Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region

Adamu, A. K.; Jada, Mahmoud Suleiman; Haruna, Hauwa Mohammed Sani; Yakubu, Bassa Obed; Ibrahim, Mohammed; Balogun, E.O.; Sakura, Takaya; Inaoka, Daniel Ken; Kita, Kiyoshi; Hirayama, Kenji; Culleton, Richard; Shuaibu, Mohammed Nasir

doi:10.1186/s12936-020-03506-z

Cited by 17 publications

(13 citation statements)

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“…The results further show a low prevalence of Pfmdr1 1246Y mutant alleles (1.45 and 5.97%, respectively), a mutation related to CQ and quinine resistance. Our results are consistent with previous studies in Cameroon [ 10 , 12 ], Gabon [ 71 , 72 ], Nigeria [ 73 ], Mozambique [ 25 ] and Uganda [ 74 , 75 ], showing significant reduction of Pfmdr1 86Y and 1246Y mutant alleles after replacement of CQ by ACTs. However, an overall similar proportion of both alleles N86 and 86Y (49.11% vs 50.89%) was observed in this study.…”

Section: Discussionsupporting

confidence: 93%

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

et al. 2021

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The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR. Detection of SNPs was performed by nested PCR followed by allele-specific restriction analysis (ASRA). The prevalence of each genotype was compared between sites using the Chi square and Fisher’s exact tests. A high prevalence of the Pfcrt K76 wild type allele was found in both sites (88.5 and 62.29% respectively; P< 0,0001). The prevalence of Pfmdr1 mutations 86Y and 1246Y was respectively 55.83 and 1.45% in Mfou and 45.87 and 5.97% in Tibati, with significant difference between the studied areas (P<0.0001). Overall, the Pfdhfr triple-mutant genotype (51I/59R/108N) was highly prevalent (> 96%), however no SNP was detected at codon 164. In Pfdhps, the prevalence of the 437G mutation reached (90%) and was at higher frequency in Mfou (P< 0.0001). Overall, the Pfdhps mutations 540E and 581G were less common (0.33 and 3.26%, respectively). The quadruple resistant genotype (Pfdhfr 51I/59R/108N+Pfdhp437G) was found almost 90% of the samples. The wild-type genotype (Pfdhfr N51/C59/S108/164I+Pfdhps A437/K540/A581) was never identified and the sextuple mutant (Pfdhfr 51I/59R/108N+Pfdhp437G/540E/581G), kwon as super resistant appeared in two samples from Tibati. These findings demonstrate declining trends in the prevalence of mutations conferring resistance to 4-aminoquinolines, especially to chloroquine. However, a high level of mutations in P. falciparum genes related to SP resistance was detected and this raises concerns about the future efficacy of IPTp-SP and SMC in Cameroon.

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Section: Discussionsupporting

confidence: 93%

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

et al. 2021

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“…There was unsuccessful nested-PCR amplification for 38 of the samples; particularly for Pfcrt K76T codon as was the case for other studies [ 48 ]. However, amplification of Pfmsp1 gene was successful for 26 of them.…”

Section: Discussionmentioning

confidence: 89%

High prevalence of Pfcrt 76T and Pfmdr1 N86 genotypes in malaria infected patients attending health facilities in East Shewa zone, Oromia Regional State, Ethiopia

Hassen

Alemayehu

Dinka

et al. 2022

Malar J

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Background Plasmodium falciparum resistance to series of anti-malarial drugs is a major challenge in efforts to control and/or eliminate malaria globally. In 1998, following the widespread of chloroquine (CQ) resistant P. falciparum, Ethiopia switched from CQ to sulfadoxine–pyrimethamine (SP) and subsequently in 2004 from SP to artemether–lumefantrine (AL) for the treatment of uncomplicated falciparum malaria. Data on the prevalence of CQ resistance markers after more than two decades of its removal is important to map the selection pressure behind the targets codons of interest. The present study was conducted to determine the prevalence of mutations in Pfcrt K76T and Pfmdr1 N86Y codons among malaria-infected patients from Adama, Olenchiti and Metehara sites of East Shewa zone, Oromia Regional State, Ethiopia. Methods Finger-prick whole blood samples were collected on 3MM Whatman ® filter papers from a total of 121 microscopically confirmed P. falciparum infected patients. Extraction of parasite DNA was done by Chelex-100 method from dried blood spot (DBS). Genomic DNA template was used to amplify Pfcrt K76T and Pfmdr1 N86Y codons by nested PCR. Nested PCR products were subjected to Artherobacter protophormiae-I (APoI) restriction enzyme digestion to determine mutations at codons 76 and 86 of Pfcrt and Pfmdr1 genes, respectively. Results Of 83 P. falciparum isolates successfully genotyped for Pfcrt K76T, 91.6% carried the mutant genotypes (76T). The prevalence of Pfcrt 76T was 95.7%, 92.5% and 84.5% in Adama, Metehara and Olenchiti, respectively. The prevalence of Pfcrt 76T mutations in three of the study sites showed no statistical significance difference (χ2 = 1.895; P = 0.388). On the other hand, of the 80 P. falciparum samples successfully amplified for Pfmdr1, all carried the wild-type genotypes (Pfmdr1 N86). Conclusion Although CQ officially has been ceased for the treatment of falciparum malaria for more than two decades in Ethiopia, greater proportions of P. falciparum clinical isolates circulating in the study areas carry the mutant 76T genotypes indicating the presence of indirect CQ pressure in the country. However, the return of Pfmdr1 N86 wild-type allele may be favoured by the use of AL for the treatment of uncomplicated falciparum malaria.

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“…Hence the variable ACT efficacy may be independent of pfk13 polymorphism, with suggested links to multi-locus genotypes encompassing pfcrt, pfmdr1, pfcoronin, pfap2μ or pfubp1 genes ( Sutherland et al, 2017 ). Specifically, haplotype NFD (N86, 184F, D1246) in pfmdr1 , the mutation S160N/T in pfap2μ and D1525E, E1528D and E1531D in pfubp-1 have been involved in the development of tolerance or resistance to AL ( Henrici et al, 2020 ; Adamu et al, 2020 ). Here we present a brief case report and genotyping data of parasites ( Table 1 ) isolated from the recurrence episode of two patients returning to Portugal from Angola and Mozambique.…”

Section: Introductionmentioning

confidence: 99%

Artemether-lumefantrine treatment failure of uncomplicated Plasmodium falciparum malaria in travellers coming from Angola and Mozambique

Silva‐Pinto

Domingos

Cardoso

et al. 2021

International Journal of Infectious Diseases

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Plasmodium falciparum multidrug resistance gene-1 polymorphisms in Northern Nigeria: implications for the continued use of artemether-lumefantrine in the region

Cited by 17 publications

References 54 publications

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

High prevalence of Pfcrt 76T and Pfmdr1 N86 genotypes in malaria infected patients attending health facilities in East Shewa zone, Oromia Regional State, Ethiopia

Artemether-lumefantrine treatment failure of uncomplicated Plasmodium falciparum malaria in travellers coming from Angola and Mozambique

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