Welcome everybody to this lecture on insecticide resistance and its management. I'll go through the main classes of insecticides that are used for public health, explain insecticide resistance, describe mechanisms of insecticide resistance, and lastly, explain different strategies for managing insecticide resistance. There are four major classes of insecticides that are used for malaria vector control. These are organochlorines, such as DDT and dieldrin, organophosphates such as paramethos methide. Carbamates, such as bendiab. And pyrethroids, for example, pamethergine, dithamethergine, and lamdasihalotrin. These insecticides have different modes of action which determine their mechanisms of resistance. Other class of insecticides include biopesticides such as bacteria. The most common of these bacteria are Bacillus thuringiensis israelensis, abbreviated as Bti, and Bacillus sphaericus. These bacteria produce proteins that are toxic to mosquito and black flies larvae. Dependent on the requirements of various application methods, storage, and delivery systems there are different insecticide formulations including water disposable powders, abbreviated as WDP, emulsifiable concentrates are abbreviated as EC and suspension concentrates. A water disposable powder is a dry powder mixed with surface-active agent that allows insecticide to dissolve in water as suspension. Emulsifiable concentrate consists of solvent plus emulsifying agent in which the insecticide is dissolved. When you mixed it with water, it forms milky emulsion of finely suspended particles. Suspension of flowable concentrate consists of particles of insecticide with a wetting agent and some water. Pyrethroids are the only class of insecticides that have been approved for use in insecticide treated nets or long-lasting treated nets. This is due to the fact that they have a rapid knockdown effect and they have no adverse effects on humans. However, pyrethroids are faced with the several challenges, including development of behavioral resistance such as exophily, in which mosquitoes tend to avoid internal walls treated with insecticides. Another one is a development of pyrethroid resistance which has become widespread in many major malaria vectors thus threatening access and ability of both ITNs and IRS scaling-up programs. By definition, insecticide resistance is a developed ability in a strain of insects to tolerate doses of insecticides which prove lethal to the majority of individuals in a normal population of the same species. There are two broad mechanisms of insecticide resistance. These are target-site insensitivity and insecticide detoxification. Target-site insensitivity is due to modification of a neural target of a particular insecticide. And there are three types of these. The first one is reduced sensitivity to DDT and pyrethroids due to knockdown resistance mutation or kdr mutation. The second one is reduced sensitivity to carbamates and organophosphates following a development of Ace-1 mutation. And the third one is reduced sensitivity to cyclodiene insecticides such dieldrin following mutation in GABA receptors. The kdr mutation is due to mutation in the gene that encodes for the voltage-gated sodium channel. It occurs in domain two, in this sixth segment of this domain of the sodium channel protein. And this is important for channel activation. It induces a change of one of the amino acids, of the target site for DDT and all pyrethroids. The point mutation in a gene leads into an amino acid change. For West African kdr mutation we have transformation of leucine amino acid into phenylalanine. While for East African type of kdr mutation you have leucine amino acid change into serine amino acid. For Ace-1 mutation we have a single point of mutation in the Ace-1 gene that encodes for acetylcholinesterase. Which is the target binding site of both organophosphates and carbamates. It results in a substitution of glycine into serine amino acid at the position 119 of the encoded protein. There are three classes enzymes that are involved in insecticide detoxification. These cytochrome P450s that confer resistance to pyrethroids, DDT, and organophosphates. Non-specific esterases which confer resistance to carbamates, organophosphates, and pyrethroids. And lastly glutathione-S-transferases or GSTs that had been implicated in DDT resistance. Resistant insects may produce large amount of enzymes, which either break down the insecticide molecule or bind to it so tightly that it cannot function. And this process is defined as sequestration. Cross-resistance occurs when resistance to one insecticide confers resistance to another insecticide, even where the insect has not been exposed to the latter product. It can be to another insecticide within the same class or to insecticides different classes, depending on the mechanism. For example, cross-resistance has been observed between DDT and the pyrethroids. And these chemicals are chemically unrelated, but they both act on the same target site. This is a summary of cross-resistance patterns of different classes of insecticides. And as you can see, modified target sites conferred resistance to carbamates and organophosphates while the kdr mutation confers resistance pyrethroids and DDT. And for the enzymes we have oxidized enzymes, or monooxygenases that confer resistance to pyrethroids, DDT and organophosphates, while for esterases enzymes we have cross-resistance here to organophosphates, carbamates, and pyrethroids. Multiple resistance is a common phenomenon and it occurs when several different resistance mechanisms are present simultaneously in resistant insects. In this case, we may have different resistance mechanisms that combine to produce resistance to multiple classes of products. Multiple resistance has been documented in malaria vectors in several African countries, including Ivory Coast, that is Cote d'Ivoire, Burkina Faso, and Cameroon. Management of insecticide resistance is aimed at preventing onset of resistance to prolong as long as possible the effective life of existing insecticides. This requires a reliable system for vector surveillance and resistance monitoring with an ultimate knowledge of the genetical, biochemical and the physiological basis of the resistance mechanisms in each instance. Strategies that I used for managing resistance may be different types or kinds. However, insecticide resistance management can be undertaken using insecticide based approaches in conjunction with other non-insecticidal vector control approaches, constituting integrated vector and pest management. Insecticide based approaches takes several forms, including the use of mixtures, rotations, mosaics, and the use of synergists. As far as mixtures are concerned, we have two mixed compounds that applied so that the individuals may be exposed simultaneous to each compound. The rotations involve rotation over time of two or preferably more insecticide classes with different modes of action. With mosaics we are referring to distant areas being treated simultaneously with different insecticides. We make of a synergist such as piperonyl butoxide to enhance the effective several classes of insecticides, including pyrethroids. And in this case, a good example of using synergists is the tool for managing resistance where we have all set of plans. That is, the long lasting insecticide treated net and PBO to enhance the activity of and that vector control strategy. Thank you for listening.
