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Molecular markers have been proposed as a method of monitoring malaria drug resistance and could potentially be used to prolong the life span of antimalarial drugs. Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum gene pfmdr1 and increased gene copy number have been associated with in vitro drug resistance but have not been well studied in vivo. In a prospective cohort study of malaria patients receiving mefloquine treatment on the Thai-Myanmar border, there was no significant association between either pfmdr1 SNPs or in vitro drug sensitivity and mefloquine resistance in vivo. Increased pfmdr1 gene copy number was significantly associated with recrudescence (relative risk 2.30, 95% CI 1.27–4.15). pfmdr1 gene copy number may be a useful surveillance tool for mefloquine-resistant falciparum malaria in Thailand.
Received June 16, 2004. Accepted for publication October 28, 2004.
Acknowledgments: Many thanks go to the nursing and laboratory staff at AFRIMS for contributing their expertise and for their daily dedication to the populations they serve. Thanks also to Dr. Kanungnit Congpuong, the staff of KRCH, and the Vector Borne Diseases Control Unit No. 9 (Sangkhlaburi) for their assistance and support.
Financial support: This work was supported by NIH grant R23 AI054590 and U.S. Department of Defense–Global Emerging Infections Surveillance and Response Program (DoD-GEIS).
Authors’ addresses: Amy L. Nelson, University of North Carolina Department of Epidemiology, McGavran-Greenberg Hall, Chapel Hill, NC 27599-7435, 2358 Antiqua Ct., Reston, VA 20191, Telephone: 919-966-7414. Anne Purfield, University of North Carolina School of Medicine, Department of Microbiology and Immunology, Mary Ellen Jones Building, Chapel Hill, NC 27599, Telephone: 919-843-4384, Fax: 919-966-2089. Philip McDaniel, 10803 SE Cherry Blossom Dr., Portland, OR 97216, Telephone: 503-261-7200, Fax: 503-261-7226; Nichipat Uthaimongkol, AFRIMS, 315/6 Rajvithi Rd., Bangkok 10400, Thailand. Nillawan Buathong, AFRIMS, 315/6 Rajvithi Rd., Bangkok 10400, Thailand. Sabaitip Sriwichai, AFRIMS, 315/6 Rajvithi Rd, Bangkok 10400, Thailand. R. Scott Miller, AFRIMS, 315/6 Rajvithi Rd., Bangkok 10400, Thailand. Chansuda Wongsrichanalai, U.S. Naval Medical Research Unit No. 2 (NAMRU-2), Jakarta, Indonesia. Steven R. Meshnick, University of North Carolina School of Public Health, McGavran Greenberg Hall, Chapel Hill, NC 27599-7435, Telephone: 919-966-7414 or 843-4385, Fax: 919-966-2089.
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