Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether-lumefantrine treatment in Mali.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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%.

CONCLUSION:

Malian post-AL P. falciparum isolates were less susceptible to artemether and lumefantrine than baseline isolates.

• Authors: Souleymane Dama, Hamidou Niangaly, Amed Ouattara, Issaka Sagara, Sekou Sissoko, Oumar Bila Traore, Amadou Bamadio, Niawanlou Dara, Moussa Djimde, Mohamed Lamine Alhousseini, Siaka Goita, Hamma Maiga, Antoine Dara, Ogobara K Doumbo, Abdoulaye A Djimde
• Journal: Malaria journal (Malar J) Vol. 16 Issue 1 Pg. 59 (02 02 2017) ISSN: 1475-2875 [Electronic] England
• PMID: 28148267 (Publication Type: Journal Article)

Chemical References

• Antimalarials
• Artemether, Lumefantrine Drug Combination
• Artemisinins
• Drug Combinations
• Ethanolamines
• Fluorenes

Topics

• Administration, Oral
• Antimalarials (pharmacology)
• Artemether, Lumefantrine Drug Combination
• Artemisinins (pharmacology)
• Drug Combinations
• Drug Resistance
• Ethanolamines (pharmacology)
• Fluorenes (pharmacology)
• Humans
• Malaria, Falciparum (parasitology)
• Mali
• Parasitemia (parasitology)
• Plasmodium falciparum (drug effects)
• Recurrence