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Immunogenetics of Visceral Leishmaniasis

NCT00342823 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 7000

Last updated 2017-07-02

No results posted yet for this study

Summary

Visceral leishmaniasis is a potentially fatal disease caused in South America by the protozoan Leishmania chagasi. In neighborhoods with high exposure rates, the outcome of human infection with L. chagasi ranges from asymptomatic to a disseminated wasting disease called visceral leishmaniasis (VL). Several studies document familial clustering of VL in populations at risk. Segregation analyses favor a genetic over an environmental model for susceptibility to L. chagasi infection. A peri-urban outbreak of VL near the Universidade Federal do Rio Grande do Norte (UFRN) in Natal, northeast Brazil, has allowed us to identify endemic neighborhoods with ongoing transmission of L. chagasi infection. Natal is ideal for this study because endemic neighborhoods are easily accessible, people are motivated to cooperate with measures to control VL, and other forms of leishmaniasis are not transmitted in the region. Dr. Jeronimo of the UFRN, and Dr. Mary Wilson at University of Iowa have collected clinical data and DNA from 400 VL families living in these endemic neighborhoods. We have created an unprecedented cohort through which we can identify four distinct phenotypic responses after L. chagasi exposure. We documented familial clustering of L. chagasi infection, and results of both correlation and segregation analyses are consistent with the hypothesis that genetic factors predispose, in part, to the diverse clinical outcomes after infection. Polymorphism in the TNF locus is associated with developing symptomatic as opposed to asymptomatic disease after infection. We recently completed a genome-wide scan of the quantitative immune response (DTH) and identified potential linkage regions on chromosomes 2, 13, 15 and 19. We have also identified a small linkage peak on chromosome 9 for VL. In our ongoing study, we will next perform fine mapping of these regions using dense SNPs to identify genes that may determine susceptibility to L. chagasi infection. Additionally, we will also analyze candidate genes for association/linkage with susceptibility to or protection from L. chagasi disease. We recently identified an association on chromosome 5 with the DTH immune response among two linkage disequilibrium blocks spanning multiple immune related genes.

Conditions

  • Visceral Leishmaniasis

Sponsors & Collaborators

  • National Human Genome Research Institute (NHGRI)

    lead NIH

Eligibility

Min Age
1 Year
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2003-10-20
Completion
2010-06-30

Countries

  • Brazil

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00342823 on ClinicalTrials.gov