A Unique Plasmodium falciparum K13 Gene Mutation in Northwest Ethiopia

Bayih, Abebe Genetu; Getnet, Gebeyaw; Alemu, Abebe; Getie, Sisay; Mohon, Abu Naser; Pillai, Dylan R.

doi:10.4269/ajtmh.15-0477

Cited by 58 publications

(59 citation statements)

References 17 publications

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“…The absence of known mutations in the k13 propeller gene augurs favorably for the antimalarial efficacy of ACTs at least in the western part of Burkina Faso with high malaria transmission. Nevertheless, a recent study reported the identification of a unique K13 mutation from Ethiopia [4]. This R622I mutation is located on blade 5 of the K13 propeller domain and had not been seen in previous investigations in Africa.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms inK13, pfcrt, pfmdr1, pfdhfr, andpfdhpsin parasites isolated from symptomatic malaria patients in Burkina Faso

et al. 2016

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Background: The emergence of resistance to artemisinin derivatives in western Cambodia is threatening to revert the recent advances made toward global malaria control and elimination. Known resistance-mediating polymorphisms in the K13, pfcrt, pfmdr1, pfdhfr, and pfdhps genes are of greatest importance for monitoring the spread of antimalarial drug resistance. Methods: Samples for the present study were collected from 244 patients with uncomplicated malaria in health centers of Bobo-Dioulasso, Burkina Faso. Blood sample was collected on filter paper before the subject received any treatment. The parasite DNA was then extracted and amplified by Polymerase Chain Reaction (PCR) to evaluate the prevalence of polymorphism of pfcrtK76T, pfmdr1 (N86Y, Y184F), and pfdhps (A437G, K540E). The K13 gene polymorphism was analyzed by nested PCR followed by sequencing. Results: The overall results showed 2.26% (5/221) of K13 synonymous mutant alleles (two C469C, one Y493Y, one G496G, and one V589V), 24.78%, 19.58%, 68.75%, 60.9%, 53.7%, 63.8%, and 64.28%, respectively, for mutant pfcrt 76T, pfmdr1-86Y, pfmdr1-184F, pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps 437G. We did not report any mutation at codon 540 of pfdhps. Conclusion: These results provide baseline prevalence of known drug resistance polymorphisms and suggest that artemisinin combination therapies may retain good efficacy in the treatment of uncomplicated malaria in Burkina Faso.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms inK13, pfcrt, pfmdr1, pfdhfr, andpfdhpsin parasites isolated from symptomatic malaria patients in Burkina Faso

et al. 2016

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“…However, reports from Uganda and Equatorial Guinea have indicated the presence of resistant Pfk13 gene mutations in these countries (Pfk13 A675V and C580Y respectively) [45,46]. Another single mutation in the Pfk13 gene which might be associated with reduced clearance of parasites was reported from Ethiopia [47]. These reports are alarming for the malaria control programmes in Africa.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

Mohamed

Hussien

Mohamed

et al. 2020

Malar J

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Background: Plasmodium falciparum malaria is a public health problem worldwide. Malaria treatment policy has faced periodic changes due to emergence of drug resistant parasites. In Sudan chloroquine has been replaced by artesunate and sulfadoxine/pyrimethamine (AS/SP) in 2005 and to artemether-lumefantrine (AL) in 2017, due to the development of drug resistance. Different molecular markers have been used to monitor the status of drug resistant P. falciparum. This study aimed to determine the frequency of malaria drug resistance molecular markers in Southeast Sudan. Methods:The samples of this study were day zero dried blood spot samples collected from efficacy studies in the Blue Nile State from November 2015 to January 2016. A total of 130 samples were amplified and sequenced using illumina Miseq platform. The molecular markers included were Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfk13, exonuclease and artemisinin resistant (ART-R) genetic background (Pfmdr2, ferroredoxine, Pfcrt and Pfarps10). Results:Resistance markers for chloroquine were detected in 25.8% of the samples as mutant haplotype Pfcrt 72-76 CVIET and 21.7% Pfmdr1 86Y. Pfdhfr mutations were detected in codons 51, 59 and 108. The ICNI double-mutant haplotype was the most prevalent (69%). Pfdhps mutations were detected in codons 436, 437, 540, 581 and 613. The SGEGA triple-mutant haplotype was the most prevalent (43%). In Pfdhfr/Pfdhps combined mutation, quintuple mutation ICNI/SGEGA is the most frequent one (29%). Six of the seven treatment failure samples had quintuple mutation and the seventh was quadruple. This was significantly higher from the adequately responsive group (P < 0.01). Pfk13 novel mutations were found in 7 (8.8%) samples, which were not linked to artemisinin resistance. Mutations in ART-R genetic background genes ranged from zero to 7%. Exonuclease mutation was not detected.

