Tick toxicity caused by the Australian paralysis tick, Ixodes holocyclus, which occurs along a coastal band of eastern Australia is reported in several exotic and native species held at Taronga Zoo, Sydney, Australia. The toxin causes a progressive paralysis which may be fatal and in domestic dogs is usually accompanied by cardiopulmonary dysfunction and esophageal weakness or paralysis. In the affected zoo animals neuromuscular weakness has been the predominant feature of toxicity, but despite this, cardiopulmonary function should be assessed in every case. Affected animals are treated with antiserum-containing, concentrated gamma globulins prepared by hyperimmunizing dogs. Live ticks should be removed, and antiserum should be administered as early as possible in the course of the disease to reduce the risk of fatality and minimize the recovery time. Antisera reactions occur in domestic animals, so animals should be premedicated with a combination of corticosteroids, atropine and/or adrenaline to reduce the risk of such reactions. The availability of preventive acaricidal preparations for zoo animals effective against I. holocyclus are limited.
Tick toxicity is well documented in Australia with the vast majority of cases caused by Ixodes holocyclus. The tick occurs in a narrow coastal band from northern Australia to Lakes Entrance in Victoria. There are several genera of ticks worldwide that have been associated with paralysis, but the Australian paralysis tick (I. holocyclus) causes a progressive paralysis which may be fatal if untreated. Although native fauna, particularly the Peramelidae (bandicoots) and Phalangeroidea (possums) are the natural hosts of the tick, all warm-blooded animals are susceptible, including birds and humans. Monotremes and marsupials appear to be less susceptible to toxicity than eutherian mammals. Large numbers of domestic pets and livestock are affected annually, but fatality is most common in dogs and cats.
The toxin causes an ascending flaccid lower motor neuron paralysis due to the blocked transmission of acetylcholine at the neuromuscular junctions.4 In dogs this is often accompanied or preceded by dysphonia and/or vomiting and/or regurgitation and/or gagging and retching, associated with esophageal weakness or paralysis.6 Pulmonary congestion and oedema are a common feature of toxicity in domestic animals.2 Respiratory dysfunction in tick toxicity cases is complex and has been poorly understood, although recent studies have shown that the toxin is cardiotoxic.3 The speed of onset of signs and rate of progression is extremely variable, being influenced by tick, host and environmental factors.
Case 1: Tropical dingo, Canis familiaris dingo
A 3-year-old female dingo presented with rapid respiration, moist lung sounds, excessive salivation and profound neuromuscular weakness causing an inability to stand. Acetylpromazine (ACP 2, Delvet, Asquith, NSW, Australia) was used for sedation, and an Ixodes tick was removed from her left shoulder. The animal was given dexamethasone (Dexapent, Troy Laboratories, Smithfield, NSW, Australia) IV and then treated with tick antiserum (AVSL Ixodes holocyclus antivenom, Australian Veterinary Serum Laboratories, Lismore, NSW, Australia) 0.56 ml/kg IV, frusemide (Frusemide injection, Troy Laboratories, Smithfield, NSW, Australia) SQ and given supportive care. The pulmonary oedema worsened over the next 24 hours and a second dose of antiserum 0.3 ml/kg IV was administered, along with more frusemide and continued supportive care. Improvement of the pulmonary oedema began within 2 days. She was lifting her head with some voluntary movement within 3 days but was not able to walk until 8 days post-treatment. She recovered successfully.
Case 2: Binturong, Arctictis binturong
An 11-year-old male binturong presented with an ataxic hindlimb gait and was retching frothy fluid. He was anesthetized and an Ixodes tick was removed from the head. Dexamethasone and atropine (Atrosite injection, Troy Laboratories, Smithfield, NSW, Australia) were given IV, followed by the administration of tick antiserum 0.5 ml/kg IV, topical application of fipronil spray (Frontline Spray, Merial Australia, Parramatta, NSW, Australia) and supportive care provided. Improvement was seen the following day and recovery was complete in 4 days.
