<it>In vitro </it>susceptibility to quinine and microsatellite variations of the <it>Plasmodium falciparum </it>Na + /H + exchanger (<it>Pfnhe-1) </it>gene: the absence of association in clinical isolates from the Republic of Congo

<p>Abstract</p> <p>Background</p> <p>Quinine is still recommended as an effective therapy for severe cases of <it>Plasmodium falciparum </it>malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na⁺/H⁺exchanger, <it>Pfnhe-1</it>, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of <it>Pfnhe </it>on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a <it>Pfnhe </it>polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between <it>Pfnhe </it>and QNR is investigated in a series of isolates from central Africa.</p> <p>Methods</p> <p>The sequence analysis of the polymorphisms at the <it>Pfnhe-1 </it>ms4760 microsatellite and the evaluation of <it>in vitro </it>quinine susceptibility (by isotopic assay) were conducted in 74 <it>P. falciparum </it>isolates from the Republic of Congo.</p> <p>Results</p> <p>Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the <it>Pfnhe-1 </it>ms4760 microsatellite were not associated with quinine susceptibility.</p> <p>Conclusions</p> <p>The polymorphism in the microsatellite ms4760 in <it>Pfnhe-1 </it>that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of <it>Pfnhe </it>as a molecular marker for QNR. The contribution of <it>Pfnhe </it>to the <it>in vitro </it>response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure.</p>

Abstract licence: CC BY-NC-ND

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