Search

Aim: The aim of the study was to assess the efficacy of pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) combination therapy in treatment-naive patients with chronic hepatitis C in Estonia.Methods: Out of 121 outpatients with chronic hepatitis C (73 males, 48 females, aged 19-63) enrolled in the study, 76 were infected with HCV genotype 1b and 45 with genotype 3a. At baseline, the viral load in 75.2% of patients was higher than 600,000 IU/mL. Histologically, 88.4% of patients had fibrosis score F0-2. Patients received 180 microg of Peg-IFN alpha-2a weekly plus daily ribavirin 1,000 or 1,200 mg, depending on body weight, in HCV genotype 1b, or 800 mg/day in genotype 3a infection.Results: The overall sustained virologic response (SVR) rate in our study was 60.3%, being statistically lower for patients with HCV genotype 1b as compared to patients with genotype 3a (46.1% vs. 84.4%, p < 0.05). The non-response and relapse rates were significantly higher in patients infected with HCV genotype 1b compared with patients infected with genotype 3a (19.7% vs. 2.2%, p = 0.01; and 17.1% vs. 4.4%, p = 0.04; respectively). The SVR rate was higher in patients younger than 40 years compared with older patients (76.4% vs. 47.0%, p < 0.01), regardless of the genotype. Thirteen patients infected with HCV genotype 1b required dose reduction of PegIFN and/or RBV because of adverse side effects. Nine of them achieved SVR.Conclusion: HCV genotype and age younger than 40 years predetermined SVR rate in treatment-naive Estonian patients with chronic hepatitis C treated with Peg-IFN alpha-2a plus ribavirin. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is prevalent worldwide and is a significant cause of morbidity and mortality. This article describes the trend in HBV occurrence in Estonia from 1990 to 2005 in Estonia, with the aim of highlighting key determinants in transmission dynamics, risk groups, and possible implications for prevention and control. A marked increase in reported numbers of new HBV cases occurred in mid 1990s (reaching 39 per 100,000 population) and decline thereafter. We present data on HBV prevalence from different population groups (persons with verified sexually transmitted infection, prisoners, medical personnel, blood donors and injection drug users). Special vaccination programmes introduced in Estonia have been successful in the prevention of HBV, however, we suggest that the main risk groups such as injection drug users (IDUs), men having sex with men (MSM) and HIV infected persons should be actively encompassed into HBV vaccination programme. [ABSTRACT FROM AUTHOR]

A total of 381 hepatitis B virus (HBV) DNA sequences collected from nine groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strains from Central Asian republics and Mongolia. Different HBV subgenotypes predominated in various native Siberian populations. Subgenotype D1 was dominant in Altaian Kazakhs (100%), Tuvans (100%), and Teleuts (100%) of southern Siberia as well as in Dolgans and Nganasans (69%), who inhabit the polar Taimyr Peninsula. D2 was the most prevalent subgenotype in the combined group of Nenets, Komi, and Khants of the northern Yamalo-Nenets Autonomous Region (71%) and in Yakuts (36%) from northeastern Siberia. D3 was the main subgenotype in South Altaians (76%) and Buryats (40%) of southeastern Siberia, and in Chukchi (51%) of the Russian Far East. Subgenotype C2 was found in Taimyr (19%) and Chukchi (27%), while subgenotype A2 was common in Yakuts (33%). In contrast, D2 was dominant (56%) in urban populations of the former western USSR, and D1 (62%) in Central Asian republics and Mongolia. Statistical analysis demonstrated that the studied groups are epidemiologically isolated from each other and might have contracted HBV from different sources during the settlement of Siberia.

