Abstract

BackgroundQuinine (QN) remains an effective drug for malaria treatment. However, quinine resistance (QNR) in Plasmodium falciparum has been reported in many malaria-endemic regions particularly in African countries. Genetic polymorphism of the P. falciparum Na+/H+ exchanger (pfnhe1) is considered to influence QN susceptibility. Here, ms4760 alleles of pfnhe1 were analysed from imported African P. falciparum parasites isolated from returning travellers in Wuhan, Central China.MethodsA total of 204 dried-blood spots were collected during 2011–2016. The polymorphisms of the pfnhe1 gene were determined using nested PCR with DNA sequencing.ResultsSequences were generated for 99.51% (203/204) of the PCR products and 68.63% (140/204) of the isolates were analysed successfully for the pfnhe1 ms4760 haplotypes. In total, 28 distinct ms4760 alleles containing 0 to 5 DNNND and 1 to 3 NHNDNHNNDDD repeats were identified. For the alleles, ms4760–1 (22.86%, 32/140), ms4760–3 (17.86%, 25/140), and ms4760–7 (10.71%, 15/140) were the most prevalent profiles. Furthermore, 5 undescribed ms4760 alleles were reported.ConclusionsThe study offers an initial comprehensive analysis of pfnhe1 ms4760 polymorphisms from imported P. falciparum isolates in Wuhan. Pfnhe1 may constitute a good genetic marker to evaluate the prevalence of QNR in malaria-endemic and non-endemic regions.

Highlights

  • Quinine (QN) remains an effective drug for malaria treatment

  • Another study illustrated that the increased number of DNNND repeats (Block II) was related to a decreasing trend in QN susceptibility, and the increased number of NHNDNHNNDDD repeats (Block V) was related to increased QN susceptibility [28]

  • In light of these reports, we investigated the prevalence of pfnhe1 in patients who were infected with P. falciparum returning from different African countries and assessed whether pfnhe1 can be used as a molecular marker of quinine resistance (QNR)

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Summary

Introduction

Quinine resistance (QNR) in Plasmodium falciparum has been reported in many malaria-endemic regions in African countries. SNPs at codons 790, 894 and 950 and microsatellite variations in three different repeat sequences (msR1, ms3580 and ms4760) located on chromosome 13 of the P. falciparum genome have been identified [4]. These SNPs and microsatellite variations in msR1 and ms3580 showed no significant association with QN susceptibility [4]. Another study illustrated that the increased number of DNNND repeats (Block II) was related to a decreasing trend in QN susceptibility, and the increased number of NHNDNHNNDDD repeats (Block V) was related to increased QN susceptibility [28]

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