A new generation of long-lasting insecticidal nets

Abstract

The scale-up of malaria interventions over the past two decades has resulted in substantial reductions in malaria burden, especially in sub-Saharan Africa, which accounts for 95% of the global malaria burden. 1 Bhatt S Weiss DJ Cameron E et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature. 2015; 526: 207-211 Crossref PubMed Scopus (1439) Google Scholar , 2 WHOWorld malaria report 2020: 20 years of global progress and challenges. https://www.who.int/publications/i/item/9789240015791Date: Nov 30, 2020 Date accessed: December 5, 2021 Google Scholar Between 2000 and 2019, an estimated 1·5 billion malaria cases and 7·6 million malaria deaths were averted, with many of the early gains attributed to widescale deployment of insecticide-treated nets and availability of effective drugs. 1 Bhatt S Weiss DJ Cameron E et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature. 2015; 526: 207-211 Crossref PubMed Scopus (1439) Google Scholar However, progress in global malaria control and elimination efforts have stagnated in recent years, the reasons for which are multifactorial and include the development and spread of insecticide resistance in malaria vectors. The massive scale-up of insecticide-treated nets and, later, long-lasting insecticidal nets (LLINs), which have an insecticide incorporated into the net fibre and can last longer under typical use, was accompanied by the emergence of vector resistance to pyrethroids. 3 Hancock PA Hendriks CJM Tangena JA et al. Mapping trends in insecticide resistance phenotypes in African malaria vectors. PLoS Biol. 2020; 18e3000633 Crossref PubMed Scopus (37) Google Scholar This resistance is now present in all primary vectors throughout much of sub-Saharan Africa. 3 Hancock PA Hendriks CJM Tangena JA et al. Mapping trends in insecticide resistance phenotypes in African malaria vectors. PLoS Biol. 2020; 18e3000633 Crossref PubMed Scopus (37) Google Scholar , 4 Knox TB Juma EO Ochomo EO et al. An online tool for mapping insecticide resistance in major Anopheles vectors of human malaria parasites and review of resistance status for the Afrotropical region. Parasit Vectors. 2014; 7: 76 Crossref PubMed Scopus (86) Google Scholar , 5 Moyes CL Athinya DK Seethaler T et al. Evaluating insecticide resistance across African districts to aid malaria control decisions. Proc Natl Acad Sci USA. 2020; 117: 22042-22050 Crossref PubMed Scopus (17) Google Scholar Studies have shown that a new generation of LLINs that include the synergist piperonyl butoxide have improved efficacy compared with pyrethroid-only nets. 6 WHOGlobal plan for insecticide resistance management in malaria vectors. https://apps.who.int/iris/handle/10665/44846Date: 2012 Date accessed: December 5, 2021 Google Scholar , 7 Mosha JF Kulkarni MA Lukole E et al. Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets compared with pyrethroid-only long-lasting insecticidal nets in an area with pyrethroid-resistant mosquitoes in Tanzania: a four-arm, cluster-randomised trial. Lancet. 2022; 399: 1227-1241 Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar However, although piperonyl butoxide can restore susceptibility in pyrethroid-resistant mosquito populations wherein the primary resistance mechanism is metabolic detoxification by oxidase enzymes, it has minimal impact on other mechanisms of pyrethroid resistance. Insecticide-treated nets with novel active ingredients and different modes of action are needed. The WHO Global Plan for Insecticide Resistance Management recommends the use of two or more compounds of different insecticide classes to make a single product or formulation as an approach to combating resistance. 6 WHOGlobal plan for insecticide resistance management in malaria vectors. https://apps.who.int/iris/handle/10665/44846Date: 2012 Date accessed: December 5, 2021 Google Scholar The challenge is developing products that are not only effective against pyrethroid-resistant mosquitoes but are also safe to humans and are amenable to incorporation into the net fibres. Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs in Tanzania: a four-arm, cluster-randomised trialAfter 2 years, chlorfenapyr LLINs provided significantly better protection than pyrethroid-only LLINs against malaria in an area with pyrethroid-resistant mosquitoes, and the additional cost of these nets would be considerably below plausible cost-effectiveness thresholds ($292–393 per DALY averted). Before scale-up of chlorfenapyr LLINs, resistance management strategies are needed to preserve their effectiveness. Poor textile and active ingredient durability in the piperonyl butoxide and pyriproxyfen LLINs might have contributed to their relative lack of effectiveness compared with standard LLINs. Full-Text PDF Open Access