Efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials

Abstract

Background Emergence of Plasmodium falciparum resistance to artemisinin and its derivatives poses a threat to the global effort to control malaria. The emergence of anti-malarial resistance has become a great public health challenge and continues to be a leading threat to ongoing malaria control efforts. The aim of this review was to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria among children in Africa. Methods A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Central Register of Controlled Trials’ database (CENTRAL) for retrieving randomized control trials comparing efficacy of DHA-PQ and AL for treatment of uncomplicated falciparum malaria in African children. The search was performed from August 2020 to April 2021. Using Rev-Man software (V5.4.1), R-studio and Comprehensive Meta-analysis software version 3, the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI). Results 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 the DHA-PQ treatment arm on day 28 than that of AL (RR 0.14, 95% CI 0.08–0.26; 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 0.29–0.68; participants = 8508; studies = 16; I2 = 51%, high quality of evidence) and on day 42 (RR 0.60, 95% CI 0.47–0.78; participants = 5959; studies = 17; I2 = 0%, high quality of evidence). However, the efficacy was ≥ 95% in both treatment groups on day 28. Conclusion From this review, it can be concluded that DHA-PQ reduces new infection and recrudescence on days 28 and 42 more than AL. This may trigger DHA-PQ to become a first-line treatment option.

Safety of dihydroartemisinin-piperaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria among children in Africa: a systematic review and meta-analysis of randomized control trials

“…To determine whether the co-administered milk may also affect this interaction further assessment might be needed [ 60 ]. However, the absence of effect with AL implies that the mechanism is given to DHA–PQ, most likely piperaquine [ 17 ]. Regardless of the treatment groups, most of these adverse events are associated with age (≤ 18 years), efavirenz-based ART [ 52 ], efavirenz-based ART [ 53 ], and administration of DHA-PQ with food could increase piperaquine exposure and it needs to be administered in fasting state [ 53 , 54 , 61 ].…”

“…In the majority of African countries, the first-line treatment for uncomplicated malaria is generally AL or AS/AQ, with DHA-PQ as a second-line treatment in many countries [ 11 , 12 ]. Most of the previous studies have compared the efficacies of AL and other artemisinin-based combinations [ 17 , 18 ], but also comprehensive evidence regarding their safety would be important. Given the wide range of ACT available for treatment the malaria and their potential adverse events (AEs), it is vital to compare their safety profiles.…”