Comprehensive analysis of the global impact and distribution of tick paralysis, a deadly neurological yet fully reversible condition

SUMMARY

Tick paralysis is a potentially fatal condition caused by neurotoxins secreted by the salivary glands of certain ticks. Documented cases have been reported worldwide, predominantly in the United States, Canada, and Australia, with additional reports from Europe and Africa. This condition also affects animals, leading to significant economic losses and adverse impacts on animal health and welfare. To date, 75 tick species, mostly hard ticks, have been identified as capable of causing this life-threatening condition. Due to symptom overlap with other conditions, accurate diagnosis of tick paralysis is crucial to avoid misdiagnosis, which could result in adverse patient outcomes. This review provides a comprehensive analysis of the current literature on tick paralysis, including the implicated tick species, global distribution, tick toxins, molecular pathogenesis, clinical manifestations, diagnosis, treatment, control, and prevention. Enhancing awareness among medical and veterinary professionals is critical for improving the management of tick paralysis and its health impacts on both humans and animals.

INTRODUCTION

Tick paralysis is a condition caused by neurotoxins secreted by the salivary glands of certain female or male ticks. Of the 900 known tick species, 61 hard ticks and 14 soft ticks are implicated in tick paralysis (see Table 1) (1). The condition affects both humans and animals, typically presenting with initial gait instability (2), followed by flaccid ascending motor weakness and paralysis (3). The term “tick paralysis” was first introduced in 1824 during the expedition of Hume and Hovell from Sydney to Port Phillip Bay (Melbourne) (4). Whether the condition identified by these explorers was indeed tick paralysis remains debatable.

TABLE 1.

Tick species causing tick paralysis worldwide

Family	Genus	Species (common name)	Geographical location	Hosts reported on	Reference
Ixodidae	Amblyomma	Amblyomma americanum Linnaeus, 1758 (Long Star tick)	USA (mainly coast)	Canids and humans	(5, 6)
		Amblyomma argentinae Neumann, 1905	Argentina	Reptiles	(7)
		Amblyomma cajennense Fabricius, 1787 (Cayenne tick)	Central America and South America	Ungulates	(1, 8)
		Amblyomma hebraeum Koch, 1844 (Bont tick)	South Africa	Humans, goats, and sheep	(9)
		Amblyomma maculatum Koch, 1844 (Gulf Coast tick)	Central America	Canids and humans	(10, 11)
		Amblyomma ovale Koch, 1844	Central America and South America	Humans	(12)
		Amblyomma rotundatum Koch, 1844	USA	Snakes	(13)
		Amblyomma variegatum Fabricius, 1794 (Tropical bont tick)	Africa	Sheep	(14)
	Dermacentor	Dermacentor albipictus Packard, 1869	North America	Ungulates	(15)
		Dermacentor andersoni Stiles, 1908 (Rocky Mountain wood tick)	North America	Humans and mammals	(16)
		Dermacentor auratus Supino, 1897	The South Asian Sub-Continent	Humans	(17)
		Dermacentor variabilis Say, 1821 (American dog tick)	North America	Canids and humans	(18–20)
		Dermacentor silvarum Olenev, 1931	Eurasia	Sheep	(21)
		Dermacentor rhinocerinus Denny, 1843	Africa	Rabbits	(22)
		Dermacentor reticulatus Fabricius, 1794 (Ornate cow tick)	Europe	Sheep	(23)
		Dermacentor occidentalis Marx, 1892 (Net tick)	North America	Canids, humans, and ungulates	(24)
		Dermacentor nuttalli Olenev, 1928	Palearctic realm	Ungulates	(1)
		Dermacentor marginatus Sulzer, 1776 (Ornate sheep tick)	Europe, Central Asia, and India	Humans and mouflons	(25–27)
	Haemaphysalis	Haemaphysalis chordeilis Packard, 1869 (Bird tick)	North America	Humans	(21)
		Haemaphysalis sulcata Canestrini and Fanzago, 1878	Eurasia	Humans and ungulates	(28)
		Haemaphysalis punctata Canestrini and Fanzago, 1878 (Red sheep tick)	Europe and India Peninsula	Ungulates and birds	(25, 26, 29)
		Haemaphysalis parva Neumann, 1897	Middle East	Sheep	(30)
		Haemaphysalis kutchensis Hoogstraal and Trapido, 1963 (Kutch haemaphysalid)	South Asia, India Peninsula, and Malaysia	Rabbits	(1, 31)
		Haemaphysalis inermis Birula, 1895 (Winter tick)	Europe	Ungulates	(15)
		Haemaphysalis cinnabarina Koch, 1844	Brazil	Humans and ungulate	(32)
	Hyalomma	Hyalomma truncatum Koch, 1844 (Shiny Hyalomma)	South Africa	Humans and sheep	(33, 34)
		Hyalomma detritum Schulze, 1919	South Asia, India Peninsula, and Malaysia	Sheep	(1, 35)
		Hyalomma aegyptium Linnaeus, 1758 (Bont leg tick)	Kenya and Mediterranean	Sheep and tortoise	(15, 36)
		Hyalomma excavatum Koch, 1844	Turkey and Egypt	Humans and sheep	(25, 28)
		Hyalomma dromedarii	Egypt	Humans	(28)
		Hyalomma marginatum	Turkey and Sri Lanka	Humans	(17, 37)
	Ixodes	Ixodes arboricola Schulze and Schlottke, 1930 (Tree-hole tick)	Europe	Birds	(15)
		Ixodes brunneus Koch, 1844	North America	Birds	(38)
		Ixodes gibbosus Nuttall, 1916	Middle East	Ungulates	(39)
		Ixodes frontalis Panzer, 1798 (Passerine tick)	Europe	Birds	(15)
		Ixodes eudyptidis Maskell, 1885 (New Zealand seabird tick)	Tasmania and New Zealand	Albatrosses and petrels	(40)
		Ixodes crenulatus Koch, 1844	Europe	Sheep	(41)
		Ixodes cornuatus Roberts, 1960 (Tasmanian paralysis tick) (synonym of I. robertsi)	Australia (mainly Tasmania)	Canids, felids, and humans	(42–44)
		Ixodes cookei Packard, 1869 (American Castor Bean tick)	North America	Humans	(15)
		Ixodes hexagonus Leach, 1815 (European dog tick)	Europe and USA	Humans	(30)
		Ixodes tasmani Neumann, 1899 (Common marsupial tick)	Australia	Marsupials	(45)
		Ixodes tancitarius Cooley and Kohls, 1942	Mexico	Humans	(46)
		Ixodes scapularis Say, 1821 (Black-legged tick)	North America, Europe, and China	Canids and humans	(47)
		Ixodes rubicundus Neumann, 1904 (Karoo paralysis tick)	South Africa	Humans, mammals, and rabbits	(48–50)
		Ixodes ricinus Linnaeus, 1758 (Castor bean tick)	Europe, North America, and Africa	Humans and sheep	(26)
		Ixodes redikorzevi Olenev, 1927	Middle East	Humans and dogs	(51)
		Ixodes pacificus Cooley and Kohls, 1943 (California black-legged tick)	North America	Canids, hare, and humans	(20, 52)
		Ixodes muris Bishopp and Smith, 1937 (Mouse tick)	North America	Canids and felids	(53)
		Ixodes holocyclus Neumann, 1899 (Australian paralysis tick)	Australia and Malyasia	Canids, humans, sheep, and mouse	(43, 54–56)
		Ixodes hirsti Hassall, 1931 (Hirst’s marsupial tick)	Australia (mainly Tasmania)	Felids	(41)
	Rhipicentor	Rhipicentor nuttalli Cooper and Robinson, 1908	Africa and Australia	Canids	(57)
	Rhipicephalus	Rhipicephalus annulatus Say, 1821 (Cattle tick)	Eurasia, Africa, and North America	Humans	(15)
		Rhipicephalus warburtoni Walker and Horak, 2000	South Africa	Goats and sheep	(58)
		Rhipicephalus tricuspis Dönitz, 1906	Africa	Ungulates	(15)
		Rhipicephalus simus Koch, 1844	Africa	Humans and sheep	(34, 59)
		Rhipicephalus sanguineus Latreille, 1806 (Brown dog tick)	Worldwide	Canids and humans	(28)
		Rhipicephalus punctatus Warburton, 1912	Africa	Ungulates	(34)
		Rhipicephalus praetextatus Gerstäcker, 1873	Africa	Humans	(15)
		Rhipicephalus evertsi Neumann, 1897 (Red-legged tick)	Africa	Sheep	(60)
		Rhipicephalus exophthalmos Keirans and Walker, 1993	Botswana	Goats, sheep, and rabbits	(61)
		Rhipicephalus bursa Canestrini and Fanzago, 1878	Turkey and Mediterranean region	Sheep	(1, 25)
Argasidae	Otobius	Otobius megnini Dugès, 1883 (Ear tick)	North America and South Africa	Cats and humans	(62, 63)
	Ornithodoros	Ornithodoros savignyi Audouin, 1827 (African eyed tampan)	Africa and Asia	Camel, cattle, and sheep	(64)
		Ornithodoros lahorensis Clifford, Kohls and Sonenshine, 1964	Africa and Central Asia	Cattle and sheep	(65)
		Ornithodoros capensis Neumann, 1901 (Seabird soft tick)	Oceans and coastal realm	Seabirds	(66)
	Argas	Argas africolumbae Hoogstraal, et al., 1975	South Africa	Birds	(67)
		Argas walkerae Kaiser and Hoogstraal, 1969 (Southern Fowl tampan)	Africa	Birds	(68)
		Argas sanchezi Dugès, 1887 (Adobe tick)	North America	Birds	(69)
		Argas robertsi Hoogstraal, Kaiser and Kohls, 1968 (Robert’s Australian bird argasid)	Australasia and Asia	Birds	(70)
		Argas reflexus Fabricius, 1794 (African bird Argasid)	Europe	Birds	(70)
		Argas radiatus Railliet, 1893 (North American bird Argas)	North America	Birds	(71)
		Argas persicus Oken, 1818 (Bluebug)	Europe	Birds	(72)
		Argas monolakensis Schwan, Corwin & Brown, 1992	USA	Gulls	(73)
		Argas miniatus Koch, 1844 (Chicken tick)	USA	Birds and chickens	(74)
		Argas arboreus Kaiser, Hoogstraal and Kohls, 1964 (Egyptian heron rookery argasid)	Egypt	Egrets	(75)

