[A new approach to postexposure treatment of rabies by complex of immuno- and chemotherapy in belarus].

A method for preventive treatment of rabies with a complex of immuno- and chemotherapeutics was developed. Rifampicin was used a an etiotropic drug. In the experiments on laboratory animals infected with fixed and street strains of rabies virus it was shown to prolong the incubation period and to increase the survival rate. The protective mechanisms of rifampicin against rabies should be associated with inhibition of RNA transcription, as well as immunomodulating function of macrophages, dendritic cells, B- and T-cells. Since 1992, after the approval of the Ministry of Health of Belarus rifampicin is used in complex with antirabic vaccine for postexposure treatment of rabies in people after severe bites by infected animals (wolves, foxes, dogs). For an 18-year period (1992-2009) of integrated application of chemo- and immunotherapy in Belarus there was not registered any case of hydrophobia in people even after the heaviest wolf bites, incompatible with life (penetrating injuries of the skull, scalping, multiple bites).

[Virus-induced dyslipidemias as possible risk factors in the development of somatic diseases]. / Virusindutsirovannye dislipidemii kak vozmozhnye faktory riska v razvitii somaticheskikh zabolevanii.

Experimental and clinical studies showed a number of virus infections to be accompanied by lipidemic disorders. Experimentally, dyslipidemias were found in tick-borne encephalitis (TBE) in mice, rotavirus infection in rabbits, and amyotrophic leukospongiosis in guinea pigs. The possibility of correcting the virus-induced lipidemic disorders with an antiviral drug, lincomycin, was demonstrated in TBE in mice. Dynamic study of the lipidemic status of patients with virus hepatitis A revealed marked dyslipidemia of the atherogenic type which was stable and persisted up to the time of clinical recovery. The data obtained supplement the current concepts concerning the pathogenesis of virus infections.

[The action of reserpine in experimental rabies infection]. / Izuchenie deistviia rezerpina pri éksperimental'noi rabicheskoi infektsii.

Experimental studies in laboratory animals showed reserpine in doses of 0.01-0.05 mg/kg body weight to inhibit the development of rabies infection in white mice and rabbits by 40.0-83.4% depending on the dose and mode of administration. The inhibiting properties of reserpine were demonstrated for both fixed and street rabies virus strains. The protective effect of the drug was manifested after parenteral and oral administration to the infected animals. The experimental data suggest that reserpine may be used as an antiviral drug for protective treatment of rabies in the incubation period.

[Search for inhibitors of West Nile virus among antibiotics]. / Poisk ingibitorov virusa Zapadnogo Nila sredi antibiotikov.

The activity of 24 antibiotics was studied in treatment of albino mice with experimental encephalitis caused by West Nile virus. The antiviral activity of gentamicin and kanamycin was stated. The survival rate of the animals 19. contaminated with 10-100 LD50 of the West Nile virus and treated parenterally with gentamicin in a dose of 80 to 400 micrograms/mouse was higher than that in the controls by 29.5 to 100 per cent and depended on the drug regimen. The efficacy of kanamycin was lower. The chemotherapeutic indices of gentamicin and kanamycin amounted to 100 and 10, respectively. Since there are no schemes for chemotherapy of the infection caused by the West Nile virus and the respective vaccines are not available the use of the antibiotics and gentamicin in particular appears to be promising in the disease prevention and treatment.

[Dyslipidemia and an elevated lipid level in the cells in experimental herpetic infection and their correction with antiviral chemotherapeutic agents]. / Dislipidemiia, povyshennoe soderzhanie v kletkakh lipidov pri éksperimental'noi gerpeticheskoi infektsii i ikh korrektsiia antivirusnymi khimiopreparatami.

