IVCC: Dual-Active Ingredient Bed Nets Combat Insecticide Resistance and Help Preserve Hard-Fought Progress against Malaria
Product: Interceptor® G2; Royal Guard®
Product Type: Insecticide Treated Bed Nets (commonly known as “ITNs”)
Disease: Malaria
The 2022 World Malaria Report estimates that in 2021, 247 million cases of malaria occurred worldwide (2 million more cases than in 2020 and 14 million more than in 2019). Globally, there were an estimated 619,000 deaths (6,000 fewer than in 2020), with the sub-Saharan Africa shouldering the heaviest malaria burden: 95% of cases and 96% of deaths, with around 80% of those deaths occurring among children under the age of five.[i]
Disruptions to the prevention, diagnosis, and treatment of malaria cases during the first year of the Covid-19 pandemic caused a marked increase in malaria cases and deaths between 2019 and 2020.
Even before the pandemic struck, the downward trends of incidence and mortality had stalled. Humanitarian crisis, health system challenges, a decline in effectiveness of core disease-cutting tools, the knock-on impact of the Covid-19, combined with insufficient resources for malaria prevention, continue to undermine the efforts to eradicate malaria.
In the context of these challenges, the need to protect the most biologically and economically vulnerable populations with effective vector control in malaria endemic countries is a global and national priority because of its fundamental importance for the control and elimination of malaria.
“The progress made against malaria since 2000 is threatened by the growing intensity and distribution of resistance to pyrethroids, previously the only insecticide class available to treat bed nets. By combining pyrethroids with new classes of chemistry, new ITNs have the potential to protect and save many more lives.”
—CHRISTEN FORNADEL,TECHNICAL COORDINATOR, NEW NETS PROJECT
A collaboration between BASF and IVCC delivered the Interceptor® G2, a dual-active ingredient bed net (ITN) that combines alphacypermethrin, a pyrethroid class insecticide, with chlorfenapyr, a repurposed pyrrole class pro-insecticide from agriculture with a mode of action never used in public health. The mixture of these two active ingredients coated on an ITN makes for a net that that is more effective in preventing malaria than standard ITNs and addresses the widespread resistance to pyrethroids.
Through the New Nets Project (NNP), funded by Unitaid and The Global Fund, IVCC and partners piloted the use of the Interceptor® G2 nets in moderate to high transmission areas throughout sub-Saharan Africa.
The project assessed the cost-effectiveness of the nets under pilot conditions. Ultimately seeking to not only establish the necessary evidence base needed to support an appropriate policy recommendation, but to also make the new nets a sustainable choice for countries looking for the best value for money in controlling malaria.
Epidemiological trials carried out over a 24-month period, in Tanzania (funded by the Wellcome Trust) and Benin (funded by Unitaid and the Global Fund as part of the New Nets Project) demonstrated that Interceptor® G2 nets reduced malaria incidence by 44%[ii] to 46% [iii] when compared with standard, pyrethroid-only nets.
The research to support these findings was conducted by the London School of Hygiene and Tropical Medicine (LSHTM), National Institute for Medical Research, Kilimanjaro Christian Medical University College, and the University of Ottawa in and the Centre de Recherche Entomologique de Cotonou (CREC).
Results from these trials were used by WHO to recognise the public health value of this new product against malaria and. On 14 March 2023, WHO issued a strong policy recommendation for pyrethroid-chlorfenapyr nets to be deployed for malaria prevention instead of pyrethroid-only nets in areas with pyrethroid resistance.
“This milestone is testament to how productive product-development partnerships can be in delivering high-impact, cost-effective prevention tools that are well adapted to the needs of endemic countries.”
— JUSTIN MCBEATH, IVCC CEO
A second dual-active ingredient bed net, Royal Guard®, received WHO prequalification in 2019. Royal Guard® combines a pyrethroid (alphacypermethrin) with pyriproxifen (an insect growth regulator). The combination of pyrethroid and insect growth regulator active ingredients in DCT’s Royal Guard® is intended to knockdown, kill, and reduce the numbers of offspring of any surviving mosquitoes, which would result in an overall reduction in the vector population.
While the trial results indicate RoyalGuard® ITNs did not provide additional protection against malaria infection, there was evidence for an impact to indoor transmission. Based on the evidence available, WHO-GMP has issued a conditional recommendation for the use of this class of net compared to standard, pyrethroid-only nets. Lower net use in the RoyalGuard® groups in epidemiological trials could have contribute to the reduced impact of these nets. More research is needed to fully understand the results.
The catalytic market shaping work under NNP to increase supply and demand have laid the foundation for ensuring equitable and affordable access to novel vector control products. This was enhanced by the joint work of UK-based social finance company MedAccess and the Bill & Melinda Gates Foundation who supported access to Interceptor® G2 nets in 20+ countries by providing a volume guarantee that enabled BASF to reduce the price procurers pay for the nets.
[i]World malaria report 2022. Geneva: World Health Organization.
[ii]Mosha JF, Kulkarni MA. et al. Effectiveness and cost-effectiveness against malaria of three types of dual active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroidonly LLINs in Tanzania: a four-arm, cluster-randomised trial, 2022; 399, 10331: 1227-1241.
[ii]Accrombessi M, Cook J. et al. Efficacy of pyriproxyfen-pyrethroid long-lasting insecticidal nets (LLINs) and chlorfenapyr-pyrethroid LLINs compared with pyrethroid-only LLINs for malaria control in Benin: a cluster-randomised, superiority trial, 2023 (Online first).