WHO recommends use of pyrethroid-chlorfenapyr insecticide-treated nets to prevent malaria

The World Health Organization (WHO) has updated its policy regarding the type of insecticide used on bed nets to prevent malaria.

Against the backdrop of growing resistance of disease-carrying Anopheles mosquitoes to pyrethroid, the insecticide currently used in insecticide-treated nets (ITNs), the WHO now recommends that areas with pyrethroid-resistance should instead use pyrethroid-chlorfenapyr ITNs.

The recommendations are based on over 15 years of research conducted by the London School of Hygiene & Tropical Medicine (LSHTM) and partners, notably results from two large randomized trials.

Findings from Tanzania and Benin, two countries where mosquito resistance to pyrethroids is high, supported the life-saving potential of chlorfenapyr-treated ITNs - the first time a safe and effective new insecticide for use on nets has been demonstrated for 40 years.

Dr Manfred Accrombessi, Assistant Professor of Epidemiology at LSHTM and trial manager in Benin, said: "The Tanzania and Benin trials provide sufficient evidence for the roll out of chlorfenapyr-pyrethroid insecticide treated nets. However, these new generation bed nets should be deployed under a comprehensive, long-term resistance management plan to avoid repeating the mistakes of the past."

Dr Corine Ngufor, Associate Professor of Medical Entomology at LSHTM, added: "This WHO recommendation is a major milestone in the fight against malaria, with almost two decades of innovation and research allowing us to reach this point. A massive rollout of these nets across malaria endemic countries would be expected in the next few years, which would help boost progress against malaria.

"Every effort should be made to preserve their efficacy and to remove obstacles to continuous vector control innovation."

ITNs are one of the main control strategies for malaria prevention. These nets are treated with insecticides as they are manufactured, acting as a physical barrier that can also repel and kill disease-carrying mosquitoes.

Until now, ITNs containing only pyrethroid, an insecticide that kills mosquitoes by interfering with their nervous system, were the recommended intervention by the WHO in all areas where malaria is endemic, notably in sub-Saharan Africa.

However, as mosquitoes become resistant to pyrethroids, the efficacy of these nets wanes. Subsequently, cases of malaria are rising, with 627,000 deaths recorded in 2020, mainly in Africa, and predominantly in children.

With the urgent need for solutions, LSHTM scientists helped develop a new type of net, Interceptor® G2 (IG2) (manufactured by BASF), which combines pyrethroid with another insecticide known as chlorfenapyr. Unlike pyrethroids, chlorfenapyr induces muscle cramps in mosquitoes, stopping them moving or flying. This new, unique approach means pyrethroid-resistant mosquitoes are killed after they come into contact with the insecticide.

Evidence from a two-year trial of more than 39,000 households which followed over 4,500 children aged six months to 14 years in Tanzania provided the first large-scale demonstration of the efficacy of IG2 nets. Published in The Lancet in March 2022 and led by researchers from LSHTM, the trial found that IG2 nets nearly halved cases of malaria compared to pyrethroid-only ITNs.

In a sister epidemiological trial of almost 54,000 households in Benin, a similar story to Tanzania was seen. IG2 nets reduced malaria infections in children between six months and 10 years by 46% over two years compared to pyrethroid-only nets. Published in The Lancet in January this year, the findings provided the final piece in the puzzle leading the WHO to update their policy guidance.

Collaborators for the Tanzania and Benin trials include the Centre de Recherche Entomologique de Cotonou, Kilimanjaro Christian Medical University College, National Institute for Medical Research Mwanza and the Innovative Vector Control Consortium.

Following the announcement, it is hoped that a broad rollout of IG2 nets in malaria-endemic countries will ensue, with the potential to save many young lives worldwide. Researchers who worked on the trials, however, emphasize the need for proper resistance management strategies and a combination of tools beyond nets to prevent a repeat of the resistance seen with pyrethroid.

Dr Natacha Protopopoff, Associate Professor of Entomology at LSHTM and principal investigator for both trials, said: "The IG2 recommendation is great news for all working on malaria control and is another tool to help fight malaria.

"This is the achievement of over a decade of development and evaluation and has been made possible by a strong collaboration between industries, research institutions and funding agencies. However, programs should consider appropriate replacement strategies and insecticide resistance management plans to maximize the long-term impact of these new tools."

I am extremely proud to have contributed to generating the evidence necessary for IG2 recommendation by the WHO. The roll out of this effective new tool will help to get malaria control efforts back on track and protect communities from this deadly disease in Tanzania and other sub-Saharan African countries."

Dr Jackie Mosha, National Institute for Medical Research, Tanzania

Dr Astrid Benfield, CEO of Malaria No More UK, added: "Today's news is an exciting and significant milestone in the race against insecticide resistance, with UK-based organizations LSHTM and IVCC leading the addition of an effective new tool to our malaria arsenal.

"This is a remarkable achievement in British-backed science innovation, but without strengthened funding for programs like the IVCC-led New Nets Project to test and deliver the latest technologies, these and other life-saving innovations will not reach the vulnerable populations who need them most."

Funders include Bill and Melinda Gates Foundation, Medical Research Council/Wellcome Trust under Joint Global Health trials, UNITAID, FCDO and the Global Fund.