ArticleParasites & vectors2026
Selection of the optimal long-acting injectable formulation of ivermectin for use in humans to target malaria vectors in Western Africa: evaluation of pharmacokinetics and mosquitocidal efficacy in cattle under laboratory conditions.
Article in Parasites & vectors, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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15 authors.
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Abstract
backgroundIvermectin, a semisynthetic endectocide, is widely used against parasitic nematodes in humans and animals. Its lethality to Anopheles mosquitoes that have fed on treated hosts represents a promising malaria control strategy, particularly against outdoor transmission. However, standard oral formulations for use in humans produce short-lived mosquitocidal blood concentrations, limiting epidemiological impact. To meet WHO Preferred Product Characteristics (PPC) for endectocides against malaria vectors (hazard ratio [HR] > 4 for at least 1 month), we developed three long-acting injectable ivermectin formulations (LAIFs) based on BEPO® depot technology (MedinCell, Jacou, France) and compared these in cattle to identify the most suitable candidate for future use in humans.
methodsA cattle-Anopheles model was used under laboratory conditions in Bobo-Dioulasso, Burkina Faso. Three LAIF candidates (mdc-STM-001, mdc-STM-002, mdc-STM-003) were injected into calves (n = 5 per formulation) at 0.6 mg/kg body weight, with untreated calves as controls (n = 5). Plasma ivermectin concentrations were measured over 130 days post-injection and analyzed using non-compartmental pharmacokinetics. Direct skin feeding assays were conducted at 15 time points (days 2-126 post-injection) using insecticide-susceptible Anopheles gambiae Kisumu (KIS) and wild-derived resistant (VK5) Anopheles colonies. Efficacy was assessed based on 10-day cumulative mortalities, HRs, 50% lethal concentrations (LC50) and duration of exposure above the 10-day LC50, also accounting for the extrinsic incubation period of Plasmodium falciparum.
resultsAll formulations were well tolerated. The mdc-STM-001 formulation showed the most favorable pharmacokinetic (PK) profile, with a controlled peak concentration (Cmax) of 34.5 ± 12.7 ng/ml and the lowest inter-individual variability (12%). Ten-day HRs exceeded 4 and cumulative mortalities were > 50% for at least 60 days in both strains. Median mosquito lifespan remained below 10 days for at least 90 days post-injection. The 10-day LC50 for resistant mosquitoes (3.66, 95% confidence interval 2.69-4.97 ng/ml) was maintained for ≥ 126 days.
conclusionsThe mdc-STM-001 formulation was identified as the optimal candidate for future use in humans. A single injection induced sustained mosquitocidal efficacy for at least 2 months, achieving HR > 4 against both susceptible and resistant Anopheles populations and meeting WHO PPC for malaria endectocides. Although extrapolation from cattle to humans requires caution, the favorable PK profile and robust entomological outcomes support progression to phase 1 clinical trials. Ivermectin's established safety record further strengthens the rationale for clinical development.
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