AJTMH Transactions of the Royal Society of Tropical Medicine and Hygiene
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Am. J. Trop. Med. Hyg., 75(3), 2006, pp. 381-387
Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

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POLYMORPHISMS IN PFCRT, PFMDR1, DHFR GENES AND IN VITRO RESPONSES TO ANTIMALARIALS IN PLASMODIUM FALCIPARUM ISOLATES FROM BANGUI, CENTRAL AFRICAN REPUBLIC

DIDIER MENARD*, FERDINAND YAPOU, ALEXANDRE MANIRAKIZA, DJIBRINE DJALLE, MARCELLE DIANE MATSIKA-CLAQUIN, AND ANTOINE TALARMIN
Pasteur Institute of Bangui, Bangui, Central African Republic

Drug resistance is probably the greatest challenge to most malaria-control programs. Given the limited resources for other malarial-control measures, rational drug used is crucial. Molecular markers for parasite resistance such as pfcrt, pfmdr-1, and dhfr have the potential to be used in an integrated fashion to provide timely information that is useful to policy makers. Therefore, we evaluated polymorphisms in these genes from Plasmodium falciparum and their association with in vitro antimalarial drug resistance to 135 parasites samples collected in Bangui in 2004. For the dhfr gene, we found a strong association between the dhfr genotype and chemosensitivity to pyrimethamine. For the pfcrt gene, we found that haplotypes with mutant-type alleles led to significant changes in the IC50 values for chloroquine, monodesethylamodiaquine, and quinine. We found no correlations for the pfmdr1 gene. These findings suggest that a regular monitoring and screening for resistance markers for antifolates and for chloroquine could act as an adjunct to in vivo trials.

Received July 27, 2005. Accepted for publication May 9, 2006.

Acknowledgments: The authors thank the patients for participating in the study.

Financial support: This work was supported by the French Government, via FSP/RAI 2001-168 project (French Ministry of Foreign Affairs). Sequencing was performed by Marie Thérèse Ekala (Genopole, Institut Pasteur à Paris) and supported by the UE (Contract No: QLK2-CT-2002-015) via Development of a malaria resistance DNA chip as public health tool for the management of Plasmodium falciparum malaria drug resistance, RESMALCHIP project.

* Address correspondence to Didier Menard, Institut Pasteur de Madagascar, BP 1274—Antananarivo 101. E-mail: dmenard{at}pasteur.mg

Authors’ addresses: Didier Menard, Ferdinand Yapou, Alexandre Manirakiza, Djibrine Djalle, Marcelle Diane Matsika-Claquin, and Antoine Talarmin, Institut Pasteur de Madagascar, BP 1274–Antananarivo 101.






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