Reduced incidence of tick paralysis cases in dogs and cats at two emergency clinics in South-East Queensland since 2015: new generation prophylactics as possible explanatory variables.

INTRODUCTION: This study aimed to determine the incidence of canine and feline tick paralysis cases presenting to two veterinary emergency hospitals before and after the introduction of new generation prophylactic acaricides. METHODS: This was a retrospective study, investigating the number of tick paralysis cases presenting to two emergency and critical care veterinary hospitals in South-East Queensland, from 2008 to 2021. A total of 10,914 dogs and 3696 cats were included over the course of the study. To assess if the introduction of new generation prophylactics in 2015 has coincided with any variation in case numbers, data for each species were analysed graphically and numerically in the first instance, then interrupted time series analyses were performed for the dog and cat data independently. RESULTS: Accounting for seasonal and climatic variation, we estimated a 54.8% reduction in dog (95% CI 45.3%-62.7%) and 44% reduction in cat (95% CI 19.5%-46%) tick paralysis cases presenting to these two clinics. This reduction corresponded with the timing of new generation prophylactic agents being introduced, including isoxazolines and imidacloprid/flumethrin impregnated collars. CONCLUSION: In the population studied, a significant reduction in the incidence of tick paralysis cases treated by veterinarians has occurred from 2015 onwards and was found to be associated with the timing of the release of new generation acaricidal products.

Immunomic Investigation of Holocyclotoxins to Produce the First Protective Anti-Venom Vaccine Against the Australian Paralysis Tick, Ixodes holocyclus.

Venom producing animals are ubiquitously disseminated among vertebrates and invertebrates such as fish, snakes, scorpions, spiders, and ticks. Of the ~890 tick species worldwide, 27 have been confirmed to cause paralysis in mammalian hosts. The Australian paralysis tick (Ixodes holocyclus) is the most potent paralyzing tick species known. It is an indigenous three host tick species that secretes potent neurotoxins known as holocyclotoxins (HTs). Holocyclotoxins cause a severe and harmful toxicosis leading to a rapid flaccid paralysis which can result in death of susceptible hosts such as dogs. Antivenins are generally polyclonal antibody treatments developed in sheep, horses or camels to administer following bites from venomous creatures. Currently, the methods to prevent or treat tick paralysis relies upon chemical acaricide preventative treatments or prompt removal of all ticks attached to the host followed by the administration of a commercial tick-antiserum (TAS) respectively. However, these methods have several drawbacks such as poor efficacies, non-standardized dosages, adverse effects and are expensive to administer. Recently the I. holocyclus tick transcriptome from salivary glands and viscera reported a large family of 19 holocyclotoxins at 38-99% peptide sequence identities. A pilot trial demonstrated that correct folding of holocyclotoxins is needed to induce protection from paralysis. The immunogenicity of the holocyclotoxins were measured using commercial tick antiserum selecting HT2, HT4, HT8 and HT11 for inclusion into the novel cocktail vaccine. A further 4 HTs (HT1, HT12, HT14 and HT17) were added to the cocktail vaccine to ensure that the sequence variation among the HT protein family was encompassed in the formulation. A second trial comparing the cocktail of 8 HTs to a placebo group demonstrated complete protection from tick challenge. Here we report the first successful anti-venom vaccine protecting dogs from tick paralysis.

Investigation of the efficacy of fluralaner spot-on (Bravecto®) against infestations of Ixodes holocyclus on cats.

