Efficacy and Safety of Artemether-Lumefantrine for Treatment of Uncomplicated P. Falciparum malaria in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Abamecha Abdulhakim , Yilma Daniel , Adissu Wondimagegn , Yewhalaw Delenasaw , Abdissa Alemseged 
Published: January 2021

Abstract
Background: Anti-malarial drug resistance, in particular resistance to Plasmodium falciparum, challenges the treatment and control of malaria. In Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2004. To maximize efficacy of anti-malarial drugs and ensure adequate treatment outcomes; monitoring drug efficacy regularly is vital to establish rational malaria treatment guidelines. This systematic review and meta-analysis is performed to obtain an overall stronger evidence to guide management of uncomplicated falciparum malaria from the existing literature in Ethiopia after policy changes in 2004.Methods: A systematic literature search was performed using the preferred reporting items for systematic review and meta-analysis (PRISMA) from published therapeutic efficacy studies conducted in Ethiopia from 2004 to 2020. The search was performed from Pubmed, Google Scholar and Clinical trial registry databases to identify literature. Two reviewers independently assessed study eligibility and extracted data. While computing the efficacy of AL, polymerase chain reaction (PCR)-corrected cure rate (adequate clinical and parasitological response, ACPR) at 28th day was considered as the primary endpoint. Meta-analysis was computed using OpenMeta-Analysis software to calculate the pooled ACPR. Statistical heterogeneity was evaluated with the Cochran chi-square test (X2) test and inverse variance index (I2). Publication bias was analyzed using funnel plots and Egger’s test statistics. The review protocol is registered in PROSPERO, number CRD42020201859.Results: Out of studies screened, fifteen studies fulfilled the inclusion criteria, and were included in final analysis with a total number of 1523 participants. Treatment success of AL for uncomplicated falciparum malaria in all combined studies was 98.4% [(95% CI 97.6–99.1), P< 0.001]. Polymerase chain reaction (PCR)-corrected AL treatment success rate of 98.7% [(95% CI 97.7-99.6), P<0.001)]. The efficacy of AL with PCR-corrected cure rates ranging from 95.0 to 99.4% in per-protocol analysis, and 88.8 to 97.4% in intention-to-treat analysis. Based on the analysis, Cochrane chi-square test (X2) test and inverse variance index (I2) indicated that the included studies with heterogeneity (X2=20.48, (df=14), P=0.116 and I2=31.65%). The highest parasite positivity rate at day-3 was 5.7%. Adverse events ranged from mild to serious but were not directly attributed to the drug.Conclusion: The present review has shown that AL is efficacious and safe for treatment of uncomplicated malaria in Ethiopia. However, few therapeutic efficacy studies were conducted in Ethiopia after treatment guideline was revised in 2004. AL has been used more than a decade in the study population without other alternative artemisinin-based combination therapy in Ethiopia and considering that the potential evolution of drug resistance is of a great concern, regular and continuous monitoring of its efficacy is warranted.