Tick Borne Encephalitis
Crystallographically determined structure of an envelope glycoprotein of the TBE virus. Reprinted from Rey, F.A., Heinz, F.X., Mandl, C., et al. The
envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution.
Tick-borne encephalitis (TBE) is caused by an RNA virus known, simply, as “tick-borne encephalitis virus,” or TBEV. The virus belongs to the genus Flavivirus, which contains several dozen human pathogens, including the causative agents of Yellow fever, dengue fever, West Nile encephalitis, Japanese encephalitis and Powassan fever. (The term “flavivirus” is Latin for “yellow virus”; Yellow fever was so named because of its propensity to turn its victims yellow with jaundice.) Flaviviruses are (mostly) spherical, symmetrical, linear and single stranded, and are transmitted to humans by the bite of infected arthropods, primarily mosquitoes and ticks.
The range of tick-borne encephalitis spans from Western Europe to East Asia. It is not endemic in the United States, although some of its mosquito-borne relatives, such as West Nile and St. Louis encephalitis, are. There are three subtypes of the disease: European, Siberian and Far Eastern. The European subtype is vectored by Ixodes ricinus, while the vector for the other two subtypes is Ixodes persulcatus. Transmission of the virus usually occurs within the first few minutes of the tick bite. In Europe, the countries with the highest number of cases in 2006 were Russia, Germany, Lithuania, Slovenia and Poland. Because I. ricinus is also the vector for Lyme disease in Europe, co-infection of TBEV and Borrelia burgdorferi can occur.
The morbidity associated with tick-borne encephalitis is considerable. The virus usually causes meningoencephalitis, sometimes in combination with myelitis, and about half of adults will contract a severe form of the disease. Disease severity correlates roughly with increasing age. Prospective and retrospective studies have shown that about a third of all patients will experience incomplete recovery, with neuropsychiatric symptoms figuring prominently in the sequelae. The overall fatality rate for TBE, however, is only about 1%.
Several effective vaccines exist for TBE, with protection rates estimated at 90-95%. However, full effectiveness requires three inoculations spread over one year, and periodic boosters are needed every several years, particularly in older people.
Signs and Symptoms
Map showing the range of Ixodes ricinus and Ixodes persulcatus, the vectors of tick-borne encephalitis. The border of known TBE endemicity is
defined by the red dotted line. Reprinted from Lindquist L and Vapalati O.
Tick-borne encepalitis. Lancet 2008;371:1861-71.
Symptoms of tick-borne encephalitis usually appear about one week after tick bite, but on rare occasions can be delayed by as much as a month. Manifestations in the initial phase of the illness are largely non-specific, with the primary symptoms being fever, headache, fatigue and malaise. This period, which usually lasts about five days, is then followed by a period of symptom quiescence that typically lasts around a week.
In the second stage of TBE, the manifestations are usually much more serious, ranging from mild meningitis to severe encephalitis, not infrequently with myelitis and, occasionally, spinal paralysis. Headache is typically severe, and tremors and ataxia are common. One-third of patents will experience altered consciousness and seizures can occur. The virus sometimes attacks the anterior horn of the cervical spinal cord, producing paralysis of the arms, shoulders and neck muscles. Respiratory muscles can also become paralyzed. Cranial neuritis also occurs, most commonly affecting ocular, facial, pharyngeal and vestibular nerves. The brainstem can also be involved in serious cases, often leading to circulatory failure. TBE also causes myeloradicular dysfunction characterized by pain in the back and limbs, attenuated reflexes and prominent sensory anomalies.
IgM and IgG antibodies to TBEV are usually present by the time that central nervous system involvement manifests in the second stage of TBE. The most commonly used serodiagnostic method is enzyme-linked immunosorbent assay (ELISA). Cross-reactivity with antibodies to other flaviviruses can occur. Cerebrospinal fluid can also be analyzed for antibodies to TBEV, but the development of these antibodies lags those in serum by several days. However, they will almost always be present by the 10th day of illness.
If TBE is suspected in an early case that precedes dramatic neurologic involvement, the virus can be detected in serum by polymerase chain reaction (PCR), before the development of antibodies.
Lumbar puncture of TBE patients usually shows a moderate pleocytosis and increased cerebrospinal fluid albumin. Brain MRI images reveal abnormalities in 15-20% of patients; the most commonly affected areas are the thalamus, cerebellum and brainstem. EEG will be abnormal in 75% of all patients. However, all of these findings are non-specific and the diagnosis of TBE cannot be based solely on them.
There is no specific treatment for tick-borne encephalitis; thus, clinical intervention is geared toward symptom amelioration and supportive treatment. One German study found that about 12% of patients required intensive care and 5% needed assisted ventilation.
No data exist to support the use of corticosteroids in TBE.
Centers for Disease Control & Prevention, 2009.
Lindquist L, et al. Lancet. 2008; 371(9627):1861-71.
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