Comparative effect of dihydroartemisinin-piperaquine and artemether-lumefantrine on gametocyte clearance and haemoglobin recovery in children with uncomplicated Plasmodium falciparum malaria in Africa: a systematic review and meta-analysis of randomized control trials

Assefa, Dawit; Yismaw, Gizachew; Makonnen, Eyasu

doi:10.1016/j.ijid.2021.10.013

Cited by 3 publications

(2 citation statements)

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“…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.…”

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confidence: 99%

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

Assefa

Zeleke

Molla

et al. 2022

Malar J

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Background The efficacies of artemisinin based combinations have been excellent in Africa, but also comprehensive evidence regarding their safety would be important. The aim of this review was to synthesize available evidence on the safety of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated Plasmodium 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 Center for Clinical Trial database (CENTRAL) for retrieving randomized control trials comparing safety of DHA-PQ and AL for treatment of uncomplicated P. falciparum malaria among children in Africa. The search was performed from August 2020 to 30 April 2021. Using Rev-Man software (V5.4.1), the extracted data from eligible studies were pooled as risk ratio (RR) with 95% confidence interval (CI). Results In this review, 18 studies were included, which involved 10,498 participants were included. 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), cough (RR 1.06, 95% CI 1.01 to 1.11; participants = 8013; studies = 13; I2 = 0%, high quality of evidence), and diarrhoea (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 early vomiting, diarrhoea, and cough were common were significantly more frequent in patients who were treated with the DHA-PQ than that of AL, and both drugs are well tolerated. More studies comparing AL with DHA-PQ are needed to determine the comparative safety of these drugs.

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Section: Introductionmentioning

confidence: 99%

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

Assefa

Zeleke

Molla

et al. 2022

Malar J

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“…In Africa, the most frequently used ACTs are artemether + lumefantrine (LMF) and artesunate + amodiaquine. A third ACT, dihydroartemisinin + piperaquine (DHA + PPQ), has shown 99% efficacy in curing uncomplicated malaria in African settings, as per a recent meta-analysis [ 5 , 6 ]. Dihydroartemisinin + PPQ is also proving to be effective for seasonal malaria chemoprevention (defined by the World Health Organization as the intermittent administration of full treatment courses of an antimalarial medicine to children during the malaria season in areas of highly seasonal transmission) as well as intermittent preventative treatment of pregnant women and infants (involving the administration of full therapeutic courses of an antimalarial medicine to pregnant women and infants to prevent adverse consequences of malaria infection), with DHA + PPQ having an advantage over combinations containing SP that can encounter SP-resistant parasites.…”

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Mutant PfCRT Can Mediate Piperaquine Resistance in African Plasmodium falciparum With Reduced Fitness and Increased Susceptibility to Other Antimalarials

Wicht

Small-Saunders

Hagenah

et al. 2022

The Journal of Infectious Diseases

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Background Additional therapeutic strategies could benefit efforts to reverse the recent increase in malaria cases in sub-Saharan Africa, affecting mostly young children. A primary candidate is dihydroartemisinin + piperaquine (DHA + PPQ), which is effective for uncomplicated malaria treatment, seasonal malaria chemoprevention, and intermittent preventive treatment. In Southeast Asia, Plasmodium falciparum parasites acquired PPQ resistance, mediated primarily by mutations in the P. falciparum chloroquine resistance transporter PfCRT. The recent emergence in Africa of DHA-resistant parasites creates an imperative to assess whether PPQ resistance could emerge in African parasites with distinct PfCRT isoforms. Methods We edited two PfCRT mutations known to mediate high-grade PPQ resistance in Southeast Asia into GB4 parasites from Gabon. Gene-edited clones were profiled in antimalarial concentration-response and fitness assays. Results The PfCRT F145I mutation mediated moderate PPQ resistance in GB4 parasites but with a substantial fitness cost. No resistance was observed with the PfCRT G353V mutant. Both edited clones became significantly more susceptible to amodiaquine, chloroquine, and quinine. Conclusions A single PfCRT mutation can mediate PPQ resistance in GB4 parasites, but with a growth defect that may preclude its spread without further genetic adaptations. Our findings support regional use of drug combinations that exert opposing selective pressures on PfCRT.

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Antimalarial Drug Strategies to Target Plasmodium Gametocytes

Munro

McMorran

2022

Parasitologia

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Onward transmission of Plasmodium falciparum from humans to mosquitoes is dependent upon a specialised transmission stage called the gametocyte. Despite its critical role in transmission, key questions regarding gametocyte biology remain to be answered, and there are no widely prescribed therapeutics to eliminate them. Advances in our understanding of the biology of the gametocyte in combination with growing information regarding the mechanism of action of anti-plasmodial therapies provide an emerging view as to which of the biological processes of the gametocyte present viable targets for drug intervention and explain the variable activity of existing therapies. A deeper understanding of the gametocyte and transmission stages of P. falciparum is a path to identifying and characterising novel drug targets. This review will examine how a selection of current and potential gametocytocidals mediate their effect.

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Comparative effect of dihydroartemisinin-piperaquine and artemether-lumefantrine on gametocyte clearance and haemoglobin recovery in children with uncomplicated Plasmodium falciparum malaria in Africa: a systematic review and meta-analysis of randomized control trials

Abstract: parative effect of dihydroartemisinin-piperaquine versus artemether-lumefantrine on gametocyte clearance and hemoglobin recovery in children with uncomplicated Plasmodium falciparum malaria in Africa: a systematic review and meta-analysis of randomized control trials,

Cited by 3 publications

References 58 publications

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

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

Mutant PfCRT Can Mediate Piperaquine Resistance in African Plasmodium falciparum With Reduced Fitness and Increased Susceptibility to Other Antimalarials

Antimalarial Drug Strategies to Target Plasmodium Gametocytes

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