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SOUGUE, E.

Publications and source records attributed to SOUGUE, E..

2 recordsLinked to original sources

Efficacy of a long lasting ivermectin formulation against malaria vectors in a semi-field trial in Bapla, Southwest of Burkina Faso

BackgroundIvermectin, a widely used endectocide with activity against Anopheles (An) mosquitoes, has emerged as a promising complementary tool for malaria vector control. However, currently approved oral formulations provide only short-lived plasma concentrations at mosquitocidal levels, thereby limiting their operational impact. To overcome this limitation, a long-acting injectable formulation based on ivermectin and BEPO technology (mdc-STM-001) was selected through laboratory screening using mosquito colonies. This formulation demonstrated mosquitocidal efficacy meeting WHO criteria, with a hazard ratio (HR) >4 maintained for at least two months. The present study aims to further characterize the efficacy of ivermectin under robust field conditions and to expand susceptibility assessments to wild Anopheles populations representing different species and vectorial status. Ivermectin was tested in cattle at two doses under field conditions using experimental huts and tent traps. Plasma drug levels were also monitored to characterize the pharmacokinetic profile of ivermectin. MethodsThirty-six calves were involved in the study and allocated to three groups (n = 12 per group). The mdc-STM-1.0 group received a single subcutaneous injection of the long-acting ivermectin formulation mdc-STM-001 at a dose of 1.0 mg/kg; the mdc-STM-1.5 group received the same formulation at 1.5 mg/kg and the third group served as controls. Using a three-arm design, cattle from each treatment group were simultaneously exposed to mosquitoes in experimental huts and tent traps, following a Greco-Latin Square rotation to minimize positional confounding factors. Pharmacokinetic data were collected to assess ivermectin release from the subcutaneous depot. Correlations between plasma ivermectin concentrations and mosquito mortality were explored, and survival analysis including Kaplan-Meier and cox proportional hazards models were performed to assess the effect of treatment on mosquito survival. ResultsThe mdc-STM-001 formulation was well tolerated and produced sustained, dose-dependent plasma ivermectin concentrations, with detectable levels maintained for more than 90 days after a single administration. Both doses induced strong mosquitocidal activity against wild Anopheles, with hazard ratios reaching 8.03 and 16.47 for the 1.0 and 1.5 mg/kg doses, respectively. An. funestus and An. rufipes were the most susceptible species (LC50: 5.1-6.9 ng/mL) exhibiting prolonged LC50 coverage (>75 days), whereas An. coustani was less susceptible (LC50: 12.4-19.2 ng/mL) resulting in a shorter duration of effective coverage (17-41 days). ConclusionsTaken together, our results revealed the potential of the mdc-STM-001 long-acting ivermectin formulation as an effective endectocide against residual malaria transmission by primary and secondary vectors and establish evidence basis to support its progression to early-phase clinical trials in humans.

ecology↗

Effect of pharmacokinetically-relevant ivermectin concentrations on survivorship and fecundity of Anopheles coluzzii and Aedes aegypti in Burkina Faso: a laboratory experimental study

BackgroundThe control of vector-borne diseases is increasingly challenged by widespread insecticide resistance. Therefore, innovative vector control strategies with alternative modes of action are urgently needed. Ivermectin (IVM), an endectocide, has demonstrated toxicity to mosquito species such as Anopheles and Aedes when they feed on treated humans or livestock. In this study, we conducted a laboratory experiment to assess the effect of IVM, at concentrations equivalent to human plasma levels following mass drug administration (MDA), on the survival and fecundity of Anopheles coluzzii and Aedes aegypti in Burkina Faso. MethodsTwo laboratory experiments were conducted using 3-5-day old wild-derived female An. coluzzii and Aedes aegypti. Each experiment included four replicates per IVM concentration and was performed on separate dates. Mosquitoes were fed via membrane feeding on rabbit blood treated with five concentrations of IVM (C=112 ng/ml, C2=29 ng/ml, C3=15 ng/ml, C4=6.5 ng/ml, C5=2.5ng/ml), corresponding to the mean human plasma levels at 2, 4, 7, 14, and 28 days post-MDA with IVM at a dose of 300 g/kg. A negative control (C6=0.0 ng/ml) was also included. Mosquito mortalities were recorded daily for 7 days. Fecundity was measured by counting both laid eggs and developed eggs (via ovary dissection). ResultsIVM significantly reduced the survival of An. coluzzii compared to the control group (p<0.001), with the risk of death increasing from 4.2-fold at the lowest concentration (2.5 ng/ml) to 64.2-fold at the highest (112 ng/ml). In contrast, IVM had no significant effect on Aedes aegypti (p>0.05). Additionally, in An. coluzzii, IVM significantly reduced both egg laying and egg development (p<0.0001 and p<0.001, respectively), whereas no significant impact on fecundity was observed in Ae. aegypti (all p>0.80). ConclusionIvermectin concentrations typically achieved in human plasma during mass drug administration campaigns were sufficient to significantly reduce both survival and fecundity of wild type An. coluzzii, but had no measurable effect on recently colonized Ae. aegypti. These findings highlight the species-specific efficacy of ivermectin and support its potential role in integrated vector control strategies targeting malaria vectors in Africa.

zoology↗