BACKGROUND: Infestation of cats with the Australian paralysis tick, Ixodes holocyclus continues to be a threat because of the paralysis that can result from attachment of just a single tick. The outcome can be fatal, particularly if tick removal and treatment is not initiated soon after the onset of paralysis. However, there are no published studies to guide veterinarians and owners on preventive measures. A study was therefore initiated to determine the efficacy of a systemically-acting, spot-on formulation of fluralaner (Bravecto®) for cats against existing I. holocyclus infestations, and to investigate the duration of protection following a single administration. METHODS: Healthy domestic cats, short or long-hair, immunized against holocyclotoxin, were randomly allocated to two groups of 10 cats per group, to receive either a single topically applied fluralaner treatment or no treatment. Fluralaner treatments were administered on Day 0 at a dose rate of 40 mg/kg. All cats were infested with 10 adult unfed female I. holocyclus on Day -1 and on Days 14, 28, 42, 56, 70 and 84. Ticks were assessed at 24 and 48 h after fluralaner treatment and 24, 48 and 72 hours after each subsequent re-infestation. Ticks were counted but not removed at the 24- and 48-h post-challenge assessments and were removed following the 72-h counts. RESULTS: The efficacy of fluralaner spot-on against an existing I. holocyclus infestation was 100% at 48 h post treatment. Following re-infestations, efficacy remained at 100% at the 72-h assessments for all challenges from Day 14 to Day 84. Differences between mean live tick counts on treated versus control cats were significant at all time points from the first post-treatment assessment (t-test: t(18) = 23.162; P < 0.0001) through the final challenge on Day 84 (t-test: t(18) = 21.153; P < 0.0001). No treatment-related adverse events were observed and there were no abnormal observations at the product application sites. CONCLUSIONS: A single treatment of fluralaner spot-on was well tolerated and provided 100% efficacy against I. holocyclus ticks for at least 84 days. Fluralaner spot-on can be a valuable tool to prevent tick infestation in cats, and to control the risk of I. holocyclus-induced paralysis.

Tick paralysis

Tick paralysis is caused by neurotoxins secreted by adult female ticks, primarily in North America and on the east coast of Australia. Sporadic illness is also recorded in Europe and Africa. In the European countries, including Poland, there are 6 species of ticks capable of causing tick paralysis. The disease occurs in people of all ages, but is most commonly diagnosed in children under 8 years of age. Paralysis can take different forms - from rare isolated cranial nerve infections to quadriplegia and respiratory muscles paralysis. After the tick remove, the symptoms resolve spontaneously. In severe cases with paralysis of respiratory muscles, when there is no possibility of mechanical ventilation, the disease may lead to death.

A 60-year meta-analysis of tick paralysis in the United States: a predictable, preventable, and often misdiagnosed poisoning.

Tick paralysis (TP) is a neurotoxic poisoning primarily afflicting young girls in endemic regions. Recent case series of TP have described increasing misdiagnoses of TP as the Guillain-Barré syndrome (GBS). A meta-analysis of the scientific literature was conducted using Internet search engines to assess the evolving epidemiology of TP. Fifty well-documented cases of TP were analyzed over the period 1946-2006. Cases were stratified by demographics, clinical manifestations, and outcomes. Misdiagnoses were subjected to Yates-corrected chi-square analyses to detect statistically significant differences in proportions of misdiagnoses between earlier and later reporting periods. TP occurred seasonally and sporadically in individuals and in clusters of children and adults of both sexes in urban and rural locations. The case fatality rate (CFR) for TP was 6.0% over 60 years. The proportion of misdiagnoses of TP as GBS was significantly greater (chi(2) = 7.850, P = 0.005) in more recently collected series of TP cases, 1992-2006, than the proportion of misdiagnoses in earlier series, 1946-1996. TP was a potentially lethal poisoning that occurred in children and adults in a seasonally and regionally predictable fashion. TP was increasingly misdiagnosed as GBS during more recent reporting periods. Such misdiagnoses often directed unnecessary therapies such as central venous plasmapheresis with intravenous immunoglobulin G, delayed correct diagnosis, and tick removal, and could have increased CFRs. TP should be added to and quickly excluded from the differential diagnoses of acute ataxia and ascending flaccid paralysis, especially in children living in TP-endemic regions of the USA.

