# Chlorfenapyr-pyrethroid nets for pyrethroid-resistant malaria vectors: efficacy, resistance risks, and policy implications

## TL;DR

Chlorfenapyr-pyrethroid mosquito nets are more effective than pyrethroid-only nets against resistant malaria mosquitoes but may face resistance over time, requiring careful management.

## Contribution

This study is the first to systematically evaluate the efficacy and resistance risks of chlorfenapyr-pyrethroid nets and link resistance to CYP6P4 enzyme overexpression.

## Key findings

- Chlorfenapyr-pyrethroid nets show 1.8-fold higher mosquito mortality than pyrethroid-only nets.
- Community trials report 40–60% reductions in malaria infection and transmission rates.
- Early chlorfenapyr resistance in Anopheles gambiae is linked to CYP6P4 overexpression and pesticide use.

## Abstract

The Global Technical Strategy for Malaria 2016–2030 aims to reduce malaria incidence and mortality by 90%, yet widespread pyrethroid resistance among major malaria vectors in sub-Saharan Africa threatens this goal. Thus, the World Health Organization recommends chlorfenapyr-pyrethroid combination nets as a priority intervention where pyrethroid resistance undermines vector control. This systematic review synthesizes evidence on the performance, emerging resistance risks, and policy implications of these next-generation insecticide-treated nets. A structured search of literature from 2010 to 2024 across PubMed, Embase, WHO IRIS, and Google Scholar identified 31 eligible studies from 113 records. Evidence shows that chlorfenapyr-pyrethroid nets consistently outperform pyrethroid-only nets against resistant Anopheles populations, demonstrating a 1.8-fold increase in mosquito mortality (95% CI: 1.5–2.1). Community trials report 40–60% reductions in malaria infection incidence and entomological inoculation rates following deployment. However, early signs of chlorfenapyr resistance have emerged in Anopheles gambiae populations in Central Africa (RR: 2.4, p = 0.01), linked to CYP6P4 metabolic overexpression. A significant correlation was also observed between agricultural pesticide use and vector resistance patterns (r = 0.62, p < 0.05). Although chlorfenapyr-pyrethroid nets provide an important short-term tool for managing pyrethroid resistance, their long-term effectiveness depends on integrated resistance management. Rotational deployment with other insecticide classes, strengthened genetic and phenotypic surveillance, and a coordinated ‘One Health’ approach involving both public health and agriculture are essential to sustain gains and advance progress toward the 2030 malaria targets.

Main findings: This systematic review synthesizes contemporary evidence from 2010 to 2024, establishing that chlorfenapyr-pyrethroid nets are a potent new tool against pyrethroid-resistant malaria vectors. They demonstrate a 1.8-fold higher mosquito mortality rate than standard pyrethroid-only nets and are associated with significant reductions in malaria transmission in community trials.Added knowledge: The review critically identifies and quantifies the emerging threat of chlorfenapyr resistance in Anopheles gambiae, specifically linking it to the overexpression of the CYP6P4 enzyme. This finding signals that the long-term utility of this critical intervention is time-limited without proactive management.Global health impact for policy and action: The paper advocates for strategic insecticide class rotation, enhanced molecular surveillance, and the adoption of a cross-sectoral ‘One Health’ approach to manage agricultural pesticide use. By directly connecting cutting-edge entomological findings with urgent public health strategies, this review informs and guides sustainable malaria control efforts to protect gains and advance progress toward the 2030 global targets.

Main findings: This systematic review synthesizes contemporary evidence from 2010 to 2024, establishing that chlorfenapyr-pyrethroid nets are a potent new tool against pyrethroid-resistant malaria vectors. They demonstrate a 1.8-fold higher mosquito mortality rate than standard pyrethroid-only nets and are associated with significant reductions in malaria transmission in community trials.

Added knowledge: The review critically identifies and quantifies the emerging threat of chlorfenapyr resistance in Anopheles gambiae, specifically linking it to the overexpression of the CYP6P4 enzyme. This finding signals that the long-term utility of this critical intervention is time-limited without proactive management.

Global health impact for policy and action: The paper advocates for strategic insecticide class rotation, enhanced molecular surveillance, and the adoption of a cross-sectoral ‘One Health’ approach to manage agricultural pesticide use. By directly connecting cutting-edge entomological findings with urgent public health strategies, this review informs and guides sustainable malaria control efforts to protect gains and advance progress toward the 2030 global targets.