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

Abstract

Background. Africa still bears the largest burden of malaria as the majority of infections in the continent are caused by P. falciparum. Artemether-lumefantrine (AL, Coartem®) is the most widely used artemisinin-based combination therapy (ACT), for treating uncomplicated falciparum malaria globally. However, the development of resistance to antimalarial drugs is a major challenge for malaria control. In this review, the efficacy of AL for the treatment of uncomplicated falciparum malaria in Africa was evaluated. Methods. Articles published between January 2015 and July 2019 were systematically searched using comprehensive search strings from PubMed/Medline, SCOPUS, and grey literature from Google Scholar. Interventional studies that followed patients for at least 28 days were included. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. All the included articles were measured to be good quality. While computing the efficacy of AL, polymerase chain reaction (PCR)–corrected cure rate (adequate clinical and parasitological response, ACPR) at day 28 was considered as the main endpoint. Meta-analysis was computed using STATA v 15 to calculate the pooled ACPR. Results. In this review, 39 articles that reported the treatment outcome of 8,320 patients were included. After 28 days of follow-up, the pooled PCR uncorrected and corrected APCR was at 87% (95% CI: 85-90%) and 97.0% (95% CI: 96-98%), respectively. Moreover, the proportion of early treatment failure (ETF) was almost 0%, while most of the included articles reported <8% late treatment failures. The reinfection and recrudescence rate was less than 10% and 2.6%, respectively, within 28 days. We noted rapid fever and parasite clearance in which greater than 93% and 94% patients were parasite and fever free at day three following AL treatment. Conclusions. This review discovered that despite more than a decade since its introduction, Coartem® remains effective and thus could continue to be the drug of choice for the treatment of uncomplicated falciparum malaria for all age groups in Africa. However, the risk of new emerging resistance for this combination warrants regular monitoring of its efficacy across the continent.

Effectiveness and safety of artesunate–amodiaquine versus artemether–lumefantrine for home-based treatment of uncomplicated Plasmodium falciparum malaria among children 6–120 months in Yaoundé, Cameroon: a randomized trial

“…The adjusted PCR - ACPR is lower than the rates of 96.0–100.0% reported in malaria endemic countries in sub - Saharan Africa [ 13 , 49 – 51 ], Southeast Asia [ 11 ] and South America [ 52 ]. A systematic review and meta - analysis on the therapeutic efficacy of AL (Coartem®) for the treatment of P. falciparum malaria in Africa gave a pooled PCR adjusted 97.0% [ 53 ]. The adjusted PCR cure rate for AL is higher than the range of 77.7–94.0% previously documented in several antimalarial drug effectiveness [ 16 , 44 , 46 , 48 ] and efficacy [ 15 ] studies conducted elsewhere.…”

Epidemiology and clinical features of imported malaria: a 14-year retrospective single-centre descriptive study in Prague, Czech Republic

“…Combination therapy is now recommended to reduce the risk of selecting for resistant parasite species, as artemisinin resistance was observed in the regions where monotherapy had been previously used (Cambodia, Thailand, Guyana) [ 35 – 37 ]. In this study, most cases of non-complicated P. falciparum malaria were treated with artemether/lumefantrine, the most widely used artemisinin-based combination globally [ 38 ]. Artemether typically leads to rapid clinical and parasitological responses several hours after administration and has a very short plasma elimination half-life of about 2 hours.…”

Adverse reaction to Coartem (artemether/lumefantrine) resulting in oculogyric crisis

“…Lumefantrine is an aryl amino-alcohol in the same general group as mefloquine and halofantrine, offering the maximum dual performance of AL (Fig. 2 ) [ 7 ]. Therefore, the aim of this case report is bring to fore the association of AL as a cause of drug-induced oculogyric crisis.…”