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“…On the other hand, two years later, all parasites isolated from patients with treatment failure after AS-SP carried the quintuple mutation 51I/108N + 437G/540E/581G. The efficacy of AL was investigated in two studies in Ethiopia and Somalia (Bayih et al, 2016;Warsame et al, 2017). In the first study (Bayih et al, 2016), the association between AL clinical efficacy and the pfk13 mutation was found.…”

Section: Association Of Molecular Markers and Clinical Efficacymentioning

confidence: 99%

“…The recent emergence of P. falciparum ART resistance strains in Greater Mekong Sub-region (GMS) represents a challenge to the efficacy of ART and also will postpone the goal of malaria elimination by 2030 in the region (WHO, 2015). The dissemination of these strains to Africa, where the majority of deaths due to malaria occurs, will have catastrophic results (Bayih et al, 2016). Mutation of pfatp 6 (encodes P. falciparum SERCA-type ATPase 6) has initially been linked to resistance of P. falciparum to artemether (Heuchert et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum drug resistance gene status in the Horn of Africa: A systematic review

Jalei¹,

Chai่jaroenkul²,

Na‐Bangchang³

2018

Afr. J. Pharm. Pharmacol.

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Antimalarial drug resistance monitoring is the key factor in malaria control policy for early detection and subsequent prevention of drug resistance spread. This review was performed to collate all available data of P. falciparum resistant genes in the Horn of Africa as a baseline for future appraisal of the regional malaria control policy. The search of this review was performed in January 2018 using the scientific databases Pub Med and Google Scholar. The search terms used included: Plasmodium falciparum AND drug resistance genes OR molecular marks AND Somalia OR Ethiopia OR Eritrea OR Djibouti. The majority of studies (9 of 18 studies, 50%) examined pfdhfr, pfcrt and pfmdr 1 genes. Eight (44%), 4 (22%), and 2 (11%) studies analyzed pfdhps, pfk 13 and pfatp 6 genes, respectively. The Pfcytbc1 associated with atovaquone resistance is the only gene with no mutation detected. High frequencies of pfdhfr and pfdhps mutations were reported with an association to treatment failure after the artemisinin-based combination therapy (ACT) -artesunate + sulfadoxine/pyrimethamine. The aminoquinoline resistance genes such as pfmdr1, and pfatp 6 were only reported with low frequency. The 76T mutation of pfcrt ranged from 4 to 100%, while pfmdr1 mutations at codon 86 and 184 varied depending on geographical locations. The 402V and 431K mutations of pfatp 6 were found highly prevalent at 93 % and 58 % in Southwestern Ethiopia, respectively. The pfk13 gene mutation at codon 622I was 2.4%, with an association to artemether-lumefantrine efficacy and delay of parasite clearance on day 3.

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A Unique Plasmodium falciparum K13 Gene Mutation in Northwest Ethiopia

Cited by 58 publications

References 17 publications

Polymorphisms inK13, pfcrt, pfmdr1, pfdhfr, andpfdhpsin parasites isolated from symptomatic malaria patients in Burkina Faso

Polymorphisms inK13, pfcrt, pfmdr1, pfdhfr, andpfdhpsin parasites isolated from symptomatic malaria patients in Burkina Faso

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

Plasmodium falciparum drug resistance gene status in the Horn of Africa: A systematic review

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