Encyclopedia
Please note this is a comparison between Version 1 by Felix Valcarcel and Version 2 by Peter Tang.
Ticks are forced bloodsucker ectoparasites belonging to the Order Ixodida, which comprises three families: Ixodidae (hard ticks, 720 species), Argasidae (soft ticks, 186 species), and Nuttalliellidae (1 species). Tick control is a priority in order to prevent the transmission of vector-borne diseases. The essential oil’s acaricidal activity is due to the variability of its chemical composition and the relationship between these compounds. Moreover, given their low toxicities and their solubility in water these compounds can contribute to the production of milk and animal meat free from dangerous chemicals which are harmful to humans, animals, and the environment.
- ticks
- natural compounds
- efficacy
1. Introduction
Ticks are forced bloodsucker ectoparasites belonging to the Order Ixodida, which comprises three families: Ixodidae (hard ticks, 720 species), Argasidae (soft ticks, 186 species), and Nuttalliellidae (1 species) [1][2][1,2]. They are also one of the main groups of disease vectors, and tick-borne diseases (TBDs) have long been recognized as one of the major constraints to livestock development in various countries [3], particularly in the cattle industry in tropical and subtropical regions [4]. Likewise, they are the most devastating as they cause huge economic losses [5]. These losses are estimated in the billions of US dollars [4], as a consequence of higher production costs due to constant antiparasitic treatments [6] and the effects generated by the infestation: blood loss, reduced weight gain and milk production, and skin damage at the site of attachment [7].
Many commercially available chemicals are used in current tick control strategies: arsenicals, chlorinated hydrocarbons, carbamates, macrocyclic lactones [8][9][8,9], organophosphates, formamidines, pyrethroids [8][9][10][11][8,9,10,11], fluazuron, and fipronil [10][11][10,11]. They have generally been sprinkled on, poured on, or injected into animals, with high costs for farmers [10][11][10,11].
Unfortunately, the misuse, overuse, and inappropriate application of chemical acaricides led to the development and selection of resistance in the tick population [4][7][12][13][14][15][4,7,12,13,14,15]. However, apart from their high costs, these acaricides could also be potentially hazardous through contamination of ruminant milk and meat [13][16][17][13,16,17] and thus, may have an effect on human health [18][19][18,19], as well as contamination of the environment with residues harmful to humans and animals [15][16][18][20][21][15,16,18,20,21]. Due to this and the growing interest in organic farming practices, several acaricides have undergone restriction of use in the global market, such as organochlorines, organophosphates, and pyrethroids [18]. Consequently, the development of new agents and/or effective alternative strategies for their control is necessary [6][22][6,22]. Therefore, many other current strategies used for control of resistant tick populations such as biological control using pathogens or predators, pheromone-assisted control, herbal pour-on or dip preparations including green manufactured nanoparticles, and vaccination, as well as design of acaricide resistance mitigation programs based on integrated pest management control [3][23][24][3,23,24].
Among these alternative strategies, plant-derived products can be promising acaricidal product sources, especially essential oils [6][7][15][23][24][6,7,15,23,24]. The essential oil’s acaricidal activity is due to the variability of its chemical composition and the relationship between these compounds [25]. Moreover, given their low toxicities and their solubility in water [25] these compounds can contribute to the production of milk and animal meat free from dangerous chemicals which are harmful to humans, animals, and the environment [13].
