This proposal stems from 15 years of research on S. haematobium infection in Coast Province, Kenya that have served to challenge the traditional concept of the relationship among treatment, infection and morbidity. For S. haematobium, as well as other helminth infections, infection intensity before treatment shows significant person-to person, family-to-family and village-to- village variation. In treated populations in Kenya, our long follow-up period has permitted observation of reduced infection intensity and reduced acute morbidity among schoolchildren, but the development of hydronephrosis among many in adulthood. Thus, for early infection and disease as well as morbidity later in life, the heterogeneity of worm burden and disease outcome is not adequately explained by differences in parasite exposure. Increasing evidence suggests that the aggregated distributions of infection and disease is due in significant part to differences in environmental factors, genetically based differences in human biology or by specific immunologic mechanisms in some hosts. This single-project ICIDR represents a systematic evaluation of the major sources for variation in human susceptibility to disease and morbidity. Since characteristics of the disease itself are age dependent, factors will be sought from pre-exposed children, children demonstrating early forms of disease and adults presenting with late disease will be specifically targeted. Epidemiologic, demographic, parasitologic and sociologic factors will be quantified and analyzed for associations. These quantified risk factors will in turn be used to analyze familial segregation of phenotypes, as well as linkage between genetic markers and susceptibility. The effect of pre- natal exposure to schistosome antigens and childhood TNFalpha and TGFbeta production in lymphocytes will be specifically analyzed for their contribution to the observed variability in infection and outcome. Epidemiologic factors will be evaluated in Specific Aim 1 by cross-sectional and prospective studies that will evaluate and quantify the impact of age, sex, cultural and socio- economic background, intensity of infection and water contact. These studies will provide estimates of risk variables that will be used for genetic studies in Specific Aim 2.
Specific Aim 3 will examine neonates and infants for the effect of prenatal exposure on outcome and the expression of the cytokines TNFalpha and TGFbeta in school-aged children. This information, combined with epidemiological modeling of control strategies, will allow accelerated synthesis of the next generation of control programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AI045473-05S1
Application #
6898082
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Rao, Malla R
Project Start
1999-09-01
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2004
Total Cost
$741,637
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Kariuki, H Curtis; Ivy, Julianne A; Muchiri, Eric M et al. (2017) Divergent Effects ofSchistosoma haematobiumExposure on Intermediate-Host Snail SpeciesBulinus nasutusandBulinus globosusfrom Coastal Kenya. Am J Trop Med Hyg 96:850-855
Muiruri, Samuel; Kabiru, Ephantus W; Muchiri, Eric M et al. (2015) Cross-sectional survey of Rift Valley fever virus exposure in Bodhei village located in a transitional coastal forest habitat in Lamu county, Kenya. Am J Trop Med Hyg 92:394-400
Magak, Philip; Chang-Cojulun, Alicia; Kadzo, Hilda et al. (2015) Case-Control Study of Posttreatment Regression of Urinary Tract Morbidity Among Adults in Schistosoma haematobium-Endemic Communities in Kwale County, Kenya. Am J Trop Med Hyg 93:371-6
Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric et al. (2013) Potential for autoimmune pathogenesis of Rift Valley Fever virus retinitis. Am J Trop Med Hyg 89:495-7
LaBeaud, A Desiree; Cross, Paul C; Getz, Wayne M et al. (2011) Rift Valley fever virus infection in African buffalo (Syncerus caffer) herds in rural South Africa: evidence of interepidemic transmission. Am J Trop Med Hyg 84:641-6
LaBeaud, A Desiree; Muiruri, Samuel; Sutherland, Laura J et al. (2011) Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study. PLoS Negl Trop Dis 5:e1265
Kakani, Sravan; LaBeaud, A Desiree; King, Charles H (2010) Planning for Rift Valley fever virus: use of geographical information systems to estimate the human health threat of white-tailed deer (Odocoileus virginianus)-related transmission. Geospat Health 5:33-43
Kahlon, Summerpal S; Peters, Clarence J; Leduc, James et al. (2010) Severe Rift Valley fever may present with a characteristic clinical syndrome. Am J Trop Med Hyg 82:371-5
LaBeaud, A Desiree; Muchiri, Eric M; Ndzovu, Malik et al. (2008) Interepidemic Rift Valley fever virus seropositivity, northeastern Kenya. Emerg Infect Dis 14:1240-6
King, Charles H; Dangerfield-Cha, Madeline (2008) The unacknowledged impact of chronic schistosomiasis. Chronic Illn 4:65-79

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