In Vivo Efficacy and Parasite Clearance of Artesunate + Sulfadoxine–Pyrimethamine Versus Artemether–Lumefantrine in Mali

Abstract

Abstract. Although artemisinin resistance has yet to be reported in Africa, surveillance of the efficacy of artemisininbased combination therapies (ACTs) is warranted. Here, the efficacy of artesunate + sulfadoxine-pyrimethamine (AS+SP) and artemether-lumefantrine (AL) was evaluated in Mali. Randomized open-label comparative in vivo assay of AS+SP versus AL were carried out using the 28-day follow-up World Health Organization protocol. Patients with uncomplicated falciparum malaria and at least 6 months of age were recruited between October 2010 and January 2014. A subset of these patients was selected to measure Plasmodium falciparum clearance time. Polymerase chain reactioncorrected adequate clinical and parasitological responses were 100% for AS+SP and 98.2% for AL with no significant difference (P = 0.06). The reinfection rates were comparable (P = 0.63) with 8.0% for AS+SP and 12.6% for AL. Individuals under 8 years were more susceptible to treatment failure (relative risk = 1.9; 95% confidence interval = 1.2, 3.3). Median parasite clearance half-life was 1.7 hours (interquartile range [IQR] = 1.3-2.2) for AS+SP and 1.9 hours (IQR = 1.5-2.5) for AL with no statistically significant difference (P = 0.24). Efficacy of AS+SP and AL was high. This study provides baseline information on parasite clearance half-lives after ACT treatment, particularly AS+SP, in Mali.

Efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy

“…Our findings show that AL is highly efficacious for treating uncomplicated P. falciparum malaria in the three study areas. Recent studies from malaria‐endemic countries in Africa indicate that AL remained effective (96–100% cure rate) after many years of use .…”

Multiple Phenotypic and Genotypic Artemisinin Sensitivity Evaluation of Malian Plasmodium falciparum Isolates

“…All isolates showed RSA 0-3 h values < 1.5%, which were correlated with the wild-type K13 genotype as previously reported in Southeast Asia. 20,28,49 By contrast, the recrudescence kinetic assay, RSKA 0-24 h , detected different phenotypes among artemisinin-sensitive isolates evidenced by RSA 0-3 h . Indeed, five out of eight studied isolates presented faster kinetics of recrudescence even though this in vitro response to artemisinin treatment does not appear to be associated neither with pfk13 polymorphisms nor with high survival rates in RSA 0-3 h .…”

“…Today, several SNPs of pfk13 have been described in sub-Saharan Africa, but none of them was associated with artemisinin resistance in this region. 10,22,[24][25][26] Parasite clearance time measurement is a useful monitoring tool of artemisinin resistance, 27,28 but several confounding factors such as host immunity, drug pharmacokinetics, or spleen clearance of infected red blood cells (RBCs) influence its outcomes. In vitro and ex vivo assays are not concerned by these factors as they measure the parasite intrinsic sensitivity by direct contact between the parasites and the drugs.…”

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) for the Treatment of Uncomplicated Falciparum Malaria in Africa: A Systematic Review

“…The early treatment failure (ETF) rate was almost 0%, while the proportion of late treatment failures (clinical and parasitological) was ranged between 0% and 52.6%. The common type of treatment failure was late parasitological failure (LPF) in which relatively higher proportion of such type of failure was reported by five studies; 12.3-25.4% [ 36 , 40 , 58 , 59 , 69 ] and one study at 52.6% [ 10 ]. The rest of the studies reported <8%.…”

“…Day 3 parasitemia after treatment with a full dose of AL shown to be delayed parasite clearance [ 58 ] or a good indicator of sensitivity of P. falciparum to artemisinins [ 44 ]. The artemisinin component of AL is mostly responsible for the rapid parasite clearance [ 44 ].…”