Emerg Infect DisEIDEmerging Infectious Diseases1080-60401080-6059Centers for Disease Control and Prevention17176593329094906-039510.3201/eid1210.060395Letters to the EditorTickborne Encephalitis Virus, Northeastern ItalyTickborne Encephalitis Virus, Northeastern ItalyBeltrameAnna*RuscioMaurizioCruciattiBarbaraLonderoAngela*Di PiazzaVito§CopettiRoberto§MorettiValentinoRossiPaoloGigliGian LuigiScudellerLuigia*VialePierluigi*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, ItalyAddress for correspondence: Anna Beltrame, Clinic of Infectious Diseases, University of Udine, Via Colugna no. 50, 33100 Udine, Italy; email: anna.beltrame@med.uniud.it102006121016171619Keywords: TBEVEpidemiologyItalyletter

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.

Demographic, epidemiologic, and clinical data of 20 patients with TBEV infection in Friuli-Venezia Giulia*
PatientSexAge (y)Tick biteHospitalization date (length of hospitalization [d])Definitive diagnosisSequelae
1F36Yes2003 Jul 28 (31)MEMUL paresis
2M58Yes2003 Oct 13 (15)EAbsent
3F42Yes2003 Oct 17 (19)MEAbsent
4F27No2003 Dec 30 (25)MEUL paresis, paresis of VII cranial nerve
5M16Yes2004 Apr 28 (21)MEUL tremors
6F53Yes2004 Jun 21 (18)MEDiplopia
7M43Yes2004 Jul 17 (0)FFAbsent
8M62Yes2004 Oct 10 (10)MEUL paresthesia
9M35Yes2004 Nov 8 (15)MEAbsent
10F77Yes2004 Nov 22 (0)FFAbsent
11F36Yes2005 May 8 (19)MEMUL paresis
12M12Yes2005 May 13 (27)MEAbsent
13M64Yes2005 Jun 10 (11)FFUL paresthesia, hearing impairment
14M59Yes2005 Jun 20 (12)MAbsent
15M15Yes2005 Sep 1 (10)MEAbsent
16F39Yes2005 Sep 8 (8)MAbsent
17M70Yes2005 Sep 16 (53)MEMUL paresis, RI, VAP
18M75No2005 Oct 18 (10)FFUL tremors
19M20No2005 Nov 2 (7)MUL tremors
20M61Yes2005 Nov 26 (13)EUL tremors, ataxia, opsoclonus

*TBEV, tickborne encephalitis virus; MEM, meningoencephalomyelitis; UL, upper limbs; E, encephalitis; ME, meningoencephalitis; FF, febrile form; M, meningitis; RI, respiratory insufficiency; VAP, ventilator-associated pneumonia.

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.

Suggested citation for this article: Beltrame A, Ruscio M, Cruciatti B, Londero A, Di Piazza V, Copetti R, et al. Tickborne encephalitis virus, northeastern Italy [letter]. Emerg Infect Dis [serial on the Internet]. 2006 Oct [date cited]. http://dx.doi.org/10.3201/eid1210.060395

Acknowledgments

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

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