Tick-borne Encephalitis

Tick-borne encephalitis (TBE) is a viral disease of the central nervous system transmitted through bites of certain vector ticks. It should be considered as a general term encompassing at least three syndromes caused by three subtypes of the tick-borne encephalitis virus, whose range spans an area from France and Scandinavia, across Europe (Central European tick-borne encephalitis), to far eastern Russia (Russian Spring-Summer Encephalitis).

TBE is considered to be the most relevant and dangerous viral zoonosis in North-east Europe, but also emerging in northern and central regions of the continent. Common ticks like the Castor Bean tick, Ixodes ricinus, and the Taiga tick, Ixodes persulcatus, are thought to be the main reservoir and vector of the pathogen.

Pathogens

Tick-borne encephalitis virus (TBEV, genus Flavivirus) causes tick-borne encephalitis (TBE), locally known as Russian spring-summer encephalitis (RSSE), Frühsommer-Meningoenzephalitis (FSME), Ryssjukan or Kumlingesjukan. Viruses of the genus Flavivirus form different antigenic complexes. The main complexes of medical importance are TBE (e.g. TBEV, Louping Ill virus, Powassan virus), dengue (dengue virus 1 to 4) and Japanese encephalitis (e.g. West Nile virus and others).

TBEV can be subtyped into at least three subtypes:

  • European subtype: mainly transmitted by Ixodes ricinus
  • Siberian subtype: mainly transmitted by Ixodes persulcatus
  • Far-Eastern subtype: mainly transmitted by Ixodes persulcatus

The subtypes can be distinguished by molecular means. They comprise different virulence patterns in humans and possibly also in animals.

The family Flaviviridae contains a number of viruses that are known to be transmitted by arthropods to warm-blooded animals during blood feeding. Replication of the virus in the arthropod vector is observed, which may lead to a more effective transmission to the host, as a constant and high virus titre can be reached in the arthropod. These viruses are commonly called ARBO viruses (arthropod-borne) in contrast to those, which are known to be transmitted only mechanically by arthropod vectors.

Epidemiology

Geographical distribution

The distribution of TBE is closely related to the activity of the tick vectors: The Castor Bean tick, Ixodes ricinus, in Western and Central Europe, and the Taiga tick, Ixodes persulcatus, in Central and Eastern Europe. (There is an overlap of the two species.)

The disease is endemic in Scandinavia, western and central Europe, and countries that made up the former Soviet Union. TBE is common in Austria, Estonia, Latvia, the Czech Republic, Slovakia, Germany, Hungary, Poland, Switzerland, Russia, Ukraine, Belarus, and northern regions of the former Yugoslavia. It occurs at a lower frequency in Bulgaria, Romania, Denmark, France, the Aland archipelago between Sweden and Finland and the neighbouring Finnish coastline, as well as along the coastline of Southern Sweden, from Uppsala to Karlshamn. Serologic evidence for TBE infection, as well as sporadic cases, have been reported from Albania, Greece, Northern Italy, Norway, and Turkey. The Russian spring-summer encephalitis is transmitted by I. persulcatus ticks and occurs in China, Korea, Japan, and Eastern and central areas of Russia. The Siberian and Far-eastern subtypes of TBEV were also detected in the European part of Russia including the Baltic countries.

 

Seasonal distribution 

The seasonal incidence of TBE is also closely related to the activity of the tick vectors. I. ricinus is most active in spring and autumn, with two peaks of activity: one in late March to early June, and one from August to October. I. persulcatus is usually active in spring and early summer. Apparently, I. persulcatus is more cold-hardy than I. ricinus, and thus inhabits harsher, more northern areas. Seasonal distribution may vary according to changes of temperature. Therefore, global warming due to climate change is considered to increase the transmission time during the year by shifting the activity start to earlier times.

 

Reservoirs and hosts

Main vector and reservoir for TBE virus in central and northern Europe is the widespread Castor Bean tick. In Eastern Europe and Asia it is the Taiga tick. Within the tick population, the virus is maintained in a transstadial fashion and possibly to a small extent via transovarial transmission to the next developmental stage of the tick’s life cycle. Small mammals (mainly rodents), on which larvae, nymphs and adults feed, become infected during the blood meals. Once infected, they serve as virus reservoirs, from which TBE virus is further transmitted in two ways (i) by virus uptake during viraemia of the rodent, or (ii) through co-feeding from infected to non-infected ticks feeding on the same host at the same time. Larger wild animals are considered to be not competent for virus transmission but serve as hosts and transporters for the ticks. Dogs have been screened serologically in potentially endemic regions as possible sentinels.

