No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

Abstract

Abstract. Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1-10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa.

Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali

“…To measure the prevalence of K13-propeller mutations in Mali, we genotyped 90 samples collected before drug treatment on day 0 of a prospective artesunate monotherapy efficacy study conducted in Bougoula-Hameau, Mali from December of 2010 to February of 2011. 7 Of these samples, 55 dried blood spots were also assessed for single-nucleotide polymorphisms (SNPs) at Mal10-688956 and Mal13-1718319 loci, which were previously suggested as candidate markers of artemisinin resistance 8 ; 36 samples collected during malaria studies conducted between 2003 and 2005 in BougoulaHameau and 86 samples collected between 1999 and 2002 in Bandiagara were also used to measure the prevalence of K13-propeller mutations in the region before ACTs were recommended as the first-line treatment of uncomplicated malaria in Mali. In Bougoula-Hameau, parasite clearance time (PCT) was estimated as previously described.…”

“…Parasite density was estimated by counting the number of asexual parasites per 200 leukocytes and multiplying by 40 (assuming 8,000 leukocytes/μL). 7 The study was approved by the Ethics Committee of the Faculty of Medicine and Odontostomatology and Faculty of Pharmacy of the University of Science, Techniques and Technologies of Bamako.…”

“…In Bougoula-Hameau, parasite clearance time (PCT) was estimated as previously described. 7 Briefly, thick and thin blood smears were examined for asexual and sexual parasites after staining with 5% Giemsa every 8 hours starting immediately before the first oral dose of artesunate monotherapy until three consecutive slides were negative for asexual parasites. Slides were also prepared on follow-up days 2, 3, 7, 14, 21, and 28.…”

“…The 3D7 haplotype prevalence was 89.7% (N = Slope half-lives and PC99 were only available for 87 samples from the Bougoula-Hameau 2010 and 2011 study, where parasitemia was measured every 8 hours. 7 Nine of these samples had a non-synonymous SNP in the K13-propeller domain; 78 were wild type. The means of slope half-lives of the mutant and wild-type infections were similar (Wilcoxon rank sum test, P = 0.32) ( Figure 3A).…”

“…Previously, we reported that artesunate was highly efficacious in Bougoula-Hameau, Mali, with a median parasite clearance half-life of 2.07 hours; all study participants cleared their parasitemia by 72 hours. 7 The main objective of this study was to measure the prevalence of P. falciparum K13-propeller polymorphisms in present-day artemisinin-sensitive parasite collected in Bougoula-Hameau and malaria infections that occurred before the scaling up of ACTs in Mali to detect any impact of the implementation of these therapies on the biodiversity of this gene.…”