Another episode of tick toxicity occurred in this animal 16 months later. On this occasion the binturong presented with a crouching gait. Anaesthesia was induced and an Ixodes tick was removed from the right axilla. The animal was premedicated with dexamethasone IV, acetylpromazine SQ and atropine SQ prior to the administration of tick antiserum 1.4 ml/kg IV and 0.1 ml SQ injected at the tick attachment site. He was sprayed with fipronil and provided with supportive care until complete recovery 5 days later.
Case 3: Ring-tailed lemur, Lemur catta
A 7-year-old male lemur presented with ataxia and miosis and an Ixodes tick was removed from the sternal area. The lemur was premedicated with dexamethasone IV and atropine IV prior to the administration of antiserum 0.6 ml/kg IV and 0.5 ml SQ injected at the tick attachment site. The animal was much improved the following day and fully recovered in 3 days.
Case 4: Malayan sun bear, Helarctos malayanus malayanus
A 3-year-old female sun bear presented with lethargy and inappetence of 48 hours duration. The animal was anesthetized, examined and hospitalized with no diagnosis reached. The following day it was noted that the animal appeared to exhibit mild paresis and was reluctant to walk. The animal was anesthetized again and a tick search performed, but none were found. Despite this, tick toxicity was suspected. She was premedicated with dexamethasone IV; tick antiserum 0.6 ml/kg IV was administered; fipronil was applied topically (Frontline Top Spot, Merial Australia, Parramatta, NSW, Australia) and supportive care was given. There was no evidence of pulmonary oedema. Improvement was noted the following day and she was more ambulatory. Recovery was complete 3 days post-treatment.
Ten months later, the sun bear suffered a second episode of tick toxicity, presenting with lethargy, mild hindlimb ataxia and coughing. She was anesthetized and an Ixodes tick was removed from the ventral thorax. Dexamethasone IV and acetylpromazine SQ were given and then tick antiserum 0.65 ml/kg IV and 1 ml SQ at the tick attachment site were administered. Topical fipronil was applied. The animal was fully recovered in 2 days.
A third episode of tick toxicity in this animal occurred 1 month later. The sun bear was found crawling on her ventrum around the enclosure. She was anesthetized and an Ixodes tick was removed from the right axilla. Antiserum 0.5 ml/kg IV and 0.5 ml SQ at the tick attachment site were administered after premedication with dexamethasone IV, atropine SQ and acetylpromazine SQ. It was noted that the heart rate increased from 50 bpm to 150 bpm when the antiserum was administered IV, respiration became more erratic and vomiting occurred. Oxygen saturation of hemoglobin decreased from 98% to 60% 10 minutes later. Intermittent positive-pressure ventilation with oxygen was commenced and continued for 10 minutes until the respiratory rate had settled and oxygen saturation improved. The animal was awake 7 minutes later. Despite premedication with dexamethasone and atropine prior to the administration of tick antiserum to reduce the risk of an antiserum reaction, it was suspected that an antiserum reaction had occurred. Respiratory arrest occurred 2 hours after recovery from the general anaesthetic and resuscitation was unsuccessful.
At necropsy it was revealed that there was massive pulmonary congestion and alveolar hemorrhage. This was combined with subendocardial hemorrhage which appeared to be due to increased permeability of the microvasculature, as there was no obvious vasculitis or hemorrhage surrounding large blood vessels.
Case 5: Red Panda, Ailurus fulgens fulgens
A 7-year-old male red panda presented with moderate ataxia, predominantly in the hind quarters. Under general anaesthesia, an Ixodes tick was removed from the face. The animal was premedicated with dexamethasone IM prior to the administration of tick antiserum 1 ml/kg IV. Fipronil was applied topically and supportive care given. Gradual improvement of the ataxia occurred over the next few days with apparent neuromuscular recovery in 4 days. However, the appetite and demeanor of the animal remained poor. Two weeks later the animal was hospitalized again due to inappetence and lethargy. Over a 5-week period there was gradual clinical deterioration and extensive diagnostic tests were performed. There was evidence of decompensated renal failure, potentially exacerbated by the episode of tick toxicity. It was suspected that the animal was in compensated renal failure at the time of tick attachment. A renal biopsy revealed chronic interstitial nephropathy and moderate to severe membranous glomerulopathy. The animal was euthanatized.
