Regional epidemiologic characteristics of combined foci of tick-borne encephalitis, endemic rickettsioses and leptospirosis in Western Siberia

The authors carried out complex study of combined foci of infections with natural foci in Western Siberia and their reflection in human pathology. The results of serological examination of 5917 persons and of 1743 of farm animals in respect to tick-borne encephalitis, Asian tick-borne rickettsiosis, Q-rickettsiosis, and leptospiroses are analysed. Affection of the population with all the four infections in all the landscape zones under study was shown; the intensity of this affection with different infections differed. Combined natural foci of the mentioned infections were found to be widespread; epidemiological significance of such combination was unequal in different ladscapes, this depending on the ladscape characteristics of the natural foci of infections under study and of different ways of transmission of their causative agents.     

Geographical variants in the immunological structure of the population in combined foci of tick-borne encephalitis and endemic rickettsiosis in the European part of the USSR

The zonal study of the immunological structure of the population revealed an increase in the number of infective agents with which the population comes into contact in the southern regions. In the medial boreal forest zone contacts of low intensity only with tick-borne encephalitis virus were detected (the immune stratum was found to be 5.5%, 2,178 persons were examined); in the southern boreal forest zone the foci of tick-borne encephalitis actively manifested (the immune stratum reached 38.9%, 2,854 persons were examined), and Q fever was constantly detected (1.6%). In the forest-steppe zone the population was found to have contacts with the causative agent of tick-borne encephalitis (the immune stratum was found to be 13.3%, 2,056 persons were examined), Q fever (1.2%) and tick-borne rickettsiosis (1.1%).     

The possible role of alpha 2-macroglobulin in regulating the immune components of the brain in tick-borne encephalitis

In tick-borne encephalitis certain immunopathological reactions develop in the tissues of the central nervous system; alpha 2-macroglobulin may serve as the marker of the activity of these reactions. The dynamic study of liquor taken from 16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE), 8 patients with severe craniocerebral traumas accompanied by meningitis and 10 patients with osteochondrosis was made. As revealed in this study, in TBE patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable during the acute period of the disease.     

The spatial-temporal structure of fluctuations in tick-borne encephalitis morbidity in the Maritime Territory

The annual dynamics of the epidemic process in tick-borne encephalitis and its spread in the Maritime Territory, endemic for this infection, have been studied. The study has shown that in the central mountainous regions grown with boreal forest, in contrast to the rest of this focal area, a higher morbidity level and more severe outcomes of this infection are observed. This indicates that in those regions more ancient nuclei of the endemic area of this infection with the main stable elements of the natural focus are preserved.     

Biological properties of strains of tick-borne encephalitis virus isolated in the natural foci of the eastern part of the Russian plain

Strains of tick-borne encephalitis virus isolated in the natural foci of infection in the eastern part of the Russian Plain (the Kirov region) were examined for their biological properties. The strains examined were 69 strains isolated from ticks Ixodes persulcatus, 62 strains obtained from patients with the clinically manifest form of tick-borne encephalitis and 56 strains isolated from the blood of patients with the inapparent form of infection. Comparative studies on laboratory animals (albino mice, golden hamsters, suckling guinea pigs and other mammals) as well as comparative serologic studies provided evidence which suggested that all virus isolates from the Kirov region were antigenically identical with the strain "Sofin" isolated in the Far East and represent thus a single causative agent of the tick-borne encephalitis virus infection. This strain of virus is supposed to exist in two variants, in dependence on ecological conditions: one of these variants is the eastern variant (strain Sofin and strains from the Kirov region) and the other one is the western variant of tick-borne encephalitis virus.     

Clinico-epidemiological characteristics of tick-borne encephalitis in the Maritime Territory

Clinico-epidemiological analysis of tick-borne encephalitis (TBE) incidence rate in the Primorski Territory for 25 years has revealed the prevalence of focal forms of this infection (on the average, 50%) and its high mortality rate (on the average, 33% for the focal forms and 6.4% for the meningeal form). Such course and termination of this infection depend not only on the reactive capacity of the patient's body, but, to a great extent, on the virulence of TBE virus circulating in the area under study.     

An analysis of geographical differences in the appearance of tick-borne encephalitis

Reasons of differences in clinical forms of tick-borne encephalitis within certain regions and throughout all area are analysed. It is supposed that the epidemic potential of natural focus depends upon temperature conditions during the winter period.     

