Vector Control Analysis of Aedes Mosquitoes: Past, Present and Future Athanasia Karagiannis Mosquitoes:

The Aedes aegypti and Aedes albopictus mosquitoes are the most prevalent invasive species contributing to the worldwide spread of endemic and zoonotic diseases, such as chikungunya, Zika, yellow fever, and Dengue. Their recurrent evolutionary adaption to different breeding sites, feeding behavior, and climate variation, along with their competence for multiple arboviruses and pathogens, reinforces their prominence as a global public health threat. With increasing climate change and expansion in human travel and trade, the threat of Aedes mosquitoes spreading to areas of the world where limited resources and insufficient vector control programs exist is troublesome. Reviewing current technological advancements, integrated vector management, and global engagement is important to improve environmental, chemical, biological, and genetic vector control methods used in disease prevention. The present study is a narrative review of the past, present, and future vector control strategies and perspectives of Aedes mosquitoes to support and propose new public health initiatives that prevent and control mosquito disease transmissions globally. It is hypothesized that along with the existing vector control practices in place, there is a need for continued integrated vector and case management, sustainable government and community cooperation, and further research on novel vector control methods to globally mitigate the spread of Aedes-borne viruses. Tech


Introduction
Mosquitoes are among the most prolific invasive species contributing to the worldwide spread of endemic and zoonotic diseases [1]. The two most prevalent species are Aedes aegypti and Aedes albopictus (European Centre for Disease Prevention and Control [ECDC], 2017). They can transmit a variety of re-emerging arboviruses (arthropod-borne) that usually have no vaccine or disease-specific treatment, such as chikungunya, Zika, Dengue, yellow fever, and West Nile [2]. Due to incessant climate change and the expansion of human travel and trade, Ae. aegypti, originally from Africa, and Ae. albopictus, originally from Asia, have now spread to all continents, except Antarctica [3]. Both species are daytime biters and feed on humans and animals, increasing the risk of human bites, since it is more difficult to take protective measures during the day than at night, when bed nets are more effective [4]. Additionally, they can feed on multiple individuals within a short period of time, spreading disease more rapidly. Their eggs are incredibly resistant, having the ability to survive during the winter, out of water, and to tolerate a wide range of temperatures. Furthermore, they can be transported in large numbers over long distances, inhabiting tires, water storage containers, and plants. Originally from tropical and forest natural habitats, they have successfully adapted to suburban and urban environments, increasing their expansion capability as more countries become urbanized [5].
A range of biological, chemical, and environmental vector control and surveillance methods have been implemented globally to prevent Aedes expansions; however, most developing areas lack the resources and organized mosquito control to effectively respond to new arrivals and infections [6]. Thus, it is important to review current vector control measures and anticipate areas with potential establishment of Aedes mosquitoes, in order to develop successful public health campaigns against future disease outbreaks. This narrative review analyzes past and present mosquito control programs and existing challenges to help inform future practices on how to mitigate this emerging global public health threat [7]. It is hypothesized that, along with the existing vector control practices in place, there is a need for continued integrated vector management, sustainable government and community cooperation, and further research on novel vector control methods to globally reduce the spread of Aedes-borne viruses [8].

Search Methods
The online databases used to perform relevant literature searches were Google Scholar, Academic Search Complete, Vet Science, and MEDLINE with Full Text. Boolean/Phrase search modes were utilized to maximize search results, by combining related terms, such as "mosquito control" and "vector control." Keywords used under advanced searches included: Aedes aegypti and Aedes albopictus mosquitoes, specific biological, chemical, and environmental vector control and surveillance methods, public health interventions, programs, preventions, vector-borne diseases, projections, and past, present, and future strategies and perspectives. The literature search was done from August 2017 through June 2020. In considering article selections, the titles and abstracts were assessed. Twenty articles were selected and analyzed to assess public health initiatives that prevent and control Ae. aegypti and Ae. albopictus mosquito disease transmissions.

