Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance

Mita, Toshihiro; Tanabe, Kazuyuki

doi:10.7883/yoken.65.465

Cited by 100 publications

(72 citation statements)

References 91 publications

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“…Moreover, this resistance was firmly established in Cambodia, Thailand, Vietnam and Burma and its possible spread over the rest of South-east Asia has been documented [12,13]. On the other hand, the therapeutic failures of ACTs could be associated with single nucleotide polymorphism (SNP) in P. falciparum multidrug resistance gene-1 (Pfmdr1) [14,13], as well as with K13 propeller [15,16]. Pfmdr1 is an ATP cassette protein located on the parasite's food vacuole.…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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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“…1 The recent evidence of emerging resistance to artemisinin derivatives, including ACTs, in southeast Asia raises serious concern that such parasite populations may spread toward Africa, mirroring parasite resistance to chloroquine, 2 sulfadoxine, and pyrimethamine. 3 Recently, mutations in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in southeast Asia. 4 The Plasmodium falciparum K13-propeller domain (PF3D7_1343700) is a 727-amino acid protein encoded by a gene located on chromosome 13.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

Ouattara¹,

Koné²,

Adams³

et al. 2015

The American Society of Tropical Medicine and Hygiene

100

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Abstract. Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.

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“…Currently, the World Health Organization recommends artemisinin combination therapy as the first-line treatment but recent reports suggest emerging resistance against the artemisinins in the form of delayed parasite clearance (2,3). In light of this, there is a pressing need for new antimalarials, preferably with novel modes of action to avoid cross-resistance.…”

mentioning

confidence: 99%

A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

Lee

Goh

Ch'ng

et al. 2014

Antimicrob Agents Chemother

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Plasmodium falciparum is the etiological agent of malignant malaria and has been shown to exhibit features resembling programmed cell death. This is triggered upon treatment with low micromolar doses of chloroquine or other lysosomotrophic compounds and is associated with leakage of the digestive vacuole contents. In order to exploit this cell death pathway, we developed a high-content screening method to select compounds that can disrupt the parasite vacuole, as measured by the leakage of intravacuolar Ca 2؉ . This assay uses the ImageStream 100, an imaging-capable flow cytometer, to assess the distribution of the fluorescent calcium probe Fluo-4. We obtained two hits from a small library of 25 test compounds, quinacrine and 3=,4=-dichlorobenzamil. The ability of these compounds to permeabilize the digestive vacuole in laboratory strains and clinical isolates was validated by confocal microscopy. The hits could induce programmed cell death features in both chloroquine-sensitive and -resistant laboratory strains. Quinacrine was effective at inhibiting field isolates in a 48-h reinvasion assay regardless of artemisinin clearance status. We therefore present as proof of concept a phenotypic screening method with the potential to provide mechanistic insights to the activity of antimalarial drugs.

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Evolution of Plasmodium falciparum drug resistance: implications for the development and containment of artemisinin resistance

Cited by 100 publications

References 91 publications

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

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

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

A High-Content Phenotypic Screen Reveals the Disruptive Potency of Quinacrine and 3′,4′-Dichlorobenzamil on the Digestive Vacuole of Plasmodium falciparum

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