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Antimicrobial Agents and Chemotherapy, July 1998, p. 1811-1814, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected with Plasmodium falciparum Malaria Parasites

Leonardo K. Basco,1,2,3,* Rachida Tahar,3 and Pascal Ringwald1,2

Institut Français de Recherche Scientifique pour le Développement en Coopération (ORSTOM)1 and Laboratoire de Recherches sur le Paludisme, Laboratoire Associé Francophone 302, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC),2 Yaoundé, Cameroon, and Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France3

Received 14 January 1998/Returned for modification 2 April 1998/Accepted 6 May 1998

In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (n = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (n = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.

* Corresponding author. Mailing address: OCEAC/ORSTOM, B. P. 288, Yaoundé, Cameroon. Phone: (237) 232 232. Fax: (237) 230 061. E-mail: oceac{at}camnet.cm.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1811-1814, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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