To compare the molecular parasitology and immunology of antigenic variation in P. falciparum malaria in an area of high transmission and hyperendemic malaria (Ghana, West Africa) with that in an area of hypoendemic, unstable malaria (Sudan, East Africa) and to discover whether parasite strategies for immune evasion by antigenic variation vary under different transmission conditions.
By the end of the study we will have basic epidemiological data on the period that individuals remain asymptomatically infected at each study site and quantitative data on whether parasite densities fluctuate or remain broadly stable during asymptomatic infections at each site. The length and densities of gametocytaemia will also be known. This epidemiological data will allow us to interpret the results of the concurrent immunological and molecular biological studies on typing the PfEMP-1/var genes (using RT-PCR and human phage display library generated antibodies) in the parasites isolated from symptomatic and asymptomatic individuals.
This will allow us to assay if, and how frequently, the parasite population in the monitored asymptomatic infections is switching PfEMP-1 expression and whether asymptomatic individuals infected with an apparently genetically stable population of parasites show constant responses in mixed agglutination assays or whether these vary in concert with var gene switches.
Such reagents and information will be essential for further studies on the role of P. falciparum antigenic variation in pathogenesis.
* Cloning and sequence PfEMP-1/var genes and gene fragments from African P. falciparum samples to obtain reagents and develop assays for the analysis of the genetics of the PfEMP-1/var system and to test whether clonal antigenic variation associated with var gene switching allows the parasite to survive in the host during chronic malaria infections.
* Characterising the immunological and parasitological events associated with the acquisition of agglutinating antibody responses. To attempt to correlate agglutination responses in human infections from Sudan and Ghana with the appearance of specific responses to defined parasite encoded adhesion molecules such as PfEMP-1 and sequestrin. Building on ongoing research, to compare the acquisition of agglutinating antibody responses with the acquisition of antibody responses against variant and conserved portions of major parasite merozoite antigens such as MSP-1.
* Strengthening molecular biology and immunology research on malaria in the African partner institutions and to train junior scientists in the European partner laboratories. To promote scientific exchanges between malaria researchers in East and West Africa.
Funding SchemeCSC - Cost-sharing contracts
2200 Kobenhavn N