Is an isolated initial phase of a tick-borne encephalitis a common event?

Abstract

SIR—Tick-borne encephalitis (TBE) is one of the most important human infections of the CNS in several European countries. It has been endemic primarily in southern Scandinavia and central Europe, including a large part of Slovenia. The etiological agent of TBE is an RNA virus belonging to the Flavivirus genus of the family Flaviviridae. The hard tick Ixodes ricinus is the principal vector of the central European virus subtype. It is well known that in at least two-thirds of patients who develop CNS involvement, the disease has a characteristic biphasic course. After the initial phase of illness that corresponds to viremia, followed by an asymptomatic interval, the second phase presents signs and symptoms of meningitis, meningoencephalitis, or even meningoencephalomyelitis [1]. Seroepidemiological studies regarding TBE virus infection in endemic areas of various European countries demonstrated conclusively that asymptomatic infections are common [2‐4]. In some of the reports it was also suggested that there is an abortive form of TBE virus infection, which is manifested only by a febrile headache without meningeal involvement (i.e., the initial phase of the illness without subsequent CNS involvement) [1, 3, 5, 6]. However, it seems that this suggestion relies more on data for eastern TBE than on data for central European (western) TBE [7], which are dubious with respect to the frequency of abortive forms of TBE. Thus, in a comprehensive review article on TBE, published recently in Clinical Infectious Diseases [7], the authors state that the initial phase of the illness is followed by “an afebrile and relatively asymptomatic period, lasting 2‐10 days. In about one-third of patients infected, the second phase of disease develops.” A logical conclusion from such a statement, as suggested by Kunz [8], would be that two-thirds of clinically symptomatic TBE virus infections manifest themselves only by the initial phase of the illness. However, later in the article, in a discussion of clinical manifestations, the authors report that in the western European literature this initial phase of TBE is usually not recognized, possibly (according to Ackerman et al. [2]) because of the small proportion of such cases. We challenged these quite diverse statements with the findings of 2 prospective studies we have performed during the last few years. In one study we searched for the presence of thrombocytopenia in addition to a well-known leukopenia during the initial phase of TBE [9], and in the second study (still ongoing), we examined the etiology of febrile illnesses that occur within 6 weeks after a tick bite [10]. Inclusion criteria for both studies were the presence of a febrile illness after a tick bite, as well as clinical and laboratory assessment (including demonstration of IgM and IgG antibodies against TBE virus using diagnostic kits [Immunozyme, FSME, Immuno AG, Vienna]) at initial examination, 14 days, and 6 weeks. Using this approach, we were able to study patients referred to us by primary physicians who were in the initial phase of TBE and check for the eventual appearance of the second, encephalitic phase of the disease. From 1994 through 1997, 165 patients aged 115 years were referred to the Department of Infectious Diseases at the University Medical Centre, Ljubljana, Slovenia. These patients had a febrile illness associated with a tick bite during the 6 weeks before the onset of the disease and either normal CSF examination results or complete absence of clinical signs of meningitis. During a follow-up of 6 weeks, infection with TBE virus was demonstrated in 44 (26.7%) of 165 patients by the appearance of specific IgM and IgG antibodies against TBE virus. All of these patients lived in the central part of Slovenia in a region where TBE is known to be endemic, and none of them had been vaccinated against TBE. However, during the followup period, all 44 of the patients developed the second, meningoencephalitic phase of the disease; that is, all had clinically biphasic course of the illness with CSF abnormalities (pleocytosis) during the second phase. Therefore, none of our 44 patients developed only the isolated initial phase of the disease without later developing meningitis or meningoencephalitis. Our findings strongly support the idea that the abortive form of central European TBE is rare, if it exists at all. However, our findings do not negate the fact that a majority of patients are not recognized as having an infection with TBE virus during the initial phase of their disease.