What viral infections can be transmitted by a tick bite and how should they be evaluated and managed?

Viral Infections from Tick Bites

While ticks primarily transmit bacterial pathogens in most clinical scenarios, tick-borne encephalitis virus (TBEV) represents the most clinically significant viral infection transmitted by ticks, particularly in Europe and Asia, causing potentially severe neurological disease with mortality rates around 1% and requiring supportive care as no specific antiviral treatment exists. 1, 2

Major Tick-Borne Viral Pathogens

Tick-Borne Encephalitis Virus (TBEV)

• TBEV is the most common arbovirus transmitted by ticks in Europe, affecting 10,000-15,000 patients annually across at least 27 European and Asian countries, with reported incidence rising from 0.4 to 0.9 cases per 100,000 people between 2015 and 2020. 1, 2
• The Baltic and Central European countries have the highest incidence, though the geographic range is expanding due to climate change and environmental factors. 1, 3
• Five confirmed cases of TBE have been documented in U.S. travelers to Europe, Russia, and China between 2000-2009, indicating risk for travelers from non-endemic areas. 4

Other Tick-Borne Viruses in Europe

• Omsk hemorrhagic fever virus, louping ill virus, Powassan virus (which cross-reacts serologically with TBEV), Crimean-Congo hemorrhagic fever virus (Nairovirus), and Eyach virus (Coltivirus) can all be transmitted by ticks. 5
• These viruses cause neurological diseases and some produce hemorrhagic fever, with several classified as Biosafety Level 3 or 4 agents. 5

Powassan Virus

• Powassan virus is a rare cause of encephalitis in North America and Russia that is closely related to TBEV and cross-reacts in serologic tests, complicating diagnosis. 4
• The deer tick (Ixodes scapularis) can transmit Powassan virus (lineage II, also called deer tick virus) in addition to bacterial pathogens like Borrelia burgdorferi and Anaplasma phagocytophilum. 6

Clinical Presentation of TBEV

Biphasic Disease Course (Classic Presentation)

• After a short incubation period of 6-10 days, the initial viremic phase presents with non-specific influenza-like symptoms including fever, headache, myalgia, and malaise. 1, 2
• Following an asymptomatic interval of 2-7 days, more than half of patients progress to a neurological phase with central nervous system involvement (encephalitis, meningitis, or meningoencephalitis). 2, 4
• All four U.S. travelers to Europe/Russia with confirmed TBE demonstrated this characteristic biphasic pattern and made nearly complete recoveries. 4

Monophasic Severe Disease

• Some patients, particularly those infected with certain viral subtypes, present with monophasic illness characterized by severe encephalitis without the initial mild phase. 4
• The first reported U.S. traveler with TBE acquired in China had monophasic severe encephalitis with significant neurologic sequelae. 4

Long-Term Sequelae

• Mortality is approximately 1% of confirmed cases, varying by viral subtype. 2
• After acute TBE, a minority develop permanent neurological deficits. 2
• 40-50% of patients develop post-encephalitic syndrome that significantly impairs daily activities and quality of life, even after apparent recovery from acute illness. 2

Diagnostic Approach

When to Suspect Tick-Borne Viral Infection

• Consider TBE in any patient with meningitis or encephalitis who has traveled to endemic areas of Europe, Asia, or Russia, particularly during tick season (spring through fall). 4
• History of tick bite is important but not always present, as transmission can rarely occur through consumption of unpasteurized milk from infected animals or aerosols. 2
• Look for the characteristic biphasic illness pattern: initial flu-like symptoms, brief improvement, then neurological deterioration. 2, 4

Laboratory Confirmation

• Detection of TBEV or Powassan virus IgM antibodies in serum or cerebrospinal fluid is the primary diagnostic method. 4
• Plaque-reduction neutralization tests against both TBEV and Powassan virus are required for confirmation due to serologic cross-reactivity between these closely related flaviviruses. 4
• Send specimens to CDC or specialized reference laboratories, as these are Biosafety Level 3/4 pathogens requiring specific handling precautions. 5
• PCR detection of viral RNA may be possible during the early viremic phase but is often negative by the time neurological symptoms develop. 1

Critical Pitfall

• Do not exclude TBE based on negative acute-phase serology alone—IgM antibodies may not be detectable until the neurological phase of illness. 1

Management

Treatment Approach

• No specific antiviral therapy exists for TBEV infection; treatment is entirely supportive and symptomatic. 1, 2
• Hospitalize patients with neurological manifestations for supportive care including management of increased intracranial pressure, seizures, and respiratory support if needed. 2
• Unlike bacterial tick-borne diseases, doxycycline and other antibiotics have no role in treating viral tick-borne infections. 6

Prevention Strategies

• Active immunization with TBE vaccine is highly effective and should be recommended for individuals living in or traveling to endemic areas, especially those with occupational or recreational tick exposure. 1
• Counsel travelers about measures to reduce tick exposure: wearing protective clothing, using DEET-containing repellents, performing tick checks, and avoiding unpasteurized dairy products in endemic regions. 4
• Prompt tick removal within 24 hours significantly reduces transmission risk for most tick-borne pathogens. 6

Distinguishing Viral from Bacterial Tick-Borne Disease

Key Clinical Differences

• Bacterial tick-borne diseases (Lyme disease, anaplasmosis, ehrlichiosis, rickettsioses) typically respond dramatically to doxycycline within 24-48 hours. 6
• If a patient with suspected tick-borne illness fails to improve on appropriate antibiotic therapy, strongly consider viral etiology (particularly TBE in endemic areas) or alternative diagnoses. 6
• The biphasic pattern with initial improvement followed by neurological deterioration is characteristic of TBE and not typical of bacterial tick-borne diseases. 2, 4

Geographic Considerations

• In North America, bacterial tick-borne diseases (RMSF, anaplasmosis, ehrlichiosis, Lyme disease) are far more common than viral infections. 6
• In Europe and Asia, both bacterial and viral (particularly TBEV) tick-borne diseases must be considered in the differential diagnosis. 6, 1, 2
• Travel history is essential—TBE should be high on the differential for travelers returning from endemic European or Asian regions with encephalitis. 4

Laboratory Clues

• Leukopenia, thrombocytopenia, and elevated hepatic transaminases suggest bacterial rickettsioses or anaplasmosis rather than viral encephalitis. 6
• Cerebrospinal fluid pleocytosis with lymphocytic predominance during the neurological phase supports viral meningoencephalitis. 2

Coinfection Considerations

• The same tick species (Ixodes scapularis in North America) can transmit multiple pathogens including bacteria (Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti) and viruses (Powassan/deer tick virus). 6
• Coinfections occur in <10% of cases but can complicate diagnosis and treatment. 6
• If treating presumed Lyme disease with beta-lactam antibiotics and symptoms persist, consider coinfection with Anaplasma (requiring doxycycline) or viral pathogens. 6