Approach: We propose to advance the understanding of the impact of cryptosporidiosis on child health, and lay the foundation for new approaches to treatment and prevention. The work will be conducted through a longitudinal birth cohort study of impoverished children in Bangladesh. We will measure the incidence of infection and diarrhea by the species and genotypes of cryptosporidia, test the role of acquired immunity in protection from infection, and determine the role of human genes in influencing susceptibility to infection. Successful completion of these studies will define the natural history of infection in infants, including the contributions of parasite genetic diversity, immunity and human genetic polymorphisms. Significance: The significance of the work lies in the ability of the study to provide new approaches to treat and prevent cryptosporidiosis. Innovative aspects of the work include the description of the incidence and genetic complexity of cryptosporidia and the impact of that diversity on virulence;testing if an acquired immune response is protective;and identifying human genes that influence susceptibility as potential targets for host-directed therapy The environment for the work includes active investigation of enteric parasitic infections of humans at both the field and bench, and collaborative investigators with over 40 co-published original research papers.
Cryptosporidiosis causes severe diarrhea in infants in the developing world. There is no vaccine to prevent it, and little in the way of treatment. This study in Bangladeshi urban slum children aims to support the design of a vaccine, both by determining how the immune system protects from infection and by identifying the genotypes of the parasite that should be included in a vaccine, as well as aid in development of therapies by identifying human genes that control infection.
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