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Antimicrobial Agents and Chemotherapy, September 1999, p. 2205-2208, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Low-Dose Treatment with Sulfadoxine-Pyrimethamine Combinations Selects for Drug-Resistant Plasmodium falciparum Strains

Jürgen F. J. Kun,^1,* Leopold G. Lehman,^1,2 Bertrand Lell,^1,2,3 Ruprecht Schmidt-Ott,^1,2 and Peter G. Kremsner^1,2

Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, D-72074 Tübingen, Germany¹; Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon²; and Department of Infectious Diseases, Internal Medicine I, University of Vienna, Vienna, Austria³

Received 5 April 1999/Returned for modification 3 June 1999/Accepted 14 July 1999

A total of 252 children were enrolled in a drug trial to assess the effect of minimal doses of sulfadoxine (Sdx) and pyrimethamine (Pyr). Parasite samples isolated from these patients were analyzed before and after treatment to investigate the level of drug-resistant strains. The parasite genes encoding dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) were assayed for point mutations that are associated with resistance against drugs. Before treatment, Pyr^r genotypes of the DHFR gene were found in 42% of all samples, 8% of the patients harbored a mixed parasite population and 50% had a sensitive DHFR genotype. In terms of the DHPS gene, we found mutations in 45% of the parasites. Twenty-four percent had a Ser₄₃₆ mutation, and 26% had a Gly₄₃₇ mutation. Recrudescent parasites were highly enriched for both Pyr^r and Sdx^r strains after treatment (P < 0.001 and P = 0.029, respectively).

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^* Corresponding author. Mailing address: Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany. Phone: 49-7071-2980240. Fax: 49-7071-295189. E-mail: juergen.kun{at}uni-tuebingen.de.

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Antimicrobial Agents and Chemotherapy, September 1999, p. 2205-2208, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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