# The Perpetual Vector Mosquito Threat and Its Eco-Friendly Nemeses
## 3 Integrated Pest Management Programs (IPMPs) for Mosquito Control
### Synthetic Pesticides  
Synthetic pesticides traditionally used for mosquito control include organophosphates (e.g., malathion and Naled) and carbamates, synthetic pyrethroids (e.g., permethrin, resmethrin, and sumithrin), cyclodigenes, and organochlorides, including dichlorodiphenyl-trichloroethane (DDT), which is banned or has restricted use in many countries [64]. Organophosphates and carbamates inhibit acetylcholinesterase, which leads to a buildup of acetylcholine (ACh) in the synaptic cleft, whereas pyrethroids and DDT are neurotoxins that preferentially target voltage-gated sodium channels, leading to excitatory paralysis [65; 66; 67]. Cyclodiene insecticides, such as dieldrin, and phenyl pyrazoles, such as fipronil, target GABA (\(\gamma\)-aminobutyric acid) receptors, subsequently leading to a decrease in the stimulation of neurons [68]. Apart from the more traditional pesticides, others used in recent years include neonicotinoids, spinosyns, pyrroles, and insect growth regulators (IGRs). Neonicotinoids, such as nicotine, bind to nicotinic ACh receptors (nAChRs) and include dinotefuran and clothianidin, which show promise in mosquito control [69; 70]. Under normal physiological circumstances, a low-to-moderate activation of nAChRs by ACh elicits nervous stimulation, whereas high levels of the neurotransmitter overstimulate and block these receptors, resulting in paralysis and death. Unlike Ach, which is broken down by acetylcholinesterase, the enzyme has no effect on neonicotinoids. The pesticide binds irreversibly to the enzyme, leading to the paralytic death of the insect [71]. Spinosyns are metabolites produced by the soil bacterium, _Saccharomyces spinosa_. Members of the spinosyn family of insecticides, including Spinosad, which is composed of spinosyns A and D, have a unique mode action in that they disrupt AChR in a wide variety of arthropods, including mosquitoes, particularly _Aedes_ and _Culex_[72; 73; 74; 75]. Pyrroles and IGRs are viable alternatives to neurotoxins in mosquito control. Pyrroles, including chlorofenapyr, are broad spectrum insecticides, which, unlike neurotoxins, disrupt respiratory pathways and proton gradients through the uncoupling of oxidative phosphorylation in the mitochondria, and are effective in bed nets and indoor treatments for the control of _Anopheles_, _Culex_, and pyrethroid-resistant _Aedes aegypti_[76; 77; 78; 79]. The use of IGRs in IPMPs are attractive because of their low toxicity to mammals and non-target species. IGRs elaborate their effect by disrupting insect development; for example, methoprene mimics juvenile hormones and prevents larvae from completing their immature stage, thereby reducing the adult population, and pypriroxyfen inhibits chitin synthesis, which is essential for formation of the exoskeleton of insects [80; 81; 82]. Synthetic pesticides are generally quite effective mosquito adulticides. Despite the rapid kill they induce, unintended negative environmental and ecological impacts cannot be ignored. These chemicals can directly harm non-target invertebrate and vertebrate species, accumulate in the environment, affect food webs for protracted periods, and, in particular, impose selective pressures leading to the persistence of resistant mosquito populations [83; 84; 85]. Regarding the latter, resistance to organophosphates, including larvicidal temephos and chlorpyrifos, carbamates, organochlorines, and pyrethroids, has been documented for species of _Aedes_, _Culex_, and _Anopheles_[86; 87; 88; 89; 90]. Taken together and apart from climate change and globalization, resistance to synthetic insecticides is a major contributor to the proliferation of mosquitoes and spread of infectious diseases globally. In an excellent review by [PERSON] [83], two major mechanisms for insecticide resistance were addressed, i.e., target-site insensitivity and increased metabolite detoxification.