Temephos Resistance in Aedes aegypti in Colombia Compromises Dengue Vector Control

Abstract

BackgroundControl and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes. In Colombia, application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy. Resistance to temephos was recently detected in the dengue-endemic city of Cucuta, leading to questions about its efficacy as a control tool. Here, we characterize the underlying mechanisms and estimate the operational impact of this resistance.Methodology/Principal FindingsLarval bioassays of Ae. aegypti larvae from Cucuta determined the temephos LC50 to be 0.066 ppm (95% CI 0.06–0.074), approximately 15× higher than the value obtained from a susceptible laboratory colony. The efficacy of the field dose of temephos at killing this resistant Cucuta population was greatly reduced, with mortality rates <80% two weeks after application and <50% after 4 weeks. Neither biochemical assays nor partial sequencing of the ace-1 gene implicated target site resistance as the primary resistance mechanism. Synergism assays and microarray analysis suggested that metabolic mechanisms were most likely responsible for the temephos resistance. Interestingly, although the greatest synergism was observed with the carboxylesterase inhibitor, DEF, the primary candidate genes from the microarray analysis, and confirmed by quantitative PCR, were cytochrome P450 oxidases, notably CYP6N12, CYP6F3 and CYP6M11.Conclusions/SignificanceIn Colombia, resistance to temephos in Ae. aegypti compromises the duration of its effect as a vector control tool. Several candidate genes potentially responsible for metabolic resistance to temephos were identified. Given the limited number of insecticides that are approved for vector control, future chemical-based control strategies should take into account the mechanisms underlying the resistance to discern which insecticides would likely lead to the greatest control efficacy while minimizing further selection of resistant phenotypes.

Insecticide resistance and genetic variability in natural populations of Aedes (Stegomyia) aegypti (Diptera: Culicidae) from Colombia

“…Even though resistance to Temephos had been previously documented in Colombia (GRISALES et al 2013),our findings on Temephos resistance are important because it has been the main insecticide used to control the immature stages of natural A. aegypti populations in the country (OCAMPO et al 2011). Additionally, Temephos pressure on larvae may generate cross-resistance to PY or other OP used in the control of the adult stages (RODRÍGUEZ et al 2002, TIKAR et al 2009).…”

“…The first report of resistance was to DDT, an insecticide that is no longer used in Colombia for dengue control, in a mosquito population from Cucuta, near the border with Venezuela (GAST-GALVIN 1961). Resistance to OP Temephos was first documented in Cali, Valle del Cauca (SUÁREZ et al 1996), followed by the states of Norte de Santander, Sucre, Antioquia, Huila, Nariño, Cundinamarca, Santander, Caquetá, Meta, Guaviare and Atlántico (MAESTRE et al 2009, OCAMPO 2011, SANTACOLOMA et al 2012, GRISALES et al 2013. Regarding the evaluations of Malathion, the populations are not yet resistant to adulticide (OCAMPO et al 2011, SANTACOLOMA et al 2012.…”

Análisis exploratorio de ondículas de los patrones de estacionalidad del dengue en Colombia

“…Lo anterior resulta relevante si se considera que estos dos municipios pertenecen a las regiones del centro-oriente y centro-occidente del país, que, si bien no tienen el mayor número de población expuesta al dengue, sí contribuyen con la mayor carga de enfermedad del país, aproximadamente, 60 % de los casos (14). Con base en la bibliografía consultada, las diferencias encontradas en los ciclos estacionales de Medellín y Cúcuta, además de responder a los factores climáticos y a las condiciones sociales, podrían explicarse por el hecho de ser ciudades densamente pobladas con importante actividad comercial, gran movilidad de la población, circulación simultánea de los cuatros serotipos del virus del dengue (14), y, probablemente, con problemas de control del vector debidos a la resistencia de Aedes aegypti a los insecticidas, tal como se ha reportado en estudios en Cúcuta y en otros municipios del país (26,27).…”

Larvicidal activity of leaf extracts and seselin from Clausena anisata (Rutaceae) against Aedes aegypti

“…In addition, in cases where the chemicals are continuously used mosquitoes develop resistance. Resistance to temephos, the commonly used larvicide, has been widely reported (Grisales et al, 2013). Oils and films also suffocate non-target aquatic life and cause bird feathers to mat, and matted feathers cannot keep young birds warm and dry.…”