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Tick paralysis (toxicity) is an acute, progressive, ascending motor paralysis caused by salivary neurotoxin(s) produced by certain species of ticks. With some species, other signs of systemic toxicity (eg, cardiac, airway, bladder) may occur with or without the classic neurologic signs. Humans (usually children) and a wide variety of other mammals, birds, and reptiles may be affected. Human cases of tick paralysis caused by the genera Ixodes, Dermacentor, and Amblyomma have been reported from Australia, North America, Europe, and South Africa; these 3 plus Rhipicephalus, Haemaphysalis, Otobius, and Argas have been associated with paralysis to varying degrees in animals.
Etiology, Epidemiology, and Pathogenesis
The potential for inducing paralysis has been demonstrated, described, or suspected in 64 species of ticks belonging to 7 ixodid and 8 argasid genera. On the eastern coast of Australia, the Australia paralysis tick I holocyclus (and to a lesser extent I cornuatus and I hirstii, in which morphologic classification has been shown to be unreliable) causes the most severe form of tick paralysis, with a mortality of up to 10% in dogs (usually 4–5%), irrespective of therapy.
In North America, D andersoni (the Rocky Mountain wood tick) and D variabilis (the American dog tick) are the most common causes. Sheep, cattle, and humans may be affected, as well as dogs. D albipictus, I scapularis, Amblyomma americanum, A maculatum, R sanguineus, and O megnini may cause paralysis. In fowl, Argas radiatus and A persicus have caused paralysis. In Africa, I rubicundus (Karoo tick paralysis) and R punctatus in South Africa, R evertsi evertsi and Argas walkerae in sub-Saharan Africa, and R evertsi mimeticus in Namibia can cause the disease. Cats appear to be resistant to the disease caused by these ticks, but are affected by I holocyclus. Toxicity is usually less severe than in dogs, does not include the chest complications, and has a better prognosis.
I holocyclus in Australia causes a much more severe disease than that seen in North America and elsewhere. Dogs and cats are affected, as well as sheep, goats, calves, foals, pigs, flying foxes, poultry, birds, reptiles (snakes and lizards), and humans. Both local and systemic paresis and paralysis are seen. The natural hosts (bandicoots) are rarely affected, presumably acquiring immunity at an early age. However, without exposure to toxin they too become susceptible again.
Host factors influencing epidemiology include the species affected, sensitivity to toxin, age, acquired immunity, field behavior, concurrent work demands, reaction to environmental factors, skin reactivity, and population density. Antitoxin immunity, starting at least 2 wk after primary tick exposure and lasting a few weeks, can be boosted by further infestations, but chronic tick exposure eventually is associated with a decline in immunity, possibly due to toxin neutralizing effects of the host. Tick factors include the toxin absorption and circulation dynamics, virulence, paralysis-inducing capability, sexual activity, rate of infestation, and the frequency of the sucking phase.
The maximal incidence of tick paralysis is associated with seasonal activity of female ticks, mainly in spring and early summer, but in some areas ticks are active throughout the year. Environmental factors such as temperature and humidity also play a major role in tick morbidity and mortality (ie, ticks are easily killed by both hot/dry and wet conditions). Modern rapid transport of ticks attached to people, animals, or plant material can give rise to isolated cases of tick paralysis, far removed from the particular geographic area where the ticks are naturally found. The diagnosis may be delayed when such infested animals travel to areas where paralysis is not typically seen.
Toxicity does not relate directly to tick size or duration of attachment. The clinical signs produced in various hosts depend on several variables, including toxin secretion rate, local site responsiveness, host immunity and susceptibility, and specific organ involvement.
Systemic toxicity follows injection of toxin(s) into the host. Usually this is caused by the adult female ixodid tick during its period of rapid engorgement, although large numbers of larval or nymphal ticks may also cause paralysis. The toxin is presumed to travel from the attachment site via the lymph to the systemic circulation and thus to all areas of the body, where it has a direct effect on potassium channels at the subcellular level.
