Background: The yellow fever mosquito Aedes aegypti is a major vector of dengue and hemorrhagic fevers, causing up to 100 million dengue infections every year. As there is still no medicine and efficient vaccine available, vector control largely based on insecticide treatments remains the only method to reduce dengue virus transmission. Unfortunately, vector control programs are facing operational challenges with mosquitoes becoming resistant to commonly used insecticides. Resistance of Ae. aegypti to chemical insecticides has been reported worldwide and the underlying molecular mechanisms, including the identification of enzymes involved in insecticide detoxification are not completely understood.

BackgroundThe evolutionary dynamics of xenobiotic resistance depends on how resistance mutations influence the fitness of their bearers, both in the presence and absence of xenobiotic selection pressure. In cases of multiple resistance, these dynamics will also depend on how individual resistance mutations interact with one another, and on the xenobiotics applied against them. We compared Culex quinquefasciatus mosquitoes harbouring two resistance alleles ace-1R and KdrR (conferring resistance to carbamate and pyrethroid insecticides, respectively) to mosquitoes bearing only one of the alleles, or neither allele. Comparisons were made in environments where both, only one, or neither type of insecticide was present.ResultsEach resistance allele was associated with fitness costs (survival to adulthood) in an insecticide-free environment, with the costs of ace-1R being greater than for KdrR. However, there was a notable interaction in that the costs of harbouring both alleles were significantly less than for harbouring ace-1R alone. The two insecticides combined in an additive, synergistic and antagonistic manner depending on a mosquito's resistance status, but were not predictable based on the presence/absence of either, or both mutations.ConclusionInsecticide resistance mutations interacted to positively or negatively influence a mosquito's fitness, both in the presence or absence of insecticides. In particular, the presence of the KdrR mutation compensated for the costs of the ace-1R mutation in an insecticide-free environment, suggesting the strength of selection in untreated areas would be less against mosquitoes resistant to both insecticides than for those resistant to carbamates alone. Additional interactions suggest the dynamics of resistance will be difficult to predict in populations where multiple resistance mutations are present or that are subject to treatment by different xenobiotics.

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Five infants presented with a congenital anterolateral, unilateral bowing of the tibia. The fibula was normal but a bifid homolateral great toe was seen, associated with hand malformations. Plain films and CT disclosed a short tibial duplication, with distinct corticals. We do think that this abnormality represents a new entity, and may be related to a genetic anomaly. The long term follow up of our patients shows a spontaneously favourable prognosis without any association with pseudarthrosis. The only therapeutic problem is a limb length discrepancy.

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