The Australian paralysis tick occupies a unique and feared position among the country’s parasites. Found along the humid eastern seaboard, I. holocyclus feeds on a wide range of mammals, and its adult females secrete a potent neurotoxin known as holocyclotoxin while taking a blood meal. In young calves and other naïve animals that have not developed tolerance, this toxin can cause progressive, ascending paralysis that may prove fatal if the tick is not found and removed. For livestock producers, the tick represents both an animal welfare hazard and an economic burden, particularly in dairy and beef operations where calves graze on tick-infested pasture during the warmer months when tick activity peaks.

Existing control options leave a significant gap. Acaricide treatments used against other cattle parasites, such as the cattle tick Rhipicephalus australis, are not always reliably effective against I. holocyclus, and their persistence can be too short to cover the weeks during which calves remain vulnerable. Products registered specifically for paralysis tick control in cattle are limited, and no pour-on formulation had been approved for this purpose in Australia. Pour-on applications are attractive in practice because they avoid the stress and labor of injectable handling regimes or labor-intensive individual tick searches across large herds. Against this backdrop, fluralaner, a member of the isoxazoline class of ectoparasiticides, appeared to be a promising candidate. Isoxazolines act on the nervous systems of arthropods by blocking ligand-gated chloride channels, producing paralysis and death of the parasite, and fluralaner has already demonstrated efficacy against I. holocyclus in dogs and cats. The compound is characterized by systemic distribution and prolonged persistence in the host, which is precisely the profile needed for a long-acting tick control product.

To test the formulation rigorously, the researchers designed two randomised, controlled and blinded studies using a total of 40 healthy male dairy calves, with 20 calves allocated to each study. Within each study, calves were randomly assigned either to an untreated control group or to a fluralaner-treated group, with ten animals in each arm. On Day 0, treated calves received a single topical application of the fluralaner pour-on solution at a minimum dose of 2.5 milligrams per kilogram of body weight, applied along the topline in the manner typical of commercial pour-on products. To establish a pre-existing infestation that would allow the therapeutic effect to be measured, calves were experimentally infested with unfed adult female I. holocyclus ticks on Day −1, one day before treatment. Study 1 used an infestation challenge of ten ticks per calf, while Study 2 used fifteen ticks per calf, providing a slightly heavier parasite burden in the second trial.

The assessment protocol distinguished carefully between therapeutic and persistent efficacy. Therapeutic efficacy, the ability of the treatment to kill ticks already on the animal, was evaluated 48 hours after treatment by comparing live tick counts between treated and control calves. Ticks were first assessed in situ at 24 hours post-treatment, and then counted and removed at 48 hours. Persistent efficacy, the ability of the treatment to protect against new infestations, was assessed by re-infesting all calves weekly with fresh adult female ticks for up to six weeks after treatment. Following each re-infestation, ticks were assessed in situ at 48 hours and then counted and removed at 72 hours, with live tick counts in treated calves compared against those in untreated controls at every time point. This weekly challenge design is demanding, because it tests whether the drug remains at acaricidal concentrations in the skin and blood long after a single application.

The results were striking, particularly for persistent protection. Against the pre-existing infestation, therapeutic efficacy measured at 48 hours post-treatment was 95.5 percent in Study 1 and 69.1 percent in Study 2, indicating that the pour-on formulation killed the substantial majority of ticks already feeding on the treated calves, though the effect against established infestations was somewhat more variable in the second study. The persistent efficacy, however, was remarkable: at 72 hours after each weekly re-infestation, efficacy remained at 100 percent throughout the assessment period in Study 1, and ranged from 98.6 to 100 percent in Study 2. In practical terms, this means that for several weeks after a single application, virtually no tick that attempted to feed on a treated calf survived long enough to complete a blood meal, which is the critical threshold for preventing toxin delivery.

Statistical analysis reinforced the biological picture. Fluralaner-treated calves carried significantly fewer live ticks than untreated controls at all 72-hour assessments through to Week 4, with P values of 0.002 or lower. Beyond Week 4, efficacy declined below the 95 percent benchmark in both studies, marking the practical limit of protection from a single dose under the conditions of these trials. The authors therefore concluded that a single topical administration of the fluralaner pour-on solution provided control of existing I. holocyclus infestations and sustained protection against re-infestation for 28 days in calves under controlled experimental conditions. The four-week window aligns well with common livestock management cycles, suggesting that a monthly treatment schedule during the tick season could keep calves protected through the period of peak risk.

Safety and tolerability, always central considerations for a new use of a veterinary medicine, were also assessed. The treatment was well tolerated across all 20 treated calves, with only one mild, localized skin reaction observed at the application site. No other adverse effects were reported. The studies were conducted with animal ethics approval from the New South Wales Department of Primary Industries Secretary’s Animal Care and Ethics Committee for Study 1 and the Wongaburra Research Centre Animal Ethics Committee for Study 2, and under an Australian Pesticides and Veterinary Medicines Authority permit for small-scale trials with agricultural and veterinary chemicals. The statistical analysis was performed by Fangshi Sun of Merck Animal Health, and the studies were funded by Merck Animal Health, with both authors employed by MSD Animal Health Australia, a disclosure that readers should weigh when interpreting the uniformly positive results.

The significance of the work extends beyond the specific numbers. A pour-on isoxazoline product with a month-long duration of action against paralysis ticks would address several practical limitations of current approaches. It would reduce the frequency of handling, lower the labor required for tick surveillance in susceptible calves, and provide a margin of safety against the toxin that individual tick searches cannot guarantee, since a single engorging female can paralyze a small calf. The systemic mode of action also means protection does not depend on the tick contacting a treated patch of skin, as is the case with some repellent or topical products. Because fluralaner has an established track record against I. holocyclus in companion animal medicine, the class itself is well characterized, although dose rates, formulations and withdrawal considerations for cattle differ substantially from those for dogs and cats.

Important caveats remain before the findings translate into on-farm practice. The trials were conducted under controlled experimental conditions with fixed infestation pressures of laboratory-placed adult female ticks, which do not fully reproduce the variable exposure, weather, and mixed tick populations of commercial pastures. Efficacy against established infestations was lower in the heavier-challenge study, and protection fell below 95 percent after four weeks, so treatment intervals would need careful management. Most importantly, the authors explicitly state that at the time of publication, paralysis tick control is not an approved indication on the Australian APVMA registration of the fluralaner pour-on solution for cattle, meaning veterinarians and producers must await regulatory action before the product can be used for this purpose. Nevertheless, the study provides a robust evidence base for that next step, and it will be watched closely by producers in eastern Australia, where each tick season brings the risk of losing calves to one of the world’s most potent natural toxins.

Subject of Research: Efficacy of a fluralaner pour-on acaricide against experimental Ixodes holocyclus infestations in calves

Article Title: Efficacy of a single treatment of a fluralaner pour-on solution for cattle (Exzolt) against experimental infestations of Ixodes holocyclus on calves

Article References: de Asis, E., & Fisara, P. (2026). Efficacy of a single treatment of a fluralaner pour-on solution for cattle (Exzolt) against experimental infestations of Ixodes holocyclus on calves. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07636-2

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07636-2

Keywords: Australian paralysis tick, Ixodes holocyclus, fluralaner, isoxazoline, calves, cattle, acaricide, pour-on treatment, holocyclotoxin, Parasites & Vectors, tick control, veterinary parasitology