Epidemiology

TBE is caused by tick-borne encephalitis virus, a member of the Flaviviridae family of viruses that can affect the nervous system.

The countries with areas most affected by TBE are:^[2]

• Austria, Germany, Sweden, France, Switzerland, Norway, Denmark, Poland, Croatia, Albania, the Baltic states (Estonia, Latvia and Lithuania), the Czech and Slovak Republics, Hungary, Russia (including Siberia), Ukraine, some other countries of the former Soviet Union, and northern and eastern regions of China.
• TBE is endemic across much of Central and Eastern Europe and the incidence is increasing, with numbers estimated to be as many as 8,755 cases per year.^[3]
• The Far Eastern type is endemic in areas of China and Japan.
• TBE has never been endemic in the UK.

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 rarely 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, ie 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 can be from 2 to 28 days (usually between 7 and 14 days) and is asymptomatic. Shorter incubation times have been reported after milk-related exposure. Only a small proportion of those infected develop clinical symptoms.^[4]

• A characteristic biphasic febrile illness follows, with an initial phase that lasts 2 to 4 days - the viraemic phase.
• It is nonspecific 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 20-30% 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.

Investigations

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

• 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.^[5]

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.
• Long-lasting or permanent neuropsychiatric complications can occur in around 10-20% of patients, following the European form.
• Complications are usually more severe and can be more frequent in the Far Eastern form.

Prognosis

• In general, mortality is around 1% for the European form and 5-20% for the Far Eastern version, with deaths occurring 5 to 7 days after the onset of neurological signs.^[6]
• People aged over 60 years are most at risk of death.

Prevention

• TBE can be prevented by using insect repellents and protective clothing to prevent tick bites.
• Unpasteurised milk should not be drunk in areas at risk.
• 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.
• Up to 10% of ticks may be infected.
• Inactivated vaccines are available in the UK for the protection of those individuals at high risk of exposure to the virus, through travel or employment. See separate article Tick-borne encephalitis vaccination for further detail.