The first documented human cases of tick paralysis appeared in the scientific literature from Canada in 1912, reported by parasitologist John Todd. He documented 14 cases observed by nine medical doctors in British Columbia, all in children, with five fatalities (18). Hadwen meticulously investigated tick paralysis in both humans and animals, proposing three key findings: first, paralysis occurred only in animals on which female ticks had been feeding for approximately a week; second, the paralysis symptoms were likely caused by a toxin; and third, without tick removal, the progression from general weakness to death from respiratory paralysis was rapid (16). Subsequent studies corroborated Hadwen’s observations. Rose (76), Mail and Gregson (77), and Schmitt et al. (78) reviewed prior cases of tick paralysis in humans, noting a fatality rate of over 10%.

In this study, we reviewed a substantial number of human cases documented worldwide, with a focus on those primarily reported in the United States, Canada, and Australia (Fig. 1; Table S1), along with sporadic cases from Africa, Asia, and Europe (79). The disease typically occurs in spring and summer but can be observed year-round (80, 81). It most commonly affects children younger than 8 years, though it has been diagnosed in individuals of all ages (79). Tick paralysis also induces general weakness or neurological symptoms in birds, mammals, reptiles, and rodents (Table 1), with significant economic implications for the livestock industry (82).

Fig 1.

Global distribution of reported tick paralysis cases in humans. Areas shaded in darker red indicate a higher number of reported cases, while lighter red areas have fewer cases. Regions with no color represent areas where no cases have been reported.

Given the substantial impact of tick paralysis on both human and animal health, analyzing current literature is crucial for understanding the condition’s magnitude. Building on the insights gained from historical cases, global distribution, and the health impact on humans and animals, this review synthesizes the latest research on tick species, toxins, and strategies for prevention and control. We hope this review will enhance the knowledge of medical and veterinary professionals, as well as the public, regarding tick paralysis.

LITERATURE SEARCH METHODOLOGY AND DATA EXTRACTION

A comprehensive literature search was conducted on tick paralysis cases published up to 31 December 2023, across eight electronic bibliographic databases/search engines: PubMed, Google Scholar, ScienceDirect, Wiley, CABI (https://www.cabi.org/), CNKI (https://www.cnki.net/), VIP Chinese Journal Database (http://qikan.cqvip.com/), and Wanfang Data (https://g.wanfangdata.com.cn/index.html). For the first five databases/search engines (PubMed, Google Scholar, ScienceDirect, Wiley, and CABI), the search utilized keywords such as “tick paralysis,” “paralysis case,” “tick bite,” and “tick infection.” In the three Chinese databases (CNKI, VIP, and Wnfang), the search was conducted using the Chinese translations of these keywords. No restrictions on the publication year were applied. Duplicate entries and publications with inaccessible full texts were excluded. Information was extracted regarding the first author, year and region of the report, patient age, clinical manifestations, tick attachment site, prognosis, and the likely source of tick infestation, as detailed in Table S1.

TICK PARALYSIS AND ASSOCIATED TICK SPECIES

Although tick bites are common, tick paralysis is extraordinarily rare, with most tick bites not leading to this condition. Since the first case of tick paralysis was described in 1824, 75 out of over 900 known tick species have been implicated in causing tick paralysis (2). These include 61 hard-tick species (Family: Ixodidae) and 14 soft-tick species (Family: Argasidae). Among the hard ticks, the implicated species include 19 Ixodes spp., 10 Dermacentor spp., 10 Rhipicephalus spp., 8 Amblyomma spp., 7 Haemaphysalis spp., 6 Hyalomma spp., and 1 Rhipicentor sp. The soft ticks implicated are 10 Argas spp., 3 Ornithodoros spp., and 1 Otobius sp. (Table 1). Hard ticks are primarily responsible for causing paralysis in mammals, including humans, cats, cattle, coyotes, deer, dogs, goats, porcupines, sheep, and skunks. They are also occasionally involved in tick paralysis cases in reptiles and birds (Table 1).

Of the species causing tick paralysis, at least 26 are associated with human cases (Table S2). Most of these are ixodid ticks, with their location, detection year, and related clinic manifestations detailed in Table S1. Most reported cases (212 of 288) occurred in North America (n = 177) and Australia (n = 35). Most patients are affected by a single tick species, with the most common being Dermacentor andersoni, D. variabilis, and I. holocyclus (Tables S1 and S2; Fig. 2). In North America, D. andersoni (primarily found in the Rocky Mountain states and Pacific Northwest of the USA) and D. variabilis (found in the eastern half of the USA and along the West Coast) are the most common ticks causing human paralysis (82). Cases involving D. andersoni and D. variabilis typically present with ascending flaccid paralysis, diminished reflexes, and ataxic symptoms, although rare symptoms like typhus-like rash and dilated pupils have also been recorded (19, 83). Paralytic symptoms usually improve following tick removal. Additionally, A. americanum, A. maculatum, and I. scapularis are prevalent in the southeastern United States and are associated with human cases (84, 85).

Fig 2.

Images of the three most common ticks causing human paralysis globally. (a) Adults of the Rocky Mountain Wood Tick [D. andersoni; adapted from Bugwood.org (image 1643207; USDA Forest Service—Coeur d’Alene Field Office), published under a Creative Commons license]. (b) Adults of the American Dog Tick [D. variabilis; adapted from Bugwood.org (image 5380300; Gary Alpert, Harvard University), published under a Creative Commons license]. (c) Unfed and partially engorged female Australian paralysis tick [I. holocyclus; adapted from Bugwood.org (from left to right, images 5488684, 5488688, 5488686, and 5488687; the Pest and Diseases Image Library), published under a Creative Commons license].

In Australia, I. holocyclus, which has a wide host range (>30 species) (86), is the most common tick causing the death of thousands of domestic and wild animals annually, including dogs and cats, with up to 10% mortality (87). It is also a significant cause of tick paralysis in both animals and humans (Table 1). Most cases of paralysis due to this tick progress for at least 24 hours and require a long recovery period after tick removal, sometimes necessitating supportive care such as mechanical ventilation. Although I. holocyclus is widely distributed along the eastern coasts of Australia, Ixodes cornuatus poses a significant risk of tick paralysis in Tasmania and Victoria (86). Recently, this species was found on birds for the first time, causing their death and expanding its host ranges from mammals to birds (88). Other hard tick species cause sporadic cases in different regions or countries (Table S2).

There have also been reports of human patients infested with more than two tick species simultaneously (Table S1), though single-species infestations are more common. In Sri Lanka, H. marginatum isaaci and D. auratus are prevalent among animal populations, but they were also detected in the ear canals of 29 patients simultaneously (17). Co-infestations of R. sanguineus, H. dromedarii, Hyalomma anatolicum excavatum, and Haemaphysalis sp. were recorded in two children in Egypt (28). These co-infestations are more frequent in families living close to farm livestock or near tick-endemic regions.

Tick paralysis is caused by neurotoxins secreted by adult female ticks or immature stages during blood feeding (2). Generally, adult male hard ticks are not considered significant contributors to paralysis due to their relatively small toxin output. During the same feeding period, females secrete toxic contents in quantities several times higher than males (89). However, some clinical cases suggest that adult male ticks might play a role in tick paralysis. As early as 1914, Todd (90) documented a 2-year-old girl who was unable to walk and lacked deep tendon reflexes, with an adult female tick and an adult male tick found on her neck. The Centers for Disease Control also reported a case involving a young girl who presented with unsteady gait, inability to walk, generalized paralysis, and weak grip; a male and a female D. variabilis were detected on her scalp (91). Hadwen proposed that only animals fed by female ticks for around a week experienced paralysis (16), leading to most research focusing on females while the role of males was neglected.

