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Human Ecephalitis from Ticks

http://www.who.int/biologicals/areas/vaccines/tick_encephalitis/en/
http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06vol32/acs-03/index-eng.php#ref
http://www.bada-uk.org/wordpress/?cat=10
http://en.wikipedia.org/wiki/Tick-borne_encephaliti
http://www.springerlink.com/content/87416312lh048954/

Quick Facts

The risk of TBE infection from a single bite has been estimated at between 1 in 200 and 1 in 1,000. Report a fever, rash or any other symptoms right away.
A vaccine is available in some disease endemic areas (though not currently in the United States);
The disease is incurable once manifest, but infection can be prevented by vaccination, and the virus can be inactivated, halting disease progression. In humans, the disease is lethal in approximately 1.2% of cases and leaves 15-20% of its survivors with permanent neurological damage.
There is an antiserum (antidote) available to the virus which causes tick-borne encephalitis. You may be given this antiserum if it is suspected that you have contracted the virus. http://www.patient.co.uk/showdoc/27000510/

What is tick-borne encephalitis?


	Tick image of Ixodes species

Tick-borne encephalitis, or TBE, is a human viral infectious disease involving the central nervous system. The disease is most often manifest as meningitis (inflammation of the membrane that surrounds the brain and spinal cord), encephalitis (inflammation of the brain), or meningoencephalitis (inflammation of both the brain and meninges). Although TBE is most commonly recognized as a neurologic disease, mild febrile illnesses can also occur. Long-lasting or permanent neuropsychiatric sequelae are observed in 10-20% of infected patients.


What causes tick-borne encephalitis?

TBE is caused by tick-borne encephalitis virus (TBEV), a member of the family Flaviviridae, that was initially isolated in 1937. A closely related virus in Far Eastern Eurasia, Russian spring-summer encephalitis virus (RSSEV), is responsible for a similar disease with a more severe clinical course.

How is TBEV spread, and how do humans become infected?

Ticks act as both the vector and reservoir for TBEV. The main hosts are small rodents, with humans being accidental hosts. Large animals are feeding hosts for the ticks, but do not play a role in maintenance of the virus. The virus can chronically infect ticks and is transmitted both transtadially (from larva to nymph to adult ticks) and transovarially (from adult female tick through eggs). TBE cases occur during the highest period of tick activity (between April and November), when humans are infected in rural areas through tick bites. Infection also may follow consumption of raw milk from goats, sheep, or cows. Laboratory infections were common before the use of vaccines and availability of biosafety precautions to prevent exposure to infectious aerosols. Person-to-person transmission has not been reported. Vertical transmission from an infected mother to fetus has occurred.

Where is the disease found?

TBE is an important infectious disease of in many parts of Europe, the former Soviet Union, and Asia, corresponding to the distribution of the ixodid tick reservoir. The annual number of cases (incidence) varies from year to year, but several thousand are reported annually, despite historical under-reporting of this disease.

What are the symptoms of TBE?

The incubation period of TBE is usually between 7 and 14 days and is asymptomatic. Shorter incubation times have been reported after milk-borne exposure. A characteristic biphasic febrile illness follows, with an initial phase that lasts 2 to 4 days and corresponds to the viremic phase. It is non-specific with symptoms that may include fever, malaise, anorexia, muscle aches, headache, nausea, and/or vomiting. After about 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 (e.g., fever, headache, and a stiff neck) or encephalitis (e.g., drowsiness, confusion, sensory disturbances, and/or motor abnormalities such as paralysis) or meningoencephalitis. In contrast to RSSE, TBE is more severe in adults than in children.

During the first phase of the disease, the most common laboratory abnormalities are a low white blood cell count (leukopenia) and a low platelet count (thrombocytopenia). Liver enzymes in the serum may also be mildly elevated. After the onset of neurologic disease during the second phase, an increase in the number of white blood cells in the blood and the cerebrospinal fluid (CSF) is usually found. Virus can be isolated from the blood during the first phase of the disease. Specific diagnosis usually depends on detection of specific IgM in either blood or CSF, usually appearing later, during the second phase of the disease.

Are there any complications after recovery?

In approximately two-thirds of patients infected with the TBE virus, only the early (viremic) phase is seen. In the remaining third, patients experience either the typical biphasic course of the disease or a clinical illness that begins with the second (neurologic) phase. The convalescent period can be long and the incidence of sequelae may vary between 30 and 60%, with long-term or even permanent neurologic symptoms. Neuropsychiatric sequelae have been report in 10-20% of patients.

