found it to be higher than reported earlier. Almost all children in the study acquired cryptosporidial infection by three years of age indicating a high rate of transmission in endemic areas, most likely through asymptomatically infected individuals. This study is the first to explore whether prior natural infection offered subsequent protection from infection or disease. The study found that an earlier infection did not offer protection from infection later in life. High rates and early infection with no subsequent protection requires public health interventions aimed at routes of transmission, rather than vaccines. The results of the study provide important insights in understanding the natural history and epidemiology of cryptosporidiosis in slum communities in India where there is sustained transmission, through multiple routes. The risk factors identified in this study can help develop scientifically sound, geographically relevant and socially sustainable measures that will effectively reduce the transmission of cryptosporidiosis in this and other endemic communities. As opposed to the developed countries where water is the primary mode of transmission, in the Indian setting, the transmission of cryptosporidiosis seems to occur through multiple routes (waterborne, human-to-human and animal-to-human). Personal hygiene and safe animal handling/tethering practices hence would be the leading public health interventions in this Indian setting for short-term benefits. Social interventions such as improvement in maternal literacy, reduction of poverty and provision of basic amenities like access to safe drinking water and sanitation may also help reduce transmission in the long run, but the effect of such intervention can only be ascertained over a longer time frame. Such interventions would also involve the participation of disciplines not directly related to health, such as education, social welfare and local administration

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 hook-worm-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

Prevalence & risk factors for soil transmitted helminth infection among school children in south India

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 schoolage 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

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

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.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.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.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

Reduction in diarrhoeal rates through interventions that prevent unnecessary antibiotic exposure early in life in an observational birth cohort

Antibiotic treatment early in life is often not needed and has been associated with increased rates of subsequent diarrhea. We estimated the impact of realistic interventions, which would prevent unnecessary antibiotic exposures before 6 months of age, on reducing childhood diarrheal rates

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

Assessment of the Anthelmintic Efficacy of Albendazole in School Children in Seven Countries Where Soil-Transmitted Helminths Are Endemic

Soil-transmitted helminths (roundworms, whipworms and hookworms) infect millions of children in (sub)tropical countries, resulting in malnutrition, growth stunting, intellectual retardation and cognitive deficits. Currently, there is a need to closely monitor anthelmintic drug efficacy and to develop standard operating procedures, as highlighted in a World Health Organization–World Bank meeting on “Monitoring of Drug Efficacy in Large Scale Treatment Programs for Human Helminthiasis” in Washington DC at the end of 2007. Therefore, we have evaluated the efficacy of a commonly used treatment against these parasitic infections in school children in Africa, Asia and South-America using a standardized protocol. In addition, different statistical approaches to analyzing the data were evaluated in order to develop standardized procedures for data analysis. The results demonstrate that the applied treatment was highly efficacious against round- and hookworms, but not against whipworms. However, there was large variation in efficacy across the different trials which warrants further attention. This study also provides new insights into the statistical analysis of efficacy data, which should be considered in future monitoring and evaluation studies of large scale anthelmintic treatment programs. Finally, our findings emphasize the need to update the World Health Organization recommended efficacy threshold for the treatment of STH

Identification of Ancylostoma ceylanicum in children from a tribal community in Tamil Nadu, India using a semi-nested PCR-RFLP tool

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

Burden of diarrhea, hospitalization and mortality due to cryptosporidial infections in Indian children.

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.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.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