PROGUANIL RESISTANCE IN PLASMODIUM-FALCIPARUM AFRICAN ISOLATES - ASSESSMENT BY MUTATION-SPECIFIC POLYMERASE CHAIN-REACTION AND IN-VITRO SUSCEPTIBILITY TESTING

The antifolate proguanil is commonly used in the prophylaxis and treat ment of Plasmodium falciparum malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differentia l susceptibility of varied P. falciparum clones or isolates to this dr ug. To survey the efficiency of proguanil prophylaxis in an African en demic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility a ssays with P. falciparum isolates from Senegal, Kenya, and Niger. in p arallel, we developed a mutation-specific polymerase chain reaction as say that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previo usly available data showing that parasites harboring a point mutation from Ser108 to Asn present a decrease in susceptibility to cycloguanil (the active metabolite of proguanil), and we show that mutations in c odons 51 and 59 appear to modulate the level of resistance to cyclogua nil. No mutations in codons 16 and 164 were detected in resistant para sites, in contrast with results from some previous studies.