Aedes aegypti dispersion is the major reason for the increase in dengue transmission in South America. In Brazil, control of this mosquito strongly relies on the use of pyrethroids and organophosphates against adults and larvae, respectively. In consequence, many Ae. aegypti field populations are resistant to these compounds. Resistance has a significant adaptive value in the presence of insecticide treatment. However some selected mechanisms can influence important biological processes, leading to a high fitness cost in the absence of insecticide pressure. We investigated the dynamics of insecticide resistance and its potential fitness cost in five field populations and in a lineage selected for deltamethrin resistance in the laboratory, for nine generations. For all populations the life-trait parameters investigated were larval development, sex ratio, adult longevity, relative amount of ingested blood, rate of ovipositing females, size of egglaying and eggs viability. In the five natural populations, the effects on the life-trait parameters were discrete but directly proportional to resistance level. In addition, several viability parameters were strongly affected in the laboratory selected population compared to its unselected control. Our results suggest that mechanisms selected for organophosphate and pyrethroid resistance caused the accumulation of alleles with negative effects on different life-traits and corroborate the hypothesis that insecticide resistance is associated with a high fitness cost.

BACKGROUND Aedes aegypti populations in Brazil have been subjected to insecticide selection pressures with variable levels and sources since 1967. Therefore, the Brazilian Ministry of Health (MoH) coordinated the activities of an Ae. aegypti insecticide resistance monitoring network (MoReNAa) from 1999 to 2012. OBJECTIVES The objective of this study was to consolidate all information available from between 1985 and 2017 regarding the resistance status and mechanisms of Brazilian Ae. aegypti populations against the main insecticide compounds used at the national level, including the larvicide temephos (an organophosphate) and the adulticide deltamethrin (a pyrethroid). METHODS Data were gathered from two sources: a bibliographic review of studies published from 1985 to 2017, and unpublished data produced by our team within the MoReNAa between 1998 and 2012. A total of 146 municipalities were included, many of which were evaluated several times, totalling 457 evaluations for temephos and 274 for deltamethrin. Insecticide resistance data from the five Brazilian regions were examined separately using annual records of both the MoH supply of insecticides to each state and the dengue incidence in each evaluated municipality. FINDINGS Ae. aegypti resistance to temephos and deltamethrin, the main larvicide and adulticide, respectively, employed against mosquitoes in Brazil for a long time, was found to be widespread in the country, although with some regional variations. Comparisons between metabolic and target-site resistance mechanisms showed that one or another of these was the main component of pesticide resistance in each studied population. MAIN CONCLUSIONS (i) A robust dataset on the assessments of the insecticide resistance of Brazilian Ae. aegypti populations performed since 1985 was made available through our study. (ii) Our findings call into question the efficacy of chemical control as the sole methodology of vector control. (iii) It is necessary to ensure that sustainable insecticide resistance monitoring is maintained as a key component of integrated vector management. (iv) Consideration of additional parameters, beyond the supply of insecticides distributed by the MoH or the diverse local dynamics of dengue incidence, is necessary to find consistent correlations with heterogeneous vector resistance profiles.

Insecticides are still largely applied in public health to control disease vectors. In Brazil, organophosphates (OP) and pyrethroids (PY) are used against Aedes aegypti for years. Since 2009 Insect Growth Regulators (IGR) are also employed in the control of larvae. We quantified resistance to temephos (OP), deltamethrin (PY), and diflubenzuron (IGR) of A. aegypti samples from 12 municipalities distributed throughout the country, collected between 2010 and 2012. High levels of resistance to neurotoxic insecticides were detected in almost all populations: RR95 to temephos varied between 4.0 and 27.1; the lowest RR95 to deltamethrin was 13.1, and values higher than 70.0 were found. In contrast, all samples were susceptible to diflubenzuron (RR95 < 2.3). Biochemical tests performed with larvae and adults discarded the participation of acetylcholinesterase, the OP target, and confirmed involvement of the detoxifying enzymes esterases, mixed function oxidases, and glutathione-S-transferases. The results obtained were discussed taking into account the public chemical control component and the increase in the domestic use of insecticides during dengue epidemic seasons in the evaluated municipalities.

Key words: Aedes aegypti -chitin synthesis inhibitors -temephos -deltamethrin -novaluron -cross-resistance Among the arboviruses transmitted by mosquitoes throughout the world, dengue is presently the most relevant; it is endemic to all of the continents, except Europe (Nogueira et al. 2001, Forattini 2002, Claro et al. 2004. Brazil has an alarming dengue incidence with several outbreaks all over the country and an increasing incidence of severe cases. Therefore, major public health campaigns target this disease (Teixeira et al. 1999, Câ-mara et al. 2007, MS/SVS 2009.Specific drugs and an effective vaccine against dengue virus are not yet available (Durbin & Whitehead 2010). Consequently, the only way to control the dengue epidemiological network is to target the virus' vector, Aedes aegypti (Medronho 2006. Although the elimination of potential Aedes breeding sites is increasingly considered a crucial component of dengue control, the utilisation of chemical insecticides is still a common measure. Until very recently, the most commonly used insecticides against Aedes in Brazil were the organophosphate temephos and the pyrethroid deltamethrin, which are used to control the larval and adult populations, respectively .The continuous use of chemical insecticides can lead to the dissemination of resistance and the consequent failure of the control efforts. Therefore, alternative methods of controlling disease-transmitting vectors are urgently needed. Two examples are entomopathogenic bacteria and insect growth regulators (IGRs). The biological insecticide Bacillus thuringiensis serovar israelensis (Bti) has been employed against Ae. aegypti in various municipalities of Brazil. However, the reduced field persistence of commercially available Bti formulations is an obstacle; under tropical conditions, the maximal residual effect observed lasted four weeks .In contrast to the classical chemical insecticides and biolarvicides, IGRs are not directly toxic, but act selectively on the development, metamorphosis or reproduction of the target insect species (Hoffmann & Lorenz 1998, Martins & Silva 2004. Among IGRs, the chitin synthesis inhibitors (CSIs) act by interfering with the synthesis or deposition of chitin on the exoskeleton or other chitinised internal structures, such as the peritrophic matrix (Merzendorf & Zimoch 2003, Merzendorf 2005.Novaluron is a CSI that is already utilised in agriculture. It is highly effective against Coleoptera, Homoptera and Lepidoptera larvae of several crop pests . It can act through ingestion, as verified in the larvae of the moth species Spodoptera littoralis and Helicoverpa armigera, or through contact, as reported with the flies Bemisia tabaci and Trialeurodes vaporariorum (Ishaaya et al. 1996(Ishaaya et al. , 1998. Novaluron is also efficient against Ae. aegypti larvae, as reported by Mulla et al. (2003) and Arredondo-jiménez and Valdez-Delgado (2006). Because novaluron is recommended by the World Health Organization for use in drinking water, it represents a potential tool in the con...