**5. Possible changes on development and reproduction of insecticideresistant insects**

As previously discussed, resistance genes may cause changes or even dysfunctions upon direct physiological process and indirect life history traits. The knowledge of the insecticide resist‐ ance costs and which parameters are altered are important to better design strategies of insect control, especially considering vectors of pathogens, once general developmental and repro‐ ductive life-traits are strongly associated to their vectorial capacity. In the following, we present some examples of resistance side effects in vector mosquitoes.

The longevity of insects is generally evaluated in fitness investigations as a key parameter of vector/parasite relationship. Decreased longevity has been detected in species resistant to different classes of insecticides. Both *Culex pipiens pallens* and *A. aegypti* selected for PY resistance in laboratory presented decreased longevity [63-65]. Pyrethroid resistance also induced similar effects on the longevity of *A. gambiae* females, in this case presumably due to affected energy metabolism and oxidative stress [66]. Defenses to non neurotoxic compounds can also affect longevity, as observed in one *A. aegypti* lineage selected in the laboratory for diflubenzuron (a chitin synthesis inhibitor) resistance [67]. As resistance mechanisms vary among species and populations, especially when metabolic, the life span of the resistant insects is not always affected, even when high resistance ratios are observed. This was the case of two Brazilian field populations of *A. aegypti* resistant to both OP and PY insecticides [68].

The time to complete the larval development is also of particular interest, since the longer it takes the higher is the exposure to adverse conditions of the breeding site and to natural predators and pathogens. Likewise longevity, resistance to several insecticides can affect this parameter. Increased developmental time was observed in *Culex quinquefasciatus* and *A. aegypti* selected in the laboratory for PY resistance [64, 65], and also to an *A. aegypti* field population with high resistance level to OP [65]. Natural populations of *C. pipiens* harboring the resistance alleles *ace-1R* (modified AChE), *Ester1* and *Ester4* (overproduction of EST) also presented a longer larval developmental time [69]. The *kdr* mutation was also the prime cause for a delay in the larval development of *A. aegypti*, especially when mutant and PY susceptible larvae were reared together and under more stringent conditions [57]. Again, impacts on this parameter were not restricted to neurotoxic insecticides, as demonstrated for an *A. aegypti* laboratory strain resistant to *Bti* toxins, which presented impairment on the larval development time [70].

Some behavioral aspects can also be affected by resistance, as the ability to detect a potential host. Under laboratory conditions, for example, fewer OP resistant *A. aegypti* females respond‐ ed to the blood meal stimuli, compared to their susceptible counterparts [68]. Similar results were observed in lineages of the same vector selected for resistance to a chitin synthesis inhibitor. Additionally, these blood-fed females ingested 18-26% less blood than the suscep‐ tible lineage [67]. The blood meal acceptance and the amount engorged can directly influence the pathogen loads ingested, potentially influencing the vector competence. These parameters are also directly connected with fecundity, since blood feeding is related to the production of eggs. Indeed, the reduction in the amount of ingested blood in resistant *A. aegypti* mosquitoes was directly proportional to a lower number of eggs [67, 68]. Several studies evidenced the impact of insecticide resistance in blood-feeding aspects [64, 71, 72].

Besides longer developmental time, lower longevity, and problems with blood feeding, reproductive traits are potentially stronger parameters against dispersion and maintenance of resistance in the field. Some studies have addressed these aspects with laboratory-resistant lineages. *Aedes aegypti* populations resistant to OP and an IGR showed lower reproductive capacity, where resistant males were able to fecundate a lower number of females [67, 68]. In the same way, susceptible *C. pipiens* males had a mating advantage when competing with *Ester-4*, *Ester-1,* and *Ace-1R* resistant individuals [47].

Some advantageous resistance side effects also occur. A *D. melanogaster* with increased expression of GST enzymes lived longer. The authors suggested that this alteration also promoted a tissue protection against reactive oxygen species [73]. In the same context, the resistance allele *Cyp6g1*, also in *D. melanogaster*, conferred resistance to DDT and was associated with a higher adult fecundity and increased viability of eggs and larvae in absence of insecti‐ cide [74]. Females of the mosquito *C. quinquefasciatus* resistant to PY by MFO overexpression survived longer when maintained with sugar solution [75].
