Efficacy and Safety of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for Treatment of Uncomplicated Plasmodium Falciparum Malaria In African Children: A Systematic Review And Meta-Analysis of Randomized Control Trials
Authors: Assefa Dawit Getachew , Yesmaw Gizachew , Makonnen Eyasu 
Published: May 2021

Abstract
Background: Emergence of Plasmodium falciparum resistance to artemisinin and its derivatives poses a threat to global effort in controlling malaria. Resistance has already emerged to most antimalarial drugs in common use. On the other hand, significant number of the developing world in genral and African population in particular is sufferring from malaria of whom many are children.The aim of this review was, therefore, to compare the efficacy and safety of dihydroartemisinin-piperaquine and artemether-lumefantrine for treatment of uncomplicated P.falciparum malaria in African children.Method: A computerized systematic search method was used to search for articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL) for retrieving randomized control trials comparing efficacy and safety of DHA-PQ and AL for treatment of uncomplicated P.falciparum malaria in African children. The search was performed from August 2020 to 30 April 2021. Using Rev-Man software (V5.4), R-studio, and Comprehensive Meta-analysis software, the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI).Result: In this review, 25 studies which involved a total of 13,198 participants were included. PCR unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in DHA-PQ treatment arm on day 28 than that of AL (RR 0.14, 95% CI 0.08 to 0.26; participants = 1302; studies = 4; I2 = 0%, high quality of evidence). Consistently, the PCR adjusted treatment failure was significantly lower with DHA-PQ treatment group on day 28 (RR 0.45, 95% CI 0.29 to 0.68; participants = 8508; studies = 16; I2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47 to 0.78; participants = 5959; studies = 17; I2 = 0%, high quality of evidence). However, the efficacy was ≥95% in both treatment groups on day 28. On days 28 and 42, a significant increase in serum hemoglobin level from the baseline was also observed in DHA-PQ treatment arm (SMD 0.15, 95% CI 0.05 to 0.26; participants = 2715; studies = 4; I2 = 32%, high quality of evidence) and (MD 0.35, 95% CI 0.12 to 0.59; participants = 1434; studies = 3; I2 = 35%, high quality of evidence), respectively. Compared to AL, DHA-PQ was associated with a slightly higher frequency of early vomiting (RR 2.26, 95% CI 1.46 to 3.50; participants = 7796; studies = 10; I2 = 0%, high quality of evidence), vomiting (RR 1.02, 95% CI 0.87 to 1.19; participants = 8789; studies = 13; I2 = 20%, high quality of evidence), cough (RR 1.06, 95% CI 1.01 to 1.11; participants = 8013; studies = 13; I2 = 0%, high quality of evidence), and diarrhea (RR 1.16, 95% CI 1.03 to 1.31; participants = 6841; studies = 11; I2 = 8%, high quality of evidence) were more frequent in DHA-PQ treatment arm.Conclusion: From this review, it can be concluded that DHA-PQ reduces new infection and recrudescence with significant impact on hemoglobin recovery more than AL, and both drugs are well tolerated. DHA-PQ may, therefore be recommended as a first line treatment for uncomplicated P.falciparum malaria in Africa, while use of AL continues.