Experimental study of viremia in immune host in tick-borne encephalitis

Experimental studies of viremia in immune hosts with tick-borne encephalitis showed that triple vaccination alone, providing antibody accumulation in the blood sera of mice with a neutralization index up to 2.0 led to the survival of not more than 60% of the animals after subcutaneous inoculation of 100 LD50 of virus with the average survival time of 8.5 days. The use of vaccine in combination with exogenous mouse interferon or interferon inducer (RFf2) increased the survival rate to 75% and 80%, respectively, with an increase in the average survival time up to 9 and 9.5 days. The infected animals examined both 1--4 days after infection and at more remote intervals showed no viremia either in the blood serum or in formed elements examined by immunofluorescence. The use of interferon alone or interferon inducer alone without preliminary vaccination increased the survival rate to 55%--60% but did not result in complete elimination of the virus from the blood in the first day after inoculation.     

Immunopathogenetic features of tick-borne encephalitis under long-term viral antigenemia

The occurrence of chronic tick-borne encephalitis viral antigenemia characterized by the asymptomatic course or minimal clinical manifestations is caused by the virus-immune cell interaction. Cellular immunity was studied in 183 patients with chronic (more than 6-month) tick-borne encephalitis viral antigenemia, by evaluating the immunophenotypic and cytogenetic statuses, structural and functional features, cytokine profile, and peripheral lymphocytic apoptosis. The findings suggest impairments in the cooperation of immunocompetent cells and in the classical scheme of antiviral immunity regulation in tick-borne encephalitis viral persistence due to the changes in lymphocytic structural and functional properties.     

Cytokine production during experimental infection of mice with tick-borne encephalitis virus

An experiment with BALB/c mice, infected with a lethal dosage of the virus of tick-borne encephalitis (TE), strain 205, was accompanied by pronounced growing concentrations of the IL-1 beta, IL-6, IL-10 and TNF alpha cytokines in the blood serum of animals. The maximum values of the above cytokines were determined at the infection terminal stage. A reliably less pronounced growth of concentrations of IL-1 beta, TNF alpha and IL-10 was found in animals infected with a non-lethal TE dosage. The concentration of IL-6 in the blood serum of animals, infected with a non-lethal dosage of the virus, changed during the whole observation period. The dynamics of cytokines in the blood serum of mice, infected with a lethal dosage of the TE virus, suggests the development of SIRS at the infection terminal stage.     

Experimental study of the pathogenesis of tick-borne encephalitis]

The clinical picture of the experimental tick-borne encephalitis, the time course of viremia, the virus content in the central nervous system and the morphological picture were studied in 15 sheep inoculated intracerebrally with viruses isolated in Byelorussia. The two phases of clinical manifestations (febrile-meningeal and neurological stages) were found to be one of the pathogenetic features of the experimental infection due to both virus multiplication and toxico-allergic reactions on the part of the nervous system. This suggests differences in the pathogenesis of clinical manifestations in the general infectious and neurological stages of the acute period of tick-borne encephalitis in man.     

Quantitative indices of the immune status of persons inoculated with different vaccines against tick-borne encephalitis

Inactivated concentrated and unconcentrated vaccines against tick-borne encephalitis given to 80 normal subjects produced no suppressing effect on the quantitative values of the immune status. Immunogenesis was characterized by stimulation of both T- and B-links of the immune system of the vaccines. With the unconcentrated vaccine a greater response was demonstrated after 3 injections; the concentrated vaccine induced an intensive immune response after 2 injections.     

Dual infection of Ixodes ricinus ticks with two viruses of the tick-borne encephalitis complex

Ixodes ricinus female ticks were inoculated with Skalica (SK) virus (non-pathogenic for adult albino mice by subcutaneous route) and 14 days later they were challenged with strain 198 of Tick-borne Encephalitis (TBE) virus (highly pathogenic for adult albino mice by subcutaneous route). After additional 14 days of incubation, 42.9 to 65.0% of the adult (10-12 g) albino mice infested with these double infected ticks developed antibodies to TBE without signs of sickness (transmission of SK virus), while paralysis or death was registered in 35.0 to 57.1% of infested mice (transmission of strain 198) depending on the concentration of strain 198 used for inoculation of ticks. However, a low degree of interference to superinfection with strain 198 was observed, when the dissected tick salivary glands were examined by subcutaneous inoculation of adult albino mice (more than 90% of examined salivary glands contained strain 198 virus).     

Changes in immune parameters and their correction in human cases of tick-borne encephalitis

Tick-Borne Encephalitis virus (TBEV) causes dangerous central nervous system diseases in humans. General infection leads to the development of meningitis or encephalitis, which is characterized by swelling of the brain due to inflammation. Tetracyclines may act locally to moderate inflammation in the CNS. In this study, we investigated the potential clinical benefits of administering tetracycline hydrochloride to patients hospitalized due to suspected TBEV infection presenting with fever and evidence of a recent tick bite. We also characterized an acute immune response to TBEV by profiling certain cytokines and soluble receptors in Tetracycline-treated and untreated patients. Increased serum levels of TNF-alpha, IL-1 alpha and IL-6 were found in all patients at admission. Soluble receptors presented in the serum of patients in a magnitude higher levels than the corresponding cytokines and were increasing during first weak of hospitalization. Levels of IL-10 were also rising during that period. In our study tetracycline hydrochloride acted as an immunomodulator, which was able to reduce manifestations of inflammation response during TBE course; this action led to quicker improvement of symptoms and, consequently, to a faster clinical recovery. The positive result of tetracycline hydrochloride treatment was accompanied by certain particularities in the dynamics of studied cytokines and receptors: the concentrations of IL-6, IL-1 beta, TNF-alpha dropped quicker and reached lower levels, and the concentrations of sIL-6R, IL-1RA, sTNFR1 increased faster and reached higher maximum levels in the tetracycline-treated groups. Children had the highest levels of IL-6, which were not neurotoxic.     

Pathogenesis of an infection induced in Syrian hamsters by attenuated strains of viruses of the tick-borne encephalitis complex

The results of virological and morphological study of the pathogenesis of the infection induced by viruses of the tick-borne encephalitis complex (attenuated TP-21 and E-30 strains) in Syrian hamsters with normal and suppressed immune response are presented. The data obtained indicate long-term persistence of the virus-specific antigen: sufficiently high titres of specific antibodies in the blood serum of the animals at late periods after virus inoculation, positive immunoenzyme tests for virus antigen in the meninges of the hamsters inoculated with the TP-21 strain. Features of the pathogenesis were found to be related to strain characteristics, particularly the degree of their attenuation. Chronic destructive process and reparative gliosclerosis were observed in the CNS of some animals due to Protozoa of the genus Encephalitozoon; in this connection, the necessity of differential diagnosis between cuniculosis and a process of virus genesis is emphasized.