Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial

Abstract

Malaria Eradication Scientific Alliance (MESA) and US Centers for Disease Control and Prevention (CDC).

Optimizing systemic insecticide use to improve malaria control

“…isoxazolines and spinosyns) could be selected or alternative ways to achieve higher concentrations of drug for longer periods of time could be applied. Recently, a study demonstrated the tolerability of high doses of ivermectin in humans and the resulting increase in time that the blood was lethal to mosquitoes (47). An alternative to increasing the concentration of the delivered dose, a number of adjuvants have been reported to improve the absorption or extend the half-life of systemic insecticides, such as lipids for lipophilic drugs (48, 49) or efflux pump inhibitors that remove xenobiotics (50–54), respectively.…”

Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modeling study of three potential use cases

“…The implications for more complex within-host insecticide dynamics can be interpolated from the results presented here. For example, a 300ug/kg ivermectin dose can be compared with the modeled hypothetical SI-14 [15]. Our model also does not incorporate possible non-fatal vector outcomes of the systemic insecticide such as reduced fecundity, nor did we model any parasite killing effects since these outcomes are not well understood and the effects are likely secondary to killing the mosquito [19].…”

“…The duration of ivermectin efficacy can be extended via multiple doses over the course of weeks, but this could prove operationally challenging to deliver at scale. There has been recent interest in developing longer-lasting systemic insecticide formulations for malaria control and potential elimination, including slow release formulations [12] and high-dose ivermectin, which has been observed to reduce mosquito survival 28 days post-treatment in the field [15]. A recent study in Burkina Faso observed a 20% reduction in clinical incidence in an intervention group receiving ivermectin 6 times over 18 weeks at 3 week intervals, with young children, pregnant women, and women nursing newborns excluded from MDA eligibility [16].…”

“…Previous mathematical modeling has suggested that high-dose ivermectin can marginally improve the impact of antimalarial MDAs [15,19], a new long-lasting systemic insecticide with high efficacy lasting 30 days can substantially reduce burden when distributed with seasonal malaria chemoprevention (SMC) [13], and MDA with an isoxazoline lasting 90 days can also reduce burden in high-transmission areas [17]. However, there has not been a systematic exploration of the potential impact of long-lasting systemic insecticides across multiple use cases within the same modeling framework.…”

A systematic review and meta-analysis of the human blood index of the major African malaria vectors

“…Drugs approved for veterinary use, such as fipronil, have subsequently been demonstrated to have similar impact when livestock are dosed orally, or when the chemical is applied topically [11]. More recently, systemic insecticides have had durations of their efficacy extended through dosing with higher concentrations [12], combined dosing with adjuvants [13], and with use of sustained-release devices [14]. The stage is set for progress in development and evaluation of ivermectin for vector control [15].…”