Patient 8 is a 74-year-old man, who lives in Kristiansand and has a camper in Sogne. Since August 2003, he had increasing headache and from October 3, 2003 the headache was intense and accompanied by nausea and vomiting. His personality was altered during these weeks, with reduced memory about recent events in particular, irritability, and verbal aggressiveness. He was admitted to the hospital on October 6, 2003. Results from computed tomography were normal, and electroencephalogram showed changes consistent with encephalitis. Borrelia antibody levels in serum samples were low. Intrathecal production of Borrelia antibodies could not be detected. Nucleic acids from herpes simplex or enterovirus were not detected in spinal fluid.
High levels of TBEV IgM (OD 1.461 on October 6 and OD 1.200 on November 5) were detected in sera together with rising IgG levels (OD 0.652 on October 6 and OD 1.475 on November 11). Cut-off values were 0.281-0.286 for IgM and 0.259-0.265 for IgG. In spinal fluid from October 3, intrathecal production of TBEV antibodies could not be detected, but one month later, intrathecal IgM was produced. During hospitalization, the patient recovered well. After 10 to 11 days, he was aware, and his mental situation improved considerably. He was also able to walk on stairs. After 4 to 5 months, he was fully recovered.
The Agder counties have the highest incidence of Borrelia infections in Norway (33 cases/100,000 persons, 1997-2003). The incidence of neuroborreliosis is 10 cases per 100,000 persons. The first case of TBE in Norway was reported in 1997. The previously published clinical signs and symptoms and results from these five patients (,) are summarized as case 1-5, while the three new patients are presented as patients 6-8 (Table 1 and Table 2).
The eight patients included seven men and one woman from 42 years to 74 years of age. Biphasic courses were described in two patients. All patients had intense headache, seven had vertigo and nausea, and six had vomiting. Seven patients were hospitalized, three with reduced consciousness, two with mental disturbances; all seven had more or less severe neurologic abnormalities. Three had ataxia; one had diplopia; and one had speech difficulties, bilateral ptosis, paresis of eye and pharynx muscles, and paresis of muscles in the left shoulder. One had an epileptic seizure. All patients had fever, with temperatures from 38 C to 40 C. Serum samples were obtained from all eight patients and had signs of inflammation with C-reactive protein level of 10-105 mg/L and elevated leukocyte count of 8.3-15.4 x 109/L. Seven patients underwent lumbar puncture; CSF pleocytosis and elevated protein levels were found in all patients. Nucleic acids from herpes simplex virus, varicella-zoster virus, or enterovirus were not detected in the spinal fluid specimens, which excludes the most common differential diagnostic causes of encephalitis.
In all patients, high serum levels of TBEV IgM and IgG antibodies were detected with enzyme-linked immunosorbent assay methods. In neutralization tests, serum antibody titers increased from <5 to 10 in five of the patients, 10 to 20 in one, and 10 to 40 in one patient (,). Seven patients recovered during the first 6 months. Two had cognitive dysfunctions during the first several months. One person still had paresis and atrophy of the shoulder muscles 1 year later.
Although the diagnostic tests are not absolutely specific for TBE compared to the closely related Louping ill virus, no cases of Louping ill virus in livestock (Snorre Stuen, pers. comm.) or human infections have been reported in Norway since 1991; none of the eight patients lived close to or worked with sheep or goats. The clinical characteristics of the Norwegian patients are similar to those of Swedish patients. In Sweden, the disease is caused by TBEV subtype 1.
All eight patients with TBE in Norway became ill after being bitten by a tick in the coastal areas of the Agder counties. Four had been on Tromoy Island in Aust-Agder County before becoming ill, while one had been in Lyngdal and three in Mandal and Sogne in Vest-Agder County. None of the patients had been abroad in the 3 weeks before becoming ill.
TBE was assumed not to be present in Norway. Thus, all patients with suspicious cases of TBE may not have been tested for antibodies to TBEV. In Agder, we have tested for TBE since 1999, but the disease may still be underdiagnosed.
Some seroprevalence studies have been carried out. TBEV IgG antibodies were detected in 0.3% to 0.4% of the serum samples from persons in Agder counties. From persons on Tromoy Island, antibodies were found in 2.4% of serum samples, and in other coastal districts, the seroprevalence was 0%-11% (,). The number of human serum samples tested is limited, and the vaccination status is unknown. However, vaccination is unlikely because Norwegians are only vaccinated against flaviviruses on special travel indications.
In Sweden, the incidence of human cases of TBE has risen during the last few years, and new TBE foci have been reported. During the last 2 decades, an increased number of TBE cases have been reporting in most European countries. Changes in the distribution of TBEV have been indicated, and the Norwegian cases are from areas where new foci have been predicted.