The bacterium Francisella tularensis (Ft) is one of the most infectious agents known. Ft virulence is controlled by a unique combination of transcription regulators: the MglA-SspA heterodimer, PigR, and the stress signal, ppGpp. MglA-SspA assembles with the σ 70 -associated RNAP holoenzyme (RNAPσ 70 ), forming a virulence-specialized polymerase. These factors activate Francisella pathogenicity island (FPI) gene expression, which is required for virulence, but the mechanism is unknown. Here we report FtRNAPσ 70 -promoter-DNA, FtRNAPσ 70 -(MglA-SspA)-promoter DNA, and FtRNAPσ 70 -(MglA-SspA)-ppGpp-PigR-promoter DNA cryo-EM structures. Structural and genetic analyses show MglA-SspA facilitates σ 70 binding to DNA to regulate virulence and virulence-enhancing genes. Our Escherichia coli RNAPσ 70- homodimeric EcSspA structure suggests this is a general SspA-transcription regulation mechanism. Strikingly, our FtRNAPσ 70 -(MglA-SspA)-ppGpp-PigR-DNA structure reveals ppGpp binding to MglA-SspA tethers PigR to promoters. PigR in turn recruits FtRNAP αCTDs to DNA UP elements. Thus, these studies unveil a unique mechanism for Ft pathogenesis involving a virulence-specialized RNAP that employs two (MglA-SspA)-based strategies to activate virulence genes., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Host-derived glutathione (GSH) is an essential source of cysteine for the intracellular pathogen Francisella tularensis. In a comprehensive transposon insertion sequencing screen, we identified several F. tularensis genes that play central and previously unappreciated roles in the utilization of GSH during the growth of the bacterium in macrophages. We show that one of these, a gene we named dptA, encodes a proton-dependent oligopeptide transporter that enables growth of the organism on the dipeptide Cys-Gly, a key breakdown product of GSH generated by the enzyme γ-glutamyltranspeptidase (GGT). Although GGT was thought to be the principal enzyme involved in GSH breakdown in F. tularensis, our screen identified a second enzyme, referred to as ChaC, that is also involved in the utilization of exogenous GSH. However, unlike GGT and DptA, we show that the importance of ChaC in supporting intramacrophage growth extends beyond cysteine acquisition. Taken together, our findings provide a compendium of F. tularensis genes required for intracellular growth and identify new players in the metabolism of GSH that could be attractive targets for therapeutic intervention., Competing Interests: The authors have declared that no competing interests exist.

Hfq is an RNA chaperone that serves as a master regulator of bacterial physiology. Here we show that in the opportunistic pathogen Pseudomonas aeruginosa , the loss of Hfq can result in a dramatic reduction in growth in a manner that is dependent upon MexT, a transcription regulator that governs antibiotic resistance in this organism. Using a combination of chromatin immunoprecipitation with high-throughput sequencing and transposon insertion sequencing, we identify the MexT-activated genes responsible for mediating the growth defect of hfq mutant cells. These include a newly identified MexT-controlled gene that we call hilR We demonstrate that hilR encodes a small protein that is acutely toxic to wild-type cells when produced ectopically. Furthermore, we show that hilR expression is negatively regulated by Hfq, offering a possible explanation for the growth defect of hfq mutant cells. Finally, we present evidence that the expression of MexT-activated genes is dependent upon GshA, an enzyme involved in the synthesis of glutathione. Our findings suggest that Hfq can influence the growth of P. aeruginosa by limiting the toxic effects of specific MexT-regulated genes. Moreover, our results identify glutathione to be a factor important for the in vivo activity of MexT. IMPORTANCE Here we show that the conserved RNA chaperone Hfq is important for the growth of the opportunistic pathogen Pseudomonas aeruginosa We found that the growth defect of hfq mutant cells is dependent upon the expression of genes that are under the control of the transcription regulator MexT. These include a gene that we refer to as hilR , which we show is negatively regulated by Hfq and encodes a small protein that can be toxic when ectopically produced in wild-type cells. Thus, Hfq can influence the growth of P. aeruginosa by limiting the toxic effects of MexT-regulated genes, including one encoding a previously unrecognized small protein. We also show that MexT activity depends on an enzyme that synthesizes glutathione., (Copyright © 2019 American Society for Microbiology.)

Between June-September 2018, 20 hepatitis A cases were notified in six counties in Sweden. Combined epidemiological and microbiological investigations identified imported frozen strawberries produced in Poland as the source of the outbreak. Sequence analysis confirmed the outbreak strain IB in the strawberries with 100 % identity and the respective batch was withdrawn. Sharing the sequence information internationally led to the identification of 14 additional cases in Austria, linked to strawberries from the same producer.

