Mechanisms of Detoxification and Cross-Resistance to Multiple Insecticide Classes in Culex quinquefasciatus Populations Exposed to Irrigation Canal Agrochemicals in Kano State, North West Nigeria

Chronic sub-lethal exposure of Culex quinquefasciatus to agricultural pesticides in irrigation environments may drive the evolution of metabolic resistance mechanisms that confer cross-resistance to public health insecticides used in lymphatic filariasis control programs. This co-selection hypothesis has not been tested in Nigerian irrigation systems where pesticide use intensity is high and insecticide-based vector control programs operate simultaneously. This study investigates detoxification mechanisms and cross-resistance patterns in Cx. quinquefasciatus from irrigation-intensive areas in Kano State compared to populations from non-agricultural urban environments. WHO bioassays will screen for resistance to four insecticide classes at 16 sites across irrigation and urban gradients. Synergist assays with PBO, S,S,S-tributyl phosphorotrithioate (DEF), and diethyl maleate will attribute resistance to specific detoxification enzyme systems. Transcriptomic analysis by RNA-Seq of susceptible and resistant strains will identify differentially expressed detoxification genes. Insecticide residue analysis of water and sediment from irrigation canals will characterize the agrochemical exposure environment. Path analysis will model the causal chain from agrochemical exposure to cross-resistance expression. This study makes an original mechanistic contribution to the co-selection hypothesis with implications for insecticide resistance management policy in Nigeria's northern irrigation belt. Keywords: Culex quinquefasciatus, cross-resistance, co-selection, detoxification mechanisms, Kano State