Efficacy of Interceptor® G2 Long-Lasting Insecticidal Net Against Pyrethroid-Resistant Malaria Vector Anopheles gambiae s.l.: A Systematic Review and Meta-Analysis

Background: Malaria is a major public health issue, primarily in sub-Saharan Africa, where long-lasting insecticidal nets (LLINs) have been compromised by pyrethroid-resistant vectors of the Anopheles gambiae s.l. complex. Interceptor® G2 is a new generation alternative that is defined as a dual-insecticide LLIN with alpha-cypermethrin (100 mg/m²) and chlorfenapyr (200 mg/m²) where target-resistant vectors are killed due to a novel mode of action. This is a systematic review and meta-analysis of the entomological efficacy of Interceptor G2 under Phase II WHOPES experimental hut trials. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted for articles published between January 1991 and July 2025. Eligible studies were English Phase II WHOPES trials of Interceptor® G2, unwashed and washed 20 times, against pyrethroid-resistant An. gambiae s.l. Comparator arm controls were untreated nets, nets treated solely for chlorfenapyr, and standard Interceptor® (alpha-cypermethrin-only) nets. 72-hour lethality of mosquitoes, blood-feeding inhibition, and mosquito exit were key outcomes. Risk of bias assessment used ROBINS-I. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using a random-effects model (DerSimonian–Laird). Results: Six studies were included, with study locations in Benin, Burkina Faso, Côte d’Ivoire, and Tanzania. Interceptor® G2 (unwashed) had an edge on 72-hour mortality (OR = 47.29; 95% CI: 28.5–78.44) and blood-feeding inhibition (OR = 0.33; 95% CI: 0.21–0.53) compared to untreated ones. Interceptor® G2 washed was significantly effective (OR = 36.23; 95% CI: 21.36–61.45 for mortality). Exiting rates were also significantly enhanced for Interceptor® G2 (unwashed OR = 3.5; 95% CI: 2.49–4.90) use. Results were consistent across studies with very minimal heterogeneity for mortality and exiting outcomes. There was, however, intermediate heterogeneity (I² = 62.9%) for blood-feeding inhibition. The overall risk of bias was low to moderate in most studies. Conclusion: Interceptor® G2 nets have demonstrated significantly greater effectiveness than conventional pyrethroid-only LLINs and chlorfenapyr-only nets in increasing mosquito mortality, reducing blood-feeding, and encouraging mosquito exit behavior. This enhanced performance remains consistent even after 20 washes. These results support the expanded use of Interceptor® G2 in malaria control programs, especially in areas where mosquitoes are resistant to pyrethroids. However, additional Phase III community-level trials are needed to confirm its public health benefits and cost-effectiveness. Keywords: Malaria, Interceptor® G2, long-lasting insecticidal nets, pyrethroid resistance, chlorfenapyr, Anopheles gambiae, WHOPES, experimental huts, vector control