Skip to main content
SearchLoginLogin or Signup

Reviews of "Artemether-lumefantrine-amodiaquine or Artesunate-amodiaquine Combined with Single Low-dose Primaquine to Reduce Plasmodium Falciparum Malaria Transmission in Ouelessebougou, Mali: A Five-arm, Phase 2, Single-blind, Randomised Clinical Trial"

Reviewers: J Möhrle (Medicines for Malaria Venture) | 📘📘📘📘📘 • M Randrianarivelojosia (Institut Pasteur de Madagascar) | 📘📘📘📘📘 • I Lamine (Centre de Recherche Médicale et Saniatire) | 📘📘📘📘📘

Published onJun 06, 2024
Reviews of "Artemether-lumefantrine-amodiaquine or Artesunate-amodiaquine Combined with Single Low-dose Primaquine to Reduce Plasmodium Falciparum Malaria Transmission in Ouelessebougou, Mali: A Five-arm, Phase 2, Single-blind, Randomised Clinical Trial"
key-enterThis Pub is a Review of
Artemether-lumefantrine-amodiaquine or artesunate-amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised clinical trial
Artemether-lumefantrine-amodiaquine or artesunate-amodiaquine combined with single low-dose primaquine to reduce Plasmodium falciparum malaria transmission in Ouélessébougou, Mali: a five-arm, phase 2, single-blind, randomised clinical trial
Description

Summary Background Triple artemisinin-based combination therapies, such as artemether-lumefantrine-amodiaquine, can delay the spread of antimalarial drug resistance; artesunate-amodiaquine is widely used for uncomplicated Plasmodium falciparum malaria. We aimed to determine the efficacy of artemether-lumefantrine-amodiaquine and artesunate-amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.Methods We conducted a five-arm, single-blind, phase 2, randomised clinical trial at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Sciences, Techniques and Technologies of Bamako (Bamako, Mali). Eligible participants aged 10-50 years, with asymptomatic P. falciparum microscopy-detected gametocyte carriage, were randomised (1:1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine-amodiaquine, artemether-lumefantrine-amodiaquine plus primaquine, artesunate-amodiaquine, or artesunate-amodiaquine plus primaquine. Treatment allocation was computer randomised and concealed to all study staff other than the trial pharmacist. The primary outcome was the within-person percentage reduction in mosquito infection rate at 48 hours after treatment initiation compared to pre-treatment, assessed by direct membrane feeding assay. Data were analysed per protocol. This study is registered with ClinicalTrials.gov, NCT05550909.Findings Between Oct 16 and Dec 28, 2022, 1249 individuals were screened for eligibility, 100 of which were enrolled and randomly assigned to one of five treatment groups (n=20 per group). Before treatment, 61 (61%) of 100 participants were infectious to mosquitoes, with a median of 7·3% (IQR 3·2-23·5) of mosquitoes becoming infected. Among infectious individuals, the median percentage reduction in mosquito infection rate between pre-treatment and 2 days post-treatment was 100% (IQR 100-100) in the artemether-lumefantrine (p=0·0018), artemether-lumefantrine-amodiaquine (p=0·0018), and artemether-lumefantrine-amodiaquine plus primaquine (p=0·0009) treatment groups. In the artesunate-amodiaquine group the median percent reduction in mosquito infection rate was only 31·67% (IQR -10·9-100, p=0·1927), whereas there was 100% reduction in the artesunate-amodiaquine plus primaquine group (p=0·0009). At day 2, 10% (2/20) of participants in the artemether-lumefantrine group, 11% (2/19) in the artemether-lumefantrine-amodiaquine group, and 75% (15/20) in the artesunate-amodiaquine group infected any number of mosquitoes whilst no infected mosquitoes were observed at this time-point in the primaquine arms. No serious adverse events occurred.Interpretation These data support the effectiveness of artemether-lumefantrine alone or as part of triple combination therapy for preventing nearly all human-mosquito malaria parasite transmission within 48 hours. In contrast, substantial transmission was observed following treatment with artesunate-amodiaquine. The addition of a single low-dose of primaquine blocks transmission to mosquitoes rapidly regardless of schizonticide.Funding Bill & Melinda Gates Foundation

To read the original manuscript, click the link above.

Summary of Reviews: The study investigates the effect of adding a single low dose of primaquine to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine-amodiaquine (ALAQ) on reducing mosquito infectivity 48 hours after treatment initiation. The authors found that the combination significantly decreases Plasmodium falciparum transmission. The reviewers found the evidence and study results to be strong and significant, respectively. However, they note the need for clarification and corrections. The title is misleading as it only mentions two of the five treatment arms, and there are questions regarding the blinding of participants and compliance with the study treatment. There are also minor typographical errors and issues with the study's methodological details that need addressing. 

Reviewer 1 (Jörg M…) | 📘📘📘📘📘

Reviewer 2 (Milijaona R…) | 📘📘📘📘📘

Reviewer 3 (Ibrahim L…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

Connections
1 of 3
Comments
0
comment
No comments here
Why not start the discussion?