Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether-lumefantrine treatment in Mali.
Artemisinin-based combination therapy is the recommended first-line treatment for uncomplicated falciparum malaria worldwide. However, recent studies conducted in Mali showed an increased frequency of recurrent parasitaemia following artemether-lumefantrine (AL) treatment.



Study samples were collected during a large WANECAM study. Ex-vivo Plasmodium falciparum sensitivity to artemether and lumefantrine was assessed using the tritiated hypoxanthine-based assay. The prevalence of molecular markers of anti-malarial drug resistance (pfcrt K76T, pfmdr1 N86Y and K13-propeller) were measured by PCR and/or sequencing.



Overall 61 samples were successfully analysed in ex vivo studies. Mean IC50s increased significantly between baseline and recurrent parasites for both artemether (1.6 nM vs 3.2 nM, p < 0.001) and lumefantrine (1.4 nM vs 3.4 nM, p = 0.004). Wild type Pfmdr1 N86 allele was selected after treatment (71 vs 91%, 112 of 158 vs 95 of 105, p < 0.001) but not the wild type pfcrt K76 variant (23.5 vs 24.8%, 40 of 170 vs 26 of 105, p = 0.9). Three non-synonymous K13-propeller SNPs (A522C, A578S, and G638R) were found with allele frequencies <2%.



Malian post-AL P. falciparum isolates were less susceptible to artemether and lumefantrine than baseline isolates.
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Souleymane
S
Dama
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Hamidou
H
Niangaly
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Amed
A
Ouattara
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Issaka
I
Sagara
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Sekou
S
Sissoko
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Oumar Bila
OB
Traore
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Amadou
A
Bamadio
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Niawanlou
N
Dara
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Moussa
M
Djimde
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Mohamed Lamine
ML
Alhousseini
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Siaka
S
Goita
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Hamma
H
Maiga
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Antoine
A
Dara
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali.
Ogobara K
OK
Doumbo
Malaria Research and Training Center, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Technique and Technology of Bamako, P.O. Box 1805, Bamako, Mali. adjimde@icermali.org.
Abdoulaye A
AA
Djimde
D000284:Administration, Oral; D000962:Antimalarials / Q000494:pharmacology*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000494:pharmacology*; D004338:Drug Combinations; D004351:Drug Resistance; D004983:Ethanolamines / Q000494:pharmacology*; D005449:Fluorenes / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008302:Mali; D018512:Parasitemia / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects*; D012008:Recurrence
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes
Artemether; Ex vivo; In vivo; K13 propeller; Lumefantrine; Plasmodium