Key characteristics determining efficacy of public health insecticides for indoor residual spraying against Anopheles gambiae vectors

This PhD thesis represents an investigation of the characteristics that determine the efficacy of public health insecticides for indoor residual spraying (IRS) against Anopheles gambiae s.l. vectors, with particular emphasis on the novel active ingredient broflanilide. Malaria remains one of the deadliest infectious diseases, and causes significant socioeconomic impact, particularly in low- and middle-income countries. Despite advances in malaria control, the disease still caused over 247 million cases and 600,000 deaths in 2021. Effective vector control strategies are critical for reducing the malaria burden.

Prior to bringing novel chemistries to market for vector control, decisions need to be made on their optimal dose and formulation. This research evaluated the performance of broflanilide performance, including its discriminating concentration, risk of cross-resistance, dose response, and residual efficacy in both laboratory and semi-field settings. These evaluations gave insight into whether broflanilide can be used as a novel tool in the vector control arsenal, to address the challenges posed by widespread insecticide resistance.

Laboratory assays indicated no significant cross-resistance between susceptible and resistant mosquito strains, suggesting broflanilide has good efficacy against mosquito populations with existing resistance mechanisms. Additionally, dose-response assays were conducted to establish the relationship between broflanilide concentration and mosquito mortality, providing insights into its potency, speed-to-kill and the optimal doses for effective vector control. This led to three doses of broflanilide being selected for further evaluation in experimental hut trials.

Long-lasting insecticides are beneficial for IRS because they reduce the frequency of reapplication, enhancing the sustainability and cost-effectiveness of IRS programs. The residual efficacy of broflanilide was tested on two substrates commonly found on walls and ceilings of residential structures, mud and concrete. Broflanilide's performance was evaluated over time to determine its effective duration on different substrates. Results showed that broflanilide was efficacious for a minimum of 7 months on concrete, and 5 months on mud. Overall, semi-field evaluations showed that broflanilide WP meets WHO criteria for an IRS product on various surfaces against both susceptible and resistant mosquito strains.

This thesis also addressed the impact of suboptimal IRS application seen in IRS studies and IRS campaigns. Manual spraying can result in uneven insecticide distribution, potentially compromising the effectiveness of vector control efforts. By examining the variability in spraying through controlled experiments and semi-field experimental hut evaluations, the extent to which imperfect spraying affects insecticide efficacy was quantified. An automatic track sprayer, which could mitigate against uneven spray application was evaluated against manual spraying. Findings indicated that large variation can be found in concentration of insecticide when conducting IRS manually, and that this variation is reduced significantly when automating the spraying process.

Experimental hut evaluations with free-flying mosquitoes were used to investigate the impact of suboptimal IRS application and show no significant effect on mosquito mortality even when reducing the total sprayed wall surface by approximately 50%. This suggested that homogeneous coverage of walls inside houses is not essential for IRS to work effectively.

Overall, this research underscores the potential of broflanilide, particularly in the VectronTM T500 formulation, as a novel tool for vector control. It demonstrates that broflanilide can effectively target pyrethroid-resistant mosquitoes, offering a viable alternative to other insecticidal products. The research discusses the impact of imperfect coverage at the household level and proposes new methodologies to improve accuracy in spray deposition in experimental hut trials. Further recommendations include targeted spraying at a large scale to improve cost-effectiveness of IRS, maintaining this key intervention as a sustainable option in the vector control toolbox as we move towards malaria elimination