I holocyclus toxin also causes reversible myocardial depression and diastolic failure, which can lead to cardiogenic pulmonary edema and signs of congestive heart failure. However, primary hypoventilation is the main cause of death in most severe cases.
Clinical Findings
In tick paralysis other than that caused by I holocyclus, clinical signs are generally seen ~5–9 days after tick attachment and progress over the next 24–72 hr. When I holocyclus is involved, clinical signs usually appear in 3–5 days (rarely up to 18 days) after attachment and usually progress rapidly over the following 24–48 hr. Time periods vary with I holocyclus due to factors such as environmental humidity, temperature (micro-climate), and host factors. Both shorter onset to severe signs and delayed “quiet” attachments with minimal signs may be seen. Removal of I holocyclus ticks does not immediately halt progression of disease. Clinical signs can deteriorate for ~24 hr. In severe cases, death from respiratory muscle failure and other complications can occur within 1–2 days of the onset of signs.
Early signs may include change or loss of voice (due to laryngeal paresis), hindlimb incoordination (presumed to be due to weakness and not central CNS ataxia); change in breathing rhythm, rate, depth, and effort; gagging, grunting, or coughing; regurgitation or vomiting; and pupillary dilation. Dogs with a grunt are believed to have increased airway resistance.
Hindlimb paralysis begins as slight to pronounced incoordination and weakness, which is best observed with the animal walking away from the observer (or when climbing stairs or jumping up). As paralysis progresses, the animal becomes unable to move its hindlimbs and forelimbs, to stand, to sit, to right, and finally to lift its head.
A 4-stage classification system based on systemic limb activity may enable clinical predictability. In stage 1 the dog's voice is changed (noticed retrospectively), and it is weakened but can still walk and stand. In stage 2 it cannot walk but can stand. In stage 3 it cannot stand but can right. In stage 4 the dog cannot right. Stages 3 and 4 indicate a poor prognosis. However, some dogs show few signs due to low levels of toxin or high levels of protective skin or systemic immunology, and some show signs in only one organ (eg, esophageal paralysis in dogs). Sensation is usually preserved but it is increasingly harder to detect the clinical responses to stimuli due to motor paralysis.
Breathing abnormalities include choke, upper respiratory tract obstruction, bronchoconstriction (especially seen early in cats), progressive fatigue of respiratory muscles, and aspiration of esophageal and/or gastric contents (due to loss of pharyngeal and laryngeal function), leading to aspiration pneumonia. Aspiration can be significant and the lung severely affected prior to any obvious signs. It is possible to have a silent (no crackles), severely pneumonic lung if there is poor airflow into the affected lobe. Some dogs have profound dyspnea, no crackles, and extensive pulmonary radiographic opacity (due to aspiration pneumonia); such cases are usually terminal. Dogs with upper respiratory tract obstruction have a marked expiratory stridor (not the classic inspiratory stridor of primary laryngeal paralysis of large breeds), often with the head and forelegs extended to maximize air flow and exchange. If there is chest disease as well, the animal is usually very dyspneic. A thrill can be felt at or just below the larynx in association with the obstructed expiratory effort and stridor. The upper respiratory tract lesion can be easily missed, especially if the dog is paralyzed. Often the respiratory rate is high and forced. In cats, the doll test can be used to assess upper respiratory tract function. If compression of the larynx increases the upper respiratory tract sound, then this supports paresis or paralysis, irrespective of other respiratory tract defects. It is essential that any upper respiratory tract obstruction is diagnosed, as the associated workload and level of fatigue can quickly become terminal.
Paralysis of esophageal muscles develops in most dogs (but not cats), with or without esophageal dilation and megaesophagus. Saliva and ingested food or fluid pool in the esophagus and may be regurgitated into the pharynx and mouth. Loss of pharyngeal function makes it difficult for the animal to clear material from the upper respiratory tract, which may lead to aspiration pneumonia.
Vomiting (with evidence of bile) may occur in I holocyclus paralysis; a central action of toxin on the vomiting center has been suggested. Most cases of vomiting reported by clients are probably regurgitation, although drug-induced vomiting may be a complication. Dogs will gag and retch in an attempt to clear secretions and move their head and jaw in an odd way to further attempt clearance of materials.