Termination of RNA Polymerase II (Pol II) activity serves a vital cellular role by separating ubiquitous transcription units and influencing RNA fate and function. In the yeast Saccharomyces cerevisiae , Pol II termination is carried out by cleavage and polyadenylation factor (CPF-CF) and Nrd1-Nab3-Sen1 (NNS) complexes, which operate primarily at mRNA and non-coding RNA genes, respectively. Premature Pol II termination (attenuation) contributes to gene regulation, but there is limited knowledge of its prevalence and biological significance. In particular, it is unclear how much crosstalk occurs between CPF-CF and NNS complexes and how Pol II attenuation is modulated during stress adaptation. In this study, we have identified an attenuator in the DEF1 DNA repair gene, which includes a portion of the 5'-untranslated region (UTR) and upstream open reading frame (ORF). Using a plasmid-based reporter gene system, we conducted a genetic screen of 14 termination mutants and their ability to confer Pol II read-through defects. The DEF1 attenuator behaved as a hybrid terminator, relying heavily on CPF-CF and Sen1 but without Nrd1 and Nab3 involvement. Our genetic selection identified 22 cis -acting point mutations that clustered into four regions, including a polyadenylation site efficiency element that genetically interacts with its cognate binding-protein Hrp1. Outside of the reporter gene context, a DEF1 attenuator mutant increased mRNA and protein expression, exacerbating the toxicity of a constitutively active Def1 protein. Overall, our data support a biologically significant role for transcription attenuation in regulating DEF1 expression, which can be modulated during the DNA damage response., (Copyright © 2018 Whalen et al.)

In this cross-sectional study, we investigated veterinarians in Estonia for evidence of exposure to hepatitis E virus (HEV). In 2012, we collected sera from 158 persons attending a veterinary conference, of whom 156 completed a questionnaire covering their background information. Altogether 115 persons reported they had obtained a veterinary degree and were included in this study. The sera were tested for presence of antibodies against HEV using a commercial enzyme linked immunosorbent assay and a commercial immunoblot assay in series. A sample was considered antibody-positive if it tested positive with both tests. Antibody-positive samples were further examined for the presence of HEV RNA. Three (2.6%) of the 115 veterinarians tested positive for immunoglobulin G antibodies against HEV, whereas no immunoglobulin M antibodies against the virus were detected. The antibody-positive veterinarians were small animal practitioners. Pigs comprised no or small part of their working time or patients. No HEV RNA was detected in the antibody-positive samples. The prevalence of antibodies against HEV in veterinarians in Estonia was lower than what has been observed in veterinarians in other countries.

Aim: Study molecular epidemiology of hepatitis C (HC) in 5 departments of hemodialysis (DH) in St. Petersburg., Materials and Methods: Sequences of nucleotides of 93 isolates including 67 isolates from patents of 5 DH and 26 isolates from patients, who never had hemodialysis in anamnesis, were obtained in 2010 by a method of limited sequencing of NS5B region of HC virus genome. Phyologenetic analysis was carried out by using PHYLIP veision 3.69 program package. Evolution differences were evaluated in DNADIST program using F84 algorithm. Phylogenetic trees were constructed by using nearest neighbor and UOGMA methods in PHYLIP program package., Results: Subtype 1b was established to dominate in all the DH (69.2 - 92.9%) and the same isolates of HC virus were detected in DH, that were isolated for the first time in 1999. Comparatively higher proportion of isolates of HC subgenotype 3a (26.7 - 30.8%) was detected in 2 of 5 DH in 2010. The same proportion of 3a isolates was detected in the control group., Conclusion: The fact that HC 3a virus isolates were detected in DH in a higher proportion is proof that they have successfully integrated into circulation among dialysis patients over the last decade. ,

