West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether–Lumefantrine in Senegal, Mali, and The Gambia

Abstract

Abstract. In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites.

Absence of a High Level of Duplication of the Plasmepsin II Gene in Africa

“…It seems that other resistance mechanisms and therefore other molecular markers may exist in Africa compared to those in Asia. This phenomenon has also been observed with resistance to artemisinin, which is associated with pfk13 polymorphisms in Asia, while no polymorphism is observed in most cases of clinical failure of ACT in Africa (10,(31)(32)(33)(34)(35). To overcome the limitation of this study, i.e., the low number of samples with reduced susceptibility, it is imperative to further assess more isolates from different geographical areas of Africa, and especially more P. falciparum strains resistant to PPQ from Africa.…”

Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015–2016

“…A handful of studies over the past decade have investigated the e cacy of AL in Mali, and reported PCRcorrected e cacies greater than 98%. These include: a 2010-2014 study in Sotuba, Kolle, and Banambani [20]; a 2012-2014 study in Dioro [21]; and a 2013-2015 study in Doneguebougou and Torodo [22]. Although two of these studies [20,22] considered reinfections as treatment successes in their calculation of PCR-corrected e cacy (an approach not consistent with WHO guidelines), the e cacy results remained above 97% when recalculating e cacy using the WHO-endorsed approach of eliminating reinfections from the calculation.…”

Resistance of <i>Plasmodium falciparum</i> to Sulfadoxine-Pyrimethamine (<i>Dhfr</i> and <i>Dhps</i>) and Artemisinin and Its Derivatives (K13): A Major Challenge for Malaria Elimination in West Africa

“…In 2016 none of the previously described substitutions had been observed generally in sub-Saharan Africa apart from the P553L mutation which was observed at low frequencies in Kenya (0.53%) and in Malawi (0.59%) [37] [38]. Other studies have however observed the presence of synonymous or non-K13 mutations correlated with a delay in parasite clearance in Burkina Faso (2.26%), Senegal (5.5%) and Togo (1.8%) [8] [39] [40] (Table 4).…”

“…Most of the mutations reported in the reviewed publications relate to delayed parasite clearance but are not confirmed to be resistant to artemisinin. Artemisinin, its derivatives and artemisinin-based combinations (ACT) still remain effective as the first line of treatment for malaria in West Africa[28] [38].…”