2. Ticks and Synthetic Acaricides
Arsenic and its derivatives were intensively used at the end of the 19th and the beginning of the 20th centuries because they had a short residual effectiveness time, were cheap, stable, and water-soluble [26]. When arsenic use decreased, due to the high toxicity of its residues, its prohibition forced the appearance of the first organochlorines: dichlorodiphenyltrichloroethane (DDT), benzene hexachloride (BHC), lindane, dieldrin, or toxaphene, which were used extensively throughout the twentieth century [27]. Initially, organochlorides were highly effective against ticks showing high residual effectiveness an ease of use, but the majority accumulated residues in the environment and animal tissues [26]. In the 1960s, organophosphates and carbamate derivatives complemented or replaced organochlorides. These new acaricides offered the advantage of being biodegradable and rapidly metabolized, although they also quickly lost their effectiveness [28]. In the 1970s formamidines appeared, such as amitraz, in an attempt to avoid the fast reduction in effectiveness of the preceding products [29]. From the 1980s, the use of acaricides with low toxicity in mammals proliferated, such as pyrethrins and some biopesticides (macrocyclic lactones: avermectins and milbemycins) [30]. The pyrethrins gave rise to the pyrethroids, synthetic analogs obtained by successive isosteric modifications [31], more stable and with less residual effect. Pyrethroids are classified as first-generation (allethrin), second-generation (tetramethrin, resmethrin, bioresmethrin, biolalethrin, and fontarin), third-generation (fenvalerate and permethrin), and the current fourth-generation, which includes cypermethrin and decamethrin, among others [32]. Finally, in the late twentieth century, mite growth regulators derived from benzoyl-phenyl urea (fluazuron, for example) began to be used [28], along with other chemical acaricides, phenylpyrazoles, such as fipronil. Spinosad is a relatively recent insecticide-acaricide produced from the fermentation of metabolites of the actinomycete bacterium Saccharopolyspora spinosa and a mixture of two components A and D spinosyn [33]. In both laboratory and field tests, those products were found to be equally effective against ticks and could therefore be used as an alternative [34][35][34,35]. The latest addition to the market for ectoparasiticides for pets is isoxazolines [36][37][38][39][36,37,38,39].
3. Tick Control Methods
Several methods are applied to combat ticks and tick-borne diseases [40]. At first, tick control was based on using a mixture of lard and sulfur, a combination of lard and kerosene, cottonseed oil or fish oil from kerosene mixtures, cottonseed oil and sulfur, 10% kerosene emulsion, a mixture of cottonseed oil and crude petroleum oil, or Beaumont crude oil [8][41][8,41]. Thereafter, the treatment of cattle by baths based on mineral oil and “carbolics” by Australian researchers occurred, continuing as recently as 1895 [8][42][8,42]. Currently, the main method to control ticks is the use of chemical acaricides [27][41][27,41].
Many acaricides are available on the market such as arsenicals, organochlorines, organophosphates, carbamates, formamidines, pyrethroids, macrocyclic lactones, phenylpyrazoles, benzoylphenylurea, spinosad, and isoxazolines (Table 1) [9][10][11][14][40][41][9,10,11,14,40,41]. The use of these acaricides reduces the tick population, as well as the diseases transmitted by ticks. However, the effectiveness of an acaricide depends on the activity of a product, as well the quality and quantity of active material sprayed or injected [40]. Moreover, inappropriate and long-term application of these acaricides, frequency of treatment, underdosing, and persistent use of a chemical group for tick control enables improvement of tolerance/resistance to the chemical and leads to the evolution of resistance in many tick species [4][14][40][41][43][44][45][4,14,40,41,43,44,45].
Several studies recommended an integrated strategy for the control of ticks in cattle based on the house management, slow-burning of the wastes near the walls of the animal sheds, pasture alternation and/or rotation, pasture burning, clearance of vegetation, nutritional management, rotation of acaricides, using combinations of acaricides, immunization via vaccination, improving genetic resistance in cattle, improving resistance diagnostic tests, biological control, and ethnoveterinary practices against ticks [14][41][46][47][48][14,41,46,47,48].
Table 1. Chemical acaricidal class, mode of action, and their mechanisms of resistance.