Inclusion Criteria
Articles included were in the English language only and focused on Ae. aegypti and Ae. albopictus mosquitoes specifically and their global vector control methods and initiatives. Search results were limited to include full text, scholarly peer reviewed articles, and published literature from 2010 to 2020.

Exclusion Criteria
Articles excluded were in languages other than English and that involved other Aedes species, such as Ae. australis, Ae. cinereus, and Ae. polynesiensis.

Analysis
Aedes vector Control: Vector control remains the main existing method to protect against most Aedes transmitted diseases due to limited or no commercially available vaccines and drug treatments [9]. Currently, there are only two licensed vaccines against Aedes-borne diseases: a widely used yellow fever 17D vaccine which produces rapid, lifelong immunity, and a recently licensed Dengue vaccine (Dengvaxia) that is used in 19 countries but carries a potential risk of severe disease in Dengue-naïve individuals, making it a safety concern for global administration [10]. Other vaccine candidates for Dengue, Zika, and chikungunya are currently in different clinical trial phases [11]. Therefore, vector control methods that largely depend on removing or reducing human-vector contact are used globally to restrict Aedesviral transmissions [12]. Broadly, Aedes control measures can be separated into environmental, biological, and chemical-based tools [13].
Environmental Vector Control Methods: Before the introduction of chemical insecticides, such as DDT (dichlorodiphenyl-trichloroethane) in 1940, vector control was mainly limited to environmental management, which focused on disrupting local breeding sites and manipulating vector behavior and ecology [14]. Types of environmental vector control include house screens, aquatic habitat drainage, vegetation clearance, water container coverage, hygienic measures, waste management, protective clothing, and various other agricultural and housing improvements [15]. Looking back at the history of vector control practices, a form of environmental management was always implemented since past generations successfully connected fevers to the proximity of surface waters, like swamps and marshes [16]. There are reports of ancient Greeks, Romans, and Egyptians using drainage schemes, bed nets, and curtains as mechanical vector control measures to prevent mosquito bites [17]. Additionally, during the late 1700s, yellow fever was controlled in the US by pumping bilge water out of ships and cleaning sewers [18]. Although labor intensive, these environmental vector control methods proved largely successful in controlling yellow fever epidemics in the Americas during the early 1900s [19]. The disease was almost eliminated, but due to reduced political support and vector surveillance following its success, the yellow fever vector, Ae. aegypti, was able to reestablish itself throughout the Americas during the late 1900s. This outcome demonstrated that maintaining government support and investment in Aedes vector control methods was paramount in preventing the resurgence of arboviruses [20].    Ae. aegypti, which have a toxin-coded gene that destroys their wing muscles, preventing them from mating and searching for food and breeding sites.

Chemical Vector Control
Recently, gene editing in Aedes mosquitoes using the CRISPR-

Surveillance Methods
Effective Aedes surveillance relies on the accurate and rapid identification of collected mosquito samples to guide vector control programs. A range of surveillance methods exist that assess vector abundance and distribution and the risk of human exposure to infected mosquitoes. Standard "exposure-free" methods include indirectly estimating human-vector contact rates by surveying mosquito larvae in water containers and collecting resting adults in or around houses. To better assess the risk of human exposure to arboviral infections and predict potential outbreaks, "host-seeking" trapping methods, such as BG-sentinel (BGS) and Mosquito Electrocuting Traps (MET) are used to directly measure human biting rates. These traps use attractive odor and visual cues to lure mosquitos in and kill them on contact. Other methods of Aedes surveillance include laboratory-based techniques, such as molecular and PCR-based assays, that can more accurately identify specific mosquito species in field samples and differentiate between similar species. However, these techniques require a reliable electrical supply, costly laboratory equipment, and trained personnel, which is limited in most countries with endemic Aedes arboviral infections. Ultimately, the choice of surveillance method will depend on the country's geographical and temporal distribution of infected mosquitoes, budgetary and logistical constraints, and availability of skilled personnel.

Integrated Vector Control Management
Even though a wide variety of vector control methods exist, many countries still lack the resources, funds, preparedness, and guidance to implement sustainable vector control interventions.