Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 32-03: Other Neurotrophic Viruses + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Flaviviral encephalitis found in Eastern, Central, and occasionally Northern Europe and Asia Transmitted via ticks or ingestion of unpasteurized milk Long-term neurologic sequelae occur in 2–25% of cases +++ General Considerations ++ Occurs predominantly in the late spring through fall Usually a consequence of exposure to infected ticks Unpasteurized milk from viremic livestock is also a recognized form of transmission Transmission by transplantation of solid organs is reported leading to fatal outcomes The principal reservoirs for tick-borne encephalitis (TBE) virus are ticks with small rodents as amplifying host; humans are an accidental host Incubation period for tick-borne exposures is 7–14 days but only 3–4 days for milk ingestion There are three subtypes European subtype, transmitted by I ricinus Siberian subtypes, transmitted by I persulcatus Far Eastern subtypes, transmitted by I persulcatus Powassan virus Only North American member of the tick-borne encephalitis Vector is several Ixodes species ticks Incubation period can range from 1 to 5 weeks Most reported cases are neuroinvasive Alkhurma hemorrhagic fever A flavivirus first uncovered in Jeddah, Saudi Arabia in 1995 Reemerging in the Middle East with occurrences in tourists to Egypt, Djibouti, and possibly India Its extent of geographic distribution is currently unknown +++ Demographics ++ Virus is endemic in certain parts of Europe and Asia The number of cases reported annually fluctuates significantly depending on surveillance, human activities, socioeconomic factors, ecology, and climate + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Most cases are subclinical Many cases resemble a flu-like syndrome with 2–10 days of fever (usually with malaise, headache, and myalgias) In some cases, the disease is biphasic where the initial flu-like period is followed by a 1- to 21-day symptom-free interval followed by a second phase with fevers and neurologic symptoms Neurologic manifestations range from febrile headache to aseptic meningitis and encephalitis with or without myelitis (preferentially of the cervical anterior horn) and spinal paralysis (usually flaccid) A myeloradiculitic form can also develop but is less common Peripheral facial palsies, sometimes bilateral, tend to occur infrequently late in the course of infection, usually after encephalitis and usually are associated with a favorable outcome within 30–90 days Mortality in TBE is usually a consequence of brain edema or bulbar involvement European subtype is usually milder with up to 2% mortality and 30% neuroinvasive disease Siberian subtype is associated with 3% mortality and chronic, progressive disease Far Eastern subtype is usually more severe with up to 40% mortality and higher likelihood of neurologic involvement All three subtypes are more severe among the elderly and usually less severe among children Coinfection with Borrelia burgdorferi (the agent of Lyme disease; transmitted by the same tick vector) may result in more severe disease +++ Differential Diagnosis ++ Other causes of aseptic meningitis such as enteroviral infections, poliomyelitis (no longer reported from Eastern Europe), herpes simplex encephalitis Tularemia, the rickettsial diseases, babesiosis, Lyme disease, and other flaviviral infections Coinfections are documented with Anaplasma, Babesia, and Borrelia + Diagnosis Download Section PDF Listen +++ +++ Laboratory Findings ++ No laboratory test can distinguish between the subtypes, although an enzyme immunoassay shows promise Leukocytosis and neutrophilia are common Hyponatremia is more commonly seen than with other viral encephalitides Abnormal cerebrospinal fluid findings include a pleocytosis that may persist for up to 4 months When neurologic symptoms develop, the TBE virus is typically no longer detectable in blood and CSF samples Virus detection by reverse transcriptase-polymerase chain reaction (RT-PCR) in ticks from TBE patients, if available, can help with the diagnosis TBE virus IgM and IgG are detected by enzyme-linked immunosorbent assay (ELISA) when neurologic symptoms occur Cross-reactivity with other flaviviruses or a vaccinated state may require confirmation by detection of TBE virus–specific antibodies by plaque-reduction neutralization tests +++ Imaging Studies ++ Neuroimaging shows hyperintense lesions in the thalamus, brainstem, basal ganglia, and cerebral atrophy + Treatment Download Section PDF Listen +++ ++ Therapy is largely supportive No specific antiviral treatment + Outcome Download Section PDF Listen +++ +++ Complications ++ The main sequela is paresis Other causes of long-term morbidity include Protracted cognitive dysfunction Persistent spinal nerve paralysis The postencephalitic syndrome occurs with both subtypes and is characterized by Headache Difficulties concentrating Balance disorders Dysphasia Hearing defects Chronic fatigue A progressive motor neuron disease and partial continuous epilepsy are complications seen with the Eastern subtype Long-standing psychiatric complications include Attention deficits Slowness of thought and learning impairment Depression Lability Mutism +++ Prevention ++ There is no available TBE vaccine in the United States There are four inactivated TBE virus vaccines for adults and children licensed in Europe and 1 available in China Vaccine is safe, effective, and should provide cross-protection against all three TBE virus subtypes The initial vaccination schedule requires two to three doses given over 6 or more months with boosters every 1–5 years Recent data support adding an extra booster vaccine dose for individuals aged 50 years and older Complications of vaccine include Neuritis Neuropathies of peripheral nerves (plexus neuropathy—paresis of lower limb muscles, polyradiculopathy) +++ Prognosis ++ The three subtypes of TPE have different prognoses European subtype is usually milder with up to 2% mortality and 30% neuroinvasive disease Siberian subtype is associated with 3% mortality and chronic, progressive disease Far Eastern subtype is usually more severe with up to 40% mortality and higher likelihood of neurologic involvement All three subtypes are more severe among elderly adults compared with children Coinfection with Borrelia burgdorferi (the agent of Lyme disease; transmitted by the same tick vector) may result in more severe disease Mortality is usually a consequence of brain edema or bulbar involvement + References Download Section PDF Listen +++ + +Fischer M et al. Tickborne encephalitis. In: Centers for Disease Control and Prevention. Chapter 3 (83): CDC Health Information for International Travel 2018. New York: Oxford University Press, 2018. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/tickborne-encephalitis + +Hansson KE et al. Tick-borne encephalitis (TBE) vaccine failures: a ten-year retrospective study supporting the rationale for adding an extra priming dose in individuals at age 50 years. Clin Infect Dis. 2020 Jan 2;70(2):245–51. [PubMed: 30843030] + +Krow-Lucal ER et al. Powassan virus disease in the United States, 2006–2016. Vector Borne Zoonotic Dis. 2018 Jun;18(6):286–90. [PubMed: 29652642] + +Kunze U et al. Report of the 21st Annual Meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE): TBE - record year 2018. Ticks Tick Borne Dis. 2020 Jan;11(1):101287. [PubMed: 31522919] + +Pichler A et al. Magnetic resonance imaging and clinical findings in adults with tick-borne encephalitis. J Neurol Sci. 2017 Apr;375:266–9. [PubMed: 28320144]