Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites.
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.
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.|Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
Lorna J
LJ
Chebon
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.|Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
Bidii S
BS
Ngalah
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Luicer A
LA
Ingasia
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Dennis W
DW
Juma
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.|Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
Peninah
P
Muiruri
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Jelagat
J
Cheruiyot
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Benjamin
B
Opot
Ifakara Health Institute, Bagamoyo, Tanzania.
Emmanuel
E
Mbuba
Institute of Tropical Medicine and Infectious Diseases, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
Mabel
M
Imbuga
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Hoseah M
HM
Akala
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Wallace
W
Bulimo
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Ben
B
Andagalu
Department of Emerging and Infectious Diseases, United States Army Medical Research Directorate-Kenya, Kenya Medical Research Institute (KEMRI)/Walter Reed Project, Kisumu, Kenya.
Edwin
E
Kamau
D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001499:Bayes Theorem; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007630:Kenya; D018895:Microsatellite Repeats / Q000235:genetics; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins