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Abstract
BackgroundDrug 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.MethodsIndividuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional 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.ResultsA 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 PfdhpsS436G437K540A581A613(69%) and Pfmdr1 N86F184D1246 (53.2%).ConclusionsThe predominance of the Pf pfcrt CVIET andPfdhfrIRN 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.
Highlights
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
The emergence of artemisinin resistance in Western Cambodia of Southeast Asia (SEA) [1, 3] has prompted global concern given that CQ and SP resistance arose in the same region and spread to SubSaharan Africa (SSA) [8]
Characteristics of smear-positive participants A total of 259 participants were enrolled in this study from three different altitudes (Table 1), most of whom had uncomplicated malaria (74.8%, 190/254), reportedly had fever in the previous 48 h (67.5%), were anaemic (47.2%) and females (52.1%)
Summary
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. Recent studies suggest that resistant mutations may emerge independently in SEA and SSA [9,10,11,12,13] necessitating regional molecular monitoring of markers for the control and containment of resistant parasites. Information on parasite resistance to artemisinins, ACT partner drugs or to previously withdrawn antimalarials is vital for malaria control [14] and could justify the reintroduction of abandoned drugs [15] since drug-sensitive populations of Plasmodium falciparum resurge following long-term drug withdrawal
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