Acaricide resistance: Status, mechanism of development, methods of detection and its management

Introduction

Ticks and tick-borne diseases pose a major threat to livestock health and productivity, especially in tropical and subtropical regions. They are among the most important bloodsucking ectoparasites, causing heavy economic losses through blood loss, stress, reduced production, immune suppression, and hide damage. Ticks transmit several significant pathogens, including Theileria, Babesia, Hepatozoon, Ehrlichia, and Anaplasma species. Globally, they are second only to mosquitoes as vectors of human diseases. Acaricides remain the primary method of tick control, but ticks rapidly develop resistance due to their short life cycle and high reproductive rate. Many chemical classesorganophosphates, carbamates, pyrethroids, amidines, and macrocyclic lactones-have lost effectiveness. Of the 904 tick species known worldwide, 106 occur in India. Crossbreeding in India has altered natural immunity, increasing susceptibility to tick infestation. Hot and humid seasons further favor tick survival and amplify the burden of tick-borne diseases in livestock.

What is resistance?

Drug resistance becomes evident when a treatment no longer controls a parasitic infection, but scientifically it refers to a measurable decrease in the parasite's sensitivity to a drug. As defined by the WHO (1965), resistance is the ability of a parasite strain to survive or multiply even when the host receives recommended or higher doses of a drug. In ticks, acaricide resistance is an inherited trait and is usually recognized when acaricides fail to effectively reduce tick populations. [22] . For example, coumaphos resistance appeared after 7 years (Aguirre et al., 1986), while amitraz resistance evolved in about 12 years (Foil et al., 2004) [5] . Multiclass resistance is now widespread, especially in countries like Brazil and Mexico, where ticks often show resistance to multiple acaricide groups. [4] . The most recent reports on acaricide resistance are included below.

Different Kind of Acaricide and it's Modes of Action

India

The most recent reports on acaricide resistance are included below.

Drug Reference State Diazinone

Kumar et al., 2011 [13] Uttar Pradesh Deltamethrin, cypermethrin and Diazinone Shyma et al., 2012 [18] Uttar Pradesh Amitraz Kumar et al., 2014 [14] Uttar Pradesh Malathion, Coumaphos, Fenvalerate and Fipronil Kumar et al., 2014 [14] Uttar Pradesh Deltamethrin, cypermethrin and Diazinone Ghosh et al., 2015 [10] Uttar Pradesh Cypermethrin Ghosh et al., 2017 [9] Uttar Pradesh Ivermectin Nandi et al., 2018 [17] Uttar Pradesh Deltamethrin and Cypermethrin Upadhyay et al., 2020 Uttar Pradesh Deltamethrin Jyothimol et al., 2014 [12] Kerala Deltamethrin Ahanger et al., 2015 [1] Jammu & Kashmir Ivermectine Singh et al., 2015 [19,20] Punjab Deltamethrin and Diazinone Gaur et al., 2016 [7] Haryana and Rajsthan Deltamethrin, Cypermethrin and Amitraz Kumar et al., 2017 [15] Andhra Pradesh Deltamethrin and Chlorpyriphos Kutari et al., 2017 Madhya Pradesh Deltamethrin and Cypermethrin Godara et al., 2019 [1] Jammu Amitraz Singh et al., 2015 [19,20] SKnagar, Gujarat Deltamethrin, Flumethrin and Fipronil Shyma et al., 2016 [18] SKnagar, Gujarat Deltamethrin, cypermethrin and Ivermectin Kumar et al., 2017 [15] Junagadh, Gujarat [2] . Acetylcholinesterase gene mutation: Changes in the AChE gene alter the target site of OPs, preventing the drug from inhibiting the enzyme effectively, thereby conferring resistance (Fournier & Mutero, 1994) [6] . Organochlorines act by binding to the picrotoxinin site of the GABA-gated chloride channel, blocking Cl⁻ entry and causing nerve hyperexcitation leading to death. Widespread resistance has developed against lindane, dieldrin, and DDT due to both target-site and metabolic mechanisms. In Rhipicephalus microplus, resistance to dieldrin and DDT is linked to mutations in the GABA-gated chloride channel and voltage-gated sodium channel genes, causing key amino acid changes (Bandara & Karunaratne, 2017) [3] . Carbamates are carbamic acid esters that act similarly to organophosphates but are generally less harmful to mammals. Their primary mode of action is the inhibition of acetylcholinesterase, leading to disrupted nerve function (Spickett, 1998) [21] .