Body temperature may be normal in the early stages; however, due to the toxin's effect on airways, normal thermoregulation is lost. This can cause hyper- and hypothermia as animals are affected by local environmental factors. Shivering is also lost in severe cases. Profound hypo- and hyperthermia can occur suddenly and can be easily misdiagnosed; hypothermia clinically resembles tick paralysis in several ways. When body temperature is restored, the level of tick paralysis in such cases can be mild.
In dogs, overt congestive heart failure can present (as for a classical degenerative cardiomyopathy case) with extensive pulmonary edema, due to diastolic myocardial dysfunction (the myocardium is unable to correctly relax, reducing efficient chamber filling and therefore systolic cardiac output). Venous return may also be reduced.
Some dogs have a prolonged QT interval on ECG, which can result in a lethal ventricular arrhythmia. The frequency of these unexplained deaths, which follow complete gross clinical recovery, is not known, but most veterinarians who treat many cases report such events.
Cats with moderate to severe toxicity can be anxious. It is essential not to interfere with these animals until they have settled in their cage. If procedures are forced upon them, these animals can die from dyspnea and the (presumed) associated hypoxemia, acidosis, and hypercapnea. Cats are not as systemically affected as are dogs, especially with regard to respiratory complications, but they can deteriorate if compromised with hospital stress (eg, nursing attention, noise, smell).
Cats may present with an asthma-like airway constriction, usually when they are mildly paretic; expiratory wheeze on auscultation, forced abdominal expiratory effort and very easily induced exercise intolerance are classical signs for this presentation. These cats often have a positive doll test and will, after a few steps, sit on their hindquarters with the chest in a more upright vertical position than normal, often with an increased respiratory focus or effort. Feline asthma can be easily misdiagnosed at this stage, if a tick is not found or suspected.
Diagnosis
The presence of a tick in conjunction with the sudden appearance of limb weakness and/or respiratory impairment is diagnostic. The offending tick may no longer be attached, but a tick “crater” (a hole 1–2 mm deep and 1–3 mm wide, surrounded by a variably raised and inflamed area) in the skin confirms the diagnosis. Sometimes neither tick nor crater can be found (ticks attached deep in the ear, between toes, or in the mouth or anus may be missed). However, with the appropriate clinical signs, in a known tick area without another obvious cause of lower motor neuron or neuromuscular disease, treatment is still indicated. Recovery following treatment subjectively confirms the provisional diagnosis.
Specific laboratory diagnostic techniques are not available, but procedures that may be generally helpful include a PCV, serum protein, and lateral thoracic radiography to assess presence and degree of pulmonary edema, megaesophagus, and pneumonia due to aspiration. Specific signs (eg, congestive heart failure) require routine workup of that body area or system.
Botulism, polyradiculoneuritis, acute peripheral neuropathies, snakebite, hypokalemia, and toadfish and ciguatera toxicity are differential diagnoses. In regions where ticks are endemic, tick paralysis is usually high on the list of differential diagnoses for any flaccid clinically ascending motor paralysis. It should also be considered in the differential diagnosis of megaesophagus, unexplained vomiting, acute left-sided congestive heart failure (dogs), or asthma (cats). The tick season is usually well known for various areas (eg, a local creek) within the environment of a particular practice, and often most tick paralysis cases come from a few well-defined, highly endemic areas.
Blood and serum values are unchanged in the early stages. Increased PCV (with normal serum protein) indicates a fluid shift into the lungs and a more guarded prognosis. Other changes may include increased levels of blood glucose, cholesterol, phosphate, and CK, and a decrease in blood potassium levels, but none of these changes are specific for tick paralysis or indicate severity or prognosis.
