Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013

Torrentino-Madamet, Marylin; Fall, B.; Nicolas, B.; Camara, Cheikhou; Amalvict, Rémy; Fall, Mansour; Dionne, Pierre; Fall, K. Bâ; Nakoulima, Aminata; Diatta, Bakary; Diémé, Yaya; Ménard, Didier; Wade, B.; Pradines, Bruno

doi:10.1186/1475-2875-13-472

Cited by 90 publications

(85 citation statements)

References 23 publications

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“…In contrast, a recent WHO report (27) indicates that 13 polymorphisms inside the propeller domain are either associated and/or confirmed with artemisinin resistance. The predominant polymorphisms previously reported in Senegal are alleles K189T and K189N, outside the propeller domain (25,26), consistent with our own findings (Table S1). The mutant allele A578S, which is not associated with artemisinin resistance, has been reported in multiple regions in Africa (18,19,24,28) (Table S2).…”

Section: Discussionsupporting

confidence: 81%

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Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

Talundzic

Ndiaye

Déme

et al. 2017

Antimicrob Agents Chemother

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The emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the P. falciparum kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms. The results were compared to previously reported Pfk13 polymorphisms from around the world. A total of 22 Pfk13 propeller domain polymorphisms were identified in this study, of which 12 have previously not been reported. Interestingly, of the 10 polymorphisms identified in the present study that were also previously reported, all had a different amino acid substitution at these codon positions. Most of the polymorphisms were present at low frequencies and were confined to single isolates, suggesting they are likely transient polymorphisms that are part of naturally evolving parasite populations. The results of this study underscore the need to identify potential drug resistance loci existing within a population, which may emerge under increasing drug pressure.

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Section: Discussionsupporting

confidence: 81%

“…Monitoring the changes in Pfk13 allele frequencies over time will be critical for guiding both treatment policy and elimination campaigns. To date, only a limited number of Pfk13 polymorphisms have been reported in Senegal (23,25,26), and overall ACT efficacy remains high (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

Talundzic

Ndiaye

Déme

et al. 2017

Antimicrob Agents Chemother

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“…Clinical resistance has not been noted in Africa, as rapid parasite clearance has been the rule in many trials, including those in Uganda (7)(8)(9). In recent surveys in Uganda (10) and other locations in Africa (11)(12)(13)(14)(15), K13-propeller gene polymorphisms were identified, but these were not the mutations clearly associated with artemisinin resistance in Asian isolates. Results for a new correlate of artemisinin resistance, the ex vivo ring-stage survival assay (RSA) (3), have not been reported previously for P. falciparum isolates from Africa.…”

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confidence: 99%

Lack of Artemisinin Resistance in Plasmodium falciparum in Uganda Based on Parasitological and Molecular Assays

Cooper

Conrad

Watson

et al. 2015

Antimicrob Agents Chemother

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We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated in Kampala in 2014. By standard in vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). By the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable in 40 of 43 cultures at 72 h. Two of 53 isolates had nonsynonymous K13-propeller gene polymorphisms but did not have the mutations associated with resistance in Asia. Thus, we did not see evidence for artemisinin resistance in Uganda.A rtemisinin-based combination therapy is now the standard for treating P. falciparum malaria. However, this regimen is threatened by resistance to artemisinins, which manifests as delayed clearance of parasitemia after therapy, in Southeast Asia (1, 2). Recently, resistance has been associated with increased parasitemia in culture, compared to that in sensitive parasites, 72 h after a 6-h pulse with dihydroartemisinin (DHA) and has been associated with polymorphisms in propeller-encoding domains of the Plasmodium falciparum kelch (K13; UniProt number PF3D7_1343700) gene (3-6). Although artemisinin resistance is evident to date only in Southeast Asia, the bulk of P. falciparum malaria occurs in sub-Saharan Africa. Clinical resistance has not been noted in Africa, as rapid parasite clearance has been the rule in many trials, including those in Uganda (7-9). In recent surveys in Uganda (10) and other locations in Africa (11-15), K13-propeller gene polymorphisms were identified, but these were not the mutations clearly associated with artemisinin resistance in Asian isolates. Results for a new correlate of artemisinin resistance, the ex vivo ring-stage survival assay (RSA) (3), have not been reported previously for P. falciparum isolates from Africa. We characterized artemisinin sensitivity by this assay and assessed K13 polymorphisms in isolates from Uganda. Parasites were collected from patients diagnosed with malaria from May to August 2014 at Mulago Hospital, Kampala. Samples were delinked from patient information, so clinical data were unavailable. After malaria diagnosis, excess blood collected in a heparinized tube as part of clinical care was promptly delivered to the laboratory. Giemsastained thin smears were made, and samples containing only P. falciparum isolates with parasitemia of Ն0.1% were placed in culture after washing of erythrocytes, as previously described (16); blood was also spotted onto filter paper. Samples with parasitemia of Ͼ1% were diluted with uninfected erythrocytes for a final parasitemia of 1%.The susceptibility of fresh isolates to DHA and chloroquine was assessed by a standard ex vivo histidine-rich protein 2-based enzyme-linked immunosorbent microplate assay, as previously described (17), except that drugs were freshly diluted from frozen stocks prior to each assay. Results from single assays were fitted to a variable-slope sigmoidal function using GraphPad Prism 6.0f to generate 50% inhibitory concentrations (IC 50 s). All data were visually assessed for parasite growth above...

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“…K13-propeller gene amplification and sequencing were performed, as previously described (13). The K13 mutations were confirmed three times.…”

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confidence: 99%

K13-Propeller Polymorphisms in Plasmodium falciparum Isolates from Patients in Mayotte in 2013 and 2014

Torrentino-Madamet

Collet²,

Lepère³

et al. 2015

Antimicrob Agents Chemother

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Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013

Cited by 90 publications

References 23 publications

Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

Lack of Artemisinin Resistance in Plasmodium falciparum in Uganda Based on Parasitological and Molecular Assays

K13-Propeller Polymorphisms in Plasmodium falciparum Isolates from Patients in Mayotte in 2013 and 2014

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