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Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District, Southern Mozambique

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  • Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, and Centre for Health Research and Development, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark; Mozambican-Danish Rural Malaria Project, Morrumbene, Inhambane Province, Mozambique
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Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.

Author Notes

* Address correspondence to Michael Alifrangis, Centre for Medical Parasitology, Institute for International Health, Immunology and Microbiology, CSS, Øster Farimagsgade 5, Building 22+23, PO Box 2099, 1014 Copenhagen K, Denmark. E-mail: miclai@sund.ku.dk

Authors' addresses: Thomas T. Thomsen, Section for Functional Genomics, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark, E-mail: thomas.thomsen@bio.ku.dk. Laura B. Madsen, Helle H. Hansson, Ib C. Bygbjerg, and Michael Alifrangis, Centre for Medical Parasitology, Institute for International Health, Immunology and Microbiology, CSS, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark, E-mails: lmadsen@sund.ku.dk, hellehan@sund.ku.dk, iby@sund.ku.dk, and micali@sund.ku.dk. Elsa V. E. Tomás, Mozambican-Danish Rural Malaria Project, Morrumbene, Inhambane Province, Mozambique, E-mail: erzeliatomas@yahoo.com.br. Derek Charlwood, Centre for Health Research and Development, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark, and Instituto Nacional de Saudé, Avenida Eduardo Mondalane, Maputo, Mozambique, E-mail: jdcharlwood@gmail.com.

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