Comparison of efficacy and safety of dihydroartemisinin- piperaquine versus artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in African children: Systematic review and metaanalysis of randomized control trials

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Addis Abeba University


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. While the concern on resistance in South East Asia but with potential benefits of DHA-PQ over other ACTs, it is necessary to assess if the antimalarial treatment efficacy of this regimen in Africa has changed. 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: An electronic systematic search method was used to search for articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL) for repossessing randomized control trials comparing efficacy and safety of DHA-PQ and AL for management of uncomplicated Plasmodium falciparum malaria in African children. The search was done from August 2020 to 30 April 2021. Using Rev-Man software (V5.4), R-studio, and Comprehensive Meta-analysis software, the data obtained from the included studies were assembled as risk ratio (RR), MD, and SMD with 95% confidence interval (CI). The per-protocol analysis was used. 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 to 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; I 2 = 0%, high quality of evidence). Consistently, the risk of treatment failure adjusted by PCR 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; I 2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47 to 0.78; participants = 5959; studies = 17; I 2 = 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; I = 32%, high quality of evidence) and (MD 0.35, 95% CI 0.12 to 0.59; participants = 1434; studies = 3; I 2 = 35%, high quality of evidence), respectively. However, DHA-PQ was somewhat coupled with a higher incidence of early vomiting (RR 2.26, 95% CI 1.46 to 3.50; participants = 7796; studies = 10; I 2 = 0%, high quality of evidence), vomiting (RR 1.02, 95% CI 0.87 to 1.19; participants = 8789; studies = 13; I 2 = 20%, high quality of evidence), cough (RR 1.06, 95% CI 1.01 to 1.11; participants = 8013; studies = 13; I 2 = 0%, high quality ofevidence), and diarrhea (RR 1.16, 95% CI 1.03 to 1.31; participants = 6841; studies = 11; I = 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 recurrent infection and recrudescence with significant impact on hemoglobin recovery more than AL, and bothdrugs are well tolerated. DHA-PQ may, therefore be recommended as an alternative first linetreatment for uncomplicated falciparum malaria in Africa, while use of AL continues.



Uncomplicated Plasmodium falciparum, children, Randomized control trial, Artemisinin combination therapies, Dihydroartemisinin-piperaquine, Artemetherlumefantrine, Systematic review and meta-analysis, Africa