Proguanil Resistance in Plasmodium falciparum African Isolates: Assessment by Mutation-Specific Polymerase Chain Reaction and in Vitro Susceptibility Testing

Daniel Parzy Institut de Medecine Tropicale du Service de Sante des Armees, Institut de la Sante et de la Recherche Medicale, Unite 399, Faculte de Medecine, Marseille, France

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Christian Doerig Institut de Medecine Tropicale du Service de Sante des Armees, Institut de la Sante et de la Recherche Medicale, Unite 399, Faculte de Medecine, Marseille, France

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Bruno Pradines Institut de Medecine Tropicale du Service de Sante des Armees, Institut de la Sante et de la Recherche Medicale, Unite 399, Faculte de Medecine, Marseille, France

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Alain Rico Institut de Medecine Tropicale du Service de Sante des Armees, Institut de la Sante et de la Recherche Medicale, Unite 399, Faculte de Medecine, Marseille, France

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Thierry Fusai Institut de Medecine Tropicale du Service de Sante des Armees, Institut de la Sante et de la Recherche Medicale, Unite 399, Faculte de Medecine, Marseille, France

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Jean-Claude Doury Institut de Medecine Tropicale du Service de Sante des Armees, Institut de la Sante et de la Recherche Medicale, Unite 399, Faculte de Medecine, Marseille, France

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DOI:
https://doi.org/10.4269/ajtmh.1997.57.646
Volume/Issue:
Volume 57: Issue 6
Page(s):
646–650
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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 Ser 108 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.

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Copyright:
Copyright © 1997 by The American Society of Tropical Medicine and Hygiene 1997
Published Online:
Dec 1997
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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