However, isolated reports have linked male ticks to paralysis. In the literature by Brown (92), a male D. andersoni was collected from the left axilla of a young man exhibiting tick paralysis signs, including spotted fever, difficulty lifting arms, weakness, and pain in arms. Erasmus (36) and Swanepoel (33) observed a male H. truncatum tick in the right axilla of a 21-year-old man and a 16-year-old man, respectively, both suffering from paralysis symptoms. In 1962, Ben-Bassat (93) recorded a 19-year-old boy with complete right arm paralysis who had a male tick found in his right axilla. A male D. variabilis was implicated in the paralysis of an 82-year-old patient (94). More recently, in 2003, Edussuriya and Weilgama (17) reported a male H. marginatum isaaci in a patient’s ear. These instances suggest that male ticks may also produce neurotoxins that cause tick paralysis, though such cases are rare. Interestingly, male tick-induced paralysis has mostly occurred in adult men, with most ticks being engorged. This implies that male ticks can induce tick paralysis only when they feed continuously until neurotoxins reach a threshold. Given that a single male tick produces one-seventh as many neurotoxins as a female over the feeding period (89) and that paralysis typically does not occur until females have fed for 4–5 days, it may take approximately 20 days for a male tick to accumulate enough neurotoxins to cause paralysis.

Soft ticks can also cause tick paralysis, though less frequently compared to hard ticks. Argasid ticks mainly induce paralysis of fowls. Unlike adult female hard ticks, larvae of soft ticks can cause paralysis due to their long feeding period, which may extend to several days. Peacock (62) described a case of nymphal O. megnini found in the right ear canal of a 16-month-old boy with a paralysis illness that lasted about 2 weeks. No additional human tick-paralysis cases caused by soft ticks have been reported, although paralysis-like symptoms and tick-borne diseases involving argasids are documented (15, 95, 96), likely because argasids rarely use humans as hosts.

TICK PARALYSIS AND ASSOCIATED TOXICOSES

Tick paralysis is a serious condition caused by neurotoxins from various tick species. It leads to ascending muscle paralysis and, in severe cases, respiratory failure (97). This condition is triggered by neurotoxins produced in the salivary glands of ticks and secreted into the host during blood-feeding. The toxins are primarily produced by female or immature stages of hard ticks and immature stages of soft ticks (97–105). These toxins adversely affect the host’s neurological system, with toxin levels peaking after several days of tick attachment (106). The first identified toxin causing tick paralysis, holocyclotoxin, was discovered in I. holocyclus by Stone et al. in 1983. It is produced in the large salivary glands of feeding female ticks (107). Other paralytic toxins have since been identified in A. walkerae, D. andersoni, and R. evertsi evertsi (Table 2). In ixodid ticks, the salivary glands are composed of acini, divided into four groups (I, II, III, and IV), with group-III acini (E type cells) being the most likely source of paralysis toxins (108). Toxins first appear in hosts on day 3 of tick attachment and increase as the feeding duration extends (109).

TABLE 2.

Characteristics and comparison of the most common tick toxins, including tick paralysis toxin, sweating sickness toxin, tampan toxin, and ivotoxin

Toxicoses	Tick	Structurea	Mrb	pIb	Immunity	PDb	Mechanism of action
Sweating sickness, Mhlosinga, Magudu	H. truncatum	Three immunogenic and three non-immunogenic proteins (possible)	27–33 kDa 24–42 kDa	–c	Partial	–	–
Paralysis	R. evertsi evertsi	A trimeric complex resulting in toxin	∼11 kDa; toxin ~68 kDa	6	Limited	Inactivate	Impair the conduction along peripheral nerve fibers
Paralysis	I. holocyclus	Holocyclotoxin, three polypeptides of HT1 (with structure fold), HT2, and HT3	HT-1 ~6 kDa HT2/HT-3 ~5 kDa	8.86 4.5–5	Full	Resistant	Inhibit the release of acetylcholine from the neuromuscular junctions
Paralysis	A. walkerae	An oligomer	Complexes within 43–115 kDa; 11 kDa at acid pH (cross-reactivity with the 4B12)	4.5	Partial	–	Inhibit the release of [3H] glycine from brain synaptosomes
Tampan toxicosis	O. savignyi	Tick salivary gland proteins (TSGPs)	TSGP1, ~18 kDa; TSGP2, ~15 kDa; TSGP3, ~16 kDa; TSGP4, ~17 kDa	–	Partial	–	Ventricular tachycardia by TSGP2; Mobitz-type ventricular block by TSGP4
Paralysis	D. andersoni	Soluble polypeptides	36–43 kDa	–	Dose-dependent	–	Affect efferent pathway and suppression of acetylcholine release from the synapse
Protease inhibitors	A. hebraeum; R. evertsi evertsi Rhipicephalus microplus Rhipicephalus decoloratus H. truncatum	Four peptide fractions	~10 kDa ~5–6 kDa ~30–35 kDa ~40 kDa ~27 kDa	–	Limited	Resistant	Specific non-competitive fast-binding inhibition of trypsin (A. hebraeum);Competitive fast-binding inhibitor of trypsin (R. evertsi evertsi);Competitive slow-binding inhibitor of chymotrypsin (R. microplus);Competitive slow-binding inhibition of trypsin and fast tight-binding inhibition of chymotrypsin (R. decoloratus and H. truncatum)

^a The structure might be suspected.

^b Mr: molecular mass; pI: isoelectric point; PD: protease digestion.

^c -, unknown or unrecorded data.

Ticks can cause various forms of toxicoses, including paralysis and general toxicoses, during blood meals (15, 24, 106, 110, 111). These toxicoses are associated with tick feeding (7, 112), such as sand tampan toxicoses from O. savignyi (113), H. truncatum toxicoses, which include sweating sickness, Mhlosinga and Magudu, necrotic stomatitis nephrosis syndrome (114, 115), and other toxicoses from R. microplus (116), Rhipicephalus appendiculatus (117), D. marginatus (7, 118), I. redikorzevi (7, 119), and Ornithodoros gurneyi (120). Understanding the diverse range of toxins and their effects on hosts highlights the importance of researching tick-induced toxicoses. This understanding will be further explored through the specific mechanisms of paralysis caused by different tick families. The molecular characterization of these toxins and their pathogenesis is crucial and will be discussed in the following section.

Paralysis caused by ticks of family Ixodidae

The Ixodidae family comprises several tick species that cause paralysis through the release of neurotoxins, with each species exhibiting unique characteristics and timing of paralysis onset. For example, paralysis in R. evertsi evertsi occurs between days 4 and 5 of feeding, when the tick reaches a body mass of 15–21 mg (121, 122). Similarly, paralysis caused by I. holocyclus is detected after 4–5 days of feeding, while in D. variabilis, paralysis occurs approximately 6–8 days after attachment (78, 123). Paralysis generally occurs during rapid engorgement, between 3 and 7 days of tick attachment, when the feeding site is firmly established (124). Detailed examination of ixodid ticks reveals the complexity of their toxic effects and the need for targeted research into their specific mechanisms. Next, we will explore what toxins are released by various genera of hard ticks, how paralysis differs among these ticks and compare their effects.

Paralysis associated with Amblyomma ticks

Eight Amblyomma species have been documented to cause paralysis (Table 1). These ticks affect a wide range of hosts, including cattle, dogs, goats, humans, sheep, and snakes, with recovery occurring a few days after tick removal. However, there is a lack of experimental research to confirm their paralysis-inducing capabilities, toxicosis, or the underlying mechanisms involved.

Paralysis associated with Dermacentor ticks

Ten Dermacentor species are implicated in tick paralysis (124). D. andersoni toxins affect efferent motor neurons and can affect dogs, sheep, cattle, guinea pigs, hamsters, and humans (124, 125). These toxins act as presynaptic targets by suppressing acetylcholine (ACh) release at neuromuscular junctions (110). Early removal of D. andersoni ticks can reverse paralysis (41). Studies on hamsters have shown that the virulence of D. andersoni increases with selection over generations, posing a significant threat to the cattle industry due to their paralysis-inducing potential (126). The salivary gland proteins of these ticks increase with feeding, with antigen levels positively correlated to tick weight gain between 25 and 250 mg (127). Wikel observed that D. andersoni infestation can reduce T-lymphocyte proliferation in vitro, suggesting an immunosuppressive effect likely related to salivary gland proteins (128, 129). Further experiments confirmed this effect, with salivary gland extracts from unmated female ticks reducing T-lymphocyte responsiveness by up to 68.4% (130). Bergman et al. detected soluble proteins in the salivary gland supernatants of wood ticks that suppressed murine splenocyte proliferation in vitro (131). A 36 kDa immunosuppressive protein was later isolated from the wood tick salivary gland, and its amino acid sequence was characterized (132). This protein, presents in both male and female D. andersoni, showed temporally regulated expression during feeding (133). However, it is unclear whether this protein is associated with paralysis immunity (134). Additionally, a 39 kDa triplet and a 74 kDa doublet were identified in the salivary gland extracts of D. andersoni, although these proteins appeared non-paralyzing and less prevalent (127). No reports have yet documented the development of immunity against D. andersoni.

Paralysis associated with Haemaphysalis ticks

Seven Haemaphysalis species have been implicated in paralysis. H. cinnabarina was reported to cause paralysis in a girl (32). Both H. kutchensis and H. punctata have been confirmed to lead to animal paralysis. H. chordeilis and H. sulcata are suspected of causing paralysis in humans, possibly due to mixed infestations with other tick species (21, 28). Other Haemaphysalis species may also play a role in paralysis, but research on their toxins and pathobiology remains limited.

