**3. Challenges in mosquito control**

Controlling vectors of the major diseases constitute an important part of the global disease elimination and control programs, which if implemented successfully can lead towards tremendous reduction in the disease incidence globally. However, there are several challenges to the vector control strategies, which are outlined below:

One of the foremost challenges to the successful implantation of vector control strategies is the prevalence of high levels of insecticide resistance among vectors against the available insecticides [20]. Insecticide resistance can largely impact the control of adult vector mosquitoes, thereby leading to dire health consequences. Moreover, variation in the susceptibility of mosquitoes to different insecticides is another challenge [21]. Though employment of ITNs and IRS have resulted in the decline of some mosquito vector borne diseases such as malaria; however, insecticide resistance and failure to sustain these interventions can result in reversing the achieved goals [22]. Another challenge is to implement disease-specific vector control programs, as some measures for ITNs and IRS have shown promise in malaria control, but are limited for dengue control [23] due to variation in the ecology of *Anopheles* and *Aedes* mosquitoes. Besides these, other challenges include changes in behavior of the mosquitoes, presence of avoidance behavior, the high vector biodiversity etc. Moreover, the impact of the changing environment on the habitat of vectors, rapid urbanization and climate change [24] can have unpredictable and complicated influence on the distribution of the vectors posing other key challenges to the vector control interventions.

In addition to this, other challenges in the implementations of vector control programs include issues arising in public health interventions such as limited amount of funds or fair distribution of funds for vector control. Lack of proper surveillance systems pertaining to insecticide resistance and behavior of vectors can also weaken the vector control interventions. Also, the lack of coordination between governmental and nongovernmental organizations may influence vector control interventions. Migration of humans and goods pose challenges for vector control as well as disease emergence [25].

The techniques employing pouring of kerosene oil or chemical larvicides are effective in killing the larvae, but this technique suffers a major drawback i.e. its hazardous impact on the environment. In addition, the techniques to eliminate mosquito breeding sites, though are quite effective but these are not possible in areas having irregular water supply and also if these methods are not implemented at the grass root level, then the effectiveness of these techniques is reduced [26].

BTI (dead spores of the soil bacterium *Bacillus thuringiensis israelensis*) is also a successful technique to reduce the larval populations, but it is effective only against the larval stages. Recent reports have shown that BTI can impact the food chains and pose other potential effects on the environment [27, 28]. Moreover, techniques involving direct introduction of *Tilapia* and mosquito fish into the ecosystems without using a controlled ecosystem can also pose serious hazardous effects on the environment.

Thus, due to the deleterious effect of these chemical larvicides, development of new vector control products with the epidemiological evidence of their impact on public health must be clearly understood and evaluated by WHO before implementing in the field. Therefore, below different alternative vector control strategies and the studies being carried out are discussed. Such as the release of sterile insects by irradiation, use of *Wolbachia* and gene-drive technologies etc. are promising strategies, considered safe but public acceptability and regulatory approval necessitates a thorough risk assessment as well as extensive stakeholder participation.

For genetically engineered species, such barriers are clearly higher than for purely biological control strategies like *Wolbachia*. Secondly, employment of these interventions will place tremendous selection pressures that can result in development of resistance in either the target pathogen (in the case of *Wolbachia* or vector competence gene drive constructs) or the vector (for population suppression genetic constructs and possibly *Wolbachia*). Moreover, *Wolbachia's* long-term phenotypic stability in *Ae. aegypti* is still unknown [29].

#### *Different Strategies for Mosquito Control: Challenges and Alternatives DOI: http://dx.doi.org/10.5772/intechopen.104594*

Technique involving the use of Genetically Modified (GM) mosquitoes for vector control is also a promising strategy offering distinct advantages such as being nontoxic and also avoids the use of chemicals insecticides. However, there are several ethical concerns in the use of GM mosquitoes [30]. In addition, the potential impact of these organisms on the environment also needs to be taken into consideration [31]. Moreover, the technique to generate GM mosquitoes is quite expensive and may not be sustainable for poor endemic countries. The WHO also recommends and calls for further field trials and assessment of risk to evaluate the impact of this technique on transmission of the disease [32].

Recently, the use of green synthesis of nanoparticles has emerged as cost-effective and simple method for vector control. However, there are certain limitations to the large-scale synthesis and their possible impact on the environment. In addition, there is a large gap between the theoretical and the practical implications of this technology. Also, very little information is available on the impact of these nanoparticles on other aquatic organisms [33, 34]. Moreover, many of these nanoparticles have been tested for their acute toxicity non-target organisms or on other aquatic organisms which occur in the same ecological niche as the vector mosquitoes.

