Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether-lumefantrine treatment in Mali.
Malar J
; 16(1): 59, 2017 02 02.
Article
em En
| MEDLINE
| ID: mdl-28148267
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Resistência a Medicamentos
/
Artemisininas
/
Etanolaminas
/
Fluorenos
/
Antimaláricos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Africa
Idioma:
En
Revista:
Malar J
Assunto da revista:
MEDICINA TROPICAL
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Mali