The influence of herpes simplex virus on lipid exchange and accumulation by blood vessels cells was studied. In acute herpes infection in rabbits, typical dyslipidemia characterised by a rise in the content of total cholesterol, low and very low density lipoprotein cholesterol and triglycerides in the absence of manifest changes in concentration of high density lipoprotein was detected. HSV infection of smooth muscle cell culture of human embryo aorta was accompanied by increased accumulation of free lipids in the cells. The use of antiherpetic preparations during the infection led to correction of the lipid spectrum of the infected animals and was accompanied by normalization of intracellular lipid contents. A possible pathogenetic role of HSV in atherogenesis which may be connected with at least two processes: the development of lipidemic disturbances and formation of pathologic lipid depot in the arterial wall, is discussed.

[The efficacy of lincomycin in tick-borne encephalitis]. / Ob éffektivnosti linkomitsina pri kleshevom éntsefalite.

Lincomycin was found to inhibit tick-borne encephalitis (TBE) virus. To test antiviral potential of this drug, a clinical trial was initiated entering TBE patients from known focuses of the disease (Novosibirsk, Kemerovo, Perm and Irkutsk Provinces). The drug was given to 23 patients with meningeal and meningoencephalitic TBE. A control group of 22 matched subjects received specific immunoglobulin. Resultant efficacy of lincomycin appeared not inferior to that of anti-TBE immunoglobulin. Lincomycin can be successfully introduced in the treatment of meningeal and meningoencephalitic TBE.

[Increasing the effectiveness of immunotherapy of rabies by using rifampicin in experimental studies]. / O povyshennoi éffektivnosti immunoterapii beshchenstva s pomoshch'iu rifampitsina v éksperimente.

The experiments showed that in a dose of 35-70 mg/kg rifampicin inhibited reproduction of the fixed rabies virus in the brain of infected animals. The drug had no inhibitory effect on synthesis of the virus-neutralizing antibodies after vaccination. Combination of rifampicin with antirabies gamma-globulin had a marked synergistic effect. The animal survival after the combination use amounted to 75-100 per cent and depended on the infective dose of the virus and the scheme of the drug administration. It was concluded that rifampicin might be used in complex therapy of rabies during the incubation period (along with gamma-globulin and the vaccine) for inhibiting virus reproduction at early infection stages.

[The protection of vertebrate animals from experimental tick-borne encephalitis with active and passive immunization against tick antigens]. / Zashchita pozvonochnykh zhivotnykh ot éksperimental'nogo kleshchevogo éntsefalita pri aktivnoi i passivnoi immunizatsii protiv antigenov kleshchei.

The active and passive immunization of laboratory animals against Ixodes antigens has been experimentally shown to lead to the development of their resistance to homologous Arthropoda species and a change in the intensity of the circulation of tick-borne encephalitis virus between carriers and their hosts. The immunization of vertebrates with Ixodes antigens may supposedly lead to a decrease in the number of bloodsucking arthropods-carriers of the causative agents of infectious diseases-and protect animals from infections whose causative agents are transmitted by Ixodes ticks.

[The characteristics of the accumulation and the possibility of the long-term preservation of the tick-borne encephalitis virus in ixodid ticks]. / Osobennosti nakopleniia i vozmozhnost' dlitel'nogo khraneniia virusa kleshchevogo éntsefalita v iksodovykh kleshchakh.

A method for tick-borne encephalitis virus reproduction was developed in female Ixodes ticks in the period of postlarval development, if they were kept at elevated temperature (23-37 degrees C). It ensures further conservation of the agent in carriers by decreasing tick maintenance temperature to 4 degrees C.

[Protective action of rifampicin in experimental rabies infection of albino mice]. / Zashchitnoe deistvie rifampitsina pri éksperimental'noi rabicheskoi infektsii belykh myshei.

The paper presents the results of the experimental study of the action of rifampicin on the process of rabies infection in albino mice contaminated with 1-10 LD50 of the fixed rabies virus. Exposure to rifampicin in doses of 250 and 500 micrograms/mouse (35-70 mg/kg) resulted in survival of 66.7 and 83.4 per cent of the animals respectively while in the controls it did not exceed 16.6 and 25.0 per cent. The average life-span of the albino mice treated with the antibiotic increased 1.6-2.4-fold in comparison with the controls. The chemotherapeutic index of rifampicin representing the ratio of the maximum tolerance dose to the minimum dose providing the protective action was equal to 20. The protective action was observed either after administration of the antibiotic according to the treatment-and-prophylaxis scheme or after administration of its 2- or 3-fold dose once a day immediately after the contamination.

