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

Article scientifique 2017 Anglais

Résumé

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: s 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.

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Dama, S., Niangaly, H., Ouattara, A., Sagara, I., Sissoko, S., Traoré, O., Bamadio, A., Dara, N., Djimdé, M., Alhousseini, M., Goïta, S., Maiga, H., Dara, A., Doumbo, O., Djimdé, A. (2017). Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether–lumefantrine treatment in Mali. https://doi.org/10.1186/s12936-017-1700-8

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Souleymane Dama Hamidou Niangaly Amed Ouattara Issaka Sagara Sékou Sissoko Oumar Traoré Amadou Bamadio Niawanlou Dara Moussa Djimdé Mohamed Lamine Alhousseini Siaka Goïta Hamma Maiga Antoine Dara Ogobara K. Doumbo Abdoulaye Djimdé

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