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<jats:title>ABSTRACT</jats:title> <jats:p>We have analyzed the in vitro chemosensitivity profiles of 115 Kenyan isolates for chloroquine (CQ), piperaquine, lumefantrine (LM), and dihydroartemisinin in association with polymorphisms in <jats:italic>pfcrt</jats:italic> at codon 76 and <jats:italic>pfmdr</jats:italic> <jats:italic>1</jats:italic> at codon 86, as well as with variations of the copy number of <jats:italic>pfmdr</jats:italic> <jats:italic>1</jats:italic>. The median drug concentrations that inhibit 50% of parasite growth (IC<jats:sub>50</jats:sub>s) were 41 nM (interquartile range [IQR], 18 to 73 nM), 50 nM (IQR, 29 to 96 nM), 32 nM (IQR, 17 to 46 nM), and 2 nM (IQR, 1 to 3 nM) for CQ, LM, piperaquine, and dihydroartemisinin, respectively. The activity of CQ correlated inversely with that of LM (<jats:italic>r</jats:italic> <jats:sup>2</jats:sup> = −0.26; <jats:italic>P</jats:italic> = 0.02). Interestingly, parasites for which LM IC<jats:sub>50</jats:sub>s were higher were wild type for <jats:italic>pfcrt</jats:italic> <jats:italic>-76</jats:italic> and <jats:italic>pfmdr</jats:italic> <jats:italic>1</jats:italic>-<jats:italic>86</jats:italic>. All isolates had one <jats:italic>pfmdr</jats:italic> <jats:italic>1</jats:italic> copy. Thus, the decrease in LM activity is associated with the selection of wild-type <jats:italic>pfcrt</jats:italic>-<jats:italic>76</jats:italic> and <jats:italic>pfmdr</jats:italic> <jats:italic>1</jats:italic>-<jats:italic>86</jats:italic> parasites, a feature that accounts for the inverse relationship between CQ and LM. Therefore, the use of LM-artemether is likely to lead to the selection of more CQ-susceptible parasites.</jats:p>

Original publication

DOI

10.1128/aac.00638-09

Type

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

12/2009

Volume

53

Pages

5069 - 5073