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.

National Institute of Health (NIH)
Research Project (R01)
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Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
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Rao, Malla R
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University of Virginia
Internal Medicine/Medicine
Schools of Medicine
United States
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Azziz-Baumgartner, Eduardo; Homaira, Nusrat; Hamadani, J D et al. (2014) The prevalence and impact of intimate partner violence on maternal distress in a community of low-income Bangladeshi and displaced ethnic Bihari mothers: Dhaka, 2008-2009. Violence Against Women 20:59-73
Subramanian, Sathish; Huq, Sayeeda; Yatsunenko, Tanya et al. (2014) Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510:417-21
Salje, H; Gurley, E S; Homaira, N et al. (2014) Impact of neighborhood biomass cooking patterns on episodic high indoor particulate matter concentrations in clean fuel homes in Dhaka, Bangladesh. Indoor Air 24:213-20
Haque, Rashidul; Snider, Cynthia; Liu, Yue et al. (2014) Oral polio vaccine response in breast fed infants with malnutrition and diarrhea. Vaccine 32:478-82
Moss, Delynn M; Priest, Jeffrey W; Hamlin, Kathy et al. (2014) Longitudinal evaluation of enteric protozoa in Haitian children by stool exam and multiplex serologic assay. Am J Trop Med Hyg 90:653-60
Moonah, Shannon N; Abhyankar, Mayuresh M; Haque, Rashidul et al. (2014) The macrophage migration inhibitory factor homolog of Entamoeba histolytica binds to and immunomodulates host macrophages. Infect Immun 82:3523-30
Hsiao, Ansel; Ahmed, A M Shamsir; Subramanian, Sathish et al. (2014) Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature 515:423-6
Jiang, Nona M; Tofail, Fahmida; Moonah, Shannon N et al. (2014) Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty. BMC Pediatr 14:50
Gurley, Emily S; Salje, Henrik; Homaira, Nusrat et al. (2014) Indoor exposure to particulate matter and age at first acute lower respiratory infection in a low-income urban community in Bangladesh. Am J Epidemiol 179:967-73
Verkerke, Hans P; Sobuz, Shihab U; Petri Jr, William A (2014) Molecular diagnosis of infectious diarrhea: focus on enteric protozoa. Expert Rev Mol Diagn 14:935-46

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