Paralysis associated with Hyalomma ticks

H. truncatum is the only species in Hyalomma genus linked to tick paralysis (124). However, emerging cases suggest other Hyalomma species, such as H. excavatum, H. dromedarii, and H. marginatum, might also be involved in causing paralysis in humans (Table 1). Additionally, H. detritum and H. aegyptium have been associated with paralysis in sheep and tortoises (15, 35, 36). While H. truncatum is known for causing sweating sickness—a non-paralytic toxicosis affecting cattle, particularly young calves (135, 136) and occasionally other cloven-hoofed animals such as sheep, goats, and pigs (137)—it is important to note that this condition is distinct from paralysis. In southern Africa, H. truncatum is responsible for sweating sickness and two related but milder toxicoses, Mhlosinga and Magudu (21). The toxin responsible for sweating sickness is neither derived from the salivary glands nor associated with paralysis and thus will not be discussed further here.

Paralysis associated with Ixodes ticks

Among tick species implicated in paralysis, Ixodes species, particularly I. holocyclus, are the most significant. Female I. holocyclus ticks are the primary culprits responsible for tick paralysis in humans, dogs, and cats, although other animals, such as cattle, horses, sheep, goats, and swine, can also be affected (2, 138). The severity of tick paralysis increases with the duration of tick feeding (54, 139). Ross observed that the salivary gland extracts from I. holocyclus induced symptoms similar to tick paralysis in mice, suggesting that these extracts are responsible for the condition (140, 141). Serum from dogs heavily infested with these ticks can mitigate the toxic effects (140), supporting the development of canine anti-tick serum (142), though it is only effective in the early stages of paralysis. Kaire purified a toxin from homogenates of engorged I. holocyclus using ammonium acetate buffer on diethylaminoethyl (DEAE) cellulose columns and confirmed its toxicity and ability to cause paralysis (143). This isolated toxin was stable at pH 3–9 but was inactivated at 100°C within 15 minutes. Further purification efforts identified a molecular mass protein (40–80 kDa) associated with neurotoxic activity (123). The holocyclotoxin complex comprises three polypeptides—HT1, HT2, and HT3—each with an approximate molecular weight of 5 kDa (144), comparable to toxins found in other arachnids such as spiders (3–11 kDa) and scorpions (5–8 kDa). Additionally, a 20 kDa toxin is linked to cardiovascular failure in affected individuals (144). HT-1 and its genes were isolated, defined, and characterized through N-terminal sequencing, showing significant homology with scorpion neurotoxins (123, 145).

ht-1 contains sequence for an 18-residue signal peptide, complete initial and terminal codons, a polyadenylation signal, and a poly-A tail. Nicholson et al. proposed that ht-1, ht-2, and ht-3 may be parts of a gene complex (146). It is generally concluded that paralysis caused by I. holocyclus results from the inhibition of ACh release at neuromuscular junctions (123). Experiments revealed that muscle contraction induced by the toxin was normal at room temperature (23°C) but progressively declined and ceased under nerve stimulation when temperatures exceeded 35°C (147). This indicates that holocyclotoxin binds to neural synapses in a temperature-dependent manner, with paralysis being temperature-sensitive. Although hyperimmune serum against I. holocyclus holocyclotoxin has been developed, it does not address paralysis caused by D. andersoni (24), suggesting that the toxins from these tick species are either unrelated or very distantly related evolutionarily.

Paralysis associated with Rhipicephalus ticks

In the genus Rhipicephalus, several species are known to cause tick paralysis in ungulates, including R. warburtoni, R. tricuspis, R. punctatus, R. exophthalmos, and R. bursa (15, 25, 34, 58, 61). For humans, R. annulatus, R. simus, R. sanguineus, and R. praetextatus have been implicated in tick paralysis (15, 28, 59). R. appendiculatus causes a leukocytotropic disease in cattle, known as brown tick toxicosis (112), while R. evertsi evertsi induces motor polyneuropathy in sheep, referred to as spring lamb paralysis (148). The condition of sheep paralysis caused by R. evertsi evertsi was first reported by Hellier (149) and Ralph (150). In 1917, Du Toit documented a neuropathic syndrome in South Africa that was potentially linked to R. evertsi evertsi, although this association was not confirmed (151). Clark’s research later confirmed that R. evertsi evertsi affects young lambs, who typically recover within days following tick removal (152). A protein fraction with an isoelectric point (pI) of 6 was found to inhibit nerve pulse propagation, with a molecular mass of approximately 68 kDa determined through chromatofocusing, SDS-PAGE, and gel permeation chromatography (89). Experiments showed that salivary gland extracts from female R. evertsi evertsi ticks weighing 15–21 mg could induce nerve block (89, 122, 153). Dissected nerves exposed to these extracts or purified neurotoxin exhibited muscle contraction (89, 124). The paralysis mechanisms of R. evertsi evertsi differ from those in I. holocyclus (which inhibits ACh release at the synaptic junction); instead, the neurotoxin from R. evertsi evertsi affects nerve cells and impairs nerve impulse conduction along peripheral nerve fibers (89, 124, 154). Two proteins identified during mating and feeding were implicated as toxic components (122). A monoclonal antibody identified a paralysis toxin with an approximate molecular weight of 11 kDa, and amino acid analysis indicated similar protein mass and composition between R. evertsi evertsi and I. rubicundus (124). This suggests that the previously identified 68 kDa paralysis toxin is a trimer composed of ~11 kDa proteins.

Paralysis caused by ticks of family Argasidae

Argasidae ticks exhibit a different pattern of paralysis compared to Ixodidae ticks, primarily involving early developmental stages and demonstrating varied toxic profiles. While Ixodid ticks typically induce paralysis in adults, argasid ticks are more likely to cause paralysis during early developmental stages, such as third-stage nymphs (24). Additionally, adult argasid ticks have smaller Type II alveoli with a wrinkled surface compared to their nymphal counterparts (155). In the following sections, we will explore specific examples of paralysis caused by Argas, Ornithodoros, and Otobius ticks and discuss their implications for affected hosts (Table 1).

Paralysis associated with Argas ticks

Several Argas species are known to cause paralysis in fowl and other birds, including A. africolumbae, A. walkerae, A. sanchezi, A. robertsi, A. reflexus, A. radiatus, A. persicus, A. monolakensis, A. miniatus, and A. arboreus (Table 1). In laboratory settings, larvae of these species can induce paralysis, with symptoms emerging rapidly during the engorgement phase (156). Among these, A. walkerae has been particularly well-studied. Its toxic components have molecular masses ranging from 43 to 115 kDa, with a notable shift to 11 kDa under lower pH conditions (157). Similar to I. holocyclus and D. andersoni, paralysis caused by A. walkerae is attributed to reduced ACh production or release at neuromuscular junctions (158). Research indicates that only replete larvae of A. walkerae are capable of inducing paralysis in chickens (159). Gel permeation chromatography has identified macromolecular complexes and two bands of approximately 32 kDa and 60 kDa in purified fractions (159). A monoclonal antibody (mAb and 4B12), previously used to detect R. evertsi evertsi paralysis toxins, was employed to purify the neurotoxin from A. walkerae. Western blot analysis identified a 68 kDa protein, while an 11 kDa protein, not detected by Western blot, was isolated via enzyme-linked immunosorbent assay (ELISA) and demonstrated cross-reactivity with 4B12 (157). Lower pH conditions facilitated the formation of a more uniform toxin complex (158). Additionally, extracts from A. walkerae larvae inhibited the release of [³H] glycine from rat brain synaptosomes, stimulated by both veratridine and potassium (157).

Paralysis associated with Ornithodoros ticks

In the genus Ornithodoros, O. lahorensis has been implicated in causing paralysis in sheep and cattle, while the paralysis of marine birds due to O. capensis remains uncertain (66). Paralysis usually develops in the third stage of nymphal ticks. Other species in this genus do not cause paralysis but can induce pain, blisters, local steroid, or edema, including O. amblus, O. capensis, O. coniceps, O. coriaceus, O. gurneyi, O. muesbecki, O. savignyi, and O. rostratus (66). One of the earliest reports of toxicosis from sand tampans (O. savignyi) described the death of 10 cows within 6 hours of exposure (124). Kone (160) first described tampan toxicosis from O. savignyi, noting 10 bovine deaths from a herd of 98 cattle (160). Neitz et al. (161) improved purification methods (gel and DEAE-cellulose chromatography) for the toxin components in O. savignyi salivary secretions, detecting toxic fractions with undetermined LD50 (161). The toxin mixture was proteinaceous in nature (161).

Fresh oral secretion from O. savignyi revealed high protein nitrogen content and was heat-stable up to approximately 80°C (162). An acidic toxin with a molecular mass of approximately 15 kDa was purified and characterized, and four tick salivary gland proteins (TSGP) 1–4 involved in granule biogenesis in the salivary gland were confirmed (64). Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and N-terminal sequencing identified three TSGPs as an acidic toxic homolog (TSGP2, ~15 kDa), a nontoxic homolog (TSGP3, ~16 kDa), and a basic toxin (TSGP4, ~17 kDa) (64, 113). Toxic components isolated by paper and thin-layer chromatography induced lethal effects in animals under experimental conditions (162). Prior to discovering a protein toxin in the salivary gland and larval extracts, the mechanisms and symptoms of paralysis were unclear. Howell suggested that heart failure might be a cause of death, and Mans et al. (113) observed arrhythmic heartbeats leading to cardiac arrest following salivary gland extract injections (113, 162). Subcutaneous injection of purified toxins showed that TSGP2 primarily caused ventricular tachycardia, and TSGP4 induced Mobitz-type ventricular block (113), suggesting a distinct pathogenesis for sand tampan toxicosis by O. savignyi compared to tick paralysis.