New findings concerning the spread of natural foci of infection in the transpolar region of eastern Siberia]

New materials are presented on the presence of the foci of anthropozoonozes in the Extreme North. For the first time there was established the existence in the subarctic tundra of the Taimyr peninsula of the arbovirus foci of the tick-borne encephalitis complex. A virus of the tick-borne encephalitis complex was isolated in 1973 from the gamasida ticks Haemogamasus ambulans Thorel. and Hirstionyssus isabellinus Oudms. and the nests of the Siberian lemming Lemmus lemmus L. This pointed to the existence in the Transpolar region of the foci or arboviruses in the nest-hole biocenoses of the lemmings outside the bird colonies. Cultures of tularemia bacilli (which proved the etiology of the epizootic among the lemmings observed in 1973 and also the presence of the lemming natural foci of tularemia and their combination with the arbovirus foci) were isolated from the lemmings at the same territory. The results of serological examination of the local population and of the animals pointed to the circulation in the Transpolar region of the causative agents of leptospirosis, toxoplasmosis, Q-fever and of the Asian tick-borne rickettsiosis.     

Effectiveness of the seroprophylaxis of tick-borne encephalitis depending on the titer of homologous gamma-globulin antihemagglutinins

To give a rationale for using homologous gamma globulin with antihemagglutinin titers of 1 : 20 to 1 : 80 for the prophylaxis of tick-borne encephalitis, 5-year observations covering all persons attacked by ticks in one of the intensive natural foci of the disease in the Western Urals have been made. The threefold statistically significant difference in the morbidity rate of tick-borne encephalitis between groups of persons immunized and not immunized with gamma globulin has been shown.     

Epidemiological characterization of Ixodes tick-borne borreliosis in the Krasnoyarsk territory

The analysis of morbidity in tick-borne infections for many years indicates that in the 1960s-1990s in the total structure of the clinical forms of tick-borne encephalitis the erythematic form amounted to 1.4-20.9, which 1.9- to 3.1-fold exceeded the morbidity characteristics for the whole of Russia. The epidemiological analysis of morbidity at the territory for the period of 1992-2001 is indicative of the presence of the combined foci of tick-borne encephalitis and Ixodes tick-born borrelioses (TBB) in 42 regions of the territory. The cyclic character of morbidity and the irregularity of its spread in different regions of the territory can be observed. Among the TBB patients, town dwellers constitute, on the average, 75.8%. These tick-born infections exhibit regional differences connected with landscape variations and the patients age. However official statistics does not reflect the real epidemic situation at the territory: hypodiagnostics is primarily due to the absence of reliable laboratory confirmation in remote regions of the Krasnoyarsk territory.     

蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5的研究进展

蜱传脑炎病毒是引起严重的中枢神经系统疾病蜱传脑炎的病原体,每年在欧洲、俄罗斯远东地区、日本和中国北部报道的蜱传脑炎病例数约为10000-12000例,且在我国和多个欧洲国家的发病率逐渐增高,正成为人类健康的潜在危害。主动免疫是预防蜱传脑炎的有效措施,包括我国在内的多个国家已研制出安全性较高的疫苗,但在我国流行省份的疫苗接种较为有限,特异性抗病毒药物的研发或许是治疗蜱传脑炎病毒感染的研究方向之一。蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5因为在病毒基因组复制、加帽和宿主免疫调节中的重要作用,成为关键的抗病毒药物研发靶点。本文综述了蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5的三维结构和抑制剂研发工作,为深入探究该病毒感染的分子机制和抗病毒药物研发提供参考。     

Synthetic fragments of the NS1 protein of the tick-borne encephalitis virus exhibiting a protective effect

Potentially immunoactive regions of the NS1 nonstructural protein of the tick-borne encephalitis virus that can stimulate the antibody formation in vivo and protect animals from this disease were chosen on the basis of theoretical calculations. Eleven 16- to 27-aa peptides containing the chosen regions were synthesized. The ability of the free peptides (without any high-molecular-mass carrier) to stimulate the production of antipeptide antibodies in mice of three lines and ensure the formation of protective immunity was studied. Most of these peptides were shown to exhibit the immunogenic activity in a free state. Five fragments that can protect mice from the infection by a lethal dose of tick-borne encephalitis virus were found.     