Case 6: Squirrel monkey, Saimiri boliviensis
A 14-year-old male squirrel monkey was found weak and unable to stand with an Ixodes tick visible on the neck. The animal was anesthetized and the tick removed, and the monkey was premedicated with dexamethasone IV and atropine IV prior to being treated with tick antiserum 2.5 ml/kg IV. Fipronil was applied topically and supportive care given. No pulmonary edema was detected on clinical examination or radiographs. The animal recovered fully in 2 days.
Case 7: Fennec fox, Fennecus zerda
A 4-year-old male fennec fox presented in recumbency, was unable to stand and no withdrawal reflexes were exhibited in all four limbs. The animal was still able to lift his head. He was anesthetized and an Ixodes tick was removed from the left thorax. Dexamethasone IV and atropine IV were given prior to the administration of antiserum 0.7 ml/kg IV, and fipronil spray was applied topically. No pulmonary oedema was evident on clinical examination or radiographs. The neuromuscular weakness progressed and a few hours later the animal was not able to lift his head. A second dose of antiserum 0.7 ml/kg IV was given 3 hours after the initial dose. The following day the animal was sitting up on his sternum with some hindlimb movement. It took 8 days for this animal to be able to stand and 10 days until the animal exhibited a normal gait. Considerable supportive care was necessary during this recovery phase, including intravenous fluids and expressing the bladder.
Case 8: Red-collared lorikeet, Trichoglossus haematodus rubritorquis
An 11-year-old male lorikeet presented with flaccid paralysis and hyperpnoea. Two Ixodes ticks were removed from the head of the bird. Dexamethasone IV was given prior to treatment with tick antiserum 0.5 ml/kg IV and 0.02 ml SQ at the tick attachment site. Five hours later, the bird received a further 0.5 ml/kg antiserum IV. The lorikeet improved considerably within 24 hours and was fully recovered in 3 days.
In the last few years, tick toxicity has become a significant concern at Taronga Zoo, Sydney, Australia. In addition to the reported cases, there have been suspected cases in a fishing cat, another squirrel monkey and other birds, of which none received treatment. The majority of cases have presented with varying degrees of neuromuscular weakness. In dogs, pulmonary congestion and oedema commonly occur due to the cardiotoxic effects of the toxin causing reversible myocardial depression.3 For the majority of dogs that die, death is due to progressive pulmonary dysfunction rather than progression of paralysis.3,5 Cardiopulmonary effects have only been noted in the tropical dingo. In the fatal episode in the Malayan sun bear, severe pulmonary congestion and alveolar hemorrhage were evident at necropsy; however, it is unknown if this was a direct result of the tick toxicity or an antiserum reaction. Although pulmonary congestion and oedema have not been commonly detected in the zoo animal cases, cardiopulmonary function should be assessed in every case. The use of diuretics and arteriodilating drugs would be beneficial in cases of pulmonary oedema, and in severe cases ventilatory support may be required.
Esophageal muscle weakness or paralysis occurs in most cases of tick toxicity in dogs.6 A poor gag reflex, saliva pooling, megaesophagus and aspiration pneumonia are often noted in dogs.6 Again, this has not been specifically diagnosed in any of the zoo cases. The sun bear presented with coughing during its second episode of toxicity and the binturong presented with retching of frothy fluid during its first episode. It is possible that these clinical signs were related to some degree of oesophageal weakness.
Treatment protocols are currently based on those for domestic dogs and cats, as there have been no studies in other species. Few documented experiments based on therapy exist. Following further research and a National Tick Paralysis Survey in dogs completed in 1998, there have recently been new recommendations for the management of tick toxicity.5 Animals are treated with an antiserum which contains concentrated antitoxic gamma globulins prepared by hyperimmunizing dogs against the potent toxin produced by I. holocyclus. Little is known about ideal dose rates for the antiserum and its pharmacokinetic properties. However, the antiserum should be given as early as possible in the disease, as there is a delay of 8–12 hours before signs of reversal of paralysis are seen, during which time the animal tends to clinically deteriorate.6 The suggested intravenous dose rate of antiserum in dogs is 1 ml/kg, but a range of 0.1–8 ml/kg has been used, adjusted according to the severity of clinical signs.5 It is important to give a sufficient dose initially, as supplementary doses seem far less effective with prolonged recovery times. Antiserum has most commonly been administered at a dose rate of 0.5–1.0 ml/kg in the cases reported in this paper. Most of the affected zoo animals have survived, but perhaps their recovery time may be reduced by using slightly higher doses.