Paralysis associated with Otobius ticks

Most argasid ticks infest and cause paralysis primarily in poultry and livestock, including chickens, camels, cattle, and sheep. However, O. megnini is an exception, as it parasitizes equines and humans and has been associated with paralysis (62). In one case, a single O. megnini nymph found in the right ear of a 16-month-old baby resulted in weakness in the right leg, respiratory difficulty, and other paralysis-like symptoms (62). In equines, O. megnini infestations have been linked to more severe symptoms, including elevated creatine kinase levels and, in some cases, death (163). Despite these severe cases, not all O. megnini infestations cause paralysis; some only result in irritation and non-paralytic signs (164, 165). A recent case involving an 11-month-old cat demonstrated paralysis induced by an infestation of O. megnini nymphs. The cat exhibited depression, flaccid paralysis, and tachycardia (63). While no specific toxins have been identified in O. megnini, the consistent presence of nymphs in the ear canal of affected hosts suggests that the location of the infestation may be crucial in causing paralysis. Inflammatory reactions in the ear could potentially disrupt the host’s neurological system, leading to paralysis.

MECHANISMS AND NEUROLOGICAL EFFECTS OF TICK-INDUCED PARALYSIS

Tick-induced paralysis typically manifests as ascending flaccid paralysis (Fig. 3) (2). This condition arises from a conduction block in motor nerve fibers, particularly the smaller ones, disrupting the secretion and release of ACh at the neuromuscular junction and at the nodes of Ranvier, without affecting ACh biosynthesis (30, 166, 167). Normally, motor neurons generate action potentials that travel down the axon (109). ACh, synthesized and stored in intracellular vesicles, is released into the extracellular space at the presynaptic end of the neuromuscular junction (109). It binds to receptors on muscle cells, causing muscle contraction (82, 109, 168). Flaccid paralysis occurs when tick toxins block ACh secretion and/or release. Despite similar clinical manifestations across different tick species, the mechanisms of toxin action can vary. These variations in mechanisms highlight the complexity of tick-induced paralysis, necessitating a closer look at how different species produce their specific effects on the nervous system.

Fig 3.

Schematic illustration of the molecular pathogenesis of tick paralysis in humans and animals (illustration designed using FigDraw).

In D. andersoni, paralysis manifests as motor polyneuropathy that primarily affects efferent pathways, with minimal impact on afferent pathways. This condition impairs impulse transmission from muscular nerves or spinal cord synapses (15, 169), potentially due to inhibited ACh release or destruction by anticholinesterase. This process affects the terminal motor fibers at the neuromuscular junction while leaving ACh receptors largely unaffected (24). The specific targeting of efferent pathways by D. andersoni underscores the diverse ways ticks can impair neuromuscular function, indicating other tick species may differ in their approach.

In R. evertsi evertsi, paralysis also presents as motor polyneuropathy of the peripheral nervous system, similar to D. andersoni. However, it predominantly affects slow nerve fibers and respiratory muscles, potentially leading to respiratory failure (170). Neurotoxins from this tick act on the nerves rather than directly at the neuromuscular junctions, with no reported inhibition of ACh release (68, 89, 124, 171). This shows the life-threatening potential of tick paralysis and the importance of understanding species-specific toxin actions.

I. holocyclus induces paralysis by affecting anterior horn neurons and cranial nerve cells, with minimal impact on peripheral nerves and the cerebral cortex (172). The holocyclotoxin appears to antagonize ACh secretion in a temperature-dependent manner, inhibiting ACh release above 30°C, likely by targeting processes between terminal membrane depolarization and release (166). It has minimal effect on the neuromuscular microendplate potential of the mouse extensor digitorum longus muscle, suggesting it does not target calcium-independent release vesicles or postsynaptic ACh receptors. However, it reduces the endplate potential in a calcium-dependent manner, indicating a presynaptic mechanism involving voltage-gated calcium channels (172). Similar presynaptic inhibitors of potassium and sodium channels are found in spiders and scorpions (173–176). Differences in neurotoxin action between I. holocyclus and D. andersoni likely exist, with I. holocyclus affecting the spread of nerve impulses along axons and D. andersoni affecting motor neurons in the efferent pathway. Despite these differences, both toxins lead to decreased presynaptic ACh and ascending flaccid paralysis, although the exact cellular mechanisms remain unclear. The role of presynaptic inhibition in I. holocyclus paralysis highlights a unique mechanism among ticks, with implications for treatment and intervention strategies.

A. walkerae larvae cause paralysis in poultry by affecting the peripheral nervous system, particularly fast-conducting nerve fibers, which reduces the motor velocity of the median-ulnar and sciatic nerves (110, 169, 177, 178). This effect ranges from slight to moderate motor polyneuropathy, with minimal impact on the conduction velocity of afferent fibers (179). Efferent nerve fibers in respiratory muscles are also affected, leading to respiratory arrest, while cardiac muscles are generally unaffected (2). Additional studies suggest that these toxins impact not only sensory nerves but also motor nerves, affecting ACh release at neuromuscular junctions and receptor sensitivity at muscular synapses (110, 158). Larval extracts inhibit ACh release by affecting potassium- and veratrole-stimulated release of [³H] glycine from rat brain synaptosomes (158). Understanding the effects of A. walkerae on both motor and sensory nerves enhances our knowledge of tick paralysis in animals and should inform future research on its broader implications for both human and animal health.

GLOBAL ANALYSIS OF TICK PARALYSIS CASES

Human cases of tick paralysis

Although human cases of tick paralysis are rare, they have been well-documented across various regions (180–182). A total of 288 tick paralysis cases were identified in reports spanning from 1898 to 2023. Most cases originated from North America, Australia, and Europe, with fewer reports from Asia and Africa. Most patients had a history of travel or prolonged stays in forested or grassland areas, emphasizing these as potential risk factors for tick exposure. These findings underscore the geographical and demographic factors associated with tick paralysis in humans, highlighting the need for a deeper exploration of specific risk factors involved.

Demographic characteristics

Of the 288 cases, gender information was recorded for 249 individuals: 96 males (38%) and 153 females (61%), with the remaining 39 cases of unknown gender (Table S1; Fig. 4a). The data indicate a significant gender association with the illness (Fig. 4a and b, P < 0.001), with females more frequently affected across all age groups. This trend is consistent with observations in tick-borne Lyme disease (183), where females are more often affected, in contrast to diseases like Rocky Mountain spotted fever, Colorado tick fever, and tick-borne encephalitis, which are more prevalent in males (184, 185).

Fig 4.

Global distribution of reported human cases of tick paralysis by gender, age, and season, analyzed by Pearson’s chi-squared test. (a) Gender distribution. (b) Age distribution (<12, 12–50, and >50). (c) Gender distribution of cases in individuals under 12 years old. (d) Gender distribution of cases in individuals aged 12 years and older. (e) Seasonal distribution. *: P < 0.05; **: P < 0.01; ***: P < 0.001.

Patient age was recorded for 268 cases, excluding 20 with unrecorded ages, and was categorized into three age groups: under 12 years (n = 199), 12–50 years (n = 38), and over 50 years (n = 30). The age distribution was statistically significant, with children under 12 years representing the most affected group (Fig. 4b, P < 0.001). This contrasts with tick-borne encephalitis, which predominantly affects adults. The high incidence in children may be attributed to their reduced ability to detect and remove ticks, leading to prolonged tick attachment and greater toxin accumulation. Additionally, children’s lower body weight increases their relative exposure to the paralytic toxin. Among the 199 child patients (under 12 years, including 37 with unrecorded sex), girls (n = 119, 60%) were more frequently affected (Fig. 4c, P < 0.001). This may be attributed to long hair providing cover for ticks, which can hinder their detection. In patients older than 12 years, a male predominance was observed (Fig. 4d, P < 0.001), with 39 males (68%) and 18 females (32%) affected, indicating that males over 12 are more susceptible to tick infestation (Table S1). The demographic analysis highlights the increased vulnerability of certain groups, particularly females and children, highlighting the need for a closer examination of environmental and seasonal influences.

Seasonality, environmental, and geographical risk factors

Tick paralysis exhibits a strong seasonal pattern. Among the 111 cases with documented occurrence timing, most (n = 71, 64%) occurred in summer (Fig. 4e), with May being the most common month (P < 0.001). Fall (n = 20) and spring (n = 7) accounted for fewer cases, indicating season as a significant epidemiological risk factor. This seasonality may vary based on regional weather patterns and environmental factors.

Most patients with a clear history (66/77, P < 0.001) had direct exposure to natural environments, including rural living, mountain hiking, coastal trips, bushwalking, or outdoor work (Table S1). Close contact with tick-infested animals or humans was another risk factor (n = 11; Table S1). Residence in areas with abundant vegetation was identified as a significant risk factor. Geographical factors also play a role, with many cases reported from the eastern coast of Australia and the Pacific Northwest of North America. Several patients had traveled to these regions prior to the onset of paralysis. Understanding the seasonality and environmental risks is crucial for developing prevention strategies, which is closely linked to the clinical manifestations of tick paralysis.

