Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites

Abstract

Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya.

Genetic diversity and population structure of Plasmodium falciparum in Kenyan–Ugandan border areas

“…In fact, the parasite genetic diversity increased after ACTs were introduced [12]. Explanations for the persisting high genetic diversity are the increasing number of asymptomatic malaria cases with higher gametocytaemias, vector resistance against pyrethroids which sustain transmission and the removal of antimalarial drug selection pressure following the replacement of the less effective sulphadoxine-pyrimethamine in 2006 by the highly efficacious ACT [8,12,15,16,39,40]. It is also worth noting that the P. falciparum genetic diversity reported here is similar to the genetic diversity of parasite populations from other countries in sub-Saharan Africa [22,41], and it is higher than the genetic diversity of populations from low malaria-endemic settings in the Pacific Region, Southeast Asia and South America [22,[42][43][44][45][46].…”

The Role of Complement Immune Response on Artemisinin Combination Therapy in a Population from Malaria Endemic Region of Western Kenya

“…The main question of the present study was whether pre-existing immunity had an impact on the parasitological outcome after drug treatment and the kinetic of the response. The mean T [19,20]. Correlations between drug treatment outcome as determined by parasite clearance parameters (slope half-life [T 1/2 ] and clearance rate [K]) and pre-existing GIA activity in sera were assessed ( Table 2).…”

The Role of Complement Immune Response on Artemisinin Combination Therapy in a Population from Malaria Endemic Region of Western Kenya

“…The main question of the present study was whether pre-existing immunity had an impact on the parasitological outcome after drug treatment and the kinetic of the response. [19,20]. Correlations between drug treatment outcome as determined by parasite clearance parameters (slope half-life [T 1/2 ] and clearance rate [K]) and pre-existing GIA activity in sera were assessed ( Table 2).…”