Since 2000, the scale up of long-lasting insecticidal nets (LLINs) has contributed to substantial reductions in malaria burden. Effective vector control remains the foundation of malaria prevention efforts in sub-Saharan Africa where 95% of malaria cases and deaths occur. All current LLINs rely on formulations that contain pyrethroids and widespread resistance to pyrethroids threatens their effectiveness. LLINs that incorporate the synergist piperonyl butoxide have been shown to restore susceptibility to pyrethroids where P450 enzymes are the primary mechanism conferring the resistance. Recent introduction of LLINs coated with a pyrethroid and chlorfenapyr have shown promising results. The suite of LLINs and other vector control tools required for sustained malaria prevention will require the application of repurposed and novel non-pyrethroid active ingredients. Based on the principles of insecticide resistance management, formulations of dual insecticides with different modes of actions can mitigate the emergence of resistance. In the development of a dual active ingredient LLIN, the favourable safety profile and rapid killing effect of pyrethroids against <i>Anopheles </i>mosquitoes have shaped the preferred product characteristics of LLINs including personal protection against biting. Elucidating the efficacy of different modes of action will require consideration for suitable bioassay test methods. To complement bioassays, surface chemistry sampling and analytical approaches are being explored to aid in the understanding of the mosquito and netting interface. Migration as well as crystallinity of active ingredients on the net surface should also be considered. Ideally, for the purposes of insecticide resistance management, the active ingredients should decay at the same rate throughout the anticipated product lifetime. The long term view of sustained malaria prevention towards malaria elimination will also require considerations for the evolution of resistance mechanisms and the development of rational insecticide resistance management strategies including in the research and development of next generation dual active ingredient LLINs.

Considerations for next generation long-lasting insecticidal net development toward malaria elimination

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ACS Fall 2022

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