Acaricidal Class | First Year of Use | Mode of Action | First Report of Resistance | Mechanisms of Resistance | References | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arsenic | 1893 | 1937 | ||||||||||||||||||||||
Organochlorines | 1946 | GABA-gated chloride channel antagonists | Bind at the picrotoxinin site in the γ-aminobutyric acid (GABA) chloride ionophore complex. | 1952 | Enhanced metabolism and reduced absorption of the chemical | |||||||||||||||||||
Organophosphates | 1955 | Acetylcholinesterase | Inhibits the action of acetylcholinesterase | 1965 | Target-site insensitivity | |||||||||||||||||||
Carbamates | 1955 | Inhibits the action of acetylcholinesterase | 1965 | |||||||||||||||||||||
Formamidines (Amitraz) | 1975 | Octopamine receptor | α-2 agonist | Overstimulates the nervous system | 1981 | Mutations in the octopamine/tyramine receptor | Target-site insensitivity in G protein-coupled receptors | Amino acid substitution in the beta-2-adrenergic-like octopamine receptor | ||||||||||||||||
Pyrethroids | 1977 | GABA-gated chloride channel antagonists | Prolongs opening of sodium channels in nerve, muscle, and other excitable cells. | 1989 | Mutations in the voltage gated sodium channel gene | |||||||||||||||||||
Nicotinic acetylcholine receptors (nAChRs) | ||||||||||||||||||||||||
γ-amino-butyric acid (GABA) receptors | Hyperexcitation and disruption of an insect’s nervous system | |||||||||||||||||||||||
Isoxazolines | 2014 | Inhibits GABA-gated chloride ion channels |
4. Tick Resistance
Chemical products used in traditional tick control methods are at the center of eradication and control efforts because they offer relatively rapid and effective control of tick populations. However, resistance is the result of irrational and long-term use of acaricidal drugs. In addition, they are expensive and can be harmful to the environment and dangerous for consumers if the recommended withdrawal times for foods of animal origin are not respected [63][64][65][63,64,65]. Resistance is broadly defined as a change in the sensitivity of the target species to a drug [66][67][66,67]. The concept of drug resistance can be defined as “the ability of a strain of parasite to survive and/or multiply despite the administration and absorption of a drug administered to doses equal to or greater than those usually recommended but within the tolerance of the subject” (World Health Organization, 1965) or “the ability of some parasites to tolerate toxic doses of a drug that would be lethal to most of their congeners” [68][69][68,69].
There are several definitions of acaricide resistance and different types of resistance were observed. In parasitology, four types of resistance were defined:
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Natural resistance or tolerance: “present in the external body-part and in all individuals of the species and does not develop as a result of acaricidal use”. This may be due to the impermeability of the cuticle or behavioral traits. It is not necessarily transmitted to their offspring [47].
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Macrocyclic lactones | 1981 | Has a toxic effect on ticks by stimulating the release and binding of GABA at nerve endings, which eventually blocks the transmittance of electrical activity in nerves and muscle cells | Glutamate–gated Cl-channel | Blocks nerve signals by interfering with the glutamate gated chloride (GlCl) | 2001 | Insensitivity of the GABA or glutamate gated chloride ion channels | ||||||||||||||
Phenylpyrazoles (Fipronil) | 1993 | Blocks the gamma-Aminobutyric acid gated chloride ion-channel (GABA-C) | 2003 | Mutations in the GABA-Cl gene | ||||||||||||||||
Benzoylphenyl urea (Fluazuron) | 1990 | Disturbs cuticle formation | Blocks the incorporation of radiola-beled N-acetylglucosamine | 2010 | ||||||||||||||||
Spinosad (Tetracyclic-macrolide compounds) | 2001 |
The first report of tick resistance, against arsenic, was due to the indiscriminate use of this product for more than 30 years (1890–1910) to control Rhipicephalus (Boophilus) microplus (Wharton 1983), the main tick affecting domestic cattle over the world. There are many reports describing resistances to formamidine, amitraz, permethrin [70][71][72][73][70,71,72,73], and even to the more modern fipronil [53]. Unfortunately, there are instances of resistances to practically all the synthetic acaricides as reviewed by [14]. Although negative consequences of resistances have been partially relieved with the rotation products with different mechanisms of action, it continues to be a major problem in large territories of Africa and America [48][74][75][76][77][48,74,75,76,77]. This is the main threat given that most of these acaricidal groups are still applied. The development of safe and effective new acaricidal agents is therefore of great interest.