Echocardiography reveals both diastolic and secondary systolic myocardial dysfunction associated with reduced ventricular filling, possibly due to both peripheral venous pooling and poor diastolic myocardial relaxation. Nonstressful radiography gives the best available prognostic support and pulse oximetry the best continuous assessment of oxygenation. Capnography is helpful in assessing the functional level of ventilation. Arterial blood gas analysis (while invasive) gives the best overall assessment of cardiopulmonary function. However, the stress of any such testing needs to be considered; positioning for chest radiographs (dorsoventral to lateral) can tip animals into a terminal hypoventilatory decline.
Treatment
In most infestations (except I holocyclus), removal of all ticks usually results in improvement within 24 hr and complete recovery within 72 hr. If ticks are not removed, death may occur from respiratory paralysis in 1–5 days. Removal of I holocyclus ticks does not immediately halt progression of disease. Clinical signs can deteriorate for ~24 hr. In any infestation, removal of all ticks is absolutely necessary. The entire integument should be searched, diligently and repeatedly, especially on long-haired animals or those with thick coats. Most ticks are located around the head or neck, but they can be found anywhere on the body. Plucking the tick(s) yields the best result (in dogs) and does not induce anaphylaxis.
Therapy for tick toxicity must address primary tick toxemia and paralysis, secondary issues (eg, aspiration pneumonia), and potential tertiary factors (eg, chronic weakness, cardiac arrhythmia).
Tick antiserum (TAS) is an immune serum against the toxin of the tick in question (similar to tetanus antitoxin) and is the product of choice. This should be given as early in the disease as possible; subsequent “top up” doses are not effective as they are most likely too late. For dogs, a minimal dosage of 0.5–1.0 mL/kg, warmed to room temperature, should be given slowly IV over at least 20 min to avoid a shock reaction. Rapid IV use can induce clinical reactions in >80% of dogs. Anaphylaxis can occur unpredictably (as with all products), necessitating the use of high-dose, soluble cortisol and rapid fluid loading, etc. Based on retrospective case studies, cats are believed to be more susceptible than dogs, especially with a second dose a few weeks (not days) after the first dose.
Animals with multiple ticks or in the acute stages of paralysis should receive a higher dose, but there are no data for the exact dosage rates required. (Batch and brand levels of protective immunoglobulin vary.) Severely affected dogs may have less remaining unbound toxin for TAS to neutralize, however. Debate persists about the required dose of TAS. It has been suggested that a standard dose should be given, based on the amount needed to neutralize the toxin from 1 tick rather than on the weight of the dog. On this basis, a minimal dose of 10 mL is recommended for dogs (and 5 mL for cats); because the immunoprotective level/mL varies (and is not easy to detect) such arbitrary rates are controversial, however. Until the level of toxin in the affected animal and the level of specific immunoglobulin in products can be better assessed, a set dose rate cannot be established.
Giving canine serum IV to a cat can cause anaphylaxis. This risk may be minimized by routine SC injection of 3 mL of 1:10,000 epinephrine 3–4 min before administration of the TAS, but there is no proof that risk is reduced. TAS given IP is the best alternative in cats for which the IV route is an issue (eg, respiratory distress, restraint dangers, dyspnea). However, its effective half-live is believed to be short (days not weeks) and it will have little to no effect if the toxin is already bound and the animal is severely ill or about to become so.
Minimization of stress and anxiety is essential. Acepromazine (0.03 mg/kg) may be given SC before any other medication or handling that may upset the animal. However, high doses should be avoided if the animal is depressed, hypotensive, or hypothermic. Overdosage may induce hypotension and hypothermia. Opiates are an alternative (eg, methadone, 0.3–0.5 mg/kg, SC, IM).
General anesthesia may be indicated in animals that are severely dyspneic, to allow for better administration of oxygen, esophageal suction, and upper respiratory tract drainage. Pentobarbitone can be used as a constant rate infusion, or given periodically IV to induce light anesthesia, with repeat doses as needed. Its chief benefits are to reduce dyspnea, enable muscle rest, and help overcome primary muscle fatigue and general exhaustion. Periods of 6–8 hr of light anesthesia are best, with reassessment of clinical status after each period. Another potential benefit may be control of long QT syndrome, an ECG abnormality that is a rare cause of sudden death in tick paralysis.
