Role of pfmdr1 mutations on chloroquine resistance in Plasmodium falciparum isolates with pfcrt K76T from Papua New Guinea

Mita, Toshihiro; Kaneko, Akira; Hombhanje, Francis; Hwaihwanje, Ilomo; Takahashi, Nobuyuki; Osawa, Hikota; Tsukahara, Takahiro; Masta, Andrew; Lum, J. Koji; Kobayakawa, Takatoshi; Ishizaki, Takashi; Björkman, Anders

doi:10.1016/j.actatropica.2006.03.002

Cited by 38 publications

(39 citation statements)

References 38 publications

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“…Although the involvement of the pfmdr-1 mutation is still under debate, the N86Y mutation has been reported to modulate levels of CQ-resistance to a higher degree when present with the pfcrt K76T mutation (Foote et al 1990, Djimdé et al 2001, Mita et al 2006. Some previous studies have confirmed the asso-.…”

Section: Discussionsupporting

confidence: 56%

Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes in Plasmodium falciparum isolates from Odisha, India

Sutar

Gupta

Ranjit

et al. 2011

Mem. Inst. Oswaldo Cruz

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Section: Discussionsupporting

confidence: 56%

Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes in Plasmodium falciparum isolates from Odisha, India

Sutar

Gupta

Ranjit

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…Recent results suggest that www.chemmedchem.org this mutation plays a compensatory role in chloroquine-resistant isolates under CQ pressure and may also have some finetuning effects on the degree of chloroquine resistance. [51] The N86Y mutation is strongly associated with increased sensitivity to mefloquine (29), halofantrine (30), lumefantrine (31), and dihydroartemisinin (39) (see below).…”

Section: Chloroquine Resistancementioning

confidence: 99%

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

2007

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Since ancient times, humankind has had to struggle against the persistent onslaught of pathogenic microorganisms. Nowadays, malaria is still the most important infectious disease worldwide. Considerable success in gaining control over malaria was achieved in the 1950s and 60s through landscaping measures, vector control with the insecticide DDT, and the widespread administration of chloroquine, the most important antimalarial agent ever. In the late 1960s, the final victory over malaria was believed to be within reach. However, the parasites could not be eradicated because they developed resistance against the most widely used and affordable drugs of that time. Today, cases of malaria infections are on the rise and have reached record numbers. This review gives a short description of the malaria disease, briefly addresses the history of antimalarial drug development, and focuses on drugs currently available for malaria therapy. The present knowledge regarding their mode of action and the mechanisms of resistance are explained, as are the attempts made by numerous research groups to overcome the resistance problem within classes of existing drugs and in some novel classes. Finally, this review covers all classes of antimalarials for which at least one drug candidate is in clinical development. Antimalarial agents that are solely in early development stages will be addressed in a separate review.

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“…These mutations of the pfmdr1 gene were thought to play a role in the enhancement of resistance levels in CQ-resistant parasites (26). However, recently Mita et al (27) observed a significant non-random association between the pfcrt T76 and pfmdr1 Y86 alleles. They concluded that under CQ selection pressure the Y86 mutation in pfmdr1 may augment the level of CQ resistance in the T76 alleles.…”

Section: Discussionmentioning

confidence: 99%

Alta frecuencia de mutaciones puntuales en pfcrt de Plasmodium falciparum y emergencia de nuevos haplotipos mutantes en Colombia

2008

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Introduction. Studies on the molecular epidemiology of antimalarial resistance constitute a useful tool to understand the events underlying treatment failure and resistance in falciparum malaria in Colombia. Several authors have reported on the efficacy of some molecular markers to predict drug resistance in Plasmodium falciparum. The P. falciparum pfcrt gene has been widely characterized in this context. Objective. The frequency of pfcrt gene mutations in P. falciparum were associated with treatment failure to the antimalarials chloroquine, mefloquine, amodiaquine and sulfadoxine/ pyrimethamine. Materials and methods. A representative sample of 172 patients with non-complicated falciparum malaria was selected from two highly malaria-endemic areas of northeastern Colombia, the Turbo and Bajo Cauca regions. These patients were assessed for treatment response together with the status of codons 72, 74, 75 and 76 in the pfcrt gene using a PCR-RFLP approach. Results. A high frequency of treatment failure to chloroquine (82%) and to amodiaquine (29%) was confirmed, whereas mefloquine and combined therapy remained effective. The presence of the T76 mutation in pfcrt was confirmed in all samples. The most common haplotype was CMNT (67%). Conclusions. No significant association was confirmed between specific haplotypes and the treatment response in any of the treatment groups. Two haplotypes, SMET and SMNT, were reported for the first time in Colombia. Twelve percent of the samples carried both mixed mutant and wild-type alleles.

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Role of pfmdr1 mutations on chloroquine resistance in Plasmodium falciparum isolates with pfcrt K76T from Papua New Guinea

Cited by 38 publications

References 38 publications

Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes in Plasmodium falciparum isolates from Odisha, India

Sequence analysis of coding DNA fragments of pfcrt and pfmdr-1 genes in Plasmodium falciparum isolates from Odisha, India

Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development

Alta frecuencia de mutaciones puntuales en pfcrt de Plasmodium falciparum y emergencia de nuevos haplotipos mutantes en Colombia

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