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IN VITRO ANTIMALARIAL SUSCEPTIBILITY PROFILE AND PRCRT/PFMDR-1 GENOTYPES OF PLASMODIUM FALCIPARUM FIELD ISOLATES FROM MALAWI

We measured in vitro antimalarial drug susceptibility of 84 Plasmodium falciparum field isolates from Blantyre, Southern Malawi, using the WHO microtest and the lactate dehydrogenase assay. We also genotyped these isolates to investigate whether variation in their absolute drug sensitivity is associated with specific sets of pfcrt and pfmdr-1 mutations harbored by parasites. Our results show that nearly a decade after the withdrawal of chloroquine (CQ) as a first-line antimalarial in Malawi, most isolates are now sensitive to CQ and none is CQ-resistant as predicted by their drug sensitivity phenotype and pfcrt genotype. We also found that these isolates are uniformly sensitive to a range of quinoline-based antimalarials and artemisinin derivatives. These findings reinforce previous reports about a reduction in the proportion of CQ-resistant parasites after the withdrawal of CQ in 1993 and pave the way for reassessing the clinical usefulness of CQ, artemisinins and other quinoline-based antimalarials in Malawi.

Received December 13, 2006. Accepted for publication February 28, 2007.

Acknowledgments: The authors thank all parents and guardians of children that participated in this study through the donation of venous blood samples. We also thank Ruth Hughes, Mavuto Mukaka, and research nurses at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme for technical assistance.

Financial Support: This work was supported by the Gates Malaria Partnership Ph.D. studentship to Standwell Nkhoma and the Wellcome Trust, U.K.

^* Address correspondence to Standwell Nkhoma, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, P.O. Box 30096, Chichiri, Blantyre 3, Malawi. E-mail: snkhoma{at}mlw.medcol.mw

Authors’ addresses: Standwell Nkhoma and Malcolm Molyneux, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, P.O. Box 30096, Chichiri, Blantyre 3, Malawi, Telephone: +265 1 876444/+265 1 874628; Fax: +265 1 875774, E-mails: snkhoma{at}mlw.medcol.mw and mmolyneux{at}malawi.net. Stephen Ward, Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, United Kingdom, Telephone: +44 151 708 3286, Fax: +44 151 705 3371, E-mail: saward{at}liv.ac.uk.

Reprint requests: Standwell Nkhoma, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, P.O. Box 30096, Chichiri, Blantyre 3, Malawi, Telephone: +265 1 876444/+256 1 874628/+256 8 544901, Fax: +265 1 875774, E-mail: snkhoma{at}mlw.medcol.mw.