Clinical course and manifestations
The typical course of TBE is diphasic in at least two-thirds of patients, and can be described as follows. The incubation period may last between 2 and 28 days, but on average is 7 days. The first stage, which may last for 2 to 8 days, corresponds with the viremic phase. It is associated with non-specific systemic signs and symptoms such as fatigue, headache, aching back and limbs, nausea, and general malaise; in most cases the temperature is rising to 38°C or higher. Sometimes exceptionally high initial temperature may occur, rising above 40°C. An afebrile interval follows the first stage of TBE, and lasts 1 to 20 days. During this time patients are usually free of symptoms. Another sudden rise of temperature to high values marks the beginning of the second stage.
Typical temperature curve in a case of TBE after laboratory infection with the virus.
Not all individuals infected with TBE go through the entire course of the disease. In approximately two thirds of infected individuals the infection remains either silent, though viremia can be demonstrated, or the patients show the clinical picture of the initial stage of TBE, but then the symptoms subside without developing into the second stage.
About one third of those symptomatic with TBE proceed into the second stage of the disease after the virus has spread to the CNS. 50–77% of these patients go through the typical biphasic course of the infection. In the remaining 23–50% the infection is in-apparent during the first stage, and the onset of clinical illness coincides with the beginning of the second phase of the disease.
The course of disease with the Far-Eastern variety clinically differs from the European form. The onset of illness is more often gradual than acute with a prodromal phase including, fever, headache, anorexia, nausea, vomiting and photophobia. These symptoms are followed by a stiff neck, sensorial changes, visual disturbances, and variable neurological dysfunctions, including paresis, paralysis, sensory loss and convulsions. In fatal cases, death occurs within the first week after onset. The case-fatality rate is approximately 20% compared to 1–2% for the European form but these figures may be biased by the different standards of medical treatment available in Western Europe and eastern regions. It is supposed that, in contrast to the European form the disease caused by the Far-Eastern variety is more severe in children than in adults. Neurological sequelae occur in 30–80% of survivors, especially residual flaccid paralyses of the shoulder girdle and arms. Little information is available on the virulence of the recently described Siberian subtype with respect to the course of disease in humans. However, animal studies have demonstrated that the limited number of Siberian subtype strains studied have higher virulence in mice than Far-Eastern strains.