Sustained ex vivo susceptibility of Plasmodium falciparum to artemisinin derivatives but increasing tolerance to ACT partner quinolines in The Gambia [PublishAheadOfPrint]

Antimalarial interventions have yielded significant decline in malaria prevalence in The Gambia, where Artemether-Lumefantrine (AL) has been used as first line antimalarial for a decade. Clinical Plasmodium falciparum isolates collected from 2012 to 2015 were analysed ex vivo for antimalarial susceptibility and genotyped for drug resistance markers (pfcrt K76T, pfmdr1-86-184 and 1246 and pfk13) and microsatellite variation. Additionally, allele frequencies of SNPs from other drug resistance-associated genes were compared from genomic sequence datasets from 2008 (n=79) and 2014 (n=168). No artemisinin resistance associated pfk13 mutation was found and only 4% of isolates tested in 2015 showed significant growth after exposure to dihydroartemisinin. Conversely, the IC₅₀ concentrations of Amodiaquine and Lumefantrine increased within this period. pfcrt 76T and pfmdr1 184F mutants remained above 80%. pfcrt 76T was positively associated with higher IC₅₀ values to chloroquine. pfmdr1 NYD increased in frequency between 2012 and 2015 due to Lumefantrine selection. The TNYD (pfcrt 76T and pfmdr1 NYD wild type haplotype) also increased in frequency following AL implementation in 2008. These results suggest selection for pfcrt and pfmdr1 genotypes that enable tolerance to Lumefantrine. Increased tolerance to Lumefantrine calls for sustained chemotherapeutic monitoring in The Gambia to minimise complete ACT failure in the future.

http://ift.tt/2fGLGKW