Over 5 million children <5years old died in 2017. Marked heterogenicity existed however in the global distribution of this child mortality. In low and middle income countries where the death rate was high it was estimated that at least 5% of the deaths were due to water borne diarrheal disease. Cryptosporidiosis was found to be one of the top 5 causes of this diarrhea. In addition to child mortality the sub-clinical infection of malnourished infants with Cryptosporidium parasites can result in developmental delays and growth failure. Despite these short and long-term impacts on human health the pathogenic mechanisms involved are not yet understood.
- To investigate the impact of Cryptosporidiumgenetic diversity on parasite immune evasion and virulence. Recent advances in genomic sequencing coupled with the development of new protocols forCryptosporidium research are allowing me to study one of the fundamental sources of information on these organisms, the genomic DNA sequence. Method: Whole genome sequencing of theCryptosporidium parasite isolates
- Identification of antigens suitable for incorporation into a Cryptosporidiumvaccine. Method: First isolate parasites and sequence – I plan to subsequently identify the evolutionaly conserved epitopes or proteins and determine if a fecal IgA response against the evolutionarily conserved membrane proteins is associated with protection from reinfection with theCryptosporidium parasite
- To identify the pathogen reservoirs that increase the risk of a child experiencing diarrheal disease.During analysis of the data obtained during studies on the natural history of the Cryptosporidium parasite I noticed that a high risk of urban cryptosporidiosis seemed to occur during the monsoon flooding. At rural sites however, exposure to poultry infected with C. meleagridis may be linked to cryptosporidiosis. Methods: I develop and validate qPCR assays and rapid diagnostics that are useful to me in this work.
- To identify the risk of increased E. histolytica virulence associated with environmental factorsChanges in the host microbiome or immune status can play a significant role in the development of symptomatic disease upon pathogen infection. Methods: I use both 16S sequencing of the human microbiota, focused qPCR assays and (to monitor the host immune response) assay host biomarkers of inflammation.