Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea

Abstract

ObjectiveWith emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG).MethodsA total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing.ResultsSequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139).ConclusionsThis study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs).

Prevalence of <em>Plasmodium falciparum</em> antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014

“…The A578S mutation was detected in one isolate (0.4%). This mutation was often reported in Africa but it had a low prevalence (<2%) 10,12,17–20,22,23. This mutation was also identified in Bangladesh 65.…”

“…Many studies have been conducted in Africa but none of the specific Asian PfK13 mutations associated with artemisinin resistance were found 10,12–17. The A578S mutation was often reported in Africa 10,12,17–20 but all the patients carrying these mutant parasites were cured by artemether–lumefantrine or artesunate-amodiaquine (ASAQ) before day 3 10,12,17–23…”

Antimalarial Activity of an Alkaloid Mixture Isolated from the Tender Leaves of the Nectandra membranacea (Laureaceae)

“…However, prevalence remains high in various areas of Africa, Asia and South America; mainly in children, where a child dies every minute as a result of malaria [21]. Besides that it is very well known the resistance that has been registered for various strains and species of Plasmodium to chloroquine and artemisinin, it is why, one of the strategies to face this challenge is the search for plants that contain active antimalarial metabolites that contribute to the development of new treatments for the control of the disease [7,22].…”

“…For example, regions such as Myanmar, Thailand and Cambodia have forced medical authorities to change the last line of defense, by synthetic derivatives of artemisinin [7].…”

K13 Kelch Propeller Domain and mdr1 Sequence Polymorphism in Field Isolates From Northeast Region, India

“…8 But accumulation of data over time suggests that mutations in this gene vary geographically and mostly in accordance with the employed antimalarial regimens. [14][15][16][17][18][19][20][21] In a recent study, non-reference K13 mutations viz., 584V, 580Y, 574L, 568G, 553L, 543T, 539T, 493H, 481V, 449A, 255K, and 189T have been found involved in prolonged parasite clearance, and it was also stated that artemisinin resistance in SEA has emerged independently without sweeping from Cambodia. 22 In 2016, most of them became either validated or candidate K13 mutation for artemisinin resistance.…”