Cytokine Profiling of Subclinical Tick-Borne Infections in Humans.

Over many years, tick-borne infections remain one of the most serious threats to human health worldwide. The immune response to these infections in a human after confirmed bite by an infected carrier at the early stages of infection in the absence of clinical symptoms can be the first indicator of the presence of the infectious agent in the body. During viral infection, the concentration of IL-1α, IL-8, IL-10, IL-17A, and IFNγ increases; superoxide dismutase also increases, in contrast to bacterial infections. A slight decrease in the concentration is observed only for receptor antagonist IL-1Ra. During the infection caused by bacterial pathogens, very similar profiles of the innate human immune response are observed: activation of IL-1α, IL-8, and IFNα and suppression of superoxide dismutase, IL-1Ra, and IL-17A production. It has been demonstrated, that the immune response is triggered immediately after infection, and changes in the concentration of the main cytokines in the blood plasma can be detected as early as on days 2-5 after tick bite. These results can be useful in developing new methods of emergency diagnosis and prevention of tick-borne infections.

[Child and Adolescent Interepydemic Immunity to Influenza Viruses].

OBJECTIVE: Our aim was to evaluate the child and adolescent population immunity to influenza A viruses (IAV) and influenza B virus (IBV). METHODS: The concentration and specificity of antiviral antibodies was evaluated by hemagglutination inhibition assay (HAI) that was performed using commercial HAI diagnostic kits. RESULTS: The serum samples of 254 clinically healthy children and adolescents were examined in this study. 245 participants had the antibodies to IAV, 199--to IAV and IBV and only 4 children aged between 1 and 4 years and a 12-year-old boy had no immunity to IAVor IBV. The number of children with specific immunity increased in elder groups by 43% (from 81 to 116) for N0N1, and H3N2 subtypes and by 110% (from 38 to 80) for H1N1 subtype of IAV. In children younger than 4 years the titer of specific antibodies against the H1N1pdm09 was 1:210 and against the H3N2--1:270, whereas in adolescents of 10-14 years these figures were by 1.6 and 2.4 times lower (1:130 and 1:120) respectively. Antibodies to the subtypes H2N2 and H5N1 were not detected. CONCLUSION: The results indicate that 98.4% of child and adolescent population in interepidemic influenza season are immune to the various IAV (H3N2, H1N1, H0N1) as well as to the IBV. More than half of children and adolescents (57.4%) are immune to H1N1pdm09 subtype of IAV. The strength of immune response to the recent pathogens (H3N2 u H1N1pdm09) is higher in infants than in teenagers.

[Genetic characteristics of the causative agent of tick-borne encephalitis in Mongolia].

A patient with diagnosed meningoencephalitis and a history of tick bite died in Mongolia in 2008. The purpose of this paper is to characterize the virus causing the ill person's death. The virus was identified using the phylogenetic analysis of the 520-bp fragment of the tick-borne encephalitis virus (TBEV) genome, which codes the fragment of TBEV protein E between 52-223 amino acids. TBEV RNA was detected in the samples of medulla oblongata, cerebral cortex, and pia mater of brain, but not in the cerebellar tissue. The study virus fragment was genetically closest to the representatives of the Far East subtype. Its closest relative was virus 740-84 (GenBank EU878282) isolated from large-toothed redback voles (Clethrionomys glareolus) in Buryatia and greatly differed from the Far East virus Soffin. Two amino acid substitutions (H86R and VI7A) were detected within the study protein E fragment. The paper is the first to describe the causative agent of tick-borne encephalitis on the territory of Mongolia and to discuss the evolution and pathogenicity of TBEV.

[The heterogeneity of the ospa gene of Borrelia garinii and Borrelia afzelii in western Siberia and Mongolia].

48 full-length Borrelia garinii and Borrelia afzelii from West Siberia and Mongolia ospA gene nucleotide sequences was determined. Four groups of Borrelia garinii were revealed using the analysis of nucleotide sequences. The most variable ospA gene region was demonstrated to be included in region where the antigenic determinants of protein were encoded. High homology level was shown for nucleotide sequences corresponding to isolates of Borrelia afzelii.

[Molecular epidemiology of tick-borne encephalitis].

The review presents information on the development of studies into the molecular epidemiology of tick-borne encephalitis (TBE) in Russia and foreign countries. The existence of three major virus genotypes has been established by various techniques, such as genomic fragment sequencing, molecular hybridization using genotype-specific probes, and restriction fragment length polymorphism test. Each of the genotypes prevails in different parts of a natural habitat; the Ural-Siberian genotype (a Siberian subtype) is most commonly encountered. The genetic differences between the strains belonging to different genotypes are great and comparable with differences between some mammalian flaviviruses transmitted by ticks (viruses of a TBE complex). Further studies of the molecular epidemiology of TBE are of importance in understanding the evolution of the causative agent, improving the taxonomy and the classification of flavivuruses, and designing highly effective methods for the specific diagnosis, prevention, and treatment of the disease.

