Abstract
BackgroundArtemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide. Mutations in the Kelch propeller domain of PfK13 are the only known molecular markers for artemisinin resistance in this parasite. Over 100 non-synonymous mutations have been identified in PfK13 from various malaria endemic regions. This study aimed to investigate the genetic diversity of PvK12, the Plasmodium vivax ortholog of PfK13, in parasite populations from Southeast Asia, where artemisinin resistance in P. falciparum has emerged.MethodsThe PvK12 sequences in 120 P. vivax isolates collected from Thailand (22), Myanmar (32) and China (66) between 2004 and 2008 were obtained and 353 PvK12 sequences from worldwide populations were retrieved for further analysis.ResultsThese PvK12 sequences revealed a very low level of genetic diversity (π = 0.00003) with only three single nucleotide polymorphisms (SNPs). Of these three SNPs, only G581R is nonsynonymous. The synonymous mutation S88S is present in 3% (1/32) of the Myanmar samples, while G704G and G581R are present in 1.5% (1/66) and 3% (2/66) of the samples from China, respectively. None of the mutations observed in the P. vivax samples were associated with artemisinin resistance in P. falciparum. Furthermore, analysis of 473 PvK12 sequences from twelve worldwide P. vivax populations confirmed the very limited polymorphism in this gene and detected only five distinct haplotypes.ConclusionsThe PvK12 sequences from global P. vivax populations displayed very limited genetic diversity indicating low levels of baseline polymorphisms of PvK12 in these areas.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1583-0) contains supplementary material, which is available to authorized users.
Highlights
Artemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide
Following the identification of k13 gene as a molecular marker for ART resistance [7, 13], numerous studies have been performed to assess the polymorphism in this gene from various malaria endemic regions [14,15,16,17,18,19,20,21]
Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases, and this domain is present in the heat shock protein 70 protein of P. falciparum
Summary
Artemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide. Mutations in the Kelch propeller domain of PfK13 are the only known molecular markers for artemisinin resistance in this parasite. This study aimed to investigate the genetic diversity of PvK12, the Plasmodium vivax ortholog of PfK13, in parasite populations from Southeast Asia, where artemisinin resistance in P. falciparum has emerged. Malaria is a major public health problem in the Greater Mekong Subregion (GMS), including Cambodia, China, Laos, Myanmar, Thailand, and Vietnam [1]. Several mutations in the Kelch propeller domain have been associated with in vitro ring-stage survival assays and delayed parasite clearance rates in patients treated with ARTs [7, 13, 22]. Some rare alleles are found in other regions but are not associated with ART resistance [23,24,25,26]
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