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We have analyzed artemisinin sensitivity in Plasmodium falciparum isolates obtained from patients in South Vietnam and show that artemisinin sensitivity does not differ before and after drug treatment. There was an increase in the level of mefloquine resistance in the isolates after drug treatment that was concomitant with a decrease in chloroquine resistance, suggesting that treatment with artemisinin has selected for increased mefloquine resistance. Mutations in the pfmdr1 gene, previously shown to be associated with sensitivity to mefloquine, were selected against. All isolates resistant to chloroquine encoded Thr-76 in the pfcrt gene consistent with an essential role in the mechanism of chloroquine resistance. Mutations in pfmdr1 also were linked to chloroquine resistance. High levels of mutation in dhfr and dhps genes, which have previously been associated with Fansidar resistance, also were found, suggesting that this drug would not be useful for malaria control in this part of Vietnam.
Received May 2, 2002. Accepted for publication October 7, 2002.
Acknowledgments: We thank David Warhurst for providing information before publication that allowed us to genotype the pfmdr1, dhfr, and dhps genes. We would like to acknowledge the Australian Red Cross Blood Bank in Melbourne for supplying human erythrocytes and serum, and the Australian Agency for International Development for support of the field work. AFC is an International Research Scholar of the Howard Hughes Medical Institute.
Financial support: This work is supported by a grant from the National Health and Medical Research Council of Australia.
Authors’ addresses: Thanh Ngo, National Institute of Malariology, Parasitology, and Entomology, Luong The Vinh Road, Hanoi, Vietnam. Manoj Duraisingh and Alan F. Cowman, Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. Michael Reed. Tuberculosis Research Section, NIAID, Twinbrook 11, Room 235, 12441 Parklawn Drive, Rockville, MD 20852. David Hipgrave, University of Melbourne, 57 Quang Trung, Level 5, Hanoi, Vietnam. Beverley Biggs, University of Melbourne, Parkville, Victoria 3050, Australia.
Reprint requests: Alan F. Cowman, Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne, 3050, Australia, Telephone: 62-3-93452555, Fax: 62-3-93470852, E-mail: cowman{at}wehi.edu.au
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