Background: A substantial proportion of hepatitis C virus (HCV)-1b infected patients do not response to pegylated interferon-α plus ribavirin (PegIFNα/RBV) combination therapy that was partially associated with mutations in the non-structural 5A (NS5A) protein., Objectives: Analysis of NS5A polymorphisms in HCV genotype 1b pre-treatment serum samples from Estonian patients and their effect on the treatment response., Patients and Methods: Twenty-nine complete NS5A sequences obtained from patients with chronic HCV-1b infection who had received combined therapy with PegIFNα-2a/RBV were analyzed and compared with the prototype strain HCV-J. Twelve patients achieved a sustained virological response (SVR), 15 were non-SVR and 2 patients stopped treatment because of side effects., Results: No significant difference in total number of amino acid mutations was observed between isolates from SVR and non-SVR patients in any known regions of the NS5A protein. However, specific amino acid substitutions at positions 1989 and 2283 correlated significantly with SVR, mutations at positions 1979, 2107, 2171 and 2382 were associated with non-response to treatment and amino acid substitution at position 2319 was observed in relapsers. At phylogenetic analysis, NS5A nucleotide sequences have been subdivided into four groups characterized by the different treatment response. Twenty-four novel nucleotide polymorphisms and 11 novel amino acid polymorphisms were identified based on the phylogenetic tree topology., Conclusions: Specific amino acid substitutions correlating with the treatment response were found. Polymorphisms revealed by phylogenetic analysis may define the signature patterns for treatment susceptible and treatment resistant strains prevalent in Estonia.

Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.

During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty-three anti-HCV positive sera collected during 1994-2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5'-UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5'UTR-core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999-2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P < 0.05). However, both subtypes were found to co-circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia., ((c) 2007 Wiley-Liss, Inc.)

The genotypes and subtypes of 205 HBV isolates collected during 1989-2002 in Estonia and 14 other regions of the former USSR were determined by sequencing and phylogenetic analysis of the S gene. The in Europe prevailing genotypes, A and D, were also circulating in the whole territory of the former USSR including Estonia and accounted for 18.5 and 81% of the strains, respectively. All genotype A strains specified adw2, and a single genotype C strain specified adrq+. Most genotype D strains specified ayw3 and ayw2, although, three strains from Estonia and Siberia specified ayw4. Due to unique substitutions, Ser122 and Ala127, four strains could not be classified according to the subtype. One strain specifying ayw3 encoded Leu143 and Ala145 and was possibly an immune "escape" mutant. At phylogenetic analysis 93% of the Estonian genotype D strains belonged to a cluster specifying mainly ayw3 and were more similar to isolates from Siberia and the Far-East of Russia than to isolates originating from Central Russia which belonged to another cluster of strains specifying mainly ayw2. This pattern might be explained by part of the Estonian population, has roots east of European Russia, based on linguistic evidence. Eight dominant HBV strains represented by identical S gene sequences were identified, one within genotype A and seven within genotype D, three of which included isolates from Estonia and Siberia. Some of these strains were collected over a period of at least 13 years indicating there are genetically stable variants of HBV that remain conserved over decades.

The serum levels of Th1 (gamma-IFN and sIL-2r) and of Th2 (IL-10) cytokines were measured in 33 patients (23 males and 10 females, mean age 23.1 +/- 1.9) with chronic viral hepatitis (CVH) according to a disease etiology (6 patients with hepatitis B--CVHB, 15 patients with hepatitis C--CVHC, and 12 patients with a mixed form of chronic hepatitis B and C--HBV + HCV). Besides, the contents of the studied cytokines were compared with the traditional infection markers and the presence of viremia. The similar indices taken from 10 healthy persons served as controls. The concentration of gamma-IFN was found to be reliably higher (p < 0.05) in patients of all three groups (0.32 +/- 0.07, 0.34 +/- 0.09 and 0.25 +/- 0.06 pg/ml, respectively) regardless of a disease etiology and as compared with the control value (0.09 +/- 0.04) pg/ml). At the same time, the levels of gamma-IFN, sIL-2r and IL-10 (0.25 +/- 0.06 pg/ml, 166.5 +/- 31.3 IU/ml and 48.1 +/- 8.4 pg/ml, respectively) was found to be reliably (p < 0.05 and p < 0.01) higher, as compared to the controls (0.09 +/- 0.04, 57.1 +/- 5.6 and 10.8 +/- 7.8, respectively), only in patients with the mixed infection of hepatitis. Like in our previous study, a trend was established towards the growing mean values of the IL-r level from its lowest parameters in the group of CVHB patients towards its highest parameters in the group with the mixed hepatitis form. According to our data, the IL-2r level correlated reliably with the activity of AlAt (r = 0.452; p < 0.05), while the gamma-IFN content correlated reliably with the IL-10 concentration (r = 0.805; p < 0.05), and the gamma-IFN content correlated with the IL-10 concentration (r = 0.805; p < 0.01) irrespective of disease pathology.

