Polymorphisms of the <it>pfmdr1 </it>but not the <it>pfnhe-1 </it>gene is associated with <it>in vitro </it>quinine sensitivity in Thai isolates of <it>Plasmodium falciparum</it>

<p>Abstract</p> <p>Background</p> <p>The emergence of <it>Plasmodium falciparum </it>resistance to most currently used anti-malarial drugs is a major problem in malaria control along the Thai-Myanmar and Thai-Cambodia borders. Quinine (QN) with tetracycline/doxycycline has been used as the second-line treatment for uncomplicated falciparum malaria. In addition, QN monotherapy has been the first-line treatment for falciparum malaria in pregnant women. However, reduced in vitro and in vivo responses to QN have been reported. To date, a few genetic markers for QN resistance have been proposed including <it>Plasmodium falciparum </it>chloroquine resistance transporter (<it>pfcrt</it>), <it>P. falciparum </it>multidrug resistance 1 (<it>pfmdr1</it>), and <it>P. falciparum Na⁺/H⁺exchanger </it>(<it>pfnhe-1</it>). This study was to investigate the role of the <it>pfmdr1 </it>and <it>pfnhe-1 </it>gene on <it>in vitro </it>QN sensitivity in Thai isolates of <it>P. falciparum</it>.</p> <p>Methods</p> <p>Eighty-five Thai isolates of <it>P. falciparum </it>from the Thai-Myanmar and Thai-Cambodia borders from 2003-2008 were determined for <it>in vitro </it>QN sensitivity using radioisotopic assay. Polymorphisms of the <it>pfmdr1 </it>and <it>pfnhe-1 </it>gene were determined by PCR-RFLP and sequence analysis. Associations between the <it>in vitro </it>QN sensitivity and the polymorphisms of the <it>pfmdr1 </it>and <it>pfnhe-1 </it>gene were evaluated.</p> <p>Results</p> <p>The mean QN IC₅₀was 202.8 nM (range 25.7-654.4 nM). Only four isolates were QN resistant when the IC₅₀of >500 nM was used as the cut-off point. Significant associations were found between the <it>pfmdr1 </it>mutations at codons N86Y and N1042D and <it>in vitro </it>QN sensitivity. However, no associations with the number of DNNND, DDNNNDNHNDD, and NHNDNHNNDDD repeats in the microsatellite ms4760 of the <it>pfnhe-1 </it>gene were identified.</p> <p>Conclusion</p> <p>Data from the present study put doubt regarding the <it>pfnhe-1 </it>gene as to whether it could be used as the suitable marker for QN resistance in Thailand. In contrast, it confirms the influence of the <it>pfmdr1 </it>gene on <it>in vitro </it>QN sensitivity.</p>

Abstract licence: CC BY-NC-ND

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