5. Natural Products
Plant products containing bioactive metabolites represent a promising alternative for the control of ticks that are susceptible and/or resistant to conventional acaricides. Studies of the effects of essential oils and plant extracts against different classes of ticks showed efficacies of 5–100% [78]. Following the line of the search for ecological alternatives for effective tick control, products derived from microorganisms or natural products were defined as biopesticides [79]. The products derived from plants are particularly attractive due to their low toxicity, scarce environmental permanence, and the complex chemistry that hinders the development of the resistances. The use of natural products for the control of ticks offers advantages but still has certain limitations. The first disadvantage is the variability of the composition of certain products, such as essential oils, and therefore their effectiveness, for which the identification and subsequent standardization of the fractions and possible effective synergies are required. Another disadvantage could be the characteristics of the product, such as photosensitivity or high volatility, which limit the residual activity depending on the form of presentation [17]. Among the advantages, its role as an alternative in the control of resistant ticks stands out, its environmental innocuousness, and the minimum impact on animal and human health that facilitates its registration and subsequent commercialization [80]. At the beginning of the 19th century, the Caucasian and Persian tribes used pyrethrum flowers as a method of control against body lice [31]. Pyrethrum or Dalmatian pyrethrum (Tanacetum cinerariifolium or Chrysanthemum cinerariaefolium) is an evergreen plant of the Asteraceae family, with insecticidal properties of low toxicity to mammals. Another plant derivative traditionally used is the neem tree (Azadirachta indica), belonging to the Meliaceae family that originates in the Indian subcontinent. For centuries, Indians have relied on this tree to strengthen their health and remedy dozens of diseases; in addition, it has been used to protect stored food and as a natural fertilizer and pesticide for the fields, since it intervenes in the feeding of arthropods and the hormonal processes of their development [81][82][81,82]. It is now valued throughout the world as an important source of phytochemicals for use in human health and pest control. Neem oil contains at least 100 biologically active compounds [83]. Essential oils are naturally produced by plants as secondary compounds, which are obtained for commercial use by various forms of distillation, and plant extracts are obtained through various forms of solvent extraction; some of them stand out for their pesticide, growth-regulating, and repellent or dissuasive properties [17].
6. Essential Oils in Control of Ticks
6.1. Acaricidal Activity of Essential Oils against Ticks
In recent decades, natural products and their compounds have been the most productive source for new drug development. Among them, essential oils and isolated terpenoids have shown activity against diverse stages of several species of ticks [63]. Many studies have reported the ovicidal (inhibited oviposition and inhibited hatchability), effects against all the stages of ticks [3][14][34][84][85][86][87][3,14,34,84,85,86,87].
The variability in the chemical composition of essential oils and the relationship between compounds play an important role in acaricidal activity. It is difficult to attribute the observed biological effects to the major chemical compounds of essential oils. These biological effects can be attributed to a synergistic action between the minority compounds and other minor or major molecules [15]. Additionally, the substances obtained from plants have a low cost, few residual effects, and a low incidence of generating resistance [15][88][15,88].
7. Mechanisms of Action of the Essential Oils and/or Their Components against Ticks
Essential oils are the most studied plant-derived compounds for tick control and prevention [9][16][18][89][9,16,18,122]. Two effects of essential oils against ticks were observed: acaricidal or repellent effects [9][16][89][90][91][92][93][94][9,16,122,123,124,125,126,127]. They cause various effects against ticks: feeding inhibition [92][95][96][125,128,129], inhibition of chitin synthesis [9][78][96][9,78,129], decrease in growth, development, or reproduction [9][78][92][93][95][97][9,78,125,126,128,130], and affect tick behavior [96][129].
