Association of Reduced Long-Lasting Insecticidal Net Efficacy and Pyrethroid Insecticide Resistance With Overexpression of CYP6P4, CYP6P3, and CYP6Z1 in Populations of Anopheles coluzzii From Southeast Côte d’Ivoire

Abstract

Background Resistance to major public health insecticides in Côte d’Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions. Methods This study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wild Anopheles coluzzii from South-East Côte d’Ivoire in 2019. Results Phenotypic resistance was intense: more than 25% of mosquitoes survived exposure to ten times the doses of pyrethroids required to kill susceptible populations. Similarly, 24-hour mortality to deltamethrin-only LLINs was very low and not significantly different to an untreated net. Sub-lethal pyrethroid exposure did not induce significant delayed vector mortality 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide (PBO), or new insecticides, clothianidin and chlorfenapyr, were highly toxic to An. coluzzii. Pyrethroid-susceptible An. coluzzii were significantly more likely to be infected with malaria, compared to those that survived insecticidal exposure. Pyrethroid resistance was associated with significant over-expression of CYP6P4, CPY6Z1 and CYP6P3. Conclusions Study findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating PBO, chlorfenapyr or clothianidin in areas of high resistance intensity in Côte d'Ivoire.

Overabundance of Asaia and Serratia Bacteria Is Associated with Deltamethrin Insecticide Susceptibility in Anopheles coluzzii from Agboville, Côte d’Ivoire

“…gambiae s.l. from Agboville, Southeast Côte d’Ivoire, has previously been characterized as intensely resistant to pyrethroids, with average vector mortalities of 14.56% (95% CI = 8.92 to 22.88%), 61.62% (95% CI = 51.58 to 70.75%), and 73.79% (95% CI = 64.35 to 81.45%) to 1, 5, and 10 times the diagnostic doses of deltamethrin, respectively, and pyrethroid resistance associated with overexpression of CYP450 enzymes ( CYP6P4 , CYP6Z1 , and CYP6P3 ) ( 44 ).…”

Determination of the discriminating concentration of chlorfenapyr (pyrrole) and Anopheles gambiae s.l. susceptibility testing in preparation for distribution of Interceptor® G2 insecticide-treated nets

“…Insecticide selection pressure from agriculture is generally regarded as an important early driver of insecticide resistance in malaria vectors [41,42]. Chlorfenapyr resistance has been reported in several species of crop pest due to agricultural use in Asia, Europe, North America and Australia, [43][44][45].…”

Overabundance of Asaia and Serratia bacteria is associated with deltamethrin insecticide susceptibility in Anopheles coluzzii from Agboville, Côte d’Ivoire

“…gambiae s.l. from Agboville, South-East Côte d'Ivoire has previously been characterised as intensely resistant to pyrethroids, with average vector mortality of 14.56% [95% CI: .45%] to one, ve and ten times the diagnostic dose of deltamethrin, respectively, and pyrethroid resistance associated with overexpression of CYP450 enzymes (CYP6P4, CYP6Z1 and CYP6P3) [45].…”

“…This study was conducted in Agboville (GPS: 5°55'21" N 4°13'13" W), Agnéby-Tiassa region, south-east Côte d'Ivoire. The location was chosen because of its high mosquito densities, malaria prevalence (26% in children <5 years in recent estimates [44]) and intense deltamethrin resistance [45]. The main industry is agriculture, with livestock such as cows, goats and chickens living close to households and cultivation of crops including bananas, cocoa and rice [46].…”