Clinical manifestations

Initial symptoms and progression

Tick paralysis can be severe and potentially fatal; however, it is often reversible with timely tick removal and prompt treatment (186). Initial symptoms are typically mild and may include fatigue, pain, paresthesia, and ataxia (187, 188). Neurological symptoms, such as symmetric ascending flaccid weakness, usually begin 5–7 days after tick attachment (30). If the tick remains attached, paralysis may progress from the legs to the torso and arms, eventually compromising respiratory muscles within hours (187). In severe cases, muscles controlled by cranial nerves may weaken, leading to respiratory depression. Some children have died from respiratory failure without intervention (Table S1). Often, when respiratory symptoms appear, the tick has fully engorged and dropped off, explaining why some patients recover without the need for artificial ventilation or intubation. Recognizing the early signs and progression of tick paralysis is vital for effective intervention, and these symptoms can vary significantly depending on the tick species and attachment site.

Variations in clinical presentation

Tick paralysis is marked by acute, rapidly progressive muscle weakness (189), with lateral staring-induced nystagmus reported in children (188, 190). Different tick species may cause distinct clinical manifestations due to variations in toxin pathophysiology (109). For instance, blood pressure is typically normal in cases of paralysis linked to D. andersoni, whereas hypertension is often associated with paralysis caused by I. holocyclus (15).

The clinical presentation may also vary based on the tick attachment site. The scalp and ears (including ear canals) are common attachment sites (Fig. 5a). Ticks on the scalp primarily affect extremity nerves, leading to weakness or even paralysis of all extremities (Table S1; Fig. 5b). Deep tendon reflexes in the limbs are often diminished or absent (Fig. 5b). As the illness progresses, extremity weakness may be accompanied by bulbar symptoms, such as ophthalmoplegia, dysarthria, and dysphagia. Ticks in the ear canal mainly affect facial nerves, causing severe partial facial weakness, paresthesia, and potentially unilateral facial palsy. Common symptoms include ear pain and facial asymmetry (Fig. 5c). Fever and hearing loss are rare initially but may develop with worsening inflammation in the ear canal. A Weber test shows lateralization, and a Rinne test is normal under tuning fork examination (191). These signs may result from neurotoxins spreading into the middle or inner ear through a perforated tympanic membrane. Ticks can also attach to other parts of the body, such as the axilla (19, 192), back (181, 193, 194), chin (195), eyelids (196, 197), limbs (10, 46, 198, 199), necks (18, 187, 194), and shoulder (200). Similar to scalp ticks, ticks attached to other body parts or cases with unrecorded tick locations typically cause ascending flaccid extremity weakness or paralysis (Fig. 5d and e). The diversity in clinical presentations emphasizes the need for tailored treatment approaches, which is particularly important when considering the severity and potential fatality of tick paralysis.

Fig 5.

Clinical manifestations of human tick paralysis based on tick attachment locations. (a) Distribution of tick attachment sites (statistical analysis performed using Pearson’s chi-squared test, ***: P < 0.001). (b) Clinical symptoms associated with ticks infesting the scalp. (c) Clinical symptoms associated with ticks infesting the ears. (d) Clinical symptoms associated with ticks infesting the back, neck, axilla, and other parts (excluding scalps and ears). (e) Clinical symptoms of tick paralysis with unrecorded tick attachment sites.

Severity and fatality

Fatal cases

Clinical manifestations in children tend to be more severe than in adults due to their weaker immune systems. A total of 29 fatal cases were documented in Australia and North America (18, 19, 32, 201–203) (Table S1), all involving young patients. The tick species responsible for these deaths included D. andersoni (n = 3), D. variabilis (n = 5), I. holocyclus (n = 6), and H. cinnabarina (n = 1). The oldest fatality was a nearly 14-year-old boy who succumbed to respiratory failure, while the youngest was a 10-month-old infant (201). Most fatalities resulted from respiratory failure or paralytic complications. The severity of tick paralysis, especially in children, highlights the importance of early detection and treatment, and the necessity to examine how these factors vary across different regions.

Regional variation in tick paralysis

Prompt tick removal usually reverses tick paralysis, often reducing clinical symptoms within hours. However, in some countries, symptoms can significantly worsen after tick removal (188). Patients from North America and Australia experience different clinical progressions and prognoses after tick removal. Australian cases tend to worsen before gradually improving, in contrast to North American patients (109). However, clinical progression and prognosis appear more closely related to the specific neurotoxins of the tick species involved. For example, 13 cases caused by I. holocyclus deteriorated after tick removal for several days before symptoms began to regress, eventually leading to complete recovery. Of these, 11 were from Australia (192, 194, 197, 204–206), with the remaining two from Japan (207) and Singapore (208). Both the Japanese and Singaporean patients had traveled to Australia, where they were infested by Australian ticks. The holocyclotoxin secreted by I. holocyclus accumulates and increases in concentration, reducing presynaptic ACh release. Holocyclotoxin onset may require a time-dependent intracellular step, which could explain the delayed development of symptoms despite tick removal. The pathophysiological process persists until the neurotoxin is reduced, at which point patients begin to recover.

Besides I. holocyclus, species from Dermacentor (19, 24, 83, 209) and Haemaphysalis (32) have also been linked to cases where symptoms worsened after tick removal, although such deterioration is rare. Gregson (24) documented irregular respiration and an imperceptible pulse in a young boy after tick removal. Taylor (83) reported a 3-year-old Canadian child bitten by D. andersoni who remained in critical condition for at least 24 hours and developed a typhus-like rash after tick removal. Both Costa (209) and Mccornak (19) recorded young children whose conditions worsened post-tick removal, with one case improving and another resulting in death from bulbar paralysis. These differences may be due to varying toxin pathologies, though the mechanism remains unclear. The regional differences in clinical outcomes suggest a strong influence of tick species and their neurotoxins.

Long-term effects and co-infections

Persistent symptoms

In most cases, patients fully recover within days after tick removal, but some experience lasting effects. A 78-year-old woman experienced persistent fatigue following a tick bite (210), although the tick species was not identified. Similar complaints of drowsiness and weakness were observed in an adult man infested by R. simus (211) and a nearly 4-year-old boy bitten by D. variabilis (19) who complained they were always drowsy and weak. Swanepoel (33) reported a 16-year-old boy bitten by H. truncatum who suffered permanent weakness in his wrist, fingers, and right-hand muscles. Gregson (24) summarized five cases where paralysis persisted for days after tick removal, only resolving when the skin at the attachment site was excised, suggesting that tick toxins may accumulate in the skin and continue to affect the body.

Co-infections

Ticks may transmit pathogens while secreting neurotoxins during feeding, leading to co-infections with tick-borne viral or bacterial diseases (207). Therefore, when patients develop fever, lymph node enlargement, or other atypical symptoms, concomitant infection with tick-borne pathogens should be considered. While most cases resolve after tick removal, some patients experience persistent symptoms or co-infections, underscoring the need for ongoing monitoring and research into tick-borne diseases in both humans and animals.

Tick paralysis in animals

This condition has been documented in various domestic and wild animals, including canids (42, 212–214), felids (180, 215), cattle (216), caprines (14, 26, 217, 218), horses (219), gray fox (220), snake (13), llama (221), mouse (222), and birds (223, 224) (Table 1). A case of tick paralysis was also reported in a wapiti (Cervus elaphus) in China, although the tick species responsible was not identified. Tick paralysis in animals shares similarities with human cases, particularly in its progression and clinical outcomes, which is evident in species-specific patterns that further our understanding of the condition.

Onset and progression of tick paralysis

In animals, tick paralysis usually manifests 4–7 days after tick attachment, though signs can take up to 13 days to appear in some cases (214). Clinical signs include weakness, gait incoordination, voice changes, and increased respiratory effort. Most animals recover with prompt treatment and supportive care (180, 212, 215, 219). However, in acute cases, signs can progress rapidly within 12 hours to 5 days, beginning with limb paresis and advancing to hind-quarter or generalized paralysis, respiratory depression, and, in severe cases, death—even after tick removal and antiserum treatment (42, 214).

Feline tick paralysis cases

Ellie Leister and colleagues analyzed 2,077 feline cases of tick paralysis caused by I. holocyclus between 2008 and 2016. Of these cases, all from the coastal city of Queensland, 46 experienced recurrent paralysis, and 1,742 resulted in death despite emergency treatment (225). These findings underscore the high mortality rate associated with tick paralysis in felines, highlighting the severity of the condition. This prompts a broader comparison with other species and geographical patterns.

Comparative mortality and geographic patterns

A comparison between feline and canine tick paralysis cases reveals a higher mortality rate in felines. Both species’ cases were reported predominantly from coastal areas, with canines also showing a significant occurrence at the city’s edge near jungles. This similar geographic distribution highlights the environmental factors contributing to tick exposure and the subsequent risk of paralysis. Comparing mortality and geographic patterns across species provides valuable insights into the environmental factors driving tick paralysis, which can inform prevention and treatment strategies.

