Expanded training in Plasmodium falciparum Parasite Div*

Harvard University (Sch Of Public Hlth), Boston MA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Malaria remains one of the leading causes of infectious disease deaths in the world, in spite of major efforts to combat malaria, through vector control, drug therapy, and advances in the basic biology of the parasite. Forty percent of the world's population lives in areas where malaria is transmitted with an estimated 300-500 million cases and 1-2 million deaths attributable to malaria each year [1995 WHO Malaria Control]. Drug resistance is emerging as a major problem and identifying and tracking emergent parasite populations is urgently needed. Parasite resistance to the existing antimalarial drugs, including chloroquine, has been well established. The research training proposed in this supplement is outside the scope of the Fogarty grant TW-1503 but relates to its specific aims 1 and 4. The supplement proposes to incorporate modern genomics techniques to increase capacity of the Senegalese trainees to determine parasite diversity in Senegal, and the frequency of known drug resistance markers, and investigate the relation between them. Our ongoing study of the molecular mechanisms of chloroquine resistance has indicated that nucleotide polymorphism from single gene (pfcrt and pfmdrl) does not always correlate with the pattern of resistance observed in vitro. We are proposing to expand our analysis to the whole genome level and look at both gene expression and DNA polymorphisms in resistant and susceptible strains. The P. falciparum Genome Project is rapidly discovering all the genes in the malaria parasite, yet there are few developing country scientists with experience in genomics or post-genomic analysis. The project detailed below will allow Senegalese researches to learn a novel technology that can address the basis of drug resistance in vivo. Analysis of genome-wide expression, combined with on-going training activities in Senegal, will expand and enhance the malaria research capabilities of the faculty of Medicine and Pharmacy at the University of Cheikh Anta Diop in Dakar. It will allow Senegalese scientists to develop independent capability and self-reliance in state of the art techniques and enable them to address the basis of drug resistance in field strains as opposed to strains grown in long-term cultures. Expertise in the microarray technology will enable Senegalese scientists to incorporate postgenomic analysis in studying other prevalent infectious diseases. The goal of this supplement would be to 1) Expand our ongoing study of the molecular mechanisms of chloroquine resistance from single gene correlates to whole genomic analysis in patient population before and after drug treatment. 2) Expand the collaboration with US researchers to include an expert in methods and data analysis of a whole genomic approach in infectious disease and 3) Provide training in sample isolation and microarray analysis to further the goal of sustainable research capacity of the scientists at the University of Cheikh Anta Diop. [unreadable] [unreadable]