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Tick-borne encephalitis

In 2012 alone, residents of the UK combined made 53.5 million visits abroad. Travel to Europe remained static while travel to long-haul destinations fell.1 Europe is the most visited region in the world and continues to see tourism growth, particularly Central and Eastern Europe, followed by Western Europe.2 The UK has a growing migrant population with increasing numbers of travellers visiting friends or relatives in their home country (VFRs). 

In the UK VFR travel is second only to holidays as the most common reason for travel, increasing by 2% in 2012.1 Destinations reflect the migrant's home country.3 Predictions for 2013 show that more people are likely to holiday in a mountain region and enjoy walking or activity holidays.4 Around 350,000 British nationals visited Poland in 2010, 730,000 visit Austria each year and two million visit Germany.5

UK travellers heading to Europe may not see the need for pre-travel advice - after all there's nothing 'tropical' about Europe. 

The European Centre for Disease Prevention and Control (ECDC) has been monitoring the changing epidemiology and geographic expansion of diseases in Europe, such as measles, malaria and West Nile Virus. ECDC recognises the importance of updating epidemiological surveillance and control of communicable disease, the need to reduce the burden of disease and develop vaccination recommendations for European Union (EU) citizens and travellers to endemic areas. Tick-borne encephalitis (TBE) was added to the list of notifiable diseases in the EU along with a new case definition.6 TBE occurs in endemic areas across large regions of Europe and Asia. Monitoring systems already exist in many EU and European Free Trade Association (EFTA) countries, but surveillance varies. 

The vector

Ticks are small arachnids and an important disease vector globally, second only to mosquitoes.7 Ticks have attracted more attention recently as tick-borne diseases are increasingly reported across Europe, perhaps because of increased surveillance, but environmental conditions, increasing travel and human activity in areas where ticks thrive may also have led to increasing exposure.7 In the UK there are 20 species of ticks.7 

Ticks don't normally feed for 12-24 hours after attaching themselves, during which time infection risk is small.8 But TBEV is transmitted within minutes from the bite of an infected tick.9 Ticks are tiny and migrate to warm moist areas to feed, such as the groin, axillae or behind ears, so these vulnerable areas should be inspected carefully.8 Having a 'tick buddy' to check for any attached ticks and removing them immediately, especially after activities in wooded areas, can save lives. 

Tick-borne encephalitis virus (TBEV) is not found in the UK but tick-borne Louping-ill (LI), a related viral infection of the central nervous system (CNS) and the only known flavivirus in the UK, exists. LI is associated with sheep, as is TBE, but can infect other domestic animals, wild animals, wild birds (eg. grouse) and occasionally humans.10

Ticks can transmit TBEV through their three lifecycle stages, each of which requires a blood meal. Once infected ticks carry the virus for life.11

Stage 1: tick larvae, hatch on the ground in shady areas and become infected through feeding on small mammals.

Stage 2: at the nymph stage ticks climb up blades of grass or shrubbery and seek a host for their blood meal. 

Stage 3: as adults, the female seeks a blood meal to reproduce and once engorged falls from the host and lays her eggs in loose soil before dying. Some infected female ticks transmit the virus to the eggs or through co-feeding.7,12

Epidemiology 

The TBEV is an important cause of CNS viral infections in eastern, central, and northern European countries, in northern China, Mongolia, and the Russian Federation.12 TBE is caused by three different subtypes of TBEV:

Western (Central European encephalitis) mainly in forested areas of central and eastern Europe.

Far Eastern (Russian spring/summer encephalitis) in the former USSR, east of the Ural Mountains and in parts of China.

Siberian subtype in eastern Russia.11 

Transmission

TBEV is transmitted through bites from infected hard ticks. Ixodes ricinus (castor-bean tick) is the main vector in central, northern and eastern regions and Ixodes persulcatus in parts of the Baltic States, Finland, and Russia. The transmission cycle is maintained in reservoir hosts, mainly small rodents.6,12 Tick saliva contains an anaesthetic so the victim is usually unaware of the bite.11 

Infected ticks are found in forested grassland and wooded areas, popular with hikers, cyclists and campers, but more rarely are they found at altitude.11 Ticks mostly live on the ground, lurking under foliage, using olfactory senses to detect passing victims and awaiting the opportunity to drop on to clothing or skin.11 Rarely, infected cows, goats or sheep pass on the virus in unpasteurised milk or milk products.12

All age groups can be affected and males are affected more frequently,12 perhaps because of related outdoor activities. Person-to-person transmission has not been described.12

Climatic conditions are important with ticks becoming active around temperatures of >8*C and in humid environments.13 Mild winters and humid springs increase tick activity. Transmission seasons vary depending on the region, with Eastern subtype more common in spring and Western subtypes in autumn.11 Seasonal risk is usually from April to November but can begin in February.14

The disease

TBE is a viral infection caused by a Flavivirus of the Flaviviridae family which includes dengue fever, yellow fever, Japanese encephalitis and West Nile viruses. TBE is usually recognised as a meningo-encephalitis but can also cause mild febrile illness.15

The disease is biphasic with an incubation period of 7-14 days. 

