The overall objective of this proposal is to prospectively investigate the interrelationships among puberty, protective immune responses, and nutritional status in adolescent Philippine residents of Schistosoma japonicum endemic areas Determining immunologic and developmental predictors of resistance in naturally exposed humans is a fundamental component of the ongoing effort to develop vaccines against schistosomiasis japonicum. Development of protective human immune responses to other schistosomes appears to occur during puberty in endemic communities. A recent hypothesis states that the hormonal changes of puberty, e.g., increasing dehydroepiandrosterone (DHEA), not cumulative exposure, initiate and promote the development of protective immune responses to schistosome infections Schistosomiasis is causally linked to malnutrition leading to the hypothesis that chronic infection results in attenuate growth for age and possibly delayed pubertal development. Animal models of chronic parasitemia have identified TNF-alpha and IL-6 as mediators of malnutrition and cachexia. Production of this mediator is significantly attenuated by increasing DHEA levels. These interrelationships suggest that a DHEA-modulated cycle of infection, pubertal delay, and malnutrition may be responsible for the marginal nutritional status of schistosome infected adolescents. This study will employ a longitudinal, treatment-reinfection design of naturally exposed humans to determine the immunologic predictors of resistance to reinfection and their interrelationships with puberty. In addition, the relationships among nutritional status, circulating mediators of inflammation and pubertal hormones will be examined. Information provided by these studies will influence all phases of vaccine development for S. japonicum including the identification of appropriate antigens, protective isotype and cytokine responses and the modulating effects of host pubertal and nutritional development on these responses.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Tropical Medicine and Parasitology Study Section (TMP)
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Rao, Malla R
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Brown University
Public Health & Prev Medicine
Schools of Medicine
United States
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