Is the disease ever fatal?

Yes, but only rarely. In general, mortality is 1% to 2%, with deaths occurring 5 to 7 days after the onset of neurologic signs.

How is TBE treated?

There is no specific drug therapy for TBE. Meningitis, encephalitis, or meningoencephalitis require hospitalization and 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.

Who is at risk for TBEV infection?

In disease endemic areas, people with recreational or occupational exposure to rural or outdoor settings (e.g., hunters, campers, forest workers, farmers) are potentially at risk for infection by contact with the infected ticks. Furthermore, as tourism expands, travel to areas of endemicity broadens the definition of who is at risk for TBE infection.

How can TBEV infections be prevented?

Like other tick-borne infectious diseases, TBEV infection can be prevented by using insect repellents and protective clothing to prevent tick bites. A vaccine is available in some disease endemic areas (though not currently in the United States); however, adverse vaccine-reactions in children limit the utility of the product.

Other related viruses.

The family Flaviviridae includes other tick-borne viruses affecting humans and these viruses are closely related to TBEV and RSSEV, such as Omsk hemorrhagic fever virus in Siberia and Kyasanur Forest disease virus in India. Louping ill virus (United Kingdom) is a member of this family; it cases disease primarily in sheep, and has been reported as a cause of a TBE-like illness in laboratory workers and persons at risk for contact with sick sheep (e.g., veterinarians, butchers).

Suggested Reading

Dumpis, U., Crook, D., Oksi, J. Tick-borne encephalitis. Clinical Infectious Diseases. 1999; 28:882-890.

Haglund, M., Forsgren, M., Lindh, G., Lindquist, L. A 10-year follow-up study of tick-borne encephalitis in the Stockholm area and a review of the literature - Need for a vaccination strategy. Scandinavian Journal of Infectious Diseases. 1996; 28(3)217-224.

Kaiser, R., Holzmann, H. Laboratory findings in tick-borne encephalitis. Correlation with clinical outcome. Infection. 2000; 28(2)78-84.

Logar, M., Arnez, M., Kolbl, J., Avsic-Zupanc, T., Strle, F. Comparison of the epidemiological and clinical features of tick-borne encephalitis in children and adults. Infection. 2000; 28(2)74-77.

Mikiene, A., Laiskonis, A., Gunther, G., Vene, S., Lundkvist, A., Lindquist, L. Tick-borne encephalitis in an area of high endemicity in Lithuania: disease severity and long-term prognosis. Clinical Infectious Diseases. 2002; 35(6)650-658.

Resources

http://www.cdc.gov/ncidod/dvrd/Spb/mnpages/dispages/TBE.htm

Tick Borne Encephalitis Vaccine

Vaccination against TBE is considered to be the most effective means of preventing TBE for those living in endemic countries (9). The vaccine has been used in national vaccination campaigns in Austria since 1982 and has continued on an annual basis since. There is also widespread use of TBE vaccine in many other central European countries.

Vaccine should be considered for travellers to endemic areas (see indications below).

Vaccine Availability

The vaccines FSME-IMMUN and FSME-IMMUN Junior were re-named TicoVac and TicoVac Junior in December 2007. The vaccine itself is unchanged. Both these vaccines are now licensed in the UK.

Details of these vaccines can be found in the summary table below.

Indications for use of TBE vaccine

Tick borne encephalitis vaccine should be considered for:

All persons living in TBE-endemic areas
Those at occupational risk in endemic areas, e.g. farmers, forestry workers, soldiers
Travellers to rural endemic areas during late spring and summer e.g. campers, hikers, Scout / Guide groups

The optimum time to begin the course of vaccination against TBE is during the winter months in order to ensure protection prior to the start of the tick season in spring.

TicoVac is effective against the Far Eastern and Siberian subtypes as well as the European subtype of TBE (10).

Vaccine Schedules

The Summary of Product Characteristics (SmPC) for the individual vaccines should be consulted prior to the administration of any vaccine (available at www.emc.medicines.org.uk), together with the appropriate chapter in the Department of Health publication Immunisation against Infectious disease.

