Pyrethroids are currently the only insecticides recommended by the World Health Organization for the treatment of insecticidal materials against mosquitoes of public health importance . The great success of pyrethroids is related to their strong efficacy at low dose, fast killing effect and relative low cost of production. Their low toxicity to humans and stability over time ensure a safe and effective personal protection against a wide range of pests and vectors . Since the 1980s, they have been widely used for house spraying and impregnation of mosquito nets for malaria control .
Unfortunately, pyrethroid resistance is now widespread in mosquitoes. Mechanisms of resistance involve target site modification due to mutation within structural receptor genes and metabolic resistance via increased detoxification of insecticides . Resistance represents a serious obstacle for vector control as demonstrated recently with insecticide-treated mosquito nets and indoor residual sprayings in Benin , as well as control of Aedes aegypti during space spraying in the Caribbean .
In this context, new molecules and strategies are urgently needed to preserve the efficacy of insecticide-treated materials used in public health . Among the different strategies proposed, the combination of a repellent with a carbamate or an organophosphate (OP) on treated materials showed promising results for malaria vector control under simulated field conditions [8, 9]. The strong killing effect of cholinesterase inhibitors added to the high personal protection of repellents reproduced pyrethroid features against several mosquito vectors. For example, a mixture of DEET (the gold standard for synthetic repellent) and propoxur (carbamate) showed equivalent toxicity to deltamethrin at the dose that killed 100% (LD100) of susceptible Ae. Aegypti. Moreover, on the kdr homozygous strain of the same species, the mixture performed significantly better than deltamethrin . This strong efficacy was attributed to the synergistic interactions occurring between propoxur and DEET. These interactions were also observed between an organophosphate, pyrimiphos-methyl and the two repellents DEET and picaridin® on bed nets against Anopheles gambiae in both laboratory and field experiments, confirming that this strategy may be promising for the control of pyrethroid resistant mosquitoes [8, 9].
However, the physiological mechanisms involved in these interactions remain unclear. While carbamates and OPs inhibit acetylcholinesterase in insects , controversies remain over DEET mode of action [12, 13] and toxicity in insects [14–16]. Recent studies showed that DEET toxicity may occur through a general perturbation of insect neuronal transmission [17, 18].
As previously described by Corbel et al.  with pyrethroid-carbamate combinations, synergistic interactions between molecules having different modes of action may result from a general physiological disruption, involving different target sites in the central nervous system. Another hypothesis is the involvement of detoxification enzymes. Indeed, one component of the mixture may interfere with the detoxification of the other, thereby increasing the toxicity of both [20, 21]. Such involvement of esterases  or oxidases  has already been shown in synergism between pyrethroids and OPs. The OP prevents the degradation of the pyrethroid insecticide by competing as enzyme substrates.
In the present study, we investigated through toxicological bioassays (topical applications) the mechanisms involved in DEET and propoxur interactions by using two enzyme inhibitors (PBO and DEF) against the dengue and yellow fever vector, Aedes aegypti.