Project Summary In our preliminary studies, we have shown that substantial genetic recombination occurs in C. hominis. The impact and consequences of this is not known. We now plan to study the role of this process in generating parasite intra-host diversity and on the evolution of this parasite within the Mirpur community. Hypothesis: We hypothesize that cryptosporidiosis in humans is influenced by parasite genetic diversity. Human work: C. hominis oocysts will be isolated from asymptomatic and symptomatic children. Significance: Cryptosporidiosis is one of the top causes of diarrhea in the first 2 years of life in low-income countries but very little is known about the degree and impact of parasite genetic diversity on disease. Innovation: This proposal will allow us to study parasite natural evolution at both the community and individual level. Approach: Clinical and demographic information, as well as parasite oocysts, are being collected on Cryptosporidium positive children at an urban study in Bangladesh. Aim 1: To measure the rate of C. hominis evolution within the Mirpur community. We have already sequenced 32 C. hominis genomes and have collected DNA from an additional 59 isolates. We will sequence one hundred new isolates during this grant. Comparison of the genomes over time will identify genes under the diversifying selective pressure which underlies host-parasite interactions. Aim 2: To identify the changes that occur in the C. hominis genome during the course of an infection in an individual child. The daughter sporozoites arising from the infecting oocysts can have different alleles. We use this heterozygosity to identify genes and allele combinations important to ensuring parasite intra-host survival. The environment: My collaborators Dr. Petri and Dr. Haque are experts in field studies and I have access to genomic services and sequencing core facilities at UVa. Successful completion of this work: From this work we will understand the role of the parasite evolution in disease.