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Prevalence of Single Nucleotide Polymorphisms in the Plasmodium falciparum Multidrug Resistance Gene (Pfmdr-1) in Korogwe District in Tanzania Before and After Introduction of Artemisinin-Based Combination Therapy
Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in November of 2006 because of resistance to sulfadoxine-pyrimethamine. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance, which initially may be detected at the molecular level as temporal changes in the frequency of single nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL resistance. In Tanzania, 830 Plasmodium falciparum-positive samples collected between 2003 and 2010 were examined for SNPs of Pfmdr-1 at codons 86, 184, and 1246. Both the N86 and 184F increased from 2006 to 2010 (logistic regression; N86: odds ratio [95% confidence interval] = 1.35 [1.07–1.71], P = 0.01; 184F: odds ratio = 1.42 [1.07–1.88], P = 0.02), and no change was found for D1246 (odds ratio = 1.01 [0.80–1.28], P = 0.9). The observed changes may be because of introduction of AL, and if so, this finding gives cause for concern and argues for continued surveillance of these molecular markers.
Author Notes
Financial support: The field study was supported by the Tanzania–Denmark Enhancement of Research Capacity (ENRECA) program (104.Dan.8.L.312) and Project 91106 by the Danish International Development Agency (DANIDA).
Authors' addresses: Thomas T. Thomsen, Lasse S. Vestergaard, Thor G. Theander, Ib C. Bygbjerg, and Michael Alifrangis, Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, E-mails: thyge666@gmail.com, lvestergaard@sund.ku.dk, thor@sund.ku.dk. iby@sund.ku.dk and micali@sund.ku.dk. Deus S. Ishengoma, Bruno P. Mmbando, John P. Lusingu, and Martha M. Lemnge, National Institute for Medical Research, Tanga Medical Research Centre, Tanga, Tanzania, E-mails: dishengoma@tanga.mimcom.net, Pbruno@amani.mimcom.net, jpalusingu@yahoo.co.uk, and mlemnge@tanga.mimcom.net.