Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d’Ivoire

Abstract

Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d’Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose–response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (> 1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (< 30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (≥ 90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (< 15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22–43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r2 = 0.78, P = 0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures.

Multi-insecticide resistant malaria vectors in the field remain susceptible to malathion, despite the presence of Ace1 point mutations

“…coluzzii ) [ 27 ] and from central Côte d’Ivoire (RR 50 = 1,441 to 2,405, predominantly in An . gambiae s.s.) [ 28 ].…”

“…The prevalence of insecticide resistance in malaria vector populations is increasing across Africa with extreme resistance phenotypes being reported from West Africa [ 26 , 27 ], including Côte d’Ivoire [ 28 ]. Côte d’Ivoire has a long history of research on insecticide resistance with the first reports of PY resistance dating back to 1993 [ 29 ].…”

Increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania: implications for the evaluation of novel vector control products

“…In Misungwi district, population-level frequency of the L1014S-kdr mutation was practically fixed in An. gambiae s.s., while CYP6M2, CYP6P3, CYP6P4 and CYP9K1 were modestly upregulated by comparison to reports from West Africa [62][63][64]. These results indicate that both target site and metabolic mechanisms may be driving pyrethroid resistance in An.…”

“…gambiae s.s. in this study area. However, further investigation is necessary to identify resistance mechanisms specific to these field populations for prospective monitoring and to improve our understanding of the specificity of resistance mechanisms to individual interventions and the likelihood of selecting for cross-resistance between active ingredients [62][63][64]. Importantly, intense insecticide resistance may partially explain the persistent malaria transmission in Misungwi district, highlighting the urgent need for novel vector control tools, containing different insecticide classes and combinations.…”

Omitting age-dependent mosquito mortality in malaria models underestimates the effectiveness of insecticide-treated nets

“…(e a 2 g 2 −e a 1 g 2 ) da 2 (20) Cases (ii) and (iii) are again solved numerically. We plot some heatmaps to visualise the solutions of Eqs ( 18), (19), and (20) (Fig 7).…”