[Current approaches to emergency specific prevention of tick-borne encephalitis].

Emergency specific prevention of tick-borne encephalitis (TBE) by using homologous immunoglobulin is an important element in the package of controlling measures against this viral natural and focal infection. There are annually a few hundred thousand referrals for health care facilities for tick bites. Their maximum coverage tactics via immunoglobulin prevention is medically unreal and unjustifiable. The paper presents the results of a long-term application of another approach based on preliminary rapid studies of the ticks taken from victims or the blood of patients in the period of possible development of virusemia and preventive immunoglobulin use only in the persons bitten with TBE virus-infected ticks. Examination of the material available from more than 56 thousand referrals indicated the high epidemiological (more than 99%) and economic effectiveness of the target administration of an immunological drug. By taking into account the accumulated data on a wide spread of combined foci of TBE and other tick-borne infections and the authors' own experience, it is suggested that it is necessary to organize a comprehensive differential laboratory diagnosis and emergency prevention against the whole complex of Ixodes tick-borne infections.

[Heterogeneity of the gene P83/100 of Borrelia borrelia burgdorferi sensu lato complex].

The 35 full-length Borrelia burgdorferi sensu lato complex a83/100 gene nucleotide sequences were determined. High level of homology was observed in the nucleotide sequences corresponding to the strains and isolates of Borrelia fzelii. The analysis of the nucleotide sequences revealed two groups of Borrelia garinii. The most variable p83/100 gene region containing species-typical insertions and deletions was demonstrated to be included into the region where the antigenic determinants of protein were encoded. According to the data obtained in this work, the modification of the P83/100 protein structure and immunological properties could be suggested to exist even within species. The results of this work could be used for receiving recombinant P83/100 proteins useful for diagnostic applications.

[Clinical and laboratory characterization of Ixodes tick-borne borreliosis in the Baikal area].

Materials on Ixodes tick-borne borreliosis (ITB) for the period of 2000 - 2003 (i.e. 1,222 blood serum samples from patients with acute ITB and 629 patients with chronic ITB) were analyzed. The proportion of seropositive samples among those obtained from patients with acute and chronic ITB was determined with the use of the indirect immunofluorescence test. In addition, data on different clinical forms of the disease were presented. A high percentage of neurological manifestations in the early period of ITB (31%) and in the late period of the disease (72.8%) was noted. The conclusion was made concerning the necessity of using several diagnostic methods for more exact determination of the structure of the disease.

[Comparative data on the tick-borne encephalitis virus infectiousness of hungry and satiated taiga ticks (based on the results of an immunoenzyme analysis)]. / Sravnitel'nye dannye o zarazhennosti virusom kleshchevogo éntsefalita golodnykh i pitavshikhsia taezhnykh kleshchei (po rezul'tatam immunofermentnogo analiza).

The results of individual investigation of 25,500 Ixodes persulcatus ticks from east Siberia are presented. The ticks were collected from grass, men, and animals before their sticking and after feeding at different intervals. The quantity of positive specimens was 6-11 times higher among the fed ticks hungry ones and averaged 10.36 and 1.85%, respectively, at the first stage due to the higher aggression of the infected females at the first stage and due to viral replication when the tick had feed and its better recognition as the titers increased. The proportion of ticks having high levels of tick-borne encephalitis virus antigen among the fed ticks was also considerably higher. The content of virus antigen increased in proportion with the duration of feeding. There is a moderate correlation (r = 0.59) of the infection index of hungry and fed ticks in different years and in various areas. The findings suggest that the fed ticks should be used as an additional marker for the features of tick-borne encephalitis virus circulation.

[The distribution of tick-borne encephalitis virus-infected ticks along a linear census route]. / Raspredelenie infitsirovannykh virusom kleshchevogo éntsefalita kleshchei vdol' lineinogo uchetnogo marshruta.

An individual study of Ixodes persulcatus Schulze, 1930, established that the distribution of infected ticks differs from the normal distribution and it is most close to the Poisson distribution. There is a tendency to deviation from the uniform-random distribution associated with higher infected tick contact rates in some parts of the route.

[Multi-year changes in the morbidity of tick-borne encephalitis in the Irkutsk region]. / Mnogoletnie izmeneniia zabolevaemosti naseleniia kleshchevym éntsefalitom v Irkutskoi oblasti.

Correlation and cluster analysis of data on the number of tick-borne encephalitis cases in the Irkutsk region collected for a 31-year period allowed the authors to distinguish three areas with various morbidity dynamics, physical and geographical conditions and level of land development. Long-term morbidity prognosis is presented.