Inducing active and passive immunity in sheep to paralysis caused by Dermacentor andersoni.

Arcott sheep were evaluated as a model for studying active and passive immunity to tick paralysis caused by Dermacentor andersoni (Stiles). The incidence of tick paralysis in sheep increased from 0 at doses < or = 0.33 ticks per kg to 100% at > or = 0.8 ticks per kg. The dose required for 50% paralysis was 0.42 ticks per kg. Expressing dose as a ratio of initial ticks per unit body weight removed differences in response due to sheep weight. The interval from infestation to paralysis decreased from >12 d at 0.4 ticks per kg to <8 d at 1.3 ticks per kg. After exposure to a paralyzing doses of ticks, the incidence of paralysis varied among sheep that were naive (six of six, 100% paralysis), previously paralyzed (zero of six, 0% paralysis), and passively immunized with an intravenous treatment of 300 ml of serum from immune cattle (two of six, 33% paralysis). Sheep that were actively immunized by previous exposure had antibodies to a greater number of tick salivary antigens compared with those that were not immune. Antibodies to a 43.3-kDa antigen had 72% agreement with immunity to paralysis, and a sensitivity and specificity of 0.60 and 0.88, respectively. In conclusion, previously paralyzed sheep had developed antibodies against D. andersoni and were not susceptible to subsequent paralysis, whereas passive immunization conferred protection against paralysis in only some sheep.

Tick paralysis.

The one tick-borne disease that rarely comes under the auspices of the infectious disease specialist is not caused by an infectious agent, but is tick paralysis. This condition is caused by tick bite and typically presents as a flaccid ascending paralysis. This article discusses this entity partly because of completeness, but also because tick paralysis, or tick toxicosis as it is sometimes called, is worth the infectious disease consultant's consideration. The differential diagnosis includes entities that are infectious or caused by toxins of infectious agents, such as epidural abscess, some causes of transverse myelitis, and botulism. Lastly, in an era of antibiotic toxicity, multidrug-resistant bacteria, antigen-switching viruses, and complex antibiotic regimens, the cure for tick paralysis-removing the tick-is as simple as it is gratifying.

Tick paralysis: development of a vaccine.

The paralysis tick of Australia, Ixodes holocyclus, causes a severe toxicosis in domestic animals such as dogs and cats, livestock, and in some cases, humans. It is characterised by a rapidly ascending flaccid paralysis. The causative agent of the toxicosis is a neurotoxin(s) produced in the tick salivary glands. The current treatment for tick paralysis is in the form of a polyclonal dog antiserum. This antiserum treatment is expensive and effective only in the early stages of paralysis. The aim of current research is to develop a recombinant veterinary vaccine based on the tick neurotoxin peptide sequence. A successful vaccine would provide cost-effective, long-term protective immunity against tick-induced paralysis.

An evaluation of strategic and threshold control measures against the Karoo paralysis tick, Ixodes rubicundus (Acari: Ixodidae) in South Africa.

Paralysis caused by feeding female Ixodes rubicundus ticks is a major problem in large areas of South Africa. As the life cycle of the tick extends over a period of 2 years, it was hypothesized that strategic treatment of sheep with an acaricide over a 2 year period, timed to kill most engorging females, should markedly lower the biotic potential of the tick. Two flocks of sheep grazing in separate paddocks known to be infested with I. rubicundus were treated either strategically or on a threshold basis (i.e. only when tick challenge exceeded a predetermined critical level in terms of paralysis) for a 2 year period. The tick burdens of untreated control sheep running with the two flocks were monitored over a 4 year period and their seasonal dynamics determined. The times at which peak infestations occurred were similar for both flocks of sheep, but significant differences in mean tick burdens between the two flocks were recorded. Tick numbers on sheep in the strategically treated flock did not decrease during the third and fourth years of the trial as was expected. Possible reasons for this were low stocking densities, especially during times of peak abundance of adults and the presence of wild hosts which maintained tick populations.

