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Antimicrobial Agents and Chemotherapy, January 2002, p. 166-170, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.166-170.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pfmdr1 Alleles and Response to Ultralow-Dose Mefloquine Treatment in Gabonese Patients

Denise P. Mawili-Mboumba,1,2 Jürgen F. J. Kun,2 Bertrand Lell,1,2 Peter G. Kremsner,1,2 and Francine Ntoumi1,2*

Unité de Recherche Médicale, Hôpital Albert Schweitzer, Lambaréné, Gabon,1 Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, 72074 Tübingen, Germany2

Received 15 June 2001/ Returned for modification 8 August 2001/ Accepted 17 September 2001

The identification of parasite molecular markers involved in resistance to antimalarial compounds is of great interest for monitoring the development and spread of resistance in the field. Polymorphisms in Plasmodium falciparum multidrug resistance gene 1 (pfmdr1) have been associated with chloroquine resistance and mefloquine susceptibility. In the present study, carried out in Lambaréné, Gabon, we investigated the relationship between the presence of mutations at codons 86, 184, 1034, 1042, and 1246 in the pfmdr1 gene and the success of ultralow-dose mefloquine treatment (1.1 mg/kg of body weight). Sixty-nine patients were included in the study, and depending on the level of in vivo resistance to mefloquine, they were classified as sensitive responders (S), patients with low-grade resistance (RI), and nonresponders (NR). We found that the prevalences of the Tyr-86 mutation among isolates from patients in groups S, RI, and NR were 100, 96, and 90%, respectively, and that the prevalence of the Phe-184 mutation among the isolates was 80% in each group. A prevalence of about 10% point mutations at codons 1042 and 1246 was detected only in isolates from patients in groups RI and NR. There was no statistically significant association between the presence of the Tyr-86 mutation and the in vivo response (P = 0.79). Among the parasite isolates from patients with drug-resistant infections, 83% had the wild-type pfmdr1 genotype (S1034-N1042-D1246). No link between the presence of this genotype and parasite resistance was detected (P = 0.42). Among the isolates analyzed, 85 had double mutations (Y86-F184 or Y86-Y1246) and 11 had triple mutations (Y86-D1042-Y1246, Y86-F184-Y1246, or Y86-F184-D1042). These findings are not consistent with those of previous in vitro studies and suggest that further evaluation of pfmdr1 gene polymorphism and in vivo mefloquine sensitivity are needed.

* Corresponding author. Mailing address: Unité de Recherche Médicales, Hôpital Albert Schweitzer, Lambaréné, BP 118 Gabon, and Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany. Phone: (49) 7071 29 85 428. Fax: (49) 7071 295189. E-mail: ffntoumi{at}hotmail.com.

Antimicrobial Agents and Chemotherapy, January 2002, p. 166-170, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.166-170.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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