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Background  The emergence of  Plasmodium falciparum  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  Plasmodium falciparum  chloroquine resistance transporter ( pfcrt ),  P. falciparum  multidrug resistance 1 ( pfmdr1 ), and  P. falciparum Na + /H +  exchanger  ( pfnhe-1 ). This study was to investigate the role of the  pfmdr1  and  pfnhe-1  gene on  in vitro  QN sensitivity in Thai isolates of  P. falciparum .    Methods  Eighty-five Thai isolates of  P. falciparum  from the Thai-Myanmar and Thai-Cambodia borders from 2003-2008 were determined for  in vitro  QN sensitivity using radioisotopic assay. Polymorphisms of the  pfmdr1  and  pfnhe-1  gene were determined by PCR-RFLP and sequence analysis. Associations between the  in vitro  QN sensitivity and the polymorphisms of the  pfmdr1  and  pfnhe-1  gene were evaluated.    Results  The mean QN IC 50  was 202.8 nM (range 25.7-654.4 nM). Only four isolates were QN resistant when the IC 50  of >500 nM was used as the cut-off point. Significant associations were found between the  pfmdr1  mutations at codons N86Y and N1042D and  in vitro  QN sensitivity. However, no associations with the number of DNNND, DDNNNDNHNDD, and NHNDNHNNDDD repeats in the microsatellite ms4760 of the  pfnhe-1  gene were identified.    Conclusion  Data from the present study put doubt regarding the  pfnhe-1  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  pfmdr1  gene on  in vitro  QN sensitivity.

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