Mechanical or manual ventilation may be required but should be carefully assessed because recovery can be delayed. Generally, longer-term ventilation cases have a low recovery rate (perhaps as low as 25%).
Atropine (repeat every 6 hr, lowest dose) can be used if there are excessive GI and respiratory secretions, but its effect on tear secretion (and the host's potential for eyelid paralysis, reduced blink reflex, and corneal drying) and cardiac rate and rhythm changes should be considered.
Antiemetic therapy should be used in animals that have true vomiting. If the pet is regurgitating, the esophagus should be aspirated along with the upper respiratory tract. Correct drainage positioning then becomes a vital factor in helping to avoid aspiration.
Broad-spectrum bactericidal antibiotics are indicated to help avoid the development of aspiration pneumonia, but must be given as soon as possible. Dogs with upper respiratory tract obstruction require either tracheotomy or anesthesia and intubation to overcome the potentially lethal effects of obstruction.
High, repeat doses of a diuretic (eg, furosemide), with maximally appropriate oxygen treatment are indicated to treat congestive heart failure, as is regular nonstressful assessment of pulmonary and alveolar ventilation (eg, pulse oximetry, expired CO2 levels). Verapamil (0.1 mg/kg, IV bolus) is the only cardiac drug indicated to help relieve the basic toxic myocardial effect of a failure to relax (rather than a failure to contract). The toxin does unbind, so if the animal can be kept free of terminal pulmonary edema (or arrhythmia), the cardiac failure will reverse over a few days, provided routine support is given. Esmolol has been used to treat affected animals that have a long QT interval and the potential for a lethal unpredictable ventricular arrhythmia.
Fluid therapy should be used with great care because the induction of pulmonary edema can occur easily. Staying below maintenance levels and ensuring the case is assessed for edema, both before and during IV fluid therapy, should be routine. If the PCV is >70%, colloid or heta- or pentastarch fluids should be considered rather than crystalloids. Dehydration can occur in tick paralysis, but not usually until day 2 of hospitalization, when increased PCV and protein values may be evident. In small patients, SC or IP fluids can be given if lung status is a concern. Exceptional cases may require extensive rehydration (eg, paralyzed in the sun with high humidity and temperature for a day prior to presentation) but the extent of the underlying organ dysfunction should be assessed before intensive fluids are given.
The asthma-like disease in cats is hard to reverse because routine bronchodilators do not seem to work. Such cats easily become dyspneic, and if they have upper respiratory tract obstruction they can become extremely distressed with restraint. These cats are best left completely alone to recover in a quiet (but observable) area. They can then be given anxiolytics (eg, opiates) prior to further handling.
With the hypoxemia and hypercapnea of profound hypoventilation, little can be done (if ventilation is deteriorating) except for the use of a ventilator (manual or mechanical).
Muscle fatigue can be reduced (with recovery of some muscle strength) by short periods (6–8 hr) of anesthesia. The animals remain hypercapneic but, with endotracheal intubation and O2 therapy, they can establish reasonable hemoglobin saturation levels (>95%), provided there is no significant alveolar disease.
Intoxicated animals lose their capacity to regulate body temperature. Animals that have fallen below 32ºC (90ºF) for a long period may be hard to resuscitate. Various heating mechanisms are used (hot water bottles, blankets, hot air flow blankets), but peripheral heat absorption cannot occur if arteriovenous shunts are shut due to the effect of the toxin and the host's vasoconstrictive reaction to hypothermia. Warmth applied at the lower limbs (especially the back legs) will be of maximal benefit; direct application to the groin area may also potentially be useful. Some cases may need warmed fluids IV or rectally to reverse a very cold presentation (eg, 32ºC or lower). Sudden hyperthermia (>42ºC) can be seen in hospitalized dogs. They usually show exaggerated head and possibly foreleg movements and signs of anxiousness. With cooling (eg, wet towels, direct fan flow, high rate of air changes), these signs abate.
