Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Mali: a systematic review and meta-analysis

Abstract

Background: Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic.

Methods: A systematic review of the literature maintained in the bibliographic databases accessible through the PubMed, ScienceDirect and Web of Science search engines was performed to identify research studies on ACT occurring at Mali study sites. Selected studies included trials occurring at Mali study sites with reported polymerase chain reaction (PCR)-corrected adequate clinical and parasite response rates (ACPRcs) at 28 days. Data were stratified by treatment arm (artemether-lumefantrine (AL), the first-line treatment for falciparum malaria in Mali and non-AL arms) and analysed using random-effects, meta-analysis approaches.

Results: A total of 11 studies met the inclusion criteria, and a risk of bias assessment carried out by two independent reviewers determined low risk of bias among all assessed criteria. The ACPRc for the first-line AL at Mali sites was 99.0% (95% CI (98.3%, 99.8%)), while the ACPRc among non-AL treatment arms was 98.9% (95% CI (98.3%, 99.5%)). The difference in ACPRcs between non-AL treatment arms and AL treatment arms was not statistically significant (p = .752), suggesting that there are potential treatment alternatives beyond the first-line of AL in Mali.

Conclusions: ACT remains highly efficacious in treating uncomplicated falciparum malaria in Mali. Country-specific meta-analyses on ACT are needed on an ongoing basis for monitoring and evaluating drug efficacy patterns to guide local malaria treatment policies, particularly in the wake of observed artemisinin resistance in Southeast Asia and partial resistance in Rwanda.

Keywords: Artemether–lumefantrine; Artemisinin-based combination therapy; Malaria; Mali; Systematic review.

Fig. 1

Selection process for included studies. A total of 11 ACT studies were selected for inclusion, where 8 of these studies included an AL treatment arm. ACT: artemisinin-based combination therapy; ACPR: adequate clinical and parasite response; AL: artemether–lumefantrine

Fig. 2

Field study locations for included artemisinin combination therapy trials in Mali. The majority of the study locations were situated in the southern, rural parts of Mali where most of its population resides. ACT: artemisinin-based combination therapy

Fig. 3

Forest plot of artemether–lumefantrine polymerase chain reaction-corrected adequate clinical and parasite responses for included studies. The pooled ACPRc for AL treatment arms was 99.0% (95% CI 98.3%, 99.8%). ACPRc: polymerase chain reaction-corrected adequate clinical and parasite response for falciparum malaria at 28 days; AL: artemether–lumefantrine; PCR: polymerase chain reaction

Fig. 4

Forest plot of polymerase chain reaction-corrected adequate clinical and parasite responses for studies with non- artemether–lumefantrine treatment arms. Among non-AL treatment arms including at least two studies, AS + AQ and AS + Pyr were the only treatment arms with pooled ACPRcs less than 100.0% (97.7% (95% CI 95.9%, 99.4%) and 97.6% (95% CI 92.7%, 100.0%), respectively. The overall ACPRc for non-AL treatment arms was 98.9% (95% CI 98.3%, 99.5%). Only treatment arms with at least two representative studies are shown. ACPRc: polymerase chain reaction-corrected adequate clinical and parasite response for falciparum malaria at 28 days; AL: artemether–lumefantrine; PCR: polymerase chain reaction

Fig. 5

Uncorrected versus corrected malaria polymerase chain reaction-corrected adequate clinical and parasite responses for artemisinin-based combination therapy arms in Mali trials. AL and non-AL treatment arms did not significantly differ according to ACPRs or ACPRcs (p = .120 and p = .752, respectively). The error bars denote the 95% confidence intervals for each combination of treatment arm (AL or non-AL) and outcome (ACPR or ACPRc). ACPR: adequate clinical and parasite response; ACPRc: polymerase chain reaction-corrected adequate clinical and parasite response for falciparum malaria at 28 days; ACT: artemisinin-based combination therapy

Fig. 6

Risk of bias assessment for included studies. A Shows the risk of bias graph, and B shows the Risk of bias summary figure. High risk of bias was not reported for any of the criteria in any of the studies, and 63.6% (7/11) of the studies reported low risk of bias for all assessed criteria