Consortial Project 2
Genetic determinants of immune responses to malaria
Consortial Project 2 aims to elucidate the functional effects of genetic variation on the immune response to malaria, focusing on how polymorphisms in known immune response genes influence antibody production to malarial antigens. This Consortial Project has study sites in seven malaria-endemic countries, all of which have a well-established infrastructure for immunoepidemiological studies in the community.
Study sites
- Burkina Faso: The Centre National de Recherche et de Formation sur le Paludisme are completing longitudinal and cross-sectional surveys in 4 villages. More>>
- Kenya: The KEMRI-Wellcome Reseach Programme is contributing samples from individuals under continous surveillance for malaria.
- Mali: The University of Bamako has two different CP2 study projects at Manteourou More>> and Pongonon More>>
- Tanzania: The Joint Malaria Programme, Kilimanjaro Christian Medical Centre recruited samples from cross-sectional surveys at two different altitudes. More>>
- Tanzania: The National Institute for Medical Research recruited samples from eight villages in the Muheza district. More>>
- Senegal: The Institut Pasteur de Dakar recruited samples from a long-term longitudinal study in two communities. More>>
- Sri Lanka: The University of Colombo is following up on a cohort study with active case dectection carried out in 1992/3. More>>
- Sudan:The University of Khartoum performed a continuous surveillance in two villages in an area of low malaria endemicity and transmission rates.
Scientific rationale
Consortial Project 2 focuses on two basic questions. First, across multiple study sites, do SNPs in immune response genes correlate with anti-malarial antibody levels? Second, within individual sites, do both immune gene SNPs and anti-malarial antibody levels correlate with key clinical phenotypic variables, such as disease severity?
The operational work of this Consortial Project (DNA sample collection, genotyping, linking to clinical data) bears some similarity to that of Consortial Project 1, but the experimental and analytical design is fundamentally different. The project plan allows each partner institution to collect and analyze data according to their unique research framework, and in that sense we are conducting nine independent studies. However, several of the hypotheses being tested by Consortial Project 2 span all nine study sites. These hypotheses address questions including whether selected SNPs are associated with malaria antibody levels, and whether occurrence these SNPs correlates with the incidence of relapse or with symptomatic and/or asymptomatic parasite load. Likewise, Consortial Project 2 will ask whether malaria antibody levels themselves correlate with the number of malaria episodes or with parasite load.
Key operational progress for Consortial Project 2 has been made in the development of a standardized, scalable antibody-detection assay for known malarial antigens; this assay will greatly facilitate uniform data collection across study sites. However, we are still in the phase of gathering data, with sample collection, SNP genotyping, antibody measurements, and clinical data recording at various stages of progress across studies. There are, however, already signs of experimental success. Preliminary analysis from at least one site suggests that genetic variation in a known malaria resistance gene can affect the immune response to infection. We will expand on this observation in the coming year by confirming the observation in a larger sample size and across multiple study sites.