Alerts and Notices
SynopsisTick-borne encephalitis (TBE) is caused by 3 closely related tick-borne flaviviruses causing 3 subtypes of TBE: Far Eastern (formerly known as Russian spring-summer encephalitis), Siberian, and European (also known as Central European encephalitis). TBE was first described in Austria in 1931, but isolation of the TBE virus was reported in 1948. The Far Eastern subtype is endemic in eastern Russian, Korea, China, and Hokkaido Island, Japan. The Siberian subtype is found in western Siberia. The European subtype is widely distributed in countries in Europe and Scandinavia. Vectors responsible for transmission of TBE are different depending on the subtype and geographic distribution of Ixodes spp. Ixodes ricinus (European castor bean tick) is the vector for the European subtype, and Ixodes persulcatus (taiga tick) is the vector for the other 2 subtypes. Rodents, deer, and insectivores are the reservoirs for the TBE virus, while humans are accidental hosts.
Routine surveillance for tick-borne disease has discovered a patient with a febrile illness with an unknown cause in the Chinese town of Alongshan. The Alongshan virus (ALSV) has subsequently been confirmed.
Transmission of TBE occurs within minutes of a tick bite through the saliva of an infected tick. Thus, early removal of ticks does not have an impact on prevention of transmission of disease. Disease transmission occurs most frequently when the ticks are most active, in the spring and summer in temperate zones or in fall and winter in the Mediterranean. Ingestion of unpasteurized milk products from infected sheep and goats is a common source of TBE outbreaks.
The virus replicates at the site of inoculation, disseminates through the lymphatic system, and eventually reaches the central nervous system through the capillary endothelium. The incubation period is usually 7-10 days. Most patients (two-thirds) recall a tick bite. The clinical course may be monophasic or biphasic. Biphasic is the more common presentation, seen in up to 75% of cases:
- The first phase is characterized by flu-like symptoms, including fever, fatigue, malaise, headache, and myalgia. It usually lasts for 2-7 days, followed by a week of a symptom-free interval.
- The second phase usually presents with neurological manifestations that range from mild meningitis to severe encephalitis.
Laboratory findings include leukopenia, thrombocytopenia, and a slight increase of liver enzymes. Magnetic resonance imaging (MRI) findings of neuroinvasive disease of TBE are nonspecific: signal abnormalities located in the thalamus, caudate nucleus, and brain stem. Typical cerebrospinal fluid (CSF) findings are lymphocytic pleocytosis (usually <100 white blood cells [WBC]/mm3) and high protein level. Diagnosis is confirmed by the presence of serum or CSF virus-specific IgM, or a fourfold increase in virus-specific IgG in paired acute and convalescent sera.
Prognosis is poor for patients with meningoencephalomyelitis, resulting in death 5-7 days after the onset of neurological symptoms. In children, the disease usually presents as meningitis without encephalitis features and has a better prognosis than in adults. Far Eastern subtype infection, multiple tick bites, older age, severity of illness in the acute stage, low initial neutralizing antibody titers, and low early CSF IgM response are associated with more severe forms of the disease.
The case fatality rates with the Far Eastern subtype, the Siberian subtype, and the European subtype are 20%-40%, 2%-3%, and 1%-2%, respectively. Immunity following infection is lifelong; however, a postencephalitic syndrome characterized by chronic cognitive and neuropsychiatric impairments, balance disorders, dysphasia, and paresis occurs in up to 40%-60% of patients, especially with the Siberian subtype.
Powassan Virus Infection
Powassan virus (POWV) was first isolated in 1958. It belongs to the Flavivirus genus and is related to the TBE virus. It is a causative agent of encephalitis found in eastern Canada, as well as north central and northeastern United States. The vectors responsible for POWV include 4 tick species: Ixodes cookei, Ixodes marxi, Ixodes spinipalpis, and Dermacentor andersoni. Multiple mammals act as reservoirs for the virus. Transmission of infection usually occurs from June to September.
Asymptomatic infection is thought to be common. The incubation period is 8-34 days. Few patients recall a tick bite, unlike patients with TBE infection. Symptomatic patients present with fever, headache, nonspecific upper respiratory symptoms, and gastrointestinal complaints. If infection progresses to meningoencephalitis, confusion, seizures, and hemiplegia may ensue.
CSF analysis findings are similar to those seen in TBE. MRI of the brain may reveal abnormalities in the parietal and temporal lobes. Significant morbidity with residual neurological impairment occurs in most cases of meningoencephalitis following infection.
Diagnosis is made by measuring CSF or serum for POWV-specific IgM antibodies or detecting a fourfold rise of virus-specific IgG in paired acute and convalescent sera. The case fatality rate is estimated at 5%-10%.
Deer tick virus, also known as Powassan virus lineage II, has also been reported as a cause of encephalitis. It is a Flavivirus antigenically related to POWV, with 84% of its RNA sequence being identical to POWV. The main vector identified to date is Ixodes scapularis. Although the prevalence of adult deer ticks with the virus is high in the north central and northeastern United States, the first case of deer tick virus encephalitis in humans was reported only in 2009.
A84.9 – Tick-borne viral encephalitis, unspecified
414093008 – Encephalitis due to tick-borne encephalitis virus
Differential Diagnosis & Pitfalls
- Bacterial meningitis – Difficult to clinically distinguish from the meningeal form of TBE. CSF analysis in the early phase of TBE may be difficult to distinguish from bacterial meningitis if polymorphonuclear cells are predominant. Antimicrobial therapy must be given until this diagnosis is excluded.
- Lyme disease – Coinfection with TBE has been reported because the I. ricinus tick also carries Borrelia spp. responsible for Lyme disease in Europe. Serology may help distinguishing these entities, and treatment of Lyme disease may be initiated while awaiting diagnostic confirmation if clinical suspicion is high.
- Anaplasmosis – Coinfection with TBE has been described in certain endemic areas in Europe because I. ricinus transmits Anaplasma phagocytophilum. Laboratory findings on biochemistry, peripheral smear, and serology may aid in the differential. Empiric treatment with doxycycline if there is a high index of clinical suspicion.
- Poliomyelitis – Presents with ascending paralysis that progresses over days to months. Ataxia is absent.
- Tick-borne relapsing fever – High fever (>39°C [102.2°F]) in relapsing episodes that last 1-3 days. This may also present with neurological manifestations including cranial nerve palsies and meningitis but is usually associated with splenomegaly and hepatomegaly.
- Herpes simplex virus (HSV) encephalitis – Brain MRI usually shows abnormal findings in the temporal lobes. HSV polymerase chain reaction (PCR) in CSF can be diagnostic. Effective antiviral therapy for HSV is available.
- Leptospiral meningitis (see bacterial meningitis, see leptospirosis) – May cause aseptic meningitis. Leptospirosis PCR in CSF is available. Antimicrobial therapy is available.
- Tuberculous meningitis (see bacterial meningitis, see tuberculosis) – Diagnosis is important because treatment must not be delayed. Mycobacterium tuberculosis complex PCR in CSF and CSF acid-fast bacillus (AFB) culture may help in diagnosis.