Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 12, Number 10—October 2006

Tickborne Encephalitis Virus, Northeastern Italy

On This Page
Article Metrics
citations of this article
EID Journal Metrics on Scopus

Cite This Article

To the Editor: Approximately 3,000 cases of tickborne encephalitis virus (TBEV) disease are registered annually in Europe (1). In Italy, indigenous TBEV infection cases have been only sporadically recorded from 1975 through 2001; in addition, serologic investigations in populations at risk in northern Italy have shown only a low prevalence of specific antibodies (0.6%–5%) (2,3). A surveillance system for TBEV infections was started after autochthonous TBEV was recognized in late summer and fall 2003 in Friuli-Venezia Giulia (FVG), a small region of northeastern Italy with nearly 1 million inhabitants (4). Surveillance is based on systematic microbiologic screening of all patients referred to the emergency departments of regional hospitals for suspected community-acquired central nervous system infections or fever and headache with a history of tick bite in the past 6 weeks. Screening for TBEV was performed on sera or cerebrospinal fluid (CSF) by enzyme immunoassay (Enzygnost Anti-TBE virus Ig, Dade Behring Marburg GmbH, Marburg, Germany) and repeated on convalescent-phase sera. Demonstration of specific immunoglobulin M (IgM) in serum or CSF in the acute phase or >4-fold rise in serum antibody titer in the convalescent phase was interpreted as an indicator of recent TBEV infection. For surveillance purposes, TBEV infection was defined when hemagglutination-inhibition antibody test and neutralization assay by a reference laboratory confirmed ELISA results (5). Data were collected at a regional reference center, where cases were classified as possible, probable, and confirmed, according to the new TBEV case definition (6).

From July 2003 through November 2005, 20 cases of TBEV infection were detected; their demographic, epidemiologic, and clinical characteristics are given in the Table. Cases occurred throughout the year, with a biphasic peak in June and September–November. A biphasic clinical course was reported in 10 patients. The median period between tick bite and date of referral to hospital was 22 days (range 15–46 days). Seventeen cases were classified as confirmed, 2 as probable, and 1 case could not be classified because symptoms started after tick season (December) (6). Two patients were coinfected with Borrelia burgdorferi.

The most common symptoms were fever, headache, nausea, vomiting, and myalgia; the most common central nervous system signs were stiff neck, irritability, and limb paresis. Five patients only reported headache and fever without neurologic signs. Lumbar puncture, performed in 15 patients, showed mild pleocytosis with neutrophil predominance in 13 patients, elevated protein level in 14 patients, and normal glucose level in all.

The clinical syndrome was classified, in accordance with Kaiser et al., into febrile form (4 cases), aseptic meningitis (3 cases), encephalitis (2 cases), meningoencephalitis (8 cases), and meningoencephalomyelitis (3 cases) (7). None of the patients died, but 3 required respiratory support in the intensive care unit. Outcome was favorable for 9 patients; major neurologic sequelae were observed in 6 and minor sequelae in 5.

During the past 20 years, TBEV has reemerged in several European areas that had been disease free (1,8). In FVG, which borders disease-endemic areas such as Slovenia and Austria, the first cases of TBEV infection were documented recently (4). Several explanations, in addition to the well-established role of climate change, can be proposed (1). First, in Slovenia, after the end of the Communist regime, recreational activities increased considerably, with the creation of natural parks and hunting grounds, densely populated with deer, chamois, rodents, foxes, and other wild animals that can easily cross national borders (9). Second, after the 1976 earthquake that destroyed a large number of mountain villages in FVG, economic activities were progressively concentrated in the plains of the region, which rapidly increased urbanization of the plains towns. As a consequence, the mountains in the northern part of the region were progressively abandoned by humans and returned to wilderness. A final possible explanation is that TBEV cases were undiagnosed because awareness among local physicians was low; however, this variable likely played a minor role, since a recent serologic survey of persons at high risk (forest rangers) yielded a low positivity ratio (3). If even workers at risk had a low seroprevalence, TBEV cases were likely uncommon in the region.

