Insect-borne diseases remain to be potential threat to global public health, particularly in the resource-limited settings [1]. It has been estimated that nearly half the world’s population is at risk and they account to over seventeen percent of all infectious diseases. They contribute to more than one billion infections and over one million deaths every year [2]. It indirectly affects human lives in more spheres and domains in terms of poverty, social debility and negative socioeconomic development [3]. Majority of the victims often belong to the poorest section of the society, particularly where there is a lack of access to quality healthcare, adequate housing, safe potable-water and sanitation [2]. In order to emphasize the significance of vector control interventions, the WHO has highlighted the slogan called ’Small bite, big threat’.

Mosquitoes are considered as one of the most dangerous creatures on the planet because of their capability to transmit several dreadful diseases such as malaria, filariasis, dengue, yellow fever, Japanese encephalitis and other arbo-viral diseases (Table 1). Disease geographical distribution is often determined by a complex dynamic of environmental, behavioral and socio-economic factors, and in the recent years, the disease transmission patterns have significantly altered due to several concomitant factors like: (a) explosive global economic development, (b) increased international travel, (c) new water development projects, (d) global warming, (e) changes in agricultural practices, and (f) unplanned urbanization [4-6]. The impacts of bio-geographic factorsand anthropogenic activities spurt the unprecedented major mosquito-borne disease outbreaks like dengue, chikungunya and West Nile virus (Table 1), even in the countries where they were previously unknown.

Table 1: Major mosquito-borne diseases and the important mosquito genus with distribution and global disease burden.

Mosquitoes (Family: Culicidae) belong to the insects order known as Diptera [Spanish; (di-two and ptera-means wings)] and they are easily distinguishable from other group of insects through their long piercing and sucking tubular proboscis (mouthparts) for blood-feeding and hairy scales on their body. There are approximately 3500 mosquito specieses grouped into forty-one genera [6]. Mosquitoes are found on all continents except Antarctica. Anopheles [Greek anopheles-useless: anwithout+ ophelos-advantage] [7] is a genus of mosquito first described and named by Meigen (1818) [8], and about 460 Anopheles species are recognized while, only thirty-to-forty serve as human malaria vectors in the wide-range of endemic settings [9]. Nearly 550 and 700 of Culex and Aedes cosmo-tropical species are found worldwide, respectively (Table 1). It is important to note that the dominant vector species varies from region to region, and different species are observed to play different roles for sustaining the transmission of the pathogens.

Most mosquito species are either nocturnal or crepuscular both indoors (endophagic) and outdoors (exophagic) [10,11]. Typically, both male and female mosquitoes (phytophagous) feed on nectar and plant juices. However, in addition to nectar, female mosquitoes (hematophagous) require blood-meals to carry out egg production, and such blood meals are the link between the human and the mosquito hosts in the digenetic parasite life cycle [6]. Majority of the Anopheles mosquito specieses are showed highly anthropophagic behavior (prefer to feed on human), while a few mosquitoes which feed upon animals (zoophagic) in order to obtain the blood meals. Subsequently, after feeding, the mosquito rests for two or three days for the digestion of a blood-meal and the simultaneous development of eggs. Depending on the species some mosquitoes prefer to rest indoors (endophilic) while others prefer outdoors (exophilic). A female mosquito chooses oviposition sites by a combination of visual and chemical cues.

The mosquito goes through four separate and distinct stages of its life cycle: egg, larva, pupa, and imago (adult) (Figure 1). The first three stages occur in water, but the adult is an active flying insect. Culex mosquito is widespread across urban and semi-urban areas; the Anopheles mainly in rural areas, and Aedes, mainly in and around urban areas [12]. Aedes mosquitoes are commonly known as ‘container-breeder’ as they preferred to breed in temporary manmade water containers as well as discarded tires, closely associated with domestic and peridomestic human settings and often indoors, whereas secondary vector Ae. albopictus, prefer water-filled natural habitats [13-22].

Figure 1: The typical life-cycle of mosquito.

Over decades, vector control remains to be a cornerstone to prevent outbreaks as well as to minimize the vector-borne disease associated illness and deaths worldwide [23]. Vector control strategies rely heavily on use of synthetic insecticides [24], particularly pyrethroids through Insecticide-Treated Nets (ITNs) and Indoor Residual Spraying (IRS) as a mainstay. Besides, larvicides are also used to eliminate larvae stages in the breeding sites, whereas repellents are applied to drive-away mosquitoes from the source in order to minimize the man-vectorcontact. Currently WHO has recommended only twelve insecticides for IRS, but they belong to only four chemical classes viz.; organochlorines, organophosphates, carbamates and pyrethroids [25].

The injudicious and indiscriminate usage of pesticides, chiefly pyrethroids have led to the emergence of resistant mosquito strains via natural selection and it undermines the potentialities of chemical control interventions. Multiple and cross-resistance have also been reported in widerange of settings and therefore it is regarded as a potential threat to the global public health [24]. It makes the existing insecticides feckless and limits the available mosquito control options [26]. Although it is an evolutionary phenomenon, it can be tackled judiciously through comprehensive resistance monitoring and evaluation mechanisms prescribed within the WHO global strategic framework of integrated vector management [24].

Source reduction (larval control) is an ideal approach, as the target is very specific. However, application of conventional insecticides into the mosquitoes’ breeding sites could lead to undesirable effects in the aquatic ecosystem [1]. The repeated use of persistent pesticides in agriculture, public health, and industrial sectors has indeed resulted with ‘biomagnification’. It has led to pesticide residues in foods, vegetables, fruits and even in mothers’ breast milk [27]. Though it is a global concern, it has serious negative implications in the developing and impoverished countries due to the higher prevalence of residues in the foodstuff, exceeding the Maximum Residue Levels (MRL). In the light of current knowledge, looking for alternative potential new classes of plant-based insecticides for public health purpose could be a practicable and viable solution to address this catastrophe [25,27,28] and to sustain the current scaling-up efforts of preventing avoidable morbidity and mortality [25].