Transmission

Tick-borne encephalitis virus (TBEV) replicates in ticks leading to a constant and high virus titre in the arthropod. In contrast to bacterial and protozoal transmission, the virus enters the mammal host during the early tick feeding. TBEV, which is being accumulated in the tick salivary glands in the nymphal phase of development (Stefutkina, 1989), was detected in the first portion of the liquid saliva collected in the capillary from hungry Ixodid ticks (Chunikhin et al., 1988). Ixodid ticks (Ixodes and Dermacentor) infected parentally with the TBE virus at the adult and nymphal phase and containing the virus in the saliva, were furthermore able to transmit the agent in the first minutes after the bite of the sensitive animal host (Alekseev and Chunikhin, 1990).

Infection also can be acquired by consuming unpasteurized dairy products from infected cows, goats, or sheep.

Pathogenesis

The dominating pathological picture is that of a massive encephalitis while visceral organs are without gross lesions or histopathological findings. The meningoencephalitis is non-suppurative and is characterized by necrosis of neurons and glia cells. Almost the entire brain shows typical signs of inflammation.

Seropositivity for tick-borne encephalitis virus (TBEV) has been found in nature in many different wild and also domesticated animals, including dogs. However, the risk for a tick-infected dog to develop clinical manifest TBE is obviously rather small. However, the neuropathology of TBE in dogs is largely consistent with the neuropathology of TBE in humans.

A TBE virus infection evokes a life-long immunity. For the pathogenicity of the Siberian and Far-eastern TBEV subtypes in dogs no information is available.

TBE virus seems to be primarily pathogenic for humans. Human infection follows the bite of infected ticks, usually in people who visit or work in forests, fields, or pastures. The severity of disease, incidence of sequelae, and case-fatality rates are higher in the Far East and eastern regions of Russia than in western and central Europe. Out of the three virus subtypes the European subtype causes the mildest form of clinical disease in humans while the Far-eastern subtype exhibits the most severe form of clinical illness in humans.

Diagnosis

TBE diagnosis can only be verified by means of laboratory techniques. Definitive diagnosis of TBE is based on

  • isolation of the virus from blood or cerebrospinal fluid or from post mortem tissues;
  • serological tests for a significant titre increase of IgG or neutralising antibodies in paired sera;
  • demonstration of specific IgM in acute serum.

 

Polymerase chain reaction (PCR) can also be used to amplify viral RNA from blood or liquor samples or from post mortem brain tissues.

The suitability of different available serological and molecular test systems in canines has been an issue in Hekrlová et al. (2015) and Klaus et al. (2011). In these studies commercial TBE virus-ELISA kits proofed to be suitable for application in veterinary medicine for both, verification of clinical TBE cases and epidemiological screening. However, positive ELISA results should be verified by serum neutralization test.

Clinical Signs

 

Canine TBE

The incubation period for canine TBE in most cases is estimated between 7 and 14 days. Clinical canine TBE is a febrile illness with multifunctional neurological manifestations such as ataxia, uncoordinated movements, abnormal reflexes, convulsions, tremor, paresis, paralysis, and cranial nerve deficits such as facial paresis. The neurobiological signs are often progressive and TBE may lead to death. In detail Pfeffer and Dobler (2011) summarize the clinical signs as following: Common in the clinical course of TBE in dogs is the elevated body temperature (up to 41.4°C) and change in behaviour (denying food, increased aggressiveness, skittishness or apathia). All ill dogs showed motor failures either on the for hand or the rear legs with retarded proprioception and hyporeflexy in front and/or rear legs. More detailed clinical inspection with neurological examination reveals paresis, mostly tetraparesis, to generalized ataxia and tetraplegia, myoclonus, vestibular syndrome (strabismus), sensibility loss in the head area but cervical hyperalgesia, facial nerveparalysis, anisocoria, nystagmus, miosis or loss of eye lid closing reflex. These signs reflect the multifocal neurological disorder in the cerebrum and the brain stem. A single case description links TBE as possible cause of optic neuritis in a Siberian Husky (Stadtbäumer et al., 2004).

Leschnik et al. (2002) summarizes four different courses of TBE infection in dogs: Half of the seropositive dogs do not develop clinical signs. The peracute course leads to death within three to seven days. When the affected dog survives the first week, the prognosis becomes remarkably better. In an acute course of illness clinical signs improve after one to three weeks and disappear often without any sequelae. A chronic course has been described where affected dogs recover from their neurological deficits to a normal status within one to six months.

After natural infection, antibodies are detectable for more than 9 months in serum and for more than 2 months in cerebrospinal fluid.

The small numbers of clinical canine cases in Switzerland, Austria, Germany and Sweden prove that the risk for a TBE virus-infected dog to develop clinical manifest TBE is rather small.

 

Human TBE

The incubation period is between 3 and 28 days. The course of disease is often asymptomatic. An estimated 30% will exhibit clinical disease, mainly as a feverish flu-like disease. 10-15% of cases (increasing rate with age) will have neurological disorders with the most severe form of persisting paresis and psychiatric sequelae.