The implementation of a regional active surveillance system allows the highest sensitivity in assessing the epidemiologic features of TBEV infections, which are characterized by highly disease-endemic microfoci in areas free of the problem (10). Precisely defining areas where risk is particularly will lead to optimal use of prevention programs and design of educational programs for residents, tourists, and healthcare workers.



We are grateful to Maria Grazia Ciuffolini for TBEV serologic testing (hemagglutination-inhibition antibody test and neutralization assay).


Anna Beltrame*Comments to Author , Maurizio Ruscio†, Barbara Cruciatti‡, Angela Londero*, Vito Di Piazza§, Roberto Copetti§, Valentino Moretti†, Paolo Rossi¶, Gian Luigi Gigli¶, Luigia Scudeller*, and Pierluigi Viale*
Author affiliations: *University of Udine, Udine, Italy; †Hospital of San Daniele, San Daniele, Italy; ‡Hospital of Pordenone, Pordenone, Italy; §San Antonio Abate Hospital, Tolmezzo, Italy; ¶Hospital of Udine, Udine, Italy



  1. Günther  G, Haglund  M. Tick-borne encephalopathies: epidemiology, diagnosis, treatment and prevention. CNS Drugs. 2005;19:100932.PubMedGoogle Scholar
  2. Cristofolini  A, Bassetti  D, Schallenberg  G. Zoonoses transmitted by ticks in forest workers (tick-borne encephalitis and Lyme borreliosis): preliminary results. Med Lav. 1993;84:394402.PubMedGoogle Scholar
  3. Cinco  M, Barbone  F, Ciufolini  M, Mascioli  M, Anguero Rosenfeld  M, Stefanel  P, Seroprevalence of tick-borne infections in forestry rangers from northeastern Italy. Clin Microbiol Infect. 2004;10:105661. DOIPubMedGoogle Scholar
  4. Beltrame  A, Cruciatti  B, Ruscio  M, Scudeller  L, Cristini  F, Rorato  G, Tick-borne encephalitis in Friuli Venezia Giulia, northeastern Italy. Infection. 2005;33:1589. DOIPubMedGoogle Scholar
  5. Holzmann  H, Kundi  M, Stiasny  K, Clement  J, McKenna  P, Kunz  C, Correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis. J Med Virol. 1996;48:1027. DOIPubMedGoogle Scholar
  6. Stefanoff  P, Eidson  M, Morse  DL, Zielinski  A. Evaluation of tickborne encephalitis case classification in Poland. Euro Surveill. 2005;10:235.PubMedGoogle Scholar
  7. Kaiser  R. The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994–98: a prospective study of 656 patients. Brain. 1999;122:206778. DOIPubMedGoogle Scholar
  8. Skarpaas  T, Ljostad  U, Sundoy  A. First human cases of tickborne encephalitis, Norway. Emerg Infect Dis. 2004;10:22413.PubMedGoogle Scholar
  9. Lesnicar  G, Poljak  M, Seme  K, Lesnicar  J. Pediatric tick-borne encephalitis in 371 cases from an endemic region in Slovenia, 1959 to 2000. Pediatr Infect Dis J. 2003;22:6127. DOIPubMedGoogle Scholar
  10. Zeman  P. Objective assessment of risk maps of tick-borne encephalitis and Lyme borreliosis based on spatial patterns of located cases. Int J Epidemiol. 1997;26:11219. DOIPubMedGoogle Scholar




Cite This Article

DOI: 10.3201/eid1210.060395

Related Links


Table of Contents – Volume 12, Number 10—October 2006

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Anna Beltrame, Clinic of Infectious Diseases, University of Udine, Via Colugna no. 50, 33100 Udine, Italy

Send To

10000 character(s) remaining.


Page created: November 10, 2011
Page updated: November 10, 2011
Page reviewed: November 10, 2011
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.