Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<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





Antimicrobial Agents and Chemotherapy


American Society for Microbiology

Publication Date





5069 - 5073