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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AI043596-16
Application #
8738595
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Rao, Malla R
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Verkerke, Hans; Sobuz, Shihab; Ma, Jennie Z et al. (2016) Malnutrition Is Associated with Protection from Rotavirus Diarrhea: Evidence from a Longitudinal Birth Cohort Study in Bangladesh. J Clin Microbiol 54:2568-74
Fleece, Molly E; Heptinstall, Jack; Khan, Shaila S et al. (2016) Evaluation of a Rapid Lateral Flow Point-of-Care Test for Detection of Cryptosporidium. Am J Trop Med Hyg 95:840-841
Donowitz, Jeffrey R; Haque, Rashidul; Kirkpatrick, Beth D et al. (2016) Small Intestine Bacterial Overgrowth and Environmental Enteropathy in Bangladeshi Children. MBio 7:e02102-15
Gilchrist, Carol A; Petri, Sarah E; Schneider, Brittany N et al. (2016) Role of the Gut Microbiota of Children in Diarrhea Due to the Protozoan Parasite Entamoeba histolytica. J Infect Dis 213:1579-85
Burgess, Stacey L; Lu, Miao; Ma, Jennie Z et al. (2016) Inflammatory markers predict episodes of wheezing during the first year of life in Bangladesh. Respir Med 110:53-7
Donowitz, Jeffrey R; Alam, Masud; Kabir, Mamun et al. (2016) A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea. Clin Infect Dis 63:792-7
Korpe, Poonum S; Haque, Rashidul; Gilchrist, Carol et al. (2016) Natural History of Cryptosporidiosis in a Longitudinal Study of Slum-Dwelling Bangladeshi Children: Association with Severe Malnutrition. PLoS Negl Trop Dis 10:e0004564
Watanabe, Koji; Petri Jr, William A (2016) Environmental Enteropathy: Elusive but Significant Subclinical Abnormalities in Developing Countries. EBioMedicine 10:25-32
Taniuchi, Mami; Platts-Mills, James A; Begum, Sharmin et al. (2016) Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants. Vaccine 34:3068-75
Ramakrishnan, Girija; Wright, Marcia; Alam, Masud et al. (2016) Rapid assessment of tetanus vaccine-induced immunity in Bangladesh and the Gambia. Diagn Microbiol Infect Dis :

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