The difficulty of attaining eradication is worsened by heterogeneity and the existence of high-transmission hotspots; yet control in low-transmission areas may be easier than projected based on spatially imprecise transmission intensity projections [35].

Another most difficult task will be to make the best use of limited resources (particularly in low-income areas) to have the largest public health benefit. Extrapolation of clinical trial data to forecast population effect of each intervention in a wider variety of contexts and in conjunction with other control methods would require rigorous epidemiological research and mathematical modeling to ensure such optimal deployment. To assess the real-world effectiveness of treatments, rigorous monitoring and assessment are also required [22]. Concomitantly, the political commitment and employment of collaborative vector control strategies is the key to achieve the goal of vector control, thereby, reducing disease transmission and contributing towards disease eradication.

### **4. Alternative solutions for mosquito control**

Despite continuous efforts to control vector borne diseases by the use of existing intervention methods, we are unable to control these epidemics as almost 4 billion people are at risk of dengue virus transmission alone [36]. Thus, the present scenario necessitates the development of alternative strategies for the control of mosquito vectors. The rapid spread of insecticide resistance and adverse effects of these chemicals on non-target species strengthen the need to employ novel strategies for mosquito control.

Continuous efforts are being done to improve the current interventions and various new strategies and products are under consideration by the World Health Organization Vector Control Advisory Group (WHO VCAG). The following methods are used to as alternative solutions for mosquito control:

#### **4.1 Paratransgenesis: by the use of symbiotic bacteria, entomopathogenic fungi, pyriproxyfen: novel larvicides**

It is the process to decrease the vector competence of pathogens by the genetic manipulation of the insect symbiont. The prerequisite of this technique is that

symbiotic organisms must be cultivable and can easily propagate in the vectors. The most common species of bacteria which are found to be susceptible to genetic manipulation in mosquitoes are *Asaia* species and Pantoea *agglemorans* [37, 38]. These bacteria have been reported to colonize rapidly in tissues of various mosquito species *viz. An. stephensi*, *An. gambiae*, *Ae. albopcitus*, *Ae. aegypti* and species of *Culex* from *pipiens* complex [39].

In addition to the use of bacteria, in this approach fungal species can be used as it can survive in the environment for months. Moreover it can cause infection in mosquitoes directly through the cuticle and in *Anopheles,* Fang *et al*. used genetically transformed *Metarhizium anisopliae* and antimicrobial toxin scorpine which reduces the mosquito infectivity by interfering with *P. falciparum* development [40]. Pidiyar *et al*. reported the presence of *Aspergillus* and *Streptomyces* spp. in *Cx. Quinquefasciatus* [41]. Hence, using GM bacteria or fungus, paratransgenesis might be utilized to create an environmentally friendly, efficacious and specialized biopesticide.

#### **4.2 Spatial repellents**

These are the chemicals which work in vapor phase so as to prevent contact between humans and vector by making the space unsuitable for the insect. It is predicted that by the use of this technique by the diversion of mosquitoes to nonhuman host and will also decrease the toxic effect of chemicals to humans and other non-target organisms. In this method, the focus remains to prevent biting by the insect instead of killing it, basically a repellent is developed [42]. This method can be improved by the using novel active chemical components which will have new mode of action and affect the vector by altering the normal vector behavioral patterns. Presently, no evidence is reported regarding the epidemiological impact of this technique. To implement the use of spatial repellents as a tool in vector control, many challenges are yet to overcome as they come at very high cost. Moreover, the use of these repellents requires use of electricity and, therefore, makes them less suitable in less developed areas with high transmission rate. To ease the introduction of the use of these deterrents in vector control programs, their cost must be in concurrence with IRS or LLINs [43].

Many preliminary field studies have been carried out to test the efficacy of two spatial repellents allethrin emanators (ThermaCELL) and metofluthrin emanators (OFF! clip-ons or lamps) which have received more than 70% protection in different studies [44]. The use of these deterrents within push-pull systems ultimately helps the mosquito to push away from human host towards the baited traps. Many studies have been carried with the use of different repellents *viz.* PMD, catnip oil and delta-undecalactone.

