Increased
            <i>pfmdr1</i>
            Copy Number and Sequence Polymorphisms in Plasmodium falciparum Isolates from Sudanese Malaria Patients Treated with Artemether-Lumefantrine

Gadalla, Nahla B.; Adam, Ishag; El-zaki, Salah-Eldin G; Bashir, Sahar; Mukhtar, Izdihar; Oguike, Mary C.; Gadalla, Amal; Mansour, Fathi; Warhurst, David C.; El-Sayed, Badria; Sutherland, Colin J.

doi:10.1128/aac.05102-11

Cited by 68 publications

(98 citation statements)

References 35 publications

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“…Furthermore, for SEA, it was suggested that Pfmdr1 amplification was inversely related to the 86Y mutant allele (51), but in Africa, parasites harboring multiple copies of the Pfmdr1 gene together with the 86Y mutant allele have been reported in Sudan, Gabon, and Ethiopia (46,52,53). In the present study, this association was observed at a low prevalence.…”

Section: Discussionsupporting

confidence: 43%

Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Guerra

Neres

Salgueiro

et al. 2017

Antimicrob Agents Chemother

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Efforts to control malaria may affect malaria parasite genetic variability and drug resistance, the latter of which is associated with genetic events that promote mechanisms to escape drug action. The worldwide spread of drug resistance has been a major obstacle to controlling Plasmodium falciparum malaria, and thus the study of the origin and spread of associated mutations may provide some insights into the prevention of its emergence. This study reports an analysis of P. falciparum genetic diversity, focusing on antimalarial resistance-associated molecular markers in two socioeconomically different villages in mainland Equatorial Guinea. The present study took place 8 years after a previous one, allowing the analysis of results before and after the introduction of an artemisinin-based combination therapy (ACT), i.e., artesunate plus amodiaquine. Genetic diversity was assessed by analysis of the Pfmsp2 gene and neutral microsatellite loci. Pfdhps and Pfdhfr alleles associated with sulfadoxine-pyrimethamine (SP) resistance and flanking microsatellite loci were investigated, and the prevalences of drug resistance-associated point mutations of the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes were estimated. Further, to monitor the use of ACT, we provide the baseline prevalences of K13 propeller mutations and Pfmdr1 copy numbers. After 8 years, noticeable differences occurred in the distribution of genotypes conferring resistance to chloroquine and SP, and the spread of mutated genotypes differed according to the setting. Regarding artemisinin resistance, although mutations reported as being linked to artemisinin resistance were not present at the time, several single nucleotide polymorphisms (SNPs) were observed in the K13 gene, suggesting that closer monitoring should be maintained to prevent the possible spread of artemisinin resistance in Africa.

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Section: Discussionsupporting

confidence: 43%

Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Guerra

Neres

Salgueiro

et al. 2017

Antimicrob Agents Chemother

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“…This finding suggests that the high diversity in rural areas may be due to the low drug pressure, contrasting with urban areas of Sudan where only two haplotypes have been found [42]. Interestingly, the prevalence of the NFD haplotype, strongly involved in the decrease of AL sensitivity, was one of the lower haplotypes in the study and that could indicate a small consumption of AL in Dienga.…”

Section: Discussionmentioning

confidence: 51%

Pfmdr1 gene polymorphism of Plasmodium falciparum isolates from asymptomatic individuals of Dienga, southeastern Gabon

Pegha-Moukandja¹,

Kouna²,

Maghendji-Nzdondo³

et al. 2018

J Parasitic Diseases

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“…12 The generated data from the baseline, especially the absence of the polymorphisms D1246 and N1042, which have been reported to exhibit a strong association with resistance to MQ, However, increased gene copy number not only seems to display a positive association with decreased sensitivity to MQ and artemisinin derivatives in vitro 12 but has also been indicated with artemether-lumefantrine treatment failure in subSaharan Africa. 43 Furthermore, a recent report from Nigeria linked the N86-Y184F-D1246 genotype with artemether-lumefantrine treatment failure, 44 and the N86 haplotype has been suggested as a potential marker of lumefantrine resistance in vivo, because recurrent parasites displayed a significant increase in pfmdr1 N86 after exposure to artemether-lumefantrine in Zanzibar. 45 This polymorphism has also been postulated as the first step in a series of mutation steps leading to the selection of artemether-lumefantrine resistance.…”

Section: Discussionmentioning

confidence: 99%

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

Adhin

Labadie-Bracho²,

Bretas³

2013

The American Society of Tropical Medicine and Hygiene

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Abstract. The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname.

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Increased pfmdr1 Copy Number and Sequence Polymorphisms in Plasmodium falciparum Isolates from Sudanese Malaria Patients Treated with Artemether-Lumefantrine

Cited by 68 publications

References 35 publications

Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Pfmdr1 gene polymorphism of Plasmodium falciparum isolates from asymptomatic individuals of Dienga, southeastern Gabon

Molecular Surveillance as Monitoring Tool for Drug-Resistant Plasmodium falciparum in Suriname

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