First phase: non-specific flu-like symptoms (viraemic phase) affects two thirds of those infected and lasts one to eight days.

Asymptomatic period of one to 20 days

Second phase: There is sudden fever and CNS involvement (meningitis). One third will progress to encephalitis and maybe paralysis.12 In lethal cases, death occurs within five to seven days of onset of neurologic signs.16

In children, the second phase is usually limited to meningitis. Disease severity increases with age with a higher risk of paralysis and permanent sequelae in those over 40 years, and higher mortality rates in those over 60 years. Far Eastern subtype is more virulent with 5-20% fatality compared to 1-2% in European subtype. There is no specific treatment, only supportive care which may include intensive care.9,11At present TBE is not notifiable in the UK.15

Risk to travellers

Globally approximately 10,000 to 12,000 cases of TBE are reported annually, although this is probably an underestimate.12 Across Europe and Asia, TBEV causes thousands of cases of neuroinvasive illness and is a growing public health concern even though it is vaccine preventable. The true burden isn't clear, although TBE commands high healthcare costs for hospitalisation and the effects of long-lasting sequelae in those infected.6 Four cases involving UK travellers have been recorded by PHE recently, two following visits to Sweden and Latvia, and one to Estonia, Latvia and Lithuania in 2012, and one in 2011 in someone returning from the Czech Republic.17 The traveller's risk of TBE infection varies in the different endemic areas but increases due to:

  • Lack of awareness.
  • Travelling to countries where TBE is transmitted.
  • Undertaking outdoor activities in endemic areas.
  • Season of travel.
  • Length of stay.

Prevention

Eliminating the disease through chemical means has been unsuccessful and insecticide-impregnated clothing or repellents offer limited protection. Personal protection measures when outdoors in endemic areas can reduce the risk.12

Wear clothing or camping/cycling kit with long sleeves and long trousers (tucked into socks), treated with insecticide sprays containing permethrin.

Wear light colours to make ticks easier to spot.

Apply insect repellent containing DEET to exposed skin.

Appoint a “tick buddy” to check skin regularly and remove attached ticks.

Be particular about checking skin folds at the end of the day.

Check that pets and clothing don't carry unfed ticks home.

Remove ticks as soon as possible using tweezers or a tick remover (see Box 1).

Don't consume unpasteurised dairy products in TBE endemic areas.

Consider vaccination when planning to visit, live or work in affected areas.

TBE Vaccination15

Vaccination provides effective protection for those at risk. A risk assessment for the individual traveller will identify the potential risk of exposure and vaccine recommendation.18 TBE vaccine should be considered for travellers who are:

Planning to pursue outdoor activities in endemic areas during spring, summer and autumn months, eg. campers, hikers, cyclists.

Going to visit friends or relatives or to live in endemic areas.

At occupational risk, eg. farmers, forestry workers, the military.

The Green Book gives indications for vaccination.15 The Summary of Product Characteristics (SPC) should be consulted before administration.19a,b The Patient Information Leaflet (PIL) should be given to the vaccine recipient.18 TBE vaccine is not an NHS provision and incurs a cost to the traveller.20 In the UK, two licensed TBE vaccines are available. TicoVac® vaccines are whole virus inactivated vaccines containing the Neudörfl virus strain, presented in a pre-filled syringe for intramuscular injection and effective against the Far Eastern and Siberian subtypes, and the European subtype.19a,b

Vaccine schedules

Ideally the first two doses should be given during winter ahead of the tick season. However, if time is limited, a good antibody response is obtained after two doses giving short-term protection. Travellers should be reminded of the importance of completing the course. The third dose is especially important for older travellers, regular travellers or those living or working in risk areas.21As the immune response in older travellers is lower, boosters are recommended every three years in adults >60 years.21 

TBE is endemic in Austria where a universal, annual, national vaccination campaign began in 1980.15 Pre-campaign, hospitalised TBE cases ranged from 300 to 700 annually. With vaccination coverage now 85-90% cases have fallen to 50 to 100.22 TBE vaccine is widely used in other central European countries.15

 

Conclusion

The epidemiology of diseases in Europe is changing. New surveillance systems are being implemented to monitor the situation. ECDC is calling for universal recommendations on TBE vaccination, while the European Commission has added TBE to the list of notifiable diseases in all EU countries. 

