Limited Polymorphism the PvK12 Kelch protein in Plasmodium vivax isolates from Amazon.

Background: Since 2001, artemisinin combination therapies (ACTs) have been recommended as first-line treatment for falciparum malaria. Although the role of the P. falciparum K13 protein remains unknown, evidences suggest that it is involved in the cellular response to oxidative stress. Since 2008, Artemisinin resistance in Plasmodium falciparum has emerged as a major threat for malaria control and elimination worldwide. Recent molecular and biological studies showed that artemisinin resistance was associated with P. falciparum early ring stages and mutations in the kelch propeller domain of PfK13. As P. vivax appears to be highly sensitive to oxidative stress; in areas in which malaria is endemic and Plasmodium falciparum and Plasmodium vivax are present, either successively or concomitantly (mixed infections), these two species often undergo similar mutation-driven evolution and natural selection; and a lot of studies clearly show that antimalarial drugs used to treat falciparum malaria have a significant impact on sympatric Plasmodium species, such as P. vivax.The main objective of this research was to investigate the presence of polymorphism in the ortholog gene of the P. falciparum K13 kelch propeller domain (PVX_083080) in our blood samples collected from individuals with P. vivax malaria from 2013 to 2015 in Barcelos, Amazon state. The therapeutic efficacy of CQ in these individualswas evaluated over a 28-day follow-up period. Methods: The PCR amplification and sequencing of PvK12 propellor domain were made using protocol established by Talundizc et al, 2015. The PvK12 propellor domain sequences were compared with P. vivax Sal-1 sequence (PVX_083080). Results: Were obtained 109 PvK12 sequences from 120 P. vivax isolates collected in Barcelos between 2013 and 2015. All of them were Sal-1 wild-type alleles except two (2/109, 2.18%).Both mutant allele isolates had the same synonymous mutation at codon 489 (T489T). None of the mutations observed in the P. vivax samples were associated with artemisinin resistance in P. falciparum. Conclusions: The PvK12 propeller domain sequences from P. vivax isolates collected in Barcelos displayed very limited genetic diversity indicating low levels of baseline polymorphisms of PvK12 in this area.