Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border

Phompradit, Papichaya; Wisedpanichkij, Raewadee; Muhamad, Phunuch; Chai่jaroenkul, Wanna; Na‐Bangchang, Kesara

doi:10.1016/j.actatropica.2011.07.003

Cited by 32 publications

(28 citation statements)

References 43 publications

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“…With regards to pfmdr1 copy number, the increase of copy number found in some P. falciparum isolates in this study correlates well with the observation of decline in sensitivity of P. falciparum to artesunate and mefloquine and therefore, the chance of recrudescence/treatment failure following treatment with this artemisinin-based combination therapy regimen [25,26] . Application of the median copy number and prevalence of isolates carrying more than one gene copies can sort out the provinces with relatively high possibility of treatment failure and require close monitoring for drug resistance as Kanchanaburi, followed by Mae Hongson, Tak and Ranong, respectively.…”

Section: Discussionsupporting

confidence: 85%

Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border

Muhamad

Chai่jaroenkul

Phompradit

et al. 2013

Asian Pacific Journal of Tropical Biomedicine

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Section: Discussionsupporting

confidence: 85%

Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border

Muhamad

Chai่jaroenkul

Phompradit

et al. 2013

Asian Pacific Journal of Tropical Biomedicine

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“…Nonetheless, we show that the 86Y mutation was significantly associated with increased susceptibility to MQ (P ϭ 0.00002). These results are in accordance with previous studies in Asia (12,42) and in Benin (43) and are strengthened by field studies demonstrating MQ selection of the N86 allele in recurrent infections after treatment with artesunate plus MQ (44).…”

Section: Discussionsupporting

confidence: 82%

“…The involvement of N86Y in QN resistance is still debated: in some studies, the mutation 86Y is associated with increased susceptibility (42,55), although this is not the case in other studies (56). The 1042D mutation has been reported to induce QN resistance (38).…”

Section: Discussionmentioning

confidence: 99%

Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Wurtz

Fall

Pascual

et al. 2014

Antimicrob Agents Chemother

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The involvement of Pfmdr1 (Plasmodium falciparum multidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms in Pfmdr1 (N86Y, Y184F, S1034C, N1042D, and D1246Y) and Pfcrt (K76T) and in vitro responses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174 Plasmodium falciparum isolates from Dakar, Senegal. The Pfmdr1 86Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. The Pfmdr1 86Y mutation was significantly associated with increased susceptibility to MDAQ (P ‫؍‬ 0.0023), LMF (P ‫؍‬ 0.0001), DHA (P ‫؍‬ 0.0387), and MQ (P ‫؍‬ 0.00002). The N86Y mutation was not associated with CQ (P ‫؍‬ 0.214) or QN (P ‫؍‬ 0.287) responses. The Pfmdr1 184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P ‫؍‬ 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). The Pfmdr1 86Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P ‫؍‬ 0.0136), LMF (P ‫؍‬ 0.0019), and MQ (P ‫؍‬ 0.0001). The additional Pfmdr1 86Y mutation increased significantly the in vitro susceptibility to MDAQ (P < 0.0001), LMF (P < 0.0001), MQ (P < 0.0001), and QN (P ‫؍‬ 0.0026) in wild-type Pfcrt K76 parasites. The additional Pfmdr1 86Y mutation significantly increased the in vitro susceptibility to CQ (P ‫؍‬ 0.0179) in Pfcrt 76T CQ-resistant parasites.

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“…Some studies showed that deployments of ACTs were associated with changes of frequencies of certain mutations in PfATP6. In one study the frequency of the A623E mutation was increased in Niger after ACT use (3), whereas in another study an increase in the frequency of a deletion mutant was noticed in Peru (8,49,64). In the GMS, an epicenter of malaria drug resistance with the most extensive use of ART drugs, A623E and S769N mutations associated with reduced sensitivity to ARTs have not been detected so far (26).…”

Section: Discussionmentioning

confidence: 99%

Lack of Association of the S769N Mutation in Plasmodium falciparum SERCA (PfATP6) with Resistance to Artemisinins

Cui

Wang

Jiang

et al. 2012

Antimicrob Agents Chemother

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The recent emergence of artemisinin (ART) resistance in Plasmodium falciparum in western Cambodia, manifested as delayed parasite clearance, is a big threat to the long-term efficacy of this family of antimalarial drugs. Among the multiple candidate genes associated with ART resistance in P. falciparum, the sarcoplasmic/endoplasmic reticulum Ca 2؉ -ATPase PfATP6 has been postulated as a specific target of ARTs. The PfATP6 gene harbors multiple single-nucleotide polymorphisms in field parasite populations, and S769N has been associated with decreased sensitivity to artemether in parasite populations from French Guiana. In this study, we used an allelic exchange strategy to engineer parasite lines carrying the S769N mutations in P. falciparum strain 3D7 and evaluated whether introduction of this mutation modulated parasite sensitivity to ART derivatives. Using three transgenic lines carrying the 769N mutation and two transgenic lines carrying the wild-type 769S as controls, we found that S769N did not affect PfATP6 gene expression. We compared the sensitivities of these parasite lines to three ART derivatives, artemether, artesunate, and dihydroartemisinin, in 18 biological experiments and detected no significant effect of the S769N mutation on parasite response to these ART derivatives. This study provides further evidence for the lack of association of PfATP6 with ART resistance.

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Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border

Cited by 32 publications

References 43 publications

Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border

Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border

Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Lack of Association of the S769N Mutation in Plasmodium falciparum SERCA (PfATP6) with Resistance to Artemisinins

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