Seasonal discrepancies: canine vs human tick paralysis

In contrast to the feline cases, canine tick paralysis cases in Australia peaked at 1,124 during spring (out of a total of 1,650 cases), with a 42% recovery rate (226). This contrasts with the higher mortality rate observed in felines (225). Interestingly, the seasonality of canine tick paralysis cases contrasts with that of human cases. Over half of human paralysis cases (67 out of 105) occurred in the summer, while most canine cases were observed in spring. This discrepancy may be due to ticks seeking dogs as blood meal sources in spring when Ixodes spp. adult females are most active, whereas humans are more frequently exposed to tick bites during summer outdoor activities.

DIAGNOSIS AND RECOGNITION OF PATIENTS AT RISK

Early recognition of clinical manifestations and recent tick exposure is crucial for diagnosing tick paralysis. Diagnosis is often confirmed by identifying a tick along with generalized weakness and/or respiratory distress. A history of the patient being in tick-endemic regions or having recently visited forests is also important for accurate diagnosis. Physicians should carefully inspect areas where ticks commonly attach to humans, such as the scalp (especially under long, thick hair), ears, ear canals, groin, axilla, and perineum (Table S1). Early identification of the tick can prevent unnecessary clinical and laboratory investigations, reducing the risk of deterioration, fatal outcomes, and costly tests. Using a fine-toothed comb can be particularly useful in diagnosing tick paralysis, especially in individuals with thick, long hair, who may be more susceptible to infestation. In some cases, paralysis may develop even after the tick has detached, which is more common in Australia. Cerebrospinal fluid tests typically yield normal results. The level of tick engorgement can affect imaging results, with highly engorged ticks showing a striking T1-hyperintense signal and T2-hypointensity on magnetic resonance imaging (MRI) (227, 228).

Clinical manifestations

Tick paralysis typically presents as ascending flaccid paralysis that progresses over hours to days. Initial symptoms include fatigue, irritability, paresthesias, and muscle weakness, while fever and pain are uncommon (82). Some patients may exhibit apathy and loss of appetite, along with tingling and numbness in both the lower and upper extremities. Weakness usually begins in the lower limbs and ascends to the upper body as the toxin accumulates. Reflexes may become diminished or absent, and the condition can progress to generalized paralysis. Partial facial palsy, particularly involving the lower motor neurons, may occur, especially in cases of tick infestation in the ear canal (194, 229). Without prompt intervention, the paralysis may involve respiratory muscles, leading to respiratory depression and, ultimately, death. Mental status typically remains intact until hypoxia and hypercarbia set in, potentially causing convulsions (18, 59). Although rare, dilated pupils can be observed (19, 201). Gastrointestinal or other general intoxication symptoms are infrequent.

Differential diagnosis

Due to the rarity of tick paralysis and limited clinical experience, the condition is often misdiagnosed, causing physicians to miss the narrow therapeutic window for effective treatment (230). In cases of rapidly progressive paralysis, it is crucial to rule out tick attachment first through a thorough skin inspection. Imaging can also help detect small nodules that may indicate tick presence, preventing oversight (230). A study of 143 children with non-traumatic acute flaccid paralysis in Australia over 4.5 years found that three had tick paralysis (231). Guillain-Barré syndrome (GBS) accounted for 67 cases (47%), with transverse myelitis contributing to 27 cases (19%). Other conditions presenting with acute flaccid paralysis included acute disseminated encephalomyelitis, spinal cord lesions, botulism, myasthenia gravis, and viral encephalitis. The overlapping symptoms of these conditions, such as irritability, paresthesia, fatigue, and muscle weakness, often lead to misdiagnosis of tick paralysis (232–237). Some diseases are particularly challenging to differentiate from tick paralysis, and rare disorders may not be present in their traditional form. As summarized in Table 3, several conditions present with symptoms that overlap with tick paralysis, making differential diagnosis challenging. However, the table is not exhaustive and should be used as a guide alongside clinical judgment (232–237).

TABLE 3.

Differential diagnosis and clinical characteristics of tick paralysis and closely related disorders that may present with similar clinical features

Characteristic	TPa	GBSa	Botulisma	Polioa	ASCIa	TMa
Fever	Rare	Rare	Rare	Present	Absent	Variable
Pain	Rare	Rare	Absent	Present	Frequent	Frequent
Paresthesia	Rare	Present dominantly	Absent	Present	Frequent	Frequent
Dilated pupils	Rare	Rare	Present	Absent	Absent	Absent
Gastrointestinal signs	Absent	Present	Present	Rare	Absent	Absent
CSFb protein	Normal	Elevated	Normal	Mildly elevated	Variable	Elevated
CSF WBCcs	Normal	Normal	Normal	Elevated	Variable	Elevated
MRId	Normal	Generally normal	Normal	Abnormal	Abnormal	Abnormal
Spreadh	Tick bite	–	Eating food with toxins or bacterial spores	Fecal-oral route	–	–
Cause	Tick toxins	Problem with the immune system	Clostridium botulinum toxin	Poliovirus (types 1, 2, and 3)	Trauma to the spinal cord	Viral, bacterial, and fungal infections all included
Treatment	Tick removal, antibiotics	IVIge, PEf, and breathing aids can ease symptoms	Antitoxin, antibiotics, severe with mechanical ventilation	No cure, only prevented by the Polio vaccine	Surgery, antibiotics, long-term hospitalization and rehabilitation	IVg steroids, PE, and medication of virus
Prognosis	Generally complete recovery within hours to days	Recovery within months to years, some have lasting effects	Most patients recover, and a few die from breathing failure or secondary infections	Most people fully recover, some can be permanent paralysis or develop post-polio syndrome	Decrease or loss of sensation and organ function below the normal level	Varying lengths of time, pain, or TM recurrent mainly depending on the cause of TM

^a TP: tick paralysis; Polio: poliomyelitis; ASCI: acute spinal cord injury; TM: transverse myelitis.

^b Cerebrospinal fluid.

^c White blood cells.

^d Magnetic resonance imaging.

^e Intravenous immunoglobulin.

^f Plasma exchange.

^g Intravenous.

^h -, does not spread by external factors.

GBS is a significant differential diagnosis. Although treatments such as plasmapheresis and intravenous immunoglobulin are available, there is no definitive cure. The progression of GBS is slower than that of tick paralysis, with weakness developing over weeks rather than hours or days (238). GBS may present with oropharyngeal weakness, respiratory failure, or autonomic nervous dysfunction (239). Symptoms often include prior gastrointestinal disturbances, such as emesis or diarrhea. GBS typically involves areflexia or hyporeflexia and elevated protein levels with normal cell counts in cerebrospinal fluid (239). Additionally, GBS presents with reduced nerve conduction velocity, decreased compound muscle action potential, and a prolonged “F” wave, indicating proximal nerve root demyelination, which does not occur in tick paralysis (80).

Poliomyelitis, also known as infantile paralysis, is another differential diagnosis often confused with tick paralysis, particularly in cases involving travel to polio-endemic areas. While rare due to vaccination efforts, polio is still endemic in regions of Afghanistan and Pakistan, according to World Health Organization (WHO) reports. Poliomyelitis typically presents with fever, meningitis, and asymmetric weakness, a major cause of lameness (240, 241). Cerebrospinal fluid analysis may show mildly elevated protein and lymphocytosis (242). MRI findings may also be abnormal.

Acute spinal cord lesions, which present with flaccid paraplegia or quadriplegia, differ from tick paralysis by including symptoms such as urinary retention and bowel incontinence at the sensory level (243). These lesions typically result in decreased sensation and organ function below the affected area, and protein levels can be significantly elevated in cerebrospinal fluid (80).

Botulism, caused by C. botulinum toxin, also presents with flaccid paralysis. Like tick paralysis, botulism reduces ACh release. Symptoms often begin with cranial nerve involvement, leading to descending paralysis that primarily affects extraocular muscles and pupils (238). Patients may develop dysphonia and dysphagia due to lower cranial nerve involvement (244), and gastrointestinal symptoms may also occur. Hematological exams in botulism typically do not show abnormal protein or white blood cell elevations.

Transverse myelitis, which can be triggered by viral, bacterial, or parasitic infections, presents with pain, paresthesia, motor deficits, and bladder dysfunction (235, 245, 246). Elevated protein levels and T-lymphocytes are often seen in cerebrospinal fluid (247). MRI of the spinal cord typically shows lesions with high signal intensity on T2-weighted sequences, particularly in the cervical region, conus medullaris, or thoracic spinal cord (247, 248).

TREATMENT

The primary treatment for tick paralysis is the prompt removal of the tick(s) (249). A thorough examination of the patient’s skin is essential, including areas such as the scalp, ear canal, nose, and armpits. The recommended method involves using fine-toothed tweezers to grasp the tick parallel to the skin and applying steady, even force to remove it intact, including the mouthparts, which can be challenging to extract (8, 85). Care must be taken to avoid squeezing the tick, which could inject additional toxins and worsen the condition. When removing ticks from the ear canal, combining tick removal with antibiotic treatment may be advisable to prevent otitis media. If patients exhibit atypical symptoms during tick paralysis, a combination treatment may be necessary to address potential co-infections.

Patients should be observed for at least 24–48 hours, or longer if necessary, after tick removal to ensure steady and clear improvement. For example, in cases of paralysis caused by I. holocyclus—particularly common in Australia—there is a risk of significant deterioration after tick removal, including life-threatening angioedema (245). Patients with respiratory failure may require mechanical ventilation in an intensive care unit to manage dyspnea.

