The biologic heterogeneity that exists within local Schistosoma mansoni populations is difficult to study, yet this diversity and local parasite population dynamics are important risk factors for disease;they may assist drug design and may affect control strategies. Control programs for S. mansoni center on repeated rounds of chemotherapy every 2-3 years to reduce infection intensities and thereby reduce morbidity. Prevalence is much less affected and transmission is not interrupted, since these populations rapidly recover. The resultant effect of periodic contracting and re-expanding populations on schistosome biology is not known in large part due to the lack of tools and methodologies for differentiating subpopulations of worms. We have identified 7 polymorphic microsatellite markers that behave like single-copy loci, are species-specific, and produce interpretable patterns for DNA isolated from parasite eggs. Further, to optimize sampling, we have developed methods to isolate parasite egg DNA from stool and statistical methods that utilize allele frequencies from pooled samples rather than discrete genotypes. In order to understand how repeated chemotherapy changes S. mansoni population structure, this proposal will directly determine the allele frequency distribution of S. mansoni by isolating and genotyping egg DNA from the stool of infected individuals. These allele frequencies will then be related to the regional and microgeographic distribution of the parasite before and after yearly chemotherapy. With the tools we have developed, this project will: 1) Determine how microgeography relates to subpopulation distribution and gene flow, 2) Determine how widespread chemotherapy changes population structure, 3) Determine how populations that persist after chemotherapy are related to pre-treatment populations, 4) Measure the contribution of migration or increase in the resident population to recovery of schistosome populations, 5) Assess the contribution of local parasite transmission versus immigration to urban foci, 6) Compare urban foci to rural populations before and after therapy. Population structure will be compared using the between populations fixation index (Fsr) and by estimation of both effective population size (Ne) and the immigration rate (m). Mixed stock analysis will also be used to analyze migration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI069195-04
Application #
7777278
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Rao, Malla R
Project Start
2007-03-01
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
4
Fiscal Year
2010
Total Cost
$352,542
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
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Blanton, Ronald E; Barbosa, Lúcio M; Reis, Eliana A et al. (2015) The relative contribution of immigration or local increase for persistence of urban schistosomiasis in Salvador, Bahia, Brazil. PLoS Negl Trop Dis 9:e0003521
Ponce-Terashima, Rafael; Koskey, Amber M; Reis, Mitermayer G et al. (2014) Sources and distribution of surface water fecal contamination and prevalence of schistosomiasis in a Brazilian village. PLoS Negl Trop Dis 8:e3186
Meng, Qinglai; Rani, M R Sandhya; Sugalski, Julia M et al. (2014) Natural cytotoxicity receptor-dependent natural killer cytolytic activity directed at hepatitis C Virus (HCV) is associated with liver inflammation, African American race, IL28B genotype, and response to pegylated interferon/ribavirin therapy in chronic H J Infect Dis 209:1591-601
Barbosa, Lúcio M; Silva, Luciano K; Reis, Eliana A et al. (2013) Characteristics of the human host have little influence on which local Schistosoma mansoni populations are acquired. PLoS Negl Trop Dis 7:e2572
Conry, Sara J; Meng, Qinglai; Hardy, Gareth et al. (2012) Genetically associated CD16(+)56(-) natural killer cell interferon (IFN)-?R expression regulates signaling and is implicated in IFN-?-induced hepatitis C virus decline. J Infect Dis 205:1131-41
Anthony, Donald D; Conry, Sara J; Medvik, Kathy et al. (2012) Baseline levels of soluble CD14 and CD16+56- natural killer cells are negatively associated with response to interferon/ribavirin therapy during HCV-HIV-1 coinfection. J Infect Dis 206:969-73
Souza, Samaly S; Barbosa, Lucio M; Guimaraes, Isabel C et al. (2012) Genetic population structure of cercariae from an urban foci of Schistosoma mansoni, Brazil. Am J Trop Med Hyg 87:843-9
Blanton, Ronald E; Blank, Walter A; Costa, Jackson M et al. (2011) Schistosoma mansoni population structure and persistence after praziquantel treatment in two villages of Bahia, Brazil. Int J Parasitol 41:1093-9
Blank, Walter A; Liu, Shi Fan; Prasad, Jayendra et al. (2011) Host mouse strain is not selective for a laboratory adapted strain of Schistosoma mansoni. J Parasitol 97:518-21

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