In the last decade we have looked at the evolution of insecticide resistance in disease vectors primarily in Africa, where mosquito transmit malaria, as well as in Europe where we have some Arbovirus vectors. Insecticide resistance is a striking phenomenon, what happens is that there are several insecticides that have been used for many years to control insects and mosquitoes particularly, those insecticides impose some selection pressure, as a result of that, insects and mosquitoes evolve resistance. The use of insecticides in the last decade particularly in places like Africa, was very heavy also because public health has a small market and big companies are not very much interested to develop novel active ingredients. The big problem is that there are a very small number of insecticides, of active ingredient actually used against mosquito control. So this heavy use of very few classes of insecticides, like pyrethroid in Africa, but also very limited number of larvicides used in Europe against arbovirus vectors, as a result of that, insecticide resistance has been selected. The phenomenon briefly is that it happens that a few mosquitoes, one in a million or a few in a million, happen to have a trait which gives them some resistance to insecticides, they were a little bit different than other mosquitoes, for example they had slightly different molecular target, it had a little bit different structure so that the insecticide couldn't bind in there. What happens is that insecticide kills the rest of the mosquitoes in the population but those which happened to have the special trait managed to increase their frequency in the population and eventualy replace the initial population so that we have a resistant population. With the intense selection due to the heavy use of insecticides, the big problem is that not only one mechanism of insecticide resistance is selected for but often in some mosquitoes you have a combination of resistant mechanisms which produce a striking resistance phenomenon, so there are cases where insects don't die by usual dose of insecticides but they do not even die if you increase those doses to one or ten thousands times. Also there are mosquitoes, particularly in west Africa, that don't die by any of the registered insecticides, there are insecticides of different classes and none of them can kill those very resistant vectors. It's a very important issue given that malaria has been reduced by more than 50% in the last decade based on a paper that was published last year, and insecticides had a major role in this reduction. So it's really urgent to sustain the efficiency of insecticides to improve the sustainability of vector control interventions which are largely based on insecticides. We are working towards understanding the insecticide resistance mechanism at a molecular level, which is an important first step, so that you can manage delay or tackle insecticide resistance phenomenon. It's important to understand which genes, which mutations, which combination of biological phenomena are responsible for resistance, because this helps the development of diagnostics, molecular diagnostics to us which are very useful for the early detection of insecticide resistance and very helpful to manage insecticide resistance and delay its evolution, as well as the identification of detoxification enzymes which are capable to inactivate insecticides, once you have identified them it's a solid base for the development of enzyme inhibitors compounds that can be added to insecticide formulation and can alleviate insecticide resistance, can block those detoxification enzymes and retain the efficiency of insecticides. There are some important things that we need to keep in mind, insecticide is a very important tool for vector control, but there are also other very important efforts, scientific efforts, products development, several other tools that are under development or are at several stages of evaluation, which are extremely useful for mosquito control. What is very important to have in mind is that it's very difficult in our day to have novel tools, new paradigm so called, that will replace insecticide or it would be the magic bullet which sudently would kill mosquitos and we wouldn't have problems anymore. Because there are mosquito problem evolving, it includes invading species, maybe you heard it from other colleages, as well as insecticide resistance problem, it's very important to combine several tools in an integrated way, this is the approach called by WHO integrated vector control, it's very important and it's based on education, an education which reaches the community, because it's not the molecular biology of insecticide resistance often that makes a difference, but the removal of breeding sites close to our house which is basic environmental managment, which is the beginning of the success. And of course scientific knowledge on insecticide resistance and use of novel approaches including may be in the future transgenic mosquitos or Wolbachia based approaches needs to be use sensibly in combination with existing interventions so that first of all they sustain the efficiency of those chemical based interventions until, may be in the future, those chemicals are gradually replaced by other environmentally friendly tools. The situation of Aedes resistance in South America, in Brazil, and in Central America as well, is also worrying. Aedes aegypti in particular has developed high levels of resistance against common larvicides that are used against this vector, like temephos, and it's also very resistant against pyrethroid insecticides. Fortunately, Aedes albopictus is not that resistant to insecticides at this moment because it's exophilic and normally it's not exposed to indoor interventions which are used against Aedes. But it is a problem, I heard colleages from Brazil mentioning that there is a complete operational failure of insecticide interventions. I don't think that's the case really, just there are always people saying that insecticides don't work, it's not always the case that when someone reports insecticide resistance means that interventions have no result, but they have often reduced efficiency which epidemiological is extremely important of course. So yes the Aedes vectors have also this insecticide resistance problem. Well there was a big pressure in Brazil in the last years because you had those big sports events and the Brazilian government wanted to reduce the population size dramatically, which is not very easy to do within a few years time, because it's a biological system which has a strong evolutionary history. But I think the efforts in Brazil are substantially including testing of new paradigms and very novel approaches, like transgenic mosquitoes or Wolbachia. And I think this combination, this integrated way of using the available means, that has happened in Brazil, it's a good paradigm. Now whether the result is the elimination of mosquitoes it's not, and it's very very difficult to happen. But even if you have sustained the efficiency of control intervention it's also a big achievment. I have heard that, it's a controversial thing actually in the literature, there are reports that say that insecticide resistant insects are less capable of transmitting some diseases like filariasis for example, which is not a virus, but there is also some association between insecticide resistance in malaria vectors and malaria parasytes, but in this controversial issue which has not been studied in detail, and even if there are studies which look at that at laboratories mosquito strains, this is very different from looking at what happens in the field. But it is a research question which has been emphasized by several international foundations like NIH or WHO, which have launched thematic calls for looking at the operational impact of insecticide resistance on the epidemiology of diseases. So hopefully in the next five years we will know the link between insecticide resistance and epidemiology.