#### **4.3 Use of plant based (herbal) repellents**

Plant-based "natural" smelling repellents are now widely used across the world since plants are regarded as a safe and reliable method to prevent mosquito bites. Because of their high vapor toxicity, many plant volatiles are apt to be insect deterrents or repellents. Phytophagous (plant-eating) insects are protected by compounds found in most of the plants. Repellents, growth regulators, toxins and feeding deterrents are among the substances used [45]. Nitrogenous compounds (mainly alkaloids), terpenoids, proteinase inhibitors, phenolic compounds and growth regulators are

#### *Different Strategies for Mosquito Control: Challenges and Alternatives DOI: http://dx.doi.org/10.5772/intechopen.104594*

the best instances. The volatile components generated by herbivory are currently best recognized for their ability to repel mosquitoes and other biting insects. Volatile odors attach to odorant receptor (OR) proteins on ciliated dendrites of specialist odor receptor neurons (ORNs), which are often found on the antennae and maxillary palps of insects, allowing them to sense smell [46].

The insect repellent qualities of Lemon eucalyptus have been known for millennia and essential oil contains 85 percent citronellal which is significantly more efficient in repelling mosquitoes for many minutes. On the contrary, one of its constituents, para-menthane-3,8-diol, provides excellent protection against a wide variety of insect vectors for a long period of time due to its low vapor pressure. Nanotechnology has lately opened up new possibilities for utilizing eucalyptus extracts successfully [47]. The extract and essential oil of lemongrass are frequently used as repellents, for instance, citronella, at concentrations of 5–10%, and vanillin (5%). Nano-emulsion of citronella oil is prepared to generate stable droplets that promote oil retention and delay the release. Likewise, several field investigations in India have demonstrated that neem-based medicines also have very high effectiveness [48].

#### **4.4 Traps**

Adult mosquitoes can be caught using traps. The carbon dioxide generated when propane is broken down into water might be the attractant. Biting insects, such as mosquitoes, are attracted to the warm water vapors containing carbon dioxide. The insecticide octenol, also known as 1-octen-3-ol, has been used to attract mosquitos up to 30 m away from the trap. Mostly zoophagous mosquitoes are attracted to this attractant. A dim light is used as an attractant in some traps. Because mosquitoes are attracted to light, some mosquito traps include a fan that sucks the insects flying close into a gathering chamber or bag. The trap will collect a large number of other flying insects such as beetles, moths, and flies. Traps are most successful when they are put up, maintained, and operated appropriately. A wind may have an impact on their efficacy. If the trap is placed in an inconvenient area, mosquitoes may attack more frequently. The placement of traps, on the other hand, might be considered as one of the mosquito-prevention strategies [49, 50].

There is no adult mosquito killing or catching mechanism in the system. Mosquito traps that employ UV/visible light attract not only mosquitoes, but also beneficial pollinating insects, inflicting collateral harm. To prevent killing undesirable insects, a larvicide medication package is released; however, attracted insects may generate misleading positive image processing findings. Additionally, removing active traps that need actuators can assist to minimize power usage [51].

The BG-Sentinel (Biogents GmbH, Regensburg, Germany) is another trap for mosquitoes that uses visual, olfactory, and chemical attractants to mimic convection currents formed by the human body. Given its usefulness as a collecting technique for medically importante *Aedes* (Stegomyia) species, the BG Sentinel has been shown to gather mosquitoes efficiently in urban environment in Australia and is used extensively globally for mosquito monitoring in metropolitan regions. The BG Gravid *Aedes* Trap (BG-GAT) features no moving components, few total parts, requires no energy, and is less expensive to buy. Attractant signals for ovi-positing female mosquitoes are formed using water and organic material. Adult mosquitoes are killed with residual insecticides, for instance synthetic pyrethroids administered from a propellant can or when attached to an adhesive panel placed into the trap, after being drawn inside

the trap. Mosquitoes are unable to access the trap's water and perish on a mesh screen, where they are subsequently collected [52].

#### **4.5 Attractive toxic sugar bait (ATSB)**

It is a new and a promising strategy for mosquito control. In this method, mosquitoes are attracted to Attractive Toxic Sugar Bait (ATSB) solution by spraying it either on plants or in bait stations. ATSB solutions consists of an attractant (fruit or flower scent), a feeding stimulant (sugar solution), and an oral toxin to kill the mosquitoes. The field trial of this method has been carried out for controlling the *Anopheline* and *Culicine* mosquito species. Studies on *Culex quinquefasciatus* and *Anopheles gambiae* s.l in Florida, USA and Mali, West Africa has shown success of ATSB field trials [53]. This new method is simple, cost effective and environmentally safe.

The ATSB methods are not only efficacious, easy to perform, and cost-effective but also overcome the drawbacks of contact insecticides [54] by attracting sugarseeking mosquitoes and utilizing toxins that are non-toxic to humans and safe to the environment for example boric acid.