Most zoo animals will require anaesthesia for assessment, diagnosis and treatment. However, all forms of stress or anxiety should be avoided prior to treatment and during the recovery phase. Anxiolytic drugs such as phenothiazines, benzodiazepines and opioids can be used during the recovery phase to minimize stress.
Antisera reactions are a concern following administration. Most reactions in dogs are associated with the Bezold-Jarisch reflex which results in bradycardia and hypotension, rather than anaphylactic reactions. Atropine administered prior to the antiserum will prevent or reduce the chance of this reflex being activated.1 Atropine also has the added benefit of reducing saliva pooling but is contraindicated if an animal is hypertensive. Anaphylactic reactions are more likely to occur in zoo animals, as they do in domestic cats, given that the antiserum is derived from dogs. It is not clear whether repeated treatment with the antiserum increases the risk of anaphylaxis. Dexamethasone has been routinely used in an attempt to prevent or minimize anaphylactic reactions to the antiserum; however, adrenaline is the drug of choice for preventing and treating anaphylactic reactions. Thus, anaphylactic reactions may be better prevented by the prior administration of subcutaneous adrenaline.6 Corticosteroids will not prevent type 1 anaphylactic reactions, but may moderate some of the consequences.
Live ticks should be removed from an affected animal. In the past it was considered important to kill the tick before removing it to prevent further toxin release during removal. The National Tick Paralysis Survey in dogs in 1998 indicated that recovery times were significantly lower in cases where live ticks were removed at the time of treatment; however, mortality rates were similar whether the tick was removed alive or killed in situ before removal.5 It has also been a routine measure to inject a small volume of antiserum subcutaneously at the tick attachment site in an attempt to bind the toxin before it circulates. The same survey indicated that this procedure has no bearing on the clinical outcome.5 The antiserum administered intravenously will “mop up” existing unbound toxin and will neutralize any new toxin released from the tick attachment site.
As vegetation and natural substrates are provided in most exhibits and the zoo is surrounded by bushland, it is difficult to control ticks in the environment. Unfortunately, preventive acaricidal preparations that are effective against I. holocyclus which can be readily applied to zoo animals are limited. The most suitable preparations available in Australia for use in zoo animals are fipronil and cythioate (Proban tablets or liquid, Boehringer Ingelheim, North Ryde, NSW, Australia). The fipronil requires topical application every 2 weeks and the cythioate is given orally every second day. At Taronga Zoo the sun bears, red pandas and binturongs are trained for fipronil application, the fennec foxes receive cythioate and the dingoes are searched daily for ticks during the tick season (September–May).
1. Atwell, R.B., and F.E. Campbell. 2000. Cited in: Ixodes holocyclus, a unique Australian parasite, National Tick Paralysis Forum, Bulletin No. 2: Control and Therapy Series 217, Post Graduate Foundation in Veterinary Science, University of Sydney, Sydney, Australia, Pp. 1234–1238.
2. Atwell, R.B., and M.P. Fitzgerald. 1994. Unsolved issues in tick paralysis. Aust. Vet. Pract. 24 (3):156–161.
3. Campbell, F. E. 2000. PhD thesis, University of Queensland, Brisbane, Australia. In preparation.
4. Cooper, J.B. 1976. Studies on the pathogenesis of tick paralysis. PhD thesis, University of Sydney, Sydney, Australia.
5. Davis, R. 2000. Ixodes holocyclus, a unique Australian parasite, National Tick Paralysis Forum, Bulletin No. 2: Control and Therapy Series 217, Post Graduate Foundation in Veterinary Science, University of Sydney, Sydney, Australia, Pp. 1234–1238.
6. Fitzgerald, M.P. 1998. Ixodes holocyclus poisoning. Clinical Toxicology, Proceedings 318, Post Graduate Foundation in Veterinary Science, University of Sydney, Sydney, Australia, Pp 203–219.