Antitoxins derived from dogs are another treatment option, though they carry risks of acute anaphylaxis and neuropathy. These antitoxins are generally administered in small amounts and reserved for severely ill patients in Australia (188). The injection of anti-paralysis tick serum has demonstrated efficacy in neutralizing paralysis toxins. Recently, a synthetic anti-venom vaccine derived from holocyclotoxins has shown effectiveness in immunizing dogs (246). This suggests that synthetic or recombinant vaccines could be valuable in preventing tick paralysis and may contribute to future vaccine development, although further testing in animals is needed to assess their immunological efficacy.

CONTROL AND PREVENTION

To reduce the risk of tick-borne diseases and tick paralysis, effective repellents should be applied to the skin, such as trans-p-methane-3,8-diol and N,N-Diethyl-3-methylbenzamide (250, 251). Minimizing tick attachment is the most effective way to prevent tick paralysis. In addition to using repellents, individuals should wear appropriate outfits—such as long-sleeves, long socks—when participating in outdoor activities. It is advisable to avoid walking through dense vegetation and to take precautions when working in bushy areas. Following outdoor activities, particularly in forested environments, individuals should thoroughly check their skin for ticks. For controlling tick paralysis in dogs and cats, the development of anti-tick vaccines represents an effective strategy.

CONCLUDING REMARKS

Tick paralysis is a potentially fatal condition with significant implications for human and animal health. Its epidemiology is influenced by factors such as seasonality, geography, age, and gender. Clinical outcomes are determined by several variables, including the species and number of ticks, the rate and amount of toxin secretion, host immune response, and the sensitivity of the tick attachment site. The condition arises from neurotoxins secreted by the salivary glands of various tick species, which accumulate in the host when the tick remains attached for several days. These toxins primarily inhibit acetylcholine release at neuromuscular junctions, leading to symptoms such as lethargy, weakness, unsteady gait, dilated pupils, ascending symmetrical paralysis, slurred speech, and reduced deep tendon and gag reflexes. Severe cases may involve respiratory distress, bradycardia, decreased oxygen saturation, and asystole. Fortunately, tick paralysis is generally reversible with prompt intervention, primarily through tick removal. However, removal can sometimes exacerbate the condition, requiring respiratory support and intensive care. Immunoassays to detect and quantify antibodies against tick toxins can also be valuable in assessing immune status and monitoring post-immunization responses. Future efforts should focus on advancing our understanding of the molecular mechanisms underlying tick paralysis, improving diagnostic tools, and developing targeted therapies to enhance patient outcomes and reduce the health impacts of this condition.

Biographies

Yuan-Ping Deng received a Bachelor of Veterinary Science (B.V.Sc.) degree from Hunan Agricultural University, Changsha, China. She is a doctoral candidate at Hunan Agricultural University, Changsha, China, majoring in molecular parasitology in the College of Veterinary Medicine. Following Professor Guo-Hua Liu, her current research direction is the diversity of intestinal microbiota of ectoparasites. During her master's degree, her research direction is the mitochondrial genome of ectoparasites. She has published 20 original papers in well-regarded international journals, such as Travel Med Infect Dis, Infect Dis Poverty, Parasit Vectors, and Vet Parasitol.

Yi-Tian Fu received a Ph.D. in parasitology from Hunan Agricultural University, Changsha, China, and now she works at Xiangya School of Basic Medicine, Central South University, China for her postdoctoral training. Her current research focus on the metagenomics, transcriptomics, and gut microbiomics of important zoonotic parasite. She was awarded the Hunan Academic Research Award of student in 2022 and Hunan Natural Science Award in 2024, respectively. She has published 27 original papers in well-regarded international journals. Her research has been well supported by research grants from the China Postdoctoral Science Foundation, the Hunan Natural Science Foundation, and Central South University.

Hany M. Elsheikha, Ph.D., is a Chair Professor in the Global Health Department at the School of Veterinary Medicine and Science, University of Nottingham (SVMS-UoN). He is a diplomate of the European Veterinary Parasitology College and serves as the head of the European Scientific Counsel Companion Animal Parasites (ESCCAP) for the UK and Ireland. Prof. Elsheikha earned his Ph.D. from Michigan State University, where he researched the molecular evolution of the causative agent of equine protozoal myeloencephalitis. Following the completion of the PhD, he received the prestigious American Society for Microbiology (ASM)/National Center for Infectious Diseases (NCID) Postdoctoral Fellowship. Over the past 17 years, Prof. Elsheikha has led the development and delivery of parasitology education at SVMS-UoN. He has established a multidisciplinary research program focusing on decoding interkingdom chemical communication between host cells and neuropathogenic protozoan parasites, with particular interest in Toxoplasma gondii. He has published over 250 peer reviewed papers, along with numerous articles in professional magazines. Additionally, Prof. Elsheikha has authored eight books in veterinary parasitology for students, residents, and veterinary professionals.

Mei-Ling Cao received a Bachelor of Veterinary Science (B.V.Sc.) degree from Hunan Agricultural University, Changsha, China. She is an academic master student, majoring in Preventive Veterinary Medicine at the College of Veterinary Medicine, Hunan Agricultural University, Changsha, China. Following Professor Guo-Hua Liu, her current research direction is mitochondrial genomes of ectoparasites.

Xing-Quan Zhu obtained a Bachelor of Veterinary Science (BVSc) degree from the Sichuan Institute of Animal Sciences and Veterinary Medicine (now the Rongchang campus, Southwest University), and a Master of Veterinary Science (MVSc) degree from the Chinese Academy of Agricultural Sciences, China. He obtained his PhD and acquired postdoctoral training in molecular parasitology at the Department of Veterinary Science, The University of Melbourne between 1996-2001. He is currently the Head and Distinguished Professor of Parasitology at the Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, China. His current research integrates “multi-omics”, molecular and immunological approaches to study parasite biology and parasite-host interactions. His work has been recognized internationally through numerous scientific publications in well-regarded international journals including Lancet Infectious Diseases, Clinical Microbiology Reviews, Nature Communications, PLoS Pathogens, Trends in Parasitology, Infectious Diseases of Poverty, International Journal for Parasitology and Parasites & Vectors.

Jin-Lei Wang received a Bachelor of Veterinary Science (B.V.Sc.) degree from Shangdong Agricultural University, Taian, China, and a Ph.D. in parasitology from the Graduate School of Chinese Academy of Agricultural Sciences, Beijing, China. Dr. Wang is now a research scientist at the Department of Parasitology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China. He is interested in epidemiology, molecular phylogeny, and gene functions of parasitic protozoa as well as control strategies for parasitic infections in animals and humans.

Xue-Ling Zhang received a Bachelor of Veterinary Science (B.V.Sc.) degree from Hunan Agricultural University, Changsha, China, and a Master of Veterinary Science (M.V.Sc.) degree from Hunan Agricultural University, Changsha, China. She is a doctoral candidate in Jiangsu University of Science and Technology, majoring in parasitology in the College of Biotechnology. Her current research direction is epidemiology and metagenomics of parasites.

Shi-Chen Xie received a Master of Veterinary Science (M.V.Sc.) degree from Shihezi University, Shihezi, China, and a Ph.D. in parasitology from Hunan Agricultural University, Changsha, China. Dr. Xie is now undergoing postdoctoral training in molecular parasitology at the Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China. He is most interested in epidemiology, molecular phylogeny of parasitic protozoa and control parasitic infections in animals and humans.

Chaoqun Yao is a full professor of parasitology at Ross University School of Veterinary Medicine. He graduated with Bachelor followed by Master of Medicine from Huazhong University of Science and Technology. His PhD in Veterinary Parasitology was bestowed by University of Georgia. He held postdoctoral positions at Washington State University College of Veterinary Medicine and University of Iowa Carver College of Medicine. He was promoted to Assistant and Associate Research Scientist with a concomitant appointment of Research Health Science Specialist at Iowa City VA Medical Center. He then joined University of Wyoming as a tenure track Assistant Professor with concomitant appointments of Parasitology Lab Head, Wyoming State Veterinary Laboratory and Adjunct Assistant Professor, University of Washington. He is an associated editor for Frontiers in Cellular and Infection Microbiology – Parasite & Host, and editorial member of Veterinary Parasitology Reginal Studies and Reports and ad hoc reviewer for over one hundred journals.

Guo-Hua Liu received a Ph.D. in parasitology from Hunan Agricultural University, Changsha, China, and had his postdoctoral training in molecular parasitology at the Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, China. Dr. Liu is currently a Professor of Parasitology at the Department of Parasitology, College of Veterinary Medicine, Hunan Agricultural University, China. His current research interests focus on the genetics, genomics, transcriptomics, systematics, epidemiology, and control of parasitic infections. He was awarded the Odile Bain Memorial Prize in 2016. He has published over 150 original papers in well-regarded international journals. His research has been well supported by research grants from the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, and Hunan Agricultural University.

SUPPLEMENTAL MATERIAL

The following material is available online at https://doi.org/10.1128/cmr.00074-24.

Tables S1 and S2. cmr.00074-24-s0001.docx.

Table S1 (reported human cases of tick paralysis worldwide and the associated tick species) and Table S2 (summary of human tick paralysis cases by country).

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