In Vivo Selection ofPlasmodium falciparum pfmdr186N Coding Alleles by Artemether‐Lumefantrine (Coartem)
The Journal of Infectious Diseases2005Vol. 191(6), pp. 1014–1017
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Christin Sisowath, Johan Strömberg, Andreas Mårtensson, Mwinyi Msellem, Christine Obondo, Anders Björkman, José Pedro Gil
Abstract
Artemisinin derivative-based combination therapy is expected to suppress the development of Plasmodium falciparum drug resistance in Africa. We have performed an artemether-lumefantrine (Coartem; Novartis) follow-up clinical trial in Zanzibar, in which pfcrt K76T and pfmdr1 N86Y frequencies were determined before drug administration and in all recurrent parasites during a follow-up period of 42 days. A significant increase in pfmdr1 86N was observed after exposure to the drug. This points to 86N as a potential marker of lumefantrine resistance in vivo, while suggesting that Coartem is not robust enough to avoid selection of resistance-associated mutations in some malarial settings.
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