Mechanism of resistance:

Reduced cuticular penetration occurs when changes in the tick's outer cuticle limit the (a) Bioassay Tools: Bioassays are key tools for detecting resistant tick populations due to their simplicity and low cost, providing phenotypic data on resistance levels. Four main bioassays exist: Adult Immersion Test (AIT), Larval Packet Test (LPT), Larval Immersion Microassay (LIM), and Larval Tarsal Test (LTT). AIT gives results in 7 days but requires many engorged females, while LPT and LIM take 5-6 weeks using larvae. Bioassays detect resistance even when mechanisms are unknown but do not clarify how resistance occurs. Advantages: Simple, inexpensive, and provides phenotypic resistance data. Disadvantages: Requires sufficient engorged females, time-consuming, and offers limited insight into resistance mechanisms.

Biochemical Tool

Metabolic Resistance: The most common mechanism of acaricide resistance is metabolic, where detoxifying enzymes like esterases, monooxygenases, and GST break down or sequester multiple acaricide classes. Biochemical tests using enzyme inhibitors (e. g., chlorfenethol, EPEoxon, DEF, piperonyl butoxide) help detect resistance patterns. Methods include filter paper assays and microtitre plate tests, providing phenotypic evidence of enzymemediated resistance.

Advantages: Broad detoxification ability, shows metabolic resistance patterns, effective against multiple acaricide classes.

Disadvantages: Requires many samples, early resistance may go undetected, no genetic information revealed.

Molecular Tools

Molecular Tests for Acaricide Resistance: Molecular assays are faster than bioassays, providing results in a day, requiring fewer ticks, and detecting resistance mechanisms early. Techniques include allele-specific PCR, gene amplification, DNA/RNA sequencing, transcriptomics, and qPCR to identify resistance genes and SNP markers. They help monitor low-frequency or recessive resistance alleles and guide effective acaricide use. Advantages: Rapid results, early detection, highly sensitive, enables informed control strategies. Disadvantages: Requires precise molecular markers, skilled personnel, and costly equipment.

Management of Acaricide

Integrated Tick Management

There are numerous prevention and control techniques, including those that are taken both "on the target animal" and "off the target animal," that can be used to lessen the tick infestation on animals. The on-host precautions include manual tick removal, anti-tick vaccination, and the application of repellents. Rodent and deer control, the use of semiochemicals and kairomones as attractants, the use of entomopathogenic fungi, nematodes, and parasitoids, management of the landscape and vegetation, and the use of flame guns and steam guns are some examples of off-host measures. Some tick-control strategies, like chemical and biological acaricides, can be applied on and off the host. A smart and long-term solution to control cow ticks is to raise genetically chosen tick resistant cattle breeds. Chemical acaricides have long been the primary means of managing ticks on cattle or in the environment, but their indiscriminate use has resulted in the selection of acaricide-resistant ticks, making the majority of chemical acaricide classes useless at doing so. Additionally, the risks to the environment and human health make widespread application of chemical acaricides problematic. The management of tick infection in cattle using all available on and off host interventions failed. The complexity of the tick life cycle, genetic variety of ticks, reservoir hosts, host genetics and immunity, and their intricate interactions cannot be adequately addressed by single intervention measures due to their short duration or efficacy. Though the main factors influencing farmers and veterinarians to choose the intervention measures are market accessibility and ease of use, product shelf life, cost, and the length of time to see the visible effect on host, there is an increased interest among cattle farmers in implementing integrated tick control measures.

Conclusions

References

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