Since the prehistoric ages, mankind has exploited the wild plants for his food, clothing, housing, healthcare, insecticidal purposes and day-to-day basic amenities [29,30]. Prior to the advent of DDT (and other organic pesticides), our ancestors have been using only plantbased products as insecticidal agents against various annoying and blood-sucking insects, especially mosquitoes. Plants are known to synthesis various alkaloids, phenolics, oils and several secondary metabolites. These biological constituents possesses strong insecticidal properties and they were used by Romans and Chinese’s in the ancient days [31]. Even in the era of computational-bio-chemical, people use several plants as repellents and insecticidal agents in the form of smoke and crude extracts, respectively [32-36].

Though numerous studies have been conducted to establish and authenticate the potentiality of phytochemicals as insecticidal agents, particularly mosquitoes worldwide, only a few but notable studies are included in the Table 2. These studies indicate that plant kingdom remains as a major repository for the several potential phytotoxicalogical agents, particularly insecticides (Table 2), These can be widely used in the place of synthetic insecticides [37] as potential larvicidal, insect growth regulators, repellents and ovipositional attractant agents [38]. Domestic insecticide products (mosquito paper, mat, coil, stick. lotions and vaporizer) are extremely inevitable in the tropical and sub-tropical settings, where both mosquitoes and mosquito-borne diseases are widespread.

Table 2: Some of the notable studies that evaluated various insecticidal plants to authenticate and validate their mosquitocidal properties against important vector mosquitoes.

Consequently, the health-conscious consumers prefer plantderived insecticides due to their low mammalian and non-target toxicity [32,35] than their synthetic counterparts.In the past decades numerous researchers have evaluated over thousands of potential insecticidal plants for their mosquitocidal, larvicidal, antifeedant, repellent, oviposition deterrent, and growth regulatory activities [29]. Till today only a few of them like neem, lemon grass and pyrethrum have demonstrated their broad effectiveness against various insects [39]. Table 2 shows that plant-extracts could serve as potent larvicidal agents against mosquitoes and that it could considerably minimize the dependency on synthetic insecticides [23]. Therefore, there is an enduring demand for developing new pest control tools in terms of green pesticides or reduced-risk of pesticides by means of unique novel modes of action [29,40]. Nevertheless, in the majority of the studies, the mode of actions and their larvicidal and repellency potency is not well-studied under the field conditions. It is important to note that there are key challenges and issues that lie ahead for the advancement of the ideal plant-based insecticides [26,41-47].

Today, majority of the existing commercialized mosquito repellent’s active ingredients are derived from the well-known pyrethrum plant (Golden flower) (Asteraceae; Chrysanthemum cinerariaefolium) and citronella plant (Poeacea; Cymbopogonnardus) [48,29]. In Africa and rest of the world various indigenous peoples and ethnic groups are using numerous mosquito repellent plants without knowing their mode of action and their possible repel mechanisms (Table 2). Therefore, it demands for furthermore scientific analysis and experimentation in order to validate their insecticidal activity and their repellency. In general, green pesticides are target-specific and can be non-toxic. However, the following issues have to be considered in order to formulate novel potential green pesticides/reduced-risk pesticides in the near future [26,29],

• Though several plant species exhibit their insecticidal properties, there is a necessity of a well-advanced technological drive and analysis.

• Identification and isolation of novel bio-active molecules as well as their potentialities in terms of their repellent and insecticidal properties

• Analysis of the molecular basis of insecticidal specificity against particular insect groups.

• Evaluation of their non-target toxicity and environmental hazard.

• Establishment of sophisticated laboratory services with adequate skilled personals and funds at the regional and national level, are required.

To date, only a few plant-based insecticidal agents viz.: pyrethrum, citronella and neem have been successfully commercialized and have reached the market. In the past three decades, there have been quite a huge number of applied research conducted in the developing countries than ever before and it is an appreciable positive sign too. The primary objectives of these research were to assess the mosquitocidal properties of locally known insecticidal plants, eventually to identify and synthesize ideal green pesticides. It shows that we’re on the right track and are expected to keep moving ahead to device the innovative, scalable, sustainable and cost-effective pesticidal interventions.

There are a vast number of literature available on the mosquitocidal properties of various plants which is quite promising. However we have miserably failed to construct the ever-lasting strong inter-linking bridges among the scientific laboratories, manufacturing industries and of course the poor and needy society. Therefore, it calls for a strong workable collaboration between the research institutes, particularly, higher learning institutions and the insecticide manufacturing industries to evolve from active ingredients to new public health pesticides. The policy-makers need to play a crucial role in order to bringing all the relevant stakeholders in the common platform to identify new-classes of insecticides from the plant kingdom. It can be achieved by providing the conducive environment in all the possible way to build the everlasting bridge between laboratories and societies. The future in fact has a very bright for the synthesis of risk-reducedpesticides and eventually to attain meaningful vector-borne diseases free world in the near future.

The authors would like to acknowledge Dr. L. Melita for her sincere assistance in editing the manuscript. Our last but not least heartfelt thanks go to our colleagues from the Department of Environmental Health, Faculty of Public Health and Tropical Medicine, Jazan University, Kingdom of Saudi Arabia, for their kind support and cooperation.