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

Malar J. 2021 Aug 12;20(1):340. doi: 10.1186/s12936-021-03873-1.

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.

Keywords: Africa; Artemether-lumefantrine; Artemisinin combination therapy; Children; Dihydroartemisinin-piperaquine; Randomized control trial; Systematic review and meta-analysis; Uncomplicated Plasmodium falciparum.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adolescent
  • Africa
  • Antimalarials / administration & dosage
  • Antimalarials / therapeutic use*
  • Artemether, Lumefantrine Drug Combination / therapeutic use*
  • Artemisinins / administration & dosage
  • Artemisinins / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Combinations
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy*
  • Polymerase Chain Reaction / standards
  • Quality Control
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Regression Analysis
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Quinolines
  • artenimol
  • piperaquine