Hepatitis A virus (HAV) isolates from a large outbreak and from non-outbreak cases in Estonia were characterized by sequencing the aminoterminal VP1 region. From January 1998 to December 1999, a total of 1084 cases of hepatitis A were reported to the Harjumaa-Tallinn and Ida-Virumaa Health Protection Services in Estonia. The attack rate was highest among males aged 15-29. Initial cases were noted to be associated with injecting drug use. IgM anti-HAV positive sera were available from 107 hospitalized outbreak cases and from 68 patients sampled during 1994 to 2001. HAV RNA was detected in 42% of sera from 1994-1996 and in 88% of sera from 1998-2001. It was possible to obtain HAV sequences from 83 outbreak and 29 background cases. The outbreak strain was represented by five different sequences, all belonging to subtype IIIA. During the outbreak, this IIIA strain also spread into the general population. All available non-outbreak isolates from 1994 to 2001 but one belonged to genotype IA and formed distinct clusters as compared to isolates from other parts of the world. One subtype IIIA isolate from 1995 was unrelated to the outbreak strain. Subtype IA had been dominating in Estonia during 1994-2001, but the outbreak strain from 1998 to 1999 was IIIA. This subtype was encountered previously in addicts in Sweden during the 1980s and in Norway at the end of the 1990s. This study supports the use of limited sequencing within the aminoterminal VP1 region for studying the molecular epidemiology of hepatitis A., (Copyright 2003 Wiley-Liss, Inc.)

Forty-four patients with chronic HBV and HCV were observed. Serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and soluble IL-2 receptor (IL-2r) were measured by enzyme immunoassay in 29 patients divided into 3 groups: group 1 (n = 9) with chronic HBV, group 2 (n = 9) with chronic HCV, and group 3 (n = 11) with mixed HBV + HCV infection. Control group consisted of 10 normal subjects without HBV, HCV, or HIV infection markers. The most informative of Th1 cytokines was IL-2r: its concentration was increased significantly (p < 0.01) in all patients with hepatitis B and/or C in comparison with the control. In addition, there was a trend to an increase in the mean concentrations of IL-2r from group 1 to groups 2 and 3. The concentrations of IFH-gamma and IL-2 did not differ significantly in the patients and controls. However, the concentrations of IFN-gamma were increased significantly (p < 0.01) in comparison with the control in 3 patients from group 1 and 4 patients from group 3 with more pronounced inflammation.

During recent 10 years (1990-1999) essential changes occurred the epidemiology of viral hepatitis A (VHA) in Estonia: simultaneously with a decreased level of morbidity (morbidity rate per 100,000 of the population was 78.4 in 1990 and 7.7 in 1996, or 1,241 and 112 cases, respectively), a shift in the age structure of patients from children of preschool age to older age groups took place. Everyday contacts were the main established route of VHA transmission in recent years, but in more than 80% of cases the risk factors of the virus transmission remained obscure. During the regional outbreak of VHA in North Estonia in 1998 (937 out of 989 cases registered in the country) a rise in morbidity was observed among young people aged 15-29 years, when a wide spread of parenteral viral hepatitides B and C and drug addiction were registered in this region. During this outbreak VHA was transmitted mainly through everyday contacts. Still the considerable prevalence of injection drug users who practiced the group use of syringes and needles and took drugs from common containers, a sufficiently high level of the mixed forms of the disease (more than 18% of all registered cases of VHA), detected for the first time, make it possible to suggest that the parenteral transmission route could appear among persons belonging to the above mentioned group. Vaccination is regarded as the most effective measure for the prophylaxis of VHA.

