: Infection with Schistosoma mansoni is a major health problem in much of Africa, the Middle East, and South America. Recent data show that based on time to reinfection, adults occupationally exposed to S. mansoni are resistant, develop resistance upon multiple treatments/re-infections, or remain susceptible. This proposal will test the hypothesis that resistance in these well-characterized Kenyans correlates with specific immune responses and genetic profiles, determine the dynamic immune changes accompanying resistance acquisition in these adults and school children, and see if immune changes can predict resistance. Based on preliminary data, treatment/reinfection studies, and animal models, resistance is proposed to correlate with both Thl and Th2 immune profiles, depending on the schistosome antigen-specific responses being studied. This hypothesis will be tested in well-characterized resistant and susceptible adults, and in those actively developing resistance due to multiple treatments/re-infections. Also, the antigen-specific immune profiles of children (usually susceptible to reinfection) will be determined as they respond to multiple treatments.
The Specific Aims are: 1) Determine the antigen-specific cytokine and antibody isotype responses (immune profiles) that relate to the resistance or susceptibility of persons occupationally exposed to S. mansoni by flow cytometry, mRNA RT-PCR and gene activation micro-array analyses, in vitro culture for cytokine production and proliferation, and antibody ELISA analyses. 2) Determine the progression of immune profile changes during the actual development of resistance to S. mansoni in a prospectively followed cohort. 3) Determine if the progressive changes in immune profiles that are observed as adults become resistant to S. mansoni also occur longitudinally in multiply treated children in a highly endemic area. 4) Test the relationships of genetic polymorphisms likely to be associated with resistance or susceptibility to S. mansoni in well-characterized resistant or susceptible adults. Completion of these Specific Aims will: help establish the basis of resistance to schistosome infection that occurs upon multiple treatment/reinfection; provide both mechanistic insights into and correlates of resistance/susceptibility needed for future vaccine development against this debilitating disease; and determine if multiple mass treatment programs to control morbidity provide an added benefit by inducing a level of resistance to reinfection by S. mansoni.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI053695-01
Application #
6561537
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rao, Malla R
Project Start
2003-01-01
Project End
2007-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
1
Fiscal Year
2003
Total Cost
$514,059
Indirect Cost
Name
University of Georgia
Department
Type
Organized Research Units
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
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Abudho, Bernard O; Ndombi, Eric M; Guya, Bernard et al. (2018) Impact of Four Years of Annual Mass Drug Administration on Prevalence and Intensity of Schistosomiasis among Primary and High School Children in Western Kenya: A Repeated Cross-Sectional Study. Am J Trop Med Hyg 98:1397-1402
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Black, Carla L; Mwinzi, Pauline N M; Muok, Erick M O et al. (2010) Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni. PLoS Negl Trop Dis 4:e637
Black, Carla L; Muok, Erick M O; Mwinzi, Pauline N M et al. (2010) Increases in levels of schistosome-specific immunoglobulin E and CD23(+) B cells in a cohort of Kenyan children undergoing repeated treatment and reinfection with Schistosoma mansoni. J Infect Dis 202:399-405

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