In central Europe, the typical case of encephalitis has a biphasic course, with an early, viremic, flu-like stage, followed about a week later by the appearance of signs of meningoencephalitis. CNS (central nervous system) disease is relatively mild, but occasional severe motor dysfunction and permanent disability occur. The case fatality rate is 1% to 5%.

Russian spring-summer encephalitis (sometimes referred to as the "Far Eastern form") normally does not show a biphasic course but is characterized by massive headache, high fever, nausea, and vomiting. Delirium, coma, paralysis, and death may follow; the mortality rate is approximately 25% to 30%.

Treatment & Prevention

Since there is no chemotherapy or specific treatment available targeting the TBE virus itself, symptomatic or supportive treatment (e.g. maintenance of the water and electrolyte balances) is required. This lack of targeting treatment emphasizes the necessity of tick prophylaxis, here especially in form of repellent parasiticides.

In the case of diseased dogs emphasis has to be put on preventing secondary harm to the patient itself as well as the owner during convulsions and aggressive behaviour. For that reason, therapy should include resting as well as anticonvulsive and sedative medication (Pfeffer and Dobler, 2011). Especially in cases of long term disease physiotherapy provides high benefit and reduces occurrence of secondary symptoms like bacterial pneumonia, decubital skin lesions and muscular atrophy (Leschnik et al., 2002). Non-steroidal anti-inflammatory drugs (NSAIDs) are best used to combat the high fever, and antibiotics should be given to prevent secondary bacterial infections, in particular pneumonia (Kirtz et al., 2001). Most of the few dogs, that survived a clinical TBE needed between a half and one year to fully recover.

In Europe, there are currently two vaccines licensed for human use, including special formulations or vaccination schemes for infants and older patients (Pfeffer and Dobler, 2011). A continuous vaccination program with booster vaccinations is advisable if there is continued risk.

None of the two available human European vaccines has been licensed for any animal use including dogs. However, both vaccines have been successfully used to vaccinate various animal species (e.g. sheep, goat, roe deer, dogs) without any adverse effect. Results indicate that these vaccines can be used in dogs, but comprehensive studies on the safety and efficacy of the existing human vaccines in dogs are warranted in order to have alternative prevention measures at hand when they are needed (Pfeffer and Dobler, 2011).

In contrast to bacterial and protozoal transmission, the virus enters the mammal host during the early tick feeding. Therefore, for prevention of pathogen transmission repellent parasiticides may be the right choice to minimize attachment and subsequent feeding of the tick vector.

References

Transmission

Alekseev AN, Chunikhin SP: [The experimental transmission of the tick-borne encephalitis virus by ixodid ticks (the mechanisms, time periods, species and sex differences)]. Parazitologiia. 1990, 24, 177-85

Chunikhin SP, Alekseev AN, Reshetnikov IA: [Determination of the titre of tickborne encephalitis virus in the saliva of unfed Ixodidae.] Med Parazitol Parazit Bolezni (Moscow). 1988, 3, 89-90

Stefutkina LF: [Morphological and virological particularities of ixodid ticks cell and tissues infection caused by tick-borne encephalitis virus.] 1989, PhD thesis, Inst. Poliomyelit. Viral Encephal., Moscow

 

Diagnosis

Hekrlová A, Kubíček O, Lány P, et al.: Tick-borne encephalitis in dogs: application of "nested real-time RT-PCR" for intravital virus detection. Berl Munch Tierarztl Wochenschr. 2015, 128, 397-401

Klaus C, Beer M, Saier R, et al.: Evaluation of serological tests for detecting tick-borne encephalitis virus (TBEV) antibodies in animals. Berl Munch Tierarztl Wochenschr. 2011, 124, 443-9

 

Clinical Signs

Leschnik MW, Kirtz GC, Thalhammer JG. Tick-borne encephalitis (TBE) in dogs. Int J Med Microbiol. 2002, 291 (Suppl 33), 66-9

Pfeffer M, Dobler G. Tick-borne encephalitis virus in dogs – is this an issue? Parasit Vectors. 2011, 4, 59

Stadtbäumer K, Leschnik MW, Nell B: Tick-borne encephalitis as a possible cause of optic neuritis in a dog. Vet Ophthalmol. 2004, 7, 271-7

 

Treatment & Prevention

Kirtz G, Leschnik M, Leidinger E: [Ixodes ricinus: dangerous for dogs!] Kleintierpraxis. 2001, 46, 151-60, [in German]

Leschnik MW, Kirtz GC, Thalhammer JG. Tick-borne encephalitis (TBE) in dogs. Int J Med Microbiol. 2002, 291 (Suppl 33), 66-9

Pfeffer M, Dobler G. Tick-borne encephalitis virus in dogs – is this an issue? Parasit Vectors. 2011, 4, 59

Further Reading

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