#### **4.6 Mosquito-repellent controlled-release formulations**

Currently available insect repellents, such as lotions, roll-ons and sprays do not provide enough long-term protection. They usually need to be reapplied or updated on a regular basis. Encapsulation and liberation of repellents from a variety of matrices have emerged as a viable approach for the creation of repellent-based systems. Various types of repellent controlled-release formulations have been recently developed which have emerged as novel tools for controlling mosquitoborne diseases. These include polymer microcapsules, polymer micelles, polymer microporous formulations, liposomes, nano-emulsions, solid-lipid nanoparticles and cyclodextrins [55, 56].

Personal protection items have been linked to fewer mosquito bites and illness incidence in previous research [57]. Mosquito bite control can be successfully reduced with repellents such as DEET-based soaps [58]. Rodriguez et al. also evaluated the efficacy of several commercially available repellent based controlled release formulations against *Ae. aegypti* [59]. DEET and PMD are known to be the most efficient and long-lasting insect repellents in the market [60]. In the controlled-release formulations, the regulated release from the formulations is a type of technology that allows the active component to be released to the target at a restricted pace. Moreover, the concentration of the active component in the formulation is maintained within optimal limits for a long time. The major benefits of this technology comprise; activity prolongation over a longer duration, reduced pollution and is inexpensive [60, 61].

#### **4.7 Sterile insect technique (SIT)**

The SIT is an ecologically friendly pest management strategy that involves releasing mass-reared sterile males in a particular region to suppress an insect population. There are no progeny when these sterile males mate with females in the wild [62]. The introduction of sterile males in a systematic and recurring manner decreases the target wild insect population over time. The IAEA has been improving the SIT for use against disease-transmitting mosquitoes in collaboration with the Food and Agriculture Organization of the United Nations (FAO), and has tried it on a

modest scale in various countries, including Brazil, Cuba, Italy, Mauritius, Mexico, and Germany [17, 63, 64]. Pilot releases on a larger scale are planned as part of International Atomic Energy Agency (IAEA) research and technical cooperation operations, as well as test releases in conjunction with epidemiological studies as part of the IAEA, TDR (Special Programme for Research and Training in Tropical Diseases), and WHO partnership. Female mosquitos bite and thus spread illnesses, whereas male mosquitos do not bite and thus do not pose a risk of disease transmission. The sterile mosquitoes are likewise unable to reproduce, thus they will not contribute to the increase of the mosquito population. Sterile mosquitoes are typically released via ground, although good results were recently obtained in Brazil using a drone release method developed by the IAEA in collaboration with the FAO and others.

This approach has been used to remove the New World screwworm, tsetse fly, Queensland fruit fly, pink bollworm, melon fruit fly, and other insects. The efficiency of this technique can be further improved by creating better strains for mass production and release, identifying molecular markers to detect the released sterile insects in the field, sterilization and genetic sexing. Distinguishing between released wild and sterile insects is crucial for assessing the performance of the SIT programme [65]. The incorporation of a fluorescent transformation marker into a transgenic insect might aid in the simple identification of released insects. In mosquito species such as *Anopheles gambiae* and *Aedes aegypti* fluorescent sperm marking systems have been developed [66].

#### **4.8 Gene drives**

This technique utilizes CRISPR gene-editing tool to spread a genetic modification rapidly through a population than normal rate of inheritance. It can be used to insert a new gene or induce alteration or silencing a particular gene. After the entire drive is inserted into the genome the progeny will inherit the drive on one chromosome and the normal gene on partner chromosome. During development the CRISPER portion cuts the other copy which is repaired using the drive and thus the genome contains two copies of the gene drive. This allows passing the alteration to 100% of the progeny than 50% in the usual case. Gene drives have been proposed to be used against mosquito borne diseases and also reverse insecticide resistance. CRISPR-based HEGs (homing endonuclease genes) have shown close to 100% inheritance rates [67] in both *Anopheles gambiae* and *A. stephensi* mosquitoes. The gene drives cause a reduction in the reproductive capacity of the mosquitoes [68] CRISPR-based gene-drives, which are targeting the *doublesex* gene of *Anopheles gambiae* (vector of malaria) have been reported to efficiently suppress mosquitoes in small laboratory cages for a year and were not found to select for resistance to the gene drive [69, 70].

#### **4.9 Resistance management**

The main aim of this technique is to prolong the susceptibility of mosquito vectors to insecticides so as to maintain the effectiveness of the vector control interventions. The methods being used under this intervention include rotations, mosaics, mixtures and combinations [71]. Among these methods, rotational use of insecticide is the most common and effective solution for managing insecticide resistance. These methods are still not widely explored for the control of vectors.