[Transfer of resistance against Ixodes ticks to vertebrates with the sera and lymphocytes of immune animals]. / Peredacha pozvonochnym rezistentnosti protiv iksodovykh kleshchei s syvorotkoi i limfotsitami immunnykh zhivotnykh.

Hyperimmune serum with the high content of antibodies to the saliva of noninfected ticks when injected into vertebrates, induced the development of resistance preventing the ticks from sticking to the skin and satiation, thus reducing the number of blood-sucking ticks reaching satiation and decreasing the weight of satiated ticks; as a result, the productivity of female ticks decreased the the number of ticks sharply dropped. When ticks infected with tick-borne encephalitis virus parasitized on the animals immune against the saliva antigens of noninfected ticks, the virus titers in the blood of these animals were lower than in the controls, and no infection of ticks, formerly free of the virus, occurred.

[Possibility of protecting vertebrates against transmissive infection with tick-borne encephalitis virus]. / Izuchenie vozmozhnosti predokhraneniia pozvonochnykh zhivotnykh ot transmissivnogo zaracheniia virusom kleschevogo éntsefalita.

A previously unknown phenomenon of reproduction inhibition and limitation of dissemination of virus agents transmitted by ticks to mammals by the effect of the immunity of vertebrates directed against blood-sucking arthropods was established. Inoculation of the animals with serum immune to uninfected tick saliva antigens led to inhibition of tick-borne encephalitis virus reproduction in them by 1.75--3.0 lg LD50/0.03 ml when the animals had been infected transmissively (by feeding of infected ticks on them). On the animals containing antibody to tick saliva antigens no virus transmission from infected ticks to non-infected vectors occurred upon their simultaneous parasitizing.

[Effect of the diapause in the Ixodes ricinus (Ixodidae) tick on the multiplication of the tick-borne encephalitis virus in its body]. / Vliianie diapauzy kleshcha Ixodes ricinus (Ixodidae) na razmnozhenie v ego organizme virusa kleshchevogo éntsefalita.

The tick encephalitis virus was found to multiply more intensively in ticks developing without diapause. Thus, in larvae developing with diapause, in 4 and 8 weeks after they feed on infected animals, the virus titers were 3.0 and 3.5 lg LD50 respectively. At the development without diapause the titers were 4.3 and 5.3, respectively (P less than 0.05). The virus titers in infected nymphs developing without diapause were 2.5 to 3.9 lg LD50 higher than those of the diapausing individuals. In diapausing larvae and nymphs the tick encephalitis virus remained for a long time (8 to 10 weeks) without fall of titers. The fall of virus titers was not recorded either during the moulting of larvae for nymphs and nymphs for imago but in hungry ticks, which were maintained for a long time at 18 to 23 C, the amount of virus gradually diminished.

[Effect of the physiological state of ticks on the intensity of tick-borne encephalitis virus replication in them]. / Vliianie fiziologicheskogo sostoianiia kleshchei na intensivnost' razmnozheniia v nikh virusa kleshchevogo éntsefalita.

The features of tick-borne encephalitis (TBE) virus reproduction in Ixodes ricinus and Dermacentor anderson ticks were studied in relation to the age of ticks, duration of fasting, feeding, and conditions of keeping the ticks before and after the experiment. Parenteral infection of ticks at various intervals after molting showed that the most favourable conditions for reproduction, survival, transphase and transovarial transmission of the virus occurred when the virus was given to the ticks in the first days after the period of postlarval development followed by feeding the vectors on vertebrates. In this case, owing to increased metabolic activity and intensive organogenesis and histogenesis, the virus persisted in ticks in high titers till the moment of oviposition and penetrated into the egg batch. When the virus was inoculated into old exhausted females (8-18 months) virus titers in ticks were low and penetration of the virus into the egg batch was irregular.