Tick-paralysis toxoid: an effective immunizing agent against the toxin of Ixodes holocyclus.

Glutaraldehyde treatment of the toxin of the Australian paralysis tick Ixodes holocyclus produced a potent, immunogenic toxoid. Three subcutaneous injections (2 to 4 weeks apart) into rabbits produced very high antitoxin titres in their serum, although circulating antitoxin titres declined in the absence of stimulation. Twenty weeks later, immunized rabbits were unaffected by lethal doses of toxin injected subcutaneously.

Immunization of rabbits to produce high serum titres of neutralizing antibodies and immunity to the paralyzing toxin of Ixodes holocyclus.

Rabbits have been immunized against the effects of the paralyzing toxin of the Australian paralysis tick Ixodes holocyclus by injecting them with preparations extracted from tick salivary glands. Immunized rabbits were able to withstand doses of toxin known to kill unimmunized rabbits. Neutralizing antibodies were detectable in serum after 2-4 doses of the crude extract or of the relatively pure antigenic fraction. When injections were continued at intervals of from 2-7 weeks, hyperimmunity was retained for at least 68 weeks. Hyperimmune serum, reaching a very high titre of neutralizing antibodies, was obtained after 3-6 injections. Titres tended to decline when boosting ceased, but after a "rest period' high titres were restored by further boosting with normally lethal doses of toxin. No symptoms of tick paralysis developed despite low titres prior to boosting. Thus, once hyperimmunity had been established, high titres of circulating antibodies were not immediately essential for immunity to tick paralysis. An IgG fraction was obtained from rabbit serum using a Protein A-Sepharose method; 33.4 micrograms of IgG protein fully neutralized, and 19.5 micrograms IgG half neutralized, 1 micrograms of crude toxin protein. This procedure with rabbits may permit the production of a purified tick-paralysis antitoxin more suitable for human use than the existing antitoxin based on canine hyperimmune serum.

Paralysis of calves by the tick, Ixodes Holocyclus.

Adult female Ixodes holocyclus were collected from the field at Fig Tree Pocket, a Brisbane suburb, at Tamborine Mountain, Queensland and at Lismore, New South Wales, in November 1974. Females were also reared from engorged nymphs collected off bandicoots from Tamborine Mountain July 1974 and 1975. In November 1974 unexposed 2-3 week old British breed calves, weighing between 26 and 46 kg were infested with 2,4,8 or 10 ticks. Neither 2 nor 4 females per calf caused paralysis. A challenge of 8 to 10 females induced paralysis 6 to 9 days after infestation by which time most ticks had engorged. There was little difference between ticks from different geographic localities. The site of attachment had no influence on tick toxicity. In September 1975, 2-3 week old British breed and Sahiwal x Jersey calves were infested with female ticks which had moulted 2-4 weeks prior to infestation. All but one calf with 10 ticks and all calves with 4 ticks became paralysed 8 to 13 days after infestation. At the time of paralysis only 1 of the 86 ticks had engorged and the remainder were small (30 to 50 mg). The greater toxicity of the latter ticks may have been due to the different treatment of ticks prior to infestation or to variations in the production of toxin associated with slow feeding. Four of 7 paralysed calves were saved using canine antitick serum.

Cattle and the paralysis tick Ixodes holocyclus.

Paralysis of domestic stock by the paralysis tick Ixodes holocyclus is chiefly a disease of young animals (especially calves) and of non-habituated stock introduced into tick-infested country in spring. The tick has a wide host range, but its principal hosts are bandicoots. The tick has one generation per year and the adult female, which causes almost all paralysis, is abundant in spring and early summer and occurs most commonly in overgrown or regrowth country where bandicoots are abundant. The distribution and behavior of the long and the short-nosed bandicoots are reviewed. The number of ticks required to induce paralysis in cattle and the protection from paralysis afforded by prior experience of the tick are discussed.