2013
DOI: 10.1128/aac.02306-12
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In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes

Abstract: eThe recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC 50 ) of 252.7 nM and a range of 5… Show more

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Cited by 37 publications
(54 citation statements)
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References 46 publications
(62 reference statements)
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“…The likely influence of PfMRP2 on the parasite response to multiple drugs mirrors that reported for PfMRP1 and its proposed role in CQ, artemisinin, quinine, mefloquine, and lumefantrine (14,16,40,41). The present report adds to several independent lines of evidence by our investigators and others, suggesting the importance of MRP-like proteins in parasite drug responses, highlighting the genetic variances found herein with their potential use as molecular sentinel tools.…”
Section: Discussionsupporting
confidence: 71%
“…The likely influence of PfMRP2 on the parasite response to multiple drugs mirrors that reported for PfMRP1 and its proposed role in CQ, artemisinin, quinine, mefloquine, and lumefantrine (14,16,40,41). The present report adds to several independent lines of evidence by our investigators and others, suggesting the importance of MRP-like proteins in parasite drug responses, highlighting the genetic variances found herein with their potential use as molecular sentinel tools.…”
Section: Discussionsupporting
confidence: 71%
“…2) (P Ͻ 0.0001, Spearman's test). In addition, as we have reported previously (17), susceptibilities to the two 4-aminoquinoline drugs CQ and PQ were significantly correlated (P Ͻ 0.001). QN showed significant correlations with the two artemisinin derivatives (P Ͻ 0.01), and to a lesser extent with PND, NQ, and MFQ (P Ͻ 0.05).…”
Section: Resultssupporting
confidence: 58%
“…In comparison, parasites were relatively sensitive to the other two 4-aminoquinoline drugs, PQ and NQ, with IC 50 s to these two drugs being in the lower-nanomolar range. As reported earlier (17), the range of IC 50 s to PQ was relatively wide; the IC 50 s for the least-and most-sensitive parasite isolates differed by more than 22-fold. Likewise, IC 50 s between the least-and most-sensitive parasite isolates to NQ differed by almost 17-fold.…”
Section: Resultsmentioning
confidence: 56%
“…In isolates from western Cambodia in Pursat (2011 to 2012), chromosome 5 copy number variations were found (34), and additional clinical studies in Cambodia during 2008 to 2010 uncovered association between Pfmdr1 single-copy isolates and DHA-PPQ treatment failures (7). Likewise, Pfmdr1 amplification was associated with reduced susceptibility to MQ, LUM, and QN but increased susceptibility to PPQ and CQ in isolates from western Thailand where PPQ use is rare, although the chromosome 5 copy number variation was not seen (37,38). Evidence of association between Pfmdr1 deamplification and elevated PPQ IC 50 in clinical isolates may reflect emerging piperaquine resistance following a shift in drug pressure away from mefloquine, which had driven Pfmdr1 amplification.…”
Section: Discussionmentioning
confidence: 99%
“…However, we cannot rule out the possibility that samples uninterpretable in our assay represented haplotypes other than those we screened for, i.e., wild-type CVMNK, CVIET, and SVMNT. Similarly, China-Myanmar border isolates with a single Pfmdr1 copy and the Pfcrt K76T genotype were reported to have reduced CQ and PPQ susceptibility (38). While there appears to be a link between PPQ and CQ resistance, PPQ may have additional resistance mechanisms suggested by preserved activity against CQ-resistant isolates from Africa (41,42) and lack of correlation between Pfcrt polymorphisms and reduced PPQ susceptibility in isolates from various regions (43,44).…”
Section: Discussionmentioning
confidence: 99%