Vaccine	Manufacturer	Schedule	Rapid Schedule	Length of protection	Age range
TicoVac 0.5ml	Baxter Currently distributed by MASTA	3 doses on days 0, between 1 and 3 months later and then between 5 and 12 months after the second dose	2nd dose can be given 2 weeks after the 1st dose	*First booster no more than 3 years after 3rd dose. After this, boosters may be given at 3 - 5 year intervals if at risk	Persons at least 16 years of age
TicoVac 0.25ml Junior	Baxter Currently distributed by MASTA	3 doses on days 0, between 1 and 3 months later and then between 5 and 12 months after the second dose	2nd dose can be given 2 weeks after the 1st dose	First booster no more than 3 years after 3rd dose. After this, boosters may be given at 3 - 5 year intervals if at risk	Children above 1 year of age and below 16 years of age
FSME-IMMUN®	Baxter Corporation
Encepur®

*In those aged > 60 years, booster intervals should not exceed three years (see below).

Primary vaccination schedule

The primary course of TBE vaccine consists of three doses on days 0, between 1 and 3 months later, and then between 5 and 12 months after the second dose. If more rapid protection is required, two doses of vaccine can be administered a minimum of two weeks apart (11). In this case the 3rd dose should be administered 5 - 12 months after the second vaccination.

Booster doses of TBE vaccine

In those under the age of 60 years, the first booster dose of TBE vaccine should be given three years after the primary course. Further boosters should be administered at intervals of between 3 and 5 years.

Serologic studies indicate that the persistence of TBE immunity is compromised in the elderly and there is a more rapid decline of antibodies in those who received only three immunisations. The immune response following booster doses of vaccine is also of lower magnitude in the elderly compared to that in younger adults (12). Because of these findings, booster doses continue to be recommended every three years in adults > 60 years.

Immunogenicity

A seroconversion rate of 97% has been observed in adults between 21 and 35 days after the second dose of FSME-IMMUN. 100% of vaccinees seroconverted after the 3rd dose (13). Data for those having had the rapid schedule (i.e. two doses of TBE vaccine two weeks apart) indicate that 92% of subjects showed seropositive antibody levels by day 14 after the second dose of vaccine (14).

Children have also been shown to have a high seroconversion rate (96%) between 21 and 35 days after the second dose of vaccine and 100% seroconversion following the third dose of vaccine (11).

Contraindications

Current febrile illness
Allergies to constituents of the vaccine, including severe reactions to egg

Precautions

Persons with known or suspected auto immune disease
Persons with pre-existing cerebral disorders
Pregnancy
Lactation

Adverse Events

Adverse reactions following TBE vaccine are most commonly mild and transient. In adults they include local reactions such as swelling, redness and pain at the injection site. Generalised reactions such as fatigue, malaise, headache, muscle pain and nausea have been reported but were transient and mainly mild.

Studies in children reported mild local and systemic reactions. The most common local reactions reported were pain and tenderness at the injection site. The most frequently reported systemic reactions were fever and restlessness in young children, as well as headache in all children. Fever, particularly after the first dose, has been reported.

In rare cases there are more serious reactions, for example meningitis and neuritis.

References
http://www.nathnac.org/pro/factsheets/tick_borne.htm#Vaccine

6.3 Testing for antibodies after TBE vaccination

The EIA for IgG antibodies is a rapid and reliable test for TBE immunity. It is commonly used to assess immunity after an infection or vaccination²⁵. A comparison of six commercial IgG ELISA kits suggests that they have generally high sensitivity (73% to 99%)⁵⁹. However, there is extensive cross-reactivity with other flavivirus antibodies, such as West Nile fever, dengue, yellow fever, and Japanese encephalitis antibodies^25,60,61. These crossreactive antibodies do not neutralize TBEV and are not protective against TBE infections^60,61. Therefore, when interpreting positive EIA results, consideration must be given to possible crossreactivity with other flaviviruses. False-positive results can be minimized by taking a proper history of past flavivirus exposures and/or vaccinations. Alternatively, if available, a pre-vaccination EIA can establish a baseline, or a highly specific and sensitive neutralization test can be used^25,60,61. The neutralization test, which measures the presence of TBE-specific neutralizing antibodies, is only available in specialized laboratories (Dr. H. Peters Dade Behring, Marburg, Germany: personal communication, 2002). In the absence of prior exposure to other flaviviruses, IgG EIA results for TBE correlate well with the results of the neutralization test^25,61,62. According to Health Canada's Medical Devices Active Licence Listing (http://www.mdall.ca new window ), there are no TBE serologic tests currently licensed for sale in Canada.

Reference
http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06vol32/acs-03/index-eng.php#ref