Insecticide resistance profile and efficacy of next-generation LLINs against pyrethroid-resistant Anopheles gambiae s.l. in M’bé, central Côte d’Ivoire

Abstract

Long-lasting insecticidal nets (LLIN) combining pyrethroids with synergists or partner insecticides represent the next-generation tools for controlling malaria transmitted by resistant vectors. Because of their differing modes of action, their deployment in a given area would require prediction about their performance based on knowledge of the resistance mechanisms present in each local, major vector species. The efficacy of five WHO-prequalified LLINs, including Interceptor ® G2 (alpha-cypermethrin + chlorfenapyr), PermaNet ® 3.0 (deltamethrin + PBO), Olyset™ Plus (permethrin + PBO), Veeralin ® (alpha-cypermethrin + PBO), and MAGNet ® (alpha-cypermethrin only) was evaluated in experimental huts against wild Anopheles gambiae sensu lato in M’bé, Côte d’Ivoire. The trial assessed mosquito mortality and blood-feeding inhibition as primary outcomes, and vector deterrence and exit rate as secondary. Insecticide susceptibility in the local An. gambiae s.l. populations, and where possible, resistance intensity, was assessed using 1X, 5X and 10X the diagnostic concentrations of the pyrethroids in the LLINs (deltamethrin, alpha-cypermethrin and permethrin), both with and without PBO. For chlorfenapyr, adapted CDC bottle bioassays with concentrations 100 and 200 µg/mL was done and mortality monitored up to 72 h. Molecular identification of species composition, Plasmodium ( P .) sporozoite infection, and resistance mutations (L1014F/S- Kdr , V402L- Kdr , N1575Y- Kdr , G119S- Ace1 , E205D- CYP6P3 , I114T- Gste2 ) was performed. WHO assays confirmed high pyrethroid resistance, partially restored by PBO, whereas chlorfenapyr induced > 95% mortality at both concentrations, indicating full susceptibility. Among 6,586 mosquitoes collected, An. gambiae s.l. accounted for 49.15%, mainly An. coluzzii (90.63%) and An. gambiae sensu stricto (s.s.) (9.37%), with P. falciparum detected in 4.69%. Interceptor ® G2 induced the highest mortality at 72 h after exposure. Pairwise comparisons showed statistically significant differences in mortality between Interceptor G2 (80%) and all other nets (43–56%) ( p < 0.0001), as well as greater mortality induced by all PBO nets than the standard LLIN ( p < 0.01). The differences in mortality between the three PBO net types (45–53%) were not significant ( p > 0.05). Resistance allele frequencies were elevated in both An. coluzzii and An. gambiae s.s., ranging from 53.51 to 100% for L1014F- Kdr , 75–81% for I114T- Gste2 , and 22–42% for E205D- CYP6P3 . The emerging mutation V402L was only found in An. coluzzii at 48.25% frequency while N1575Y- Kdr was present at similar frequencies in both species (33–39%). Gathering data on phenotypic resistance, genes and the relative performance of LLINs in the same area is critical to guide malaria programme managers for optimized LLIN deployment.