Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048123-03
Application #
6632441
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rao, Malla R
Project Start
2001-07-01
Project End
2006-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$631,621
Indirect Cost

  Institution

Name
Brown University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912

  Publications

McDonald, Emily A; Cheng, Ling; Jarilla, Blanca et al. (2014) Maternal infection with Schistosoma japonicum induces a profibrotic response in neonates. Infect Immun 82:350-5
Ezeamama, Amara E; McGarvey, Stephen T; Hogan, Joseph et al. (2012) Treatment for Schistosoma japonicum, reduction of intestinal parasite load, and cognitive test score improvements in school-aged children. PLoS Negl Trop Dis 6:e1634
Fabre, Valeria; Wu, Haiwei; PondTor, Sunthorn et al. (2011) Tissue inhibitor of matrix-metalloprotease-1 predicts risk of hepatic fibrosis in human Schistosoma japonicum infection. J Infect Dis 203:707-14
Wu, Hai-Wei; Qin, Yuan-Fang; Chu, Kai et al. (2010) High prevalence of Schistosoma japonicum infection in water buffaloes in the Philippines assessed by real-time polymerase chain reaction. Am J Trop Med Hyg 82:646-52
Olson, Courtney L; Acosta, Luz P; Hochberg, Natasha S et al. (2009) Anemia of inflammation is related to cognitive impairment among children in Leyte, the Philippines. PLoS Negl Trop Dis 3:e533
Jiz, Mario; Friedman, Jennifer F; Leenstra, Tjalling et al. (2009) Immunoglobulin E (IgE) responses to paramyosin predict resistance to reinfection with Schistosoma japonicum and are attenuated by IgG4. Infect Immun 77:2051-8
Jiz, Mario; Wu, Hai-Wei; Meng, Rui et al. (2008) Pilot-scale production and characterization of paramyosin, a vaccine candidate for schistosomiasis japonica. Infect Immun 76:3164-9
Ezeamama, Amara E; McGarvey, Stephen T; Acosta, Luz P et al. (2008) The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children's anemia burden. PLoS Negl Trop Dis 2:e245
Tu, Zhengkun; Bozorgzadeh, Adel; Pierce, Robert H et al. (2008) TLR-dependent cross talk between human Kupffer cells and NK cells. J Exp Med 205:233-44
Coutinho, Hannah M; Leenstra, Tjalling; Acosta, Luz P et al. (2007) Higher serum concentrations of DHEAS predict improved nutritional status in helminth-infected children, adolescents, and young adults in Leyte, the Philippines. J Nutr 137:433-9

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