• Number of patients with objective manifestations of Lyme borreliosis [ Time Frame: up to 12 months follow-up ]
  At each visit physical examination was performed and clinical signs indicating objective manifestations of Lyme borreliosis, such as erythema migrans, were searched for and documented.
• Frequency of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia [ Time Frame: up to 12 months follow-up ]
  At each visit patients were asked to report the presence of nonspecific symptoms.

In Europe, tick-borne encephalitis (TBE) virus causing TBE is transmitted by the bite of Ixodes ricinus tick, which can also transmit Lyme borreliae , the causative agent of Lyme borreliosis (LB). Since TBE and LB are both endemic with high incidence rates in Slovenia, we should be attentive to the possibility of double infections. Double infections with TBE virus and Lyme borreliae were reported to occur rarely even in endemic countries, however reliable data on coinfection rates are rather limited. Microbiological diagnosis of TBE virus infection is quite straightforward, and there is no specific therapy for TBE available so far. This markedly differs from borrelial infection, in which case interpretation of serological test results demands more caution, but there is highly efficient antibiotic treatment available for LB. This may lead to over prescribing of antibiotics to TBE patients with documented borrelial antibodies in serum indicating possible coinfection with Lyme borreliae, but missing clinical or microbiological criteria for proven borrelial coinfection. Approximately 10% of patients who had been treated appropriately for LB and about one third of patients after TBE report nonspecific subjective complaints, such as fatigue, headache, arthralgia, and myalgia, termed post-Lyme and post-encephalitic symptoms, respectively. These may not be differentiated clearly from nonspecific symptoms occurring with a rather substantial incidence also in the general population. A trend of ascribing medically unexplained nonspecific subjective symptoms to LB in subjects with positive borrelial antibodies in serum puzzles the situation further.

The aim of this prospective observational study was to assess the proportion and clinical implication of proven and possible coinfection with Lyme borreliae in patients with TBE, and to evaluate the association between anti-borrelial antibiotic therapy and clinical outcome in the subgroup of patients with possible coinfection.

• Tick Borne Encephalitis
• Lyme Disease

• Drug: Anti-borrelial antibiotic therapy
  Beside symptomatic therapy, patients received oral doxycycline 100 mg (Doxy®) twice daily or ceftriaxone 2 g (Lendacin®) once daily for 14 days. Antibiotic therapy was left to the discretion of treating physicians. Patients reported the presence of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.
• Other: No antibiotic.
  Patients who received symptomatic therapy (paracetamol, Lekadol®, granisetron, Kytril®, metamizol, Analgin®, parenteral hydration with saline). Patients reported the presence of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.

• Anti-borrelial antibiotic therapy
  Intervention: Drug: Anti-borrelial antibiotic therapy
• No antibiotics
  Patients who received symptomatic therapy (paracetamol, Lekadol®, granisetron, Kytril®, metamizol, Analgin®, parenteral hydration with saline). Patients reported the presence of nonspecific symptoms such as headache, fatigue, arthralgia, myalgia.
  Intervention: Other: No antibiotic.

Inclusion Criteria:

• age ≥18 years
• admitted between January 2007 and December 2013 at the University Medical Centre Ljubljana, Slovenia
• tick-borne encephalitis defined according to European criteria (febrile illness with symptoms and/or signs of meningitis or meningoencephalitis, cerebrospinal fluid (CSF) pleocytosis (>5 × 106 cells/L), and demonstration of acute TBE virus infection (the presence of specific tick-borne encephalitis virus IgM and IgG antibodies in serum or demonstration of intrathecal production of specific TBE virus IgM and/or IgG antibodies in patients previously vaccinated against tick-borne encephalitis)

Exclusion Criteria:

• Lyme borreliosis in the past