Europe is the most visited region in the world and popular with UK travellers. Increased migration has led to greater numbers returning to their home country, especially to eastern and central Europe, to visit friends and relatives. These travellers are likely to stay longer in endemic areas thus increasing exposure to disease but they often fail to seek advice before travelling. TBE is vaccine-preventable, with vaccination shown to reduce the incidence of disease, but travellers to endemic areas need to be made aware of their risks, how to prevent and minimise them and report illness on return. Activity holidays are set to rise in popularity. For travellers in all age groups planning outdoor activities in TBE-endemic areas, personal protection measures including vaccination should be discussed.

 

REFERENCES

1. Office for National Statistics. Overseas Travel and Tourism, Trends in visits abroad by UK Residents. 2013. Available at:

www.ons.gov.uk/ons/rel/ott/overseas-travel-and-tourism---monthly-release...

2. World Tourism Organization (UNTWO) Press Release. 28 January 2013. Available at: http://media.unwto.org/en/press-release/2013-01-28/international-tourism....

3. Public Health England (PHE). Migrant Health Guide. Travel to visit friends and relatives.

Available at: www.hpa.org.uk/web/HPAweb&Page&MigrantHealthAutoList/Page/1281954639016.

4. ABTA The Travel Association. Travel Trends Report 2013. Available at:

www.abta.com.

5. Foreign & Commonwealth Office (FCO). Travel & Living Abroad.

www.fco.gov.uk/en/travel-and-living-abroad/travel-advice-by-country/europe.

6. Amato-Gauci AJ, Zeller H. Tick-borne encephalitis joins the diseases under surveillance in the European Union. Euro Surveill 2012;17(42):pii=20299. 

Available at: www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20299.

7. Public Health England, PHE London; Ticks.

Available at: www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Ticks. 

8. Travax, Health Protection Scotland: Insect Bite Avoidance, Ticks

Available at: www.travax.scot.nhs.uk/health-information/general-health-advice/insect-b...

9. Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet 2008;371:1861-71. 

10. Public Health England, PHE London; Louping Ill.

Available at: www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/LoupingIll/General...

11. The National Travel Health Network and Centre. Health Information Sheet; Tick-borne encephalitis. Updated March 2012.

Available at: www.nathnac.org/pro/factsheets/tick_borne.htm

12. World Health Organization. Vaccines against tick-borne encephalitis: WHO position paper. Wkly Epidemiol Rec 2011;86:241-56. Available at: www.who.int/wer/2011/wer8624.pdf

13. International Society of Travel Medicine Expert Opinion Series Case 1 2012. Martin Haditsch - TBE Advice for Honeymooners travelling to southern Austria, Switzerland and Germany. 

Available at: www.istm.org/Documents/Members/MemberResources/Publications/Handouts/Exp...

14. Tick Alert. Available at: www.tickalert.org.

15. Department of Health. Immunisation against infectious disease - The Green Book. Chapter 31: Tick borne encephalitis. London: DH; 2006. Available at: www.gov.uk/government/uploads/system/uploads/attachment_data/file/148507...

16. Centers for Disease Control and Prevention (US). Tick Borne Encephalitis Fact Sheet. Available at:

www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/TBE.htm 

17. Public Health England (PHE) London; Topics A-Z, Tick-borne encephalitis.

www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/TickborneEncephalitis.

18. Chiodini J, Boyne L, Stillwell A, Grieve S. Travel health nursing: career and competence development, RCN guidance. RCN: London; 2012.

19a. SPC. Summary of Product Characteristics. TicoVac.

Available at: www.medicines.org.uk/EMC/medicine/20115/SPC/Ticovac+0.5ml.

19b. SPC. Summary of Product Characteristics. TicoVac Junior. Available at: www.medicines.org.uk/EMC/medicine/20116/SPC/Ticovac+0.25ml+Junior.

20. General Practitioners Committee. Focus on travel immunisations: guidance for GPs. London: BMA; 2012. Available at: www.bma.org.uk/images/focustravelimmunmar2012_tcm41-212255.pdf

21. Jílková E, Vejvalková P, Stiborová I, Skorkovský J, Král V. Serological response to tick-borne encephalitis (TBE) vaccination in the elderly - results from an observational study. Expert Opinion on Biological Therapy 2009;7:797-803. Available at:

www.tickalert.org/login/downloads/BSVA161LeadingOpinionJilkova.pdf

22. European Centre for Disease Prevention and Control. Epidemiological situation of tick-borne encephalitis in the European Union and European Free Trade Association countries. Stockholm: ECDC; 2012. Available at: http://ecdc.europa.eu/en/publications/Publications/TBE-in-EU-EFTA.pdf