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)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
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
1998-09-15
Project End
2018-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
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
Steiner, Kevin L; Ahmed, Shahnawaz; Gilchrist, Carol A et al. (2018) Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study. Clin Infect Dis 67:1347-1355
Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross et al. (2018) Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study. J Infect Dis 217:861-868
Kabir, Mamun; Ahmed, Emtiaz; Hossain, Biplob et al. (2018) Giardia/Cryptosporidium QUIK CHEK Assay Is More Specific Than Quantitative Polymerase Chain Reaction for Rapid Point-of-care Diagnosis of Cryptosporidiosis in Infants in Bangladesh. Clin Infect Dis 67:1897-1903
Khalil, Ibrahim A; Troeger, Christopher; Rao, Puja C et al. (2018) Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study. Lancet Glob Health 6:e758-e768
Donowitz, Jeffrey R; Cook, Heather; Alam, Masud et al. (2018) Role of maternal health and infant inflammation in nutritional and neurodevelopmental outcomes of two-year-old Bangladeshi children. PLoS Negl Trop Dis 12:e0006363
Jiang, Nona M; Cowan, Maureen; Moonah, Shannon N et al. (2018) The Impact of Systemic Inflammation on Neurodevelopment. Trends Mol Med 24:794-804
Schnee, Amanda E; Haque, Rashidul; Taniuchi, Mami et al. (2018) Evaluation of Two New Membrane-Based and Microtiter Plate Enzyme-Linked Immunosorbent Assays for Detection of Campylobacter jejuni in Stools of Bangladeshi Children. J Clin Microbiol 56:
Korpe, Poonum S; Valencia, Cristian; Haque, Rashidul et al. (2018) Epidemiology and Risk Factors for Cryptosporidiosis in Children From 8 Low-income Sites: Results From the MAL-ED Study. Clin Infect Dis 67:1660-1669
Gilchrist, Carol A; Cotton, James A; Burkey, Cecelia et al. (2018) Genetic Diversity of Cryptosporidium hominis in a Bangladeshi Community as Revealed by Whole-Genome Sequencing. J Infect Dis 218:259-264
Mychaleckyj, Josyf C; Nayak, Uma; Colgate, E Ross et al. (2018) Multiplex genomewide association analysis of breast milk fatty acid composition extends the phenotypic association and potential selection of FADS1 variants to arachidonic acid, a critical infant micronutrient. J Med Genet 55:459-468

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