Clinical Trial on Visceral Leishmaniasis - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Visceral Leishmaniasis

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

7000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Brazil
- - Natal, Brazil
    - Universidade Federal do Rio Grande do Norte

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

We used three approaches to identify families in endemic neighborhoods, yielding three populations of families.

Population I: A neighborhood to the northeast of the city was identified through a family with two cases of disease.

Population 2: Individuals with suspected VL are admitted to one of three public hospitals in Natal. Families were interviewed and examined if they wished to participate.

Population 3: The neighboring families living closest to population 2 families were identified.

EXCLUSION CRITERIA

Individuals with ongoing illnesses other than VL were excluded from analyses.

Any medical conditions found or suspected based upon history, exam or blood tests were either treated by the investigators or referred to the appropriate medical facility in Natal.

Pregnant women and children less than 1 year were not given any skin test.

No exclusions based on ethnicity were done.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Human Genome Research Institute (NHGRI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 20, 2003

Study Completion

June 30, 2010

Study Registration Dates

First Submitted

June 19, 2006

First Submitted That Met QC Criteria