As the animal's condition is expected to deteriorate for 24 hr after ticks are removed, hospitalization with minimally invasive monitoring and good nursing care is necessary. The animal should be kept in a quiet, dark, comfortable area of the hospital where it can be easily seen. It should be placed on the sternum to maximize lung function. If laterally recumbent, left side down with the shoulder (not the pharynx or neck) as the highest point is the best position for drainage. Slight “head down” is also advised. Animals should never be rotated unless it can be done frequently (every 1–2 hr), day and night. Because the bladder cannot be emptied, catheterization is necessary and the bladder should be expressed at least twice daily. As with other localized tick toxicity effects, this blockage may persist beyond the period when the animal has generally recovered. Eye protectants should be used to prevent corneal ulceration or dryness. Suction of the pharynx, larynx, and proximal esophagus minimizes upper respiratory tract distress caused by saliva pooling and regurgitation. An esophageal tube may be slowly inserted to remove any pooled material; in some cases this is voluminous and possibly prevents choke (seen mostly in brachycephalic breeds with laryngeal blockage by foreign material). Fluid and oxygen therapy need to be monitored to ensure there is no overhydration or under-supply, respectively. Nutritional support should be performed carefully to ensure that GI and respiratory function can cope with any offered food and water.
Repeated tick searches should be performed during hospitalization, especially if the animal deteriorates unexpectedly. Long or matted hair should be clipped, especially about the head and neck. Application of an acaricide may kill any ticks missed in searching. However, the stress of searching, clipping, or bathing can be detrimental in severely affected or nervous animals, in which sedation is recommended.
Prognosis
Appropriate and timely treatment saves ~95% of affected animals, but 5% of animals are likely to die despite all treatment efforts, especially those with advanced paralysis and dyspnea. Most animals (>80%) have only 1 tick and a large attachment crater. Prolonged recovery and weight loss can be seen with various complications, and death can also occur due to choke, respiratory tract paralysis, cardiac arrhythmias, congestive heart failure, and cardiopulmonary arrest. Older animals or those with pre-existing cardiopulmonary disease are at greatest risk, as are very young pups.
Prior to discharge, the drop test can be used in cats to assess neuromuscular function and 3-dimensional gravitational control. Cats should be able to correct a fall from 10–20 cm above the top of the table. Still-affected cats will not correct in time and land more heavily with the chin hitting the table top. Recovered cats will land lightly with good head control. Jumping up to and down from the cage can also be used to assess muscle strength in cats. In dogs, jumping down from a cage can induce an upper respiratory noise, indicating unresolved respiratory paresis and forced expiratory air flow, as the unsupported abdominal momentum affects the diaphragm and lung air flow, producing a high-volume expiration. Lifting up a dog (with the holder's arms wrapped outside the fore- and hindlegs) with unresolved tick paralysis often produces stridor, indicating abnormal laryngeal function.
Owners should be advised to continue searching recovered animals for ticks; use appropriate preventive methods to avoid reattachment of ticks; and avoid high temperatures, stress, or strenuous exercise for at least the first month. Smaller, more frequent meals may also be indicated if there was esophageal dysfunction. This rest period applies more to working farm dogs, in which overexercise may lead to permanent muscle damage.
Prevention and Control
Owners should not rely solely on chemical control to prevent tick infestation, because no product is totally effective and a single attached tick can cause the disease. They should be advised about when and where their pets will be at risk; encouraged to thoroughly search the coat daily; keep the coat as short as possible; and understand the efficacy, appropriateness, safety, and limitations of available preventive products (sprays, topical spot-ons, tablets, and collars). Combination therapy (eg, spray and collar) may give better results by using 2 different modes of action, but there are no published data to support this concept.
Attempts to produce an effective vaccine against the I holocyclus toxin have so far been unsuccessful, as have been attempts at “in-field” tick control. Specific RNA studies show that ticks vary geographically, and such genetic differences may explain why clinical signs of tick paralysis vary between different areas at the same time of the year in the same season.
Last full review/revision July 2011 by Rick Atwell, BVSc, PhD, FACVSc
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