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Item does not contain fulltext, BACKGROUND: Pyronaridine-artesunate is the most recently licensed artemisinin-based combination therapy. WHO has recommended that a single low dose of primaquine could be added to artemisinin-based combination therapies to reduce Plasmodium falciparum transmission in areas aiming for elimination of malaria or areas facing artemisinin resistance. We aimed to determine the efficacy of pyronaridine-artesunate and dihydroartemisinin-piperaquine with and without single low-dose primaquine for reducing gametocyte density and transmission to mosquitoes. METHODS: We conducted a four-arm, single-blind, phase 2/3, randomised trial at the Ouélessébougou Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako (Bamako, Mali). Participants were aged 5-50 years, with asymptomatic P falciparum malaria mono-infection and gametocyte carriage on microscopy, haemoglobin density of 9·5 g/dL or higher, bodyweight less than 80 kg, and no use of antimalarial drugs over the past week. Participants were randomly assigned (1:1:1:1) to one of four treatment groups: pyronaridine-artesunate, pyronaridine-artesunate plus primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus primaquine. Treatment allocation was concealed to all study staff other than the trial pharmacist and treating physician. Dihydroartemisinin-piperaquine and pyronaridine-artesunate were administered as per manufacturer guidelines over 3 days; primaquine was administered as a single dose in oral solution according to bodyweight (0·25 mg/kg; in 1 kg bands). The primary endpoint was percentage reduction in mosquito infection rate (percentage of mosquitoes surviving to dissection that were infected with P falciparum) at 48 h after treatment compared with baseline (before treatment) in all treatment groups. Data were analysed per protocol. This trial is now complete, and is registered with ClinicalTrials.gov, NCT04049916. FINDINGS: Between Sept 10 and Nov 19, 2019

Contains fulltext : 251206.pdf (Publisher’s version ) (Open Access), BACKGROUND: Tafenoquine was recently approved as a prophylaxis and radical cure for Plasmodium vivax infection, but its Plasmodium falciparum transmission-blocking efficacy is unclear. We aimed to establish the efficacy and safety of three single low doses of tafenoquine in combination with dihydroartemisinin-piperaquine for reducing gametocyte density and transmission to mosquitoes. METHODS: In this four-arm, single-blind, phase 2, randomised controlled trial, participants were recruited at the Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako in Mali. Eligible participants were aged 12-50 years, with asymptomatic P falciparum microscopy-detected gametocyte carriage, had a bodyweight of 80 kg or less, and had no clinical signs of malaria defined by fever. Participants were randomly assigned (1:1:1:1) to standard treatment with dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus a single dose of tafenoquine (in solution) at a final dosage of 0·42 mg/kg, 0·83 mg/kg, or 1·66 mg/kg. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. Dihydroartemisinin-piperaquine was administered as oral tablets over 3 days (day 0, 1, and 2), as per manufacturer instructions. A single dose of tafenoquine was administered as oral solution on day 0 in parallel with the first dose of dihydroartemisinin-piperaquine. Tafenoquine dosing was based on bodyweight to standardise efficacy and risk variance. The primary endpoint, assessed in the per-protocol population, was median percentage change in mosquito infection rate 7 days after treatment compared with baseline. Safety endpoints included frequency and incidence of adverse events. The final follow-up visit was on Dec 23, 2021; the trial is registered with ClinicalTrials.gov, NCT04609098. FINDINGS: From Oct 29 to Nov 25, 2020, 1091 individuals were screened for eligibility, 80 of whom were enrolled and randomly assig

The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up of NMCP-led malaria control interventions has led to considerable progress, as evidenced by multiple malariometric indicators. The West Africa International Center of Excellence in Malaria Research (WA-ICEMR) is a multidisciplinary research program that works closely with the NMCP and its partners to address critical research needs for malaria control. This coordinated effort includes assessing the effectiveness of control interventions based on key malaria research topics, including immune status, parasite genetic diversity, insecticide and drug resistance, diagnostic accuracy, malaria vector populations and biting behaviors, and vectorial capacity. Several signature accomplishments of the WA-ICEMR include identifying changing malaria age demographic profiles, testing innovative approaches to improve control strategies, and providing regular reporting on drug and insecticide resistance status. The NMCP and WA-ICEMR partnership between the WA-ICEMR and the NMCP offers a comprehensive research platform that informs the design and implementation of malaria prevention and control research programs. These efforts build local expertise and capacity for the next generation of malaria researchers and guide local policy, which is crucial in sustaining efforts toward eliminating malaria in West Africa.

Item does not contain fulltext, Background: The World Health Organization recommendation on the use of a single low dose of primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria transmission requires more safety data. Methods: We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11-17 years and those aged 5-10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days after treatment. Results: Fifty-one participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n = 4) were mild. The mean largest within-person percentage change in hemoglobin level between days 0 and 10 was -9.7% (95% confidence interval [CI], -13.5% to -5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, -11.5% (95% CI, -16.1% to -6.96%) in G6PD-deficient boys aged 11-17 years, and -9.61% (95% CI, -7.59% to -13.9%) in G6PD-deficient boys aged 5-10 years. The lowest hemoglobin concentration at any point during the study was 92 g/L. Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD-deficient males in Mali. Clinical Trials Registration: NCT02535767.