Synthetic fragments of the NS1 protein of the tick-borne encephalitis virus exhibiting a protective effect

Potentially immunoactive regions of the NS1 nonstructural protein of the tick-borne encephalitis virus that can stimulate the antibody formation in vivo and protect animals from this disease were chosen on the basis of theoretical calculations. Eleven 16-to 27-aa peptides containing the chosen regions were synthesized. The ability of the free peptides (without any high-molecular-mass carrier) to stimulate the production of antipeptide antibodies in mice of three lines and ensure the formation of protective immunity was studied. Most of these peptides were shown to exhibit the immunogenic activity in a free state. Five fragments that can protect mice from the infection by a lethal dose of tick-borne encephalitis virus were found.     

Role of sialic acids in the immune response formation in tick-borne encephalitis

The content of individual forms of sialic acids and total sialic acids in the lymphocytes of tick-borne encephalitis patients has been studied. The level of sialic acids has been found to depend on the clinical form of the disease and on the content of specific IgM and IgG to tick-borne encephalitis virus. Similar dependence has been established with respect to total sialic acids in lymphocytes.     

The clinico-epidemiological characteristics of the course and diagnosis of tick-borne rickettsiosis in northern Asia

The study of tick-borne rickettsiosis in Northern Asia has made it possible to determine the clinico-epidemiological features of the modern course of this disease, which should be taken into consideration for the timely diagnosis of this infection. The laboratory verification of the diagnosis should be carried out, as recommended by the authors, in the agar precipitation and leukocytosis tests in their modification.     

Nucleotide sequence of genes and complete amino acid sequence of tick-borne encephalitis virus strain 205

The 10466 nucleotide long sequence of the cDNA copy of the tick-borne encephalitis strain 205 viral genome has been determined. It includes the 5'-nontranslating region, the genes for structural as well as nonstructural proteins and the first 93 nucleotides of 3'-nontranslating region. The difference in amino acid sequences of structural and nonstructural proteins of strains 205. Sofjin and Neudoerfl of the tick-borne encephalitis virus and the nucleotide changes in 5'- and 3'-nontranslating of these strains are discussed.     

Use of the specific rosette formation test in tick-borne encephalitis for the purpose of laboratory diagnosis

In the study of blood samples collected from patients with tick-borne encephalitis, the modified antigen-specific rosette formation test with erythrocytes, loaded with tick-borne encephalitis virus antigen via the specific immunoglobulin, has been used. The number of rosette-forming cells has been the highest during the acute period of the disease. The use of this test has confirmed the clinical diagnosis of the disease, together with hemagglutination inhibition serving as the main diagnostic test, in 35% of cases. The results of this study make it possible to recommend the antigen-specific rosette formation test for the early diagnosis of tick-borne encephalitis.     

Synthesis, immunogenicity and antigenic characteristics of the glycoprotein E fragments from the tick-borne encephalitis virus]

Six peptide fragments of the envelope protein E of the tick-borne encephalitis virus involving the predicted T-helper epitopes were synthesized. Their ability to induce antibodies without conjugation with any high-molecular-mass carrier was studied in mice of three lines. Five of six synthesized peptides exhibited immunogenic properties, which differed in dependence on the haplotype of immunized mice. The peptide binding to the antiviral antibodies was studied, and two peptides were revealed that demonstrated a high ability to recognize the viral antibodies in the horse and human sera. These peptides are promising for the development of diagnostic agents for the tick-borne encephalitis virus.     

Structural modifications of macrophages initiated by tick-borne encephalitis virus

Macrophages are cells of natural immunity and play a key role in pathogenesis of viral infections. Results of ultrastructural research on macrophages infected with tick-borne encephalitis virus (TBEV), an agent that causes dangerous infections affecting nervous system in human beings and belongs to the Flaviviridae family, were shown here. Using virology methods, it was ascertained that the TBEV is consumed by macrophages and multiplies in them. Ultrastructural research showed that the virus penetrates into the cytoplasm by means of local plasmalemma lysis and newly synthesized virus particles escape from the cell by the same path. At the same time, induration of the perinuclear space of cytoplasm was observed, where ribosomes, microfilaments, ribonucleoprotein threats, and virus-specific structures, namely, nucleocapsids, tube formations, and viroplasts, were found in large quantities. On the surface of viroplasts, newly synthesized virus particles were visualized. Thus, evidence was presented that microphages can play certain role in spreading of TBEV and are the target of the virus. Like active antigen-presenting cells, such macrophages can modulate the protective response of an organism and affect the pathogenesis of tick-borne encephalitis.