Background:Drug resistance is one of the greatest challenges of malaria control programmes,with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy(ACT)partner drugs critical to...Background:Drug resistance is one of the greatest challenges of malaria control programmes,with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy(ACT)partner drugs critical to elimination efforts.Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon.Methods:Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through crosssectional surveys from May 2013 to March 2014 along the slope of mount Cameroon.Plasmodium falciparum malaria parasitaemic blood,screened by light microscopy,was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform.Results:A total of 259 participants were enrolled in this study from three different altitudes.While some alleles associated with drug resistance in pfdhfr,pfmdr1 and pfcrt were highly prevalent,less than 3%of all samples carried mutations in the pfkelch13 gene,none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia.The most prevalent haplotypes were triple mutants PfdhfrI51R59N108I164(99%),pfcrt-C72V73I74E75T76(47.3%),and single mutants PfdhpsS_(436)G_(437)K_(540)A_(581)A_(613)(69%)and Pfmdr1 N_(86)F)(184)D_(1246)(53.2%).Conclusions:The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.展开更多
基金TOA received funding from the UK Medical Research Council—Grant no.G0600718 through the Centre for Genomics and GlobalHealth(http://www.cggh.org)while sequencing was done at the Sanger Institue thanks to the Wellcome Trust Sanger Instutte grant n0.098051 to DK.
文摘Background:Drug resistance is one of the greatest challenges of malaria control programmes,with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy(ACT)partner drugs critical to elimination efforts.Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon.Methods:Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through crosssectional surveys from May 2013 to March 2014 along the slope of mount Cameroon.Plasmodium falciparum malaria parasitaemic blood,screened by light microscopy,was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform.Results:A total of 259 participants were enrolled in this study from three different altitudes.While some alleles associated with drug resistance in pfdhfr,pfmdr1 and pfcrt were highly prevalent,less than 3%of all samples carried mutations in the pfkelch13 gene,none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia.The most prevalent haplotypes were triple mutants PfdhfrI51R59N108I164(99%),pfcrt-C72V73I74E75T76(47.3%),and single mutants PfdhpsS_(436)G_(437)K_(540)A_(581)A_(613)(69%)and Pfmdr1 N_(86)F)(184)D_(1246)(53.2%).Conclusions:The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.
