K13-Propeller Polymorphisms in Plasmodium falciparum Parasites From Sub-Saharan Africa

Kamau, Edwin; Campino, Susana; Amenga-Etego, Lucas; Drury, Eleanor; Ishengoma, Deus S.; Johnson, Kimberly J.; Mumba, Dieudonné; Kekre, Mihir; Yavo, William; Mead, Daniel; Bouyou-Akotet, Marielle Karine; Apinjoh, Tobias O.; Golassa, Lemu; Randrianarivelojosia, Milijaona; Andagalu, Ben; Maïga-Ascofaré, Oumou; Amambua-Ngwa, Alfred; Tindana, Paulina; Ghansah, Anita; MacInnis, Bronwyn; Kwiatkowski, Dominic P.; Djimdé, Abdoulaye

doi:10.1093/infdis/jiu608

Cited by 217 publications

(285 citation statements)

References 15 publications

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“…Unfortunately, artemisinin resistance, defined as delayed parasite clearance, has emerged in southeastern Asia. [6][7][8] Mutations in the kelch 13 propeller domain have been associated with artemisinin resistance in vitro and in vivo in southeast Asia. 9,10 To date, artemisinin resistance has not been reported in Africa and ACTs remained highly efficacious.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 To date, artemisinin resistance has not been reported in Africa and ACTs remained highly efficacious. [10][11][12][13][14] However, subSaharan Africa remains at risk because of drug pressure from wide use of ACTs and intercontinental movement of people. Furthermore, circulation of substandard or counterfeit drugs and nonadherence to treatment course are factors that contribute to rapidly selecting resistant parasites.…”

Section: Introductionmentioning

confidence: 99%

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In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine–Pyrimethamine Versus Artemether–Lumefantrine in Mali

Niaré¹,

Dara²,

Sagara³

et al. 2016

The American Journal of Tropical Medicine and Hygiene

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Abstract. Although artemisinin resistance has yet to be reported in Africa, surveillance of the efficacy of artemisininbased combination therapies (ACTs) is warranted. Here, the efficacy of artesunate + sulfadoxine-pyrimethamine (AS+SP) and artemether-lumefantrine (AL) was evaluated in Mali. Randomized open-label comparative in vivo assay of AS+SP versus AL were carried out using the 28-day follow-up World Health Organization protocol. Patients with uncomplicated falciparum malaria and at least 6 months of age were recruited between October 2010 and January 2014. A subset of these patients was selected to measure Plasmodium falciparum clearance time. Polymerase chain reactioncorrected adequate clinical and parasitological responses were 100% for AS+SP and 98.2% for AL with no significant difference (P = 0.06). The reinfection rates were comparable (P = 0.63) with 8.0% for AS+SP and 12.6% for AL. Individuals under 8 years were more susceptible to treatment failure (relative risk = 1.9; 95% confidence interval = 1.2, 3.3). Median parasite clearance half-life was 1.7 hours (interquartile range [IQR] = 1.3-2.2) for AS+SP and 1.9 hours (IQR = 1.5-2.5) for AL with no statistically significant difference (P = 0.24). Efficacy of AS+SP and AL was high. This study provides baseline information on parasite clearance half-lives after ACT treatment, particularly AS+SP, in Mali.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine–Pyrimethamine Versus Artemether–Lumefantrine in Mali

Niaré¹,

Dara²,

Sagara³

et al. 2016

The American Journal of Tropical Medicine and Hygiene

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“…Allele frequencies ranged between 1 and 3%. Three mutations were observed in >1 country and the A578S was present in parasites from 5 countries (Kamau et al, 2015).…”

Section: Role Of P Falciparum Kelch13 Propeller Gene Polymorphismmentioning

confidence: 96%

Methods for monitoring artemisinin-based combination therapies efficacy

Dama¹,

Djimdé²,

Doumbo³

2017

Clin. Rev. Opinions

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Plasmodium falciparum resistance to artemisinin and its derivatives is spreading in South-East Asia, and there is growing concern that this may reach other endemic countries. Methods used to assess P. falciparum resistance to artemisinin-based combination therapies (ACTs) are multiple and often divergent. This paper is a review of online accessible research publications from the past 20 years on ACTs, ranging from in vivo, in vitro/ex-vivo, molecular markers and pharmacokinetics studies. We highlight the procedures of the four main methods used for ACTs e f f i c a c y testing and provide a summary of published data. This review indicates that the most used method for ACT efficacy testing is the in vivo 28 days follow-up with molecular correction; the most widely used and reliable in vitro and ex-vivo method for artemisinin phenotyping is the ring stage survival assay from 0 to 3 h ring (RSA 0-3h ), and the main molecular marker of P. falciparum resistance to artemisinins are mutations on P. falciparum Kelch 13 propeller domain. Day 7 pharmacokinetics could help to predict resistance to artemether-lumefantrine and dihydroartemisinin-piperaquine. Findings from this review support that the combination of in vivo, in vitro/ex-vivo, molecular markers of drug resistance and day 7 PK levels of the partner drugs may be required for the optimal surveillance of artemisinin-based combination therapy efficacy in the field.

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“…• studies of the distribution of polymorphisms in the field, particularly in Africa [9][10][11][12][13];…”

Section: A New Artemisinin Susceptibility Phenotype Arises In Asiamentioning

confidence: 99%

Genetic markers of artemisinin resistance in Plasmodium spp. parasites

Sutherland

2017

Emerging Topics in Life Sciences

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The vast majority of malaria patients worldwide are currently treated with combination therapy comprising one of the artemisinin family of drugs, characterised by rapid action and short plasma half-life, co-formulated with a longer-lasting drug from the amino arylalcohol or quinoline families. There is now a widely perceived threat to treatment efficacy, as reduced susceptibility to rapid artemisinin clearance in vivo has become prevalent among populations of Plasmodium falciparum in the Greater Mekong subregion since 2008. In vitro and in vivo drug selection studies, heterologous cell expression experiments and genetic epidemiology have identified many candidate markers of reduced ring-stage susceptibility to artemisinin. Certain variants of the P. falciparum pfk13 gene, which encodes a kelch domain protein implicated in the unfolded protein response, are strongly associated with slow parasite clearance by artemisinin in the Mekong subregion. However, anomalies in the epidemiological association of pfk13 variants with true treatment failure in vivo and the curious cell-cycle stage specificity of this phenotype in vitro warrant exploration in some depth. Taken together, available data suggest that the emergence of P. falciparum expressing K13 variants has not yet precipitated a public health emergency. Alternative candidate markers of artemisinin susceptibility are also described, as K13-independent treatment failure has been observed in African P. falciparum and in the rodent malaria parasite Plasmodium chabaudi.

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K13-Propeller Polymorphisms in Plasmodium falciparum Parasites From Sub-Saharan Africa

Cited by 217 publications

References 15 publications

In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine–Pyrimethamine Versus Artemether–Lumefantrine in Mali

In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine–Pyrimethamine Versus Artemether–Lumefantrine in Mali

Methods for monitoring artemisinin-based combination therapies efficacy

Genetic markers of artemisinin resistance in Plasmodium spp. parasites

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