PMID: 9430520Jan 16, 1998Paper

Proguanil resistance in Plasmodium falciparum African isolates: assessment by mutation-specific polymerase chain reaction and in vitro susceptibility testing

The American Journal of Tropical Medicine and Hygiene
D ParzyJ C Doury

Abstract

The antifolate proguanil is commonly used in the prophylaxis and treatment of Plasmodium falciparum malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differential susceptibility of varied P. falciparum clones or isolates to this drug. To survey the efficiency of proguanil prophylaxis in an African endemic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility assays with P. falciparum isolates from Senegal, Kenya, and Niger. In parallel, we developed a mutation-specific polymerase chain reaction assay that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previously 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 codons 51 and 59 appear to modulate the level of resistance to cycloguanil. No mutations in codons 16 and 164 were detected in resistant parasites, in contrast with results from some previous studies.

Citations

May 10, 2002·Tropical Medicine & International Health : TM & IH·Christian G MeyerVirgilio Do Rosario
Jan 23, 2018·Nature Reviews. Microbiology·Kasturi HaldarInnocent Safeukui
Nov 18, 2000·Antimicrobial Agents and Chemotherapy·R DurandJ Le Bras
Dec 12, 2002·Transactions of the Royal Society of Tropical Medicine and Hygiene·Milijaona RandrianarivelojosiaRonan Jambou
Apr 2, 2003·Fundamental & Clinical Pharmacology·Jacques Le Bras, Rémy Durand

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