Helminthic infections are major health concerns in both tropical and temperate areas of the world. Researchers have consistently found that much of the parasite burden of a population is constrained to a relatively small proportion of individuals, i.e. parasites tend to be overdispersed. The marked predisposition of some individuals to high worm burdens has led international health workers to consider targeting high risk individuals for treatment, since complete eradication is not a realistic goal for soil-transmitted helminths. However, the mechanism for the increased susceptibility of a small segment of the population to high worm loads is not known, although some researchers have suggested that genetic factors may be involved. There are few studies of the genetic determinants of susceptibility to helminthic infections in humans. This project will evaluate the genetic components of susceptibility to helminthic infections using newly developed statistical genetic methods. Specifically, roundworm. hookworm, and whipworm burdens will be measured at two points in time in 1000 members (belonging to 50 pedigrees) of flee Jirel population of eastern Nepal. Hematological (red cell count. white cell count. eosinophil count, hemoglobin. and hematocrit levels) and anthropometric measures (stature, weight, and skinfolds) that are known to reflect response to helminthic infections will also be assessed. Quantitative genetic methods will be used to determine the genetic and environmental components of worm burden and associated biological responses. Pleiotropic genetic effects influencing susceptibility to multispecies helminthic infections will be examined using multivariate genetic methods. The effects of single genes on worm burden or related measures will be assessed using complex segregation analyses. Genetic effects on biological responses to helminthic infection will be tested by examination of the genotype by worm burden interaction effects on host traits such as eosinophil counts. This project will provide new information on the determinants of parasite distribution patterns that will be useful for designing intervention programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI037091-03
Application #
2457812
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1995-08-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1999-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Southwest Foundation for Biomedical Research
Department
Type
DUNS #
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Williams, Kimberly D; Blangero, John; Subedi, Janardan et al. (2013) Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal. Am J Hum Biol 25:743-50
Williams-Blangero, Sarah; Criscione, Charles D; VandeBerg, John L et al. (2012) Host genetics and population structure effects on parasitic disease. Philos Trans R Soc Lond B Biol Sci 367:887-94
Williams, Kimberly D; Nahhas, Ramzi W; Cottom, Carol R et al. (2012) Evaluation of qualitative methods for phenotyping brachymesophalangia-V from radiographs of children. Am J Hum Biol 24:68-73
Criscione, Charles D; Anderson, Joel D; Sudimack, Dan et al. (2010) Landscape genetics reveals focal transmission of a human macroparasite. PLoS Negl Trop Dis 4:e665
Williams-Blangero, Sarah; Vandeberg, John L; Subedi, Janardan et al. (2008) Two quantitative trait loci influence whipworm (Trichuris trichiura) infection in a Nepalese population. J Infect Dis 197:1198-203
Williams-Blangero, Sarah; Vandeberg, John L; Subedi, Janardan et al. (2008) Localization of multiple quantitative trait loci influencing susceptibility to infection with Ascaris lumbricoides. J Infect Dis 197:66-71
Criscione, Charles D; Anderson, Joel D; Sudimack, Dan et al. (2007) Disentangling hybridization and host colonization in parasitic roundworms of humans and pigs. Proc Biol Sci 274:2669-77
Criscione, Charles D; Anderson, Joel D; Raby, Kyle et al. (2007) Microsatellite markers for the human nematode parasite Ascaris lumbricoides: development and assessment of utility. J Parasitol 93:704-8
Williams-Blangero, Sarah; Blangero, John (2006) Collection of pedigree data for genetic analysis in isolate populations. Hum Biol 78:89-101
Kunwar, C B; Chapagain, R H; Subba, B et al. (2006) Occurrence of soil-transmitted helminths in women at the Himalayan region of Nepal. Kathmandu Univ Med J (KUMJ) 4:444-7

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