Epidemiology

TBE is caused by tick-borne encephalitis virus, a member of the family Flaviviridae.

The countries with areas most affected by TBE are³:
Austria, Hungary, Slovenia,⁴ Belarus, Latvia, Croatia, Lithuania, Czech Republic, Poland, Estonia, Russia, Germany, Slovakia and Ukraine.

Far Eastern type is endemic in areas of China and Japan.
Areas where sporadic cases have been reported include:
Albania, Bulgaria, Denmark (Bornholm Island), SW coast of Finland,⁵ France, Greece, Italy,⁶ Norway,⁷ Romania, Serbia, Southern Sweden⁸ and Switzerland.

The annual incidence varies, but several thousand cases are reported, despite under-reporting. Standardised case definitions need to be introduced, as true prevalence and incidence estimates are currently impossible. The Czech Republic reports 6-8/100,000 in people aged 25-65 years.⁹

Risk factors

In endemic areas people with recreational or occupational exposure to rural or outdoor settings are potentially at risk:

• Farmers
• Hunters
• Campers
• Forest workers

Infection also may follow consumption of raw milk from goats, sheep or cows.

Pathogenesis

• Ticks act as both the vector and reservoir for TBE virus.
• The main hosts are small rodents, with humans being accidental hosts.
• TBE cases occur during the highest period of tick activity i.e. between April and November. Sometimes in warmer southern areas, this period may be extended.
• Person-to-person transmission has not been reported.

Presentation

The incubation period of TBE is usually between 7 and 14 days and is asymptomatic. Shorter incubation times have been reported after milk-related exposure.

• A characteristic biphasic febrile illness follows, with an initial phase that lasts 2 to 4 days - the viraemic phase.
• It is non-specific with symptoms that may include:
  • Fever
  • Malaise
  • Anorexia
  • Muscle aches
  • Headache
  • Nausea and/or vomiting
• After 8 days of remission the second phase of the disease occurs in 20 to 30% of patients and involves the central nervous system with symptoms of meningitis or encephalitis or meningoencephalitis.

The course of infection with the Far-Eastern variety clinically differs from the European form:

• The onset of illness is more often gradual than acute, with a prodromal phase including fever, headache, anorexia, nausea, vomiting and
• photophobia.
• These symptoms are followed by a stiff neck, sensory changes, visual disturbances and other neurological deficits.
• In fatal cases death occurs within the first week after onset.

The case-fatality rate is approximately 20% (compared to 1-2% for the European form) but this may be due to bias against the different standards of treatment in Western and Eastern Europe.²

Investigations

During the first phase of the disease the most common laboratory abnormalities are:

• Leukopenia
• Thrombocytopenia
• Liver enzymes in the serum may also be mildly elevated
• Virus can be isolated from the blood

After the onset of neurological disease during the second phase:

• Increased white blood cells in the blood and the cerebrospinal fluid (CSF)

Diagnosis usually depends on detection of specific IgM in either blood or CSF, usually appearing during the second phase of the disease.

Management

There is no specific drug therapy for TBE.

• If bitten by a tick medical advice should be sought locally, as specific immunoglobulin may be available and advised within 48 hours. However its efficacy has been questioned. (Immunoglobulin is unlicensed in the UK but can be obtained on a named doctor/named patient basis where it is believed to be beneficial.)
• Meningitis, encephalitis or meningoencephalitis require hospital supportive care based on syndrome severity.
• Anti-inflammatory drugs such as corticosteroids, may be considered under specific circumstances for symptomatic relief.
• Intubation and ventilatory support may be necessary.¹

Complications

• Only the early phase is seen in approximately 66% of patients.
• The remaining third of patients experience either the typical biphasic course of the disease or a clinical illness that begins with the neurological symptoms.
• The recovery can be long and the incidence of sequelae may vary between 30 and 60%, with long-term or even permanent neurological symptoms. ²

Prognosis

TBE is rarely fatal. In general mortality is 1% to 5%, with deaths occurring 5 to 7 days after the onset of neurological signs.²

Prevention

• TBE can be prevented by using insect repellents and protective clothing to prevent tick bites.
  • Those in tick areas should check their skin for attached ticks, which is easier to do with a partner. However, early removal of ticks does not prevent disease.
  • Ticks should be removed as soon as possible with tweezers (or fingers covered by tissue paper if no tweezers are available) as close to the skin attachment as possible, by steady pulling without jerking or twisting.
  • Only one to two per cent of ticks are likely to be infected, although up to ten per cent may be.
• Inactivated vaccines are available in the UK for those considered at risk.¹⁰ See Tick-borne Encephalitis Vaccination record for further detail.

Document references

1. Lindquist L, Vapalahti O; Tick-borne encephalitis. Lancet. 2008 May 31;371(9627):1861-71. [abstract]
2. Tick-Borne Encephalitis. Monograph. Baxter.
3. CDC; Tick-borne Encephalitis. August 2005.
4. Jereb M, Karner P, Muzlovic I, et al; Severe tick-borne encephalitis in Slovenia in the years 2001-2005: time for a mass vaccination campaign? Wien Klin Wochenschr. 2006 Dec;118(23-24):765-8. [abstract]
5. Jaaskelainen AE, Tikkakoski T, Uzcategui NY, et al; Siberian subtype tickborne encephalitis virus, Finland. Emerg Infect Dis. 2006 Oct;12(10):1568-71. [abstract]
6. Beltrame A, Ruscio M, Cruciatti B, et al; Tickborne encephalitis virus, northeastern Italy. Emerg Infect Dis. 2006 Oct;12(10):1617-9.
7. Skarpaas T, Golovljova I, Vene S, et al; Tickborne encephalitis virus, Norway and Denmark. Emerg Infect Dis. 2006 Jul;12(7):1136-8. [abstract]
8. Johan F, Asa L, Rolf A, et al; Tick-borne encephalitis (TBE) in Skane, southern Sweden: A new TBE endemic region? Scand J Infect Dis. 2006;38(9):800-4. [abstract]
9. Kriz B, Benes C, Danielova V, et al; Socio-economic conditions and other anthropogenic factors influencing tick-borne encephalitis incidence in the Czech Republic. Int J Med Microbiol. 2004 Apr;293 Suppl 37:63-8. [abstract]
10. Health information for overseas travel 'Yellow Book'; Health Information for Overseas Travel 'Yellow Book', National Health Travel Network and Centre (NaTHNAC)

Internet and further reading

• National Travel Health Network and Centre

Acknowledgements