Abstract
BackgroundThe emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch13 propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. The objective of this study was to compare the efficacy and safety of dihydroartemisinin–piperaquine (DHA–PQ) and artemether–lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Ugandan children.MethodsA search of PubMed and the Cochrane Central Register of Controlled Trials for retrieving randomized controlled trials comparing the efficacy and safety of DHA–PQ and AL for treatment of uncomplicated falciparum malaria in Ugandan children was done. The search was performed up to 31 August 2020. The data extracted from eligible studies and pooled as risk ratio (RR) with a 95% confidence interval (CI), using Rev Man Software (5.4). The protocol was registered in PROSPERO, ID: CRD42020182354.ResultsEleven trials were included in this review and two of them only included under safety outcome. Total 3798 participants were enrolled. The PCR unadjusted treatment failure was significantly lower with DHA–PQ at day 28 (RR 0.30, 95% CI 0.19–0.49; participants = 7863; studies = 5; I2 = 93%, low quality evidence) and at day 42 (RR 0.53, 95% CI 0.38–0.76; participants = 1618; studies = 4; I2 = 79%, moderate quality of evidence). The PCR adjusted treatment failure at day 42 was significantly lower with DHA–PQ treatment group (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5, high quality of evidence), and it was below 5% in both arms at day 28 (moderate quality of evidence). AL showed a longer prophylactic effect on new infections which may last for up to 63 days (PCR-adjusted treatment failure: RR 2.04, 95% CI 1.13–3.70; participants = 1311; studies = 2, moderate quality of evidence). Compared to AL, DHA–PQ was associated with a slightly higher frequency of cough (RR 1.07, 95% CI 1.01 to 1.13; 2575 participants; six studies; high quality of evidence). In both treatment groups, the risk of recurrent parasitaemia due to possible recrudescence was less than 5% at day 28. The appearance of gametocyte between 29 and 42 days was also significantly lower in DHA–PQ than AL (RR 0.26, 95% CI 0.12 to 0.56; participants = 623; studies = 2; I2 = 0%).ConclusionCompared to AL, DHA–PQ appeared to reduce treatment failure and gametocyte carriage in Ugandan children. This may trigger DHA–PQ to become the first-line treatment option. Both treatments were safe and well-tolerated.
Highlights
The emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch13 propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria
At day 28, in two studies with HIV negative participants, the Polymerase Chain Reaction (PCR) unadjusted treatment failures was significantly lower for participants treated with DHA–PQ than those treated with AL (RR 0.52, 95% confidence interval (CI) 0.39 to 0.70; participants = 949; studies = 2; I2 = 25%, Fig. 3)
PCR‐adjusted total failure at day 42 The overall PCR adjusted treatment failures was lower for participants treated with DHA–PQ than those treated with AL (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5; I2 = 3%, Fig. 6)
Summary
The emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. Malaria remains the major cause of mortality and morbidity in sub-Saharan Africa. According to the 2019 World Malaria report, there were 228 million cases and 405,000 deaths due to malaria in 2018, where 93% of cases and 94% of deaths were from Africa [1,2,3]. Plasmodium falciparum was the predominant and lifethreatening parasite in Africa, causing 99.7% of estimated malaria cases in Africa [3]. According to the country’s 2016 national Demographic Health Survey (DHS), the prevalence of malaria had not been reduced nationally and P. falcipa‐ rum remains the species responsible for the vast majority of malaria cases, and the number of malaria cases was increasing in the country, except the West Nile region [5]
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