Optimising systemic insecticide use to improve malaria control

Abstract

BackgroundLong-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability.MethodsHere, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation.ResultsThe review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations.ConclusionsThese findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission.

Endectocides as a complementary intervention in the malaria control program: a systematic review

“…Among the 21 vector control tools evaluated in a review (shrinkingthemalariamap. org), less than 10 were supported by phase II or phase I evaluation of ivermectin, fipronil, and eprinomectin as endectocide administration in humans/animals, showing the rich pipeline of research into them at earlier stages of evaluation [11]. Endectocides are drugs applied directly to hosts to kill endoparasites and ectoparasites, mainly blood-feeding arthropods [12].…”

The effect of cattle-administered ivermectin and fipronil on the mortality and fecundity of Anopheles arabiensis Patton

“…The effectiveness of endectocides is linked to their pharmacokinetics, which vary across different species [ 59 ]. The route of administration also has a significant effect on the pharmacokinetics of endectocides [ 60 ]. Ivermectin pharmacokinetics studies have been conducted in cattle to compare subcutaneous and oral routes of administration [ 16 , 61 ].…”

Insecticide-treated livestock: a potential One Health approach to malaria control in Africa

“…A limitation of treating livestock with current endectocides is the short mosquitocidal effect (i.e., weeks), so their use was proposed in areas of seasonal malaria at the peak of transmission [67]. Recently, a study based on published PK and pharmacodynamic (PD) data on various hosts simulated the impact of a broad range of systemic insecticides, including avermectins and isoxazolines, among others [69]. In this case, isoxazolines emerged as better candidates due to their longer-lasting effects under modeled scenarios with varying endemicities.…”