Effects of multiple sclerosis and other inflammatory CNS disorders on tick-borne encephalitis serology.

The goal of the present study was to investigate whether a direct association exists between false-positive recognition of IgG antibodies and inflammatory changes in the central nervous system (CNS) and whether inflammatory diseases of the CNS affect the specificity of the enzyme-linked immunosorbent assay (ELISA) of tick-borne encephalitis (TBE) virus. A group of patients (1,815), treated in the Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany, were tested forTBE IgG antibodies by ELISA. Several subgroups of patients with and without inflammatory changes in the CSF as well as patients with and without confirmed multiple sclerosis (MS) were investigated. Overall, 4.5% of all the 1,815 patients and 4.8% of the patients with inflammatory changes in the CSF but without MS had TBE IgG antibodies. In the subgroup with inflammatory changes in the CSF and MS, 4.4% of the patients were TBE IgG-positive. In the subgroup without inflammatory changes in the CSF, 3.8% of the patients without MS were TBE IgG-positive and 4.9% of the patients with MS were TBE IgG-positive. The rate of TBE IgG positivity was not significantly different in the subgroups with and without inflammatory changes in the CSF (P = 0.45). The comparison of the subgroups with and without MS showed no significant difference in the TBE IgG titer (P = 0.83) as well. This indicates that the specificity of the ELISA was affected neither by inflammatory changes in the CSF nor by MS.

Prevalence of antibodies to tick-borne encephalitis virus and Borrelia burgdorferi sensu lato in samples from patients with abnormalities in the cerebrospinal fluid.

Within the last few years, an increase in cases of tick-borne encephalitis (TBE) as well as an expansion of TBE-endemic regions have been noted in southern Germany. In 1994, a patient was diagnosed for the first time with TBE that had been acquired in Saarland. Up to this point, the Saarland had been considered TBE-free. In a retrospective study, we tested serum samples from 904 patients with abnormalities in the cerebrospinal fluid (CSF) for TBE antibodies. The IgG ELISA used (Immunozym-FSME-IgG, Immuno GmbH, Heidelberg, Germany) yielded 47 positive and 134 borderline sera. The percentage of positive sera showed a significant increase during the time period studied (1989-1994): One IgG-positive serum sample was also IgM-positive. Of the CSF samples, 2 were IgG-positive and 7 were borderline for IgG. In three patients, a positive intrathecal antibody index (IAI) was found, indicating an incrathecal antibody production. An analysis of the vaccination history of the patients showed that only 19% of the patients with a positive TBE IgG titre and only 5.9% of the borderline patients had been vaccinated against TBE. We compared 98 patients that tested positive or borderline for TBE IgG with 98 sex-and-age-matched patients that tested negative. The parameters studied included the patient's complaints upon discharge, the average duration of stationary treatment and 16 different neurological symptoms. We did not observe any significant differences between the two groups. We also tested the sera of 704 of the 904 patients for antibodies to Borrelia burgdorferi (Borrelia burgdorferi ELISA, Genzyme Virotech GmbH, Rüsselsheim, Germany). 155 (22.0%) of the sera were IgG-positive, 136 (19.3%) were borderline, 32 patients (4.6%) had a positive intrathecal antibody index (IAI). The fact that no patient with a clinically manifest case of TBE had acquired the disease in the Saarland indicates that the actual risk of acquiring an acute TBE in the Saarland is very low, despite the high percentage of samples that tested positive for IgG in the ELISA. The increase in the number of serum samples that tested positive for TBE IgG during the last years could be explained by an expansion of TBE regions into the Saarland, increasing vaccination of the population or more travel to endemic regions. The proportion of patients with IgG antibodies to Borrelia was 22%. Because only part of the patients suffered from an acute, clinically manifest borreliosis, and since the serum IgG titre had remained positive for many years after contact with the microorganisms, we suspected that a large percentage of the population would show signs of a clinically silent infection in their sera. 4.6% of the patients had a positive IAI quotient, a clear indication of neuroborreliosis.