The functional metabolic activity of peripheral blood neutrophils in acute virus hepatitis B (VHB) and/or virus hepatitis C (VHC) was evaluated. 48 patients were examined; of these, VHB was diagnosed in 28 patients and VHC was diagnosed in 9 patients and the mixed form of virus hepatitis (VHB + VHC), in 11 patients. Determination of adhesive capacity of neutrophils, production of superoxidase anion in the nitro blue tetrazolium (NBT) test, activity of myeloperoxidase (MPO) and acidic phosphatase (AP), the amount of cation proteins (CP) was made. Most pronounced functional dysbalance of neutrophil leukocytes and considerable changes in biochemical characteristics of the activity of the infectious process in patients with the mixed form of virus hepatitis were established. These data demonstrated that in acute virus hepatitis B and C at the peak of the disease such characteristics of the functional activity of neutrophils as results of the NBT test, the activity of MPO and AP, as well as the amount of CP, were highly informative.

Distribution of hepatitis C virus (HCV) genotypes among 30 patients with chronic liver diseases and antibodies to HCV (anti-HCV) was investigated. Sera of these patients were analyzed for HCV genotype by reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) analysis of the 5'-non-coding region (5'-NCR) of the virus genome and for HCV serotype by detecting antibodies to HCV NS4 peptides by enzyme-linked immunosorbent assay (ELISA). The following distribution of genotypes was found: genotypes 1b in 32.0%, 3a in 20.0%, 2a in 12.0% and 1a/b (double infection) in 28.0%. The results of serotyping were interpretable in 92.0% and concordant with those of genotyping in 80.0% of the patients. In Northern Estonia, the genotypes 1b and 3a seem to be most common in chronically infected patients. Serotyping is an generally available and cheap assay and can be performed in most diagnostic laboratories in comparison to genotyping. However, genotyping is a more sensitive and more specific assay.

The production of alpha- and gamma-interferon (IFN) by peripheral blood cells in vitro and the concentration of serum IFN were studied in patients treated by hemodialysis at the Pelgulinna Tallinn Hospital and compared to controls. Out of 108 patients on hemodialysis, 19.4% were infected with hepatitis B (HBV), and antibodies to hepatitis C virus (HCV) were detected in 7.4%. During 3.5 years of observation, cases of hepatitis B and C infection among patients and medical staff were rare. The production of alpha- and gamma-IFN in 23 patients with HBV and/or HCV markers on hemodialysis and in 38 patients without markers was similarly decreased in comparison with the controls and the titers of serum IFN were similarly increased. Lack of reliable difference between IFN status of two groups of patients may be explained by the absence of clinical symptoms of hepatitis, confirmed by laboratory findings.

The etiological structure of viral hepatitides among the adult population of Tallinn and the occurrence of markers of hepatitis B and hepatitis C virus infections in medical workers, addict introducing drugs intravenously and hemodialysis patients were studied. Changes in the etiological structure of viral hepatitides were established: they took the form of a decrease in the level of hepatitis A morbidity and the considerable growth of the role of hepatitides B and C, as well as the newly detected circulation hepatitis D virus. About one-third in the structure of morbidity in viral hepatitides were hepatitis cases without markers of hepatitis A, B or C viruses (non-A, non-B, non-C). The highest rates of hepatitis B virus infection (78.9%) and hepatitis C virus infection (82.5%) were detected among drug addicts. Their level of HBsAg was 8.8%. In the group of medical workers, 25% of the examinees, i.e. every fourth person, had markers of hepatitis B virus, while antibodies to hepatitis C virus were detected in 5% of cases. Among hemodialysis patients these rates were 21.4% and 10.7% respectively.

In vitro production of alpha- and gamma-interferon (IF) by peripheral blood cells and the concentrations of serum IF were studied in 47 intravenous drug users infected with hepatitides viruses B and C (HBV and HCV) and in 50 inpatients with verified diagnosis of hepatitides B or C, 16 of these narcomaniacs. In acute disease, the capacity of cells to produce alpha- and gamma-IF was suppressed, while the concentration of IF circulating in the blood was increased. Suppression of alpha-IF production was more expressed in patients with hepatitides C and B+C than in those with hepatitis B. HBV and/or HCV infection without clinical signs of disease did not affect the production of IF. In narcomaniacs using opiates and ephedrine drugs for up to 5 years IF system did not depend on drug addiction.