Distribution of human gene polymorphisms allele frequencies associated with viral infections.

INTRODUCTION: The design of studies aimed at finding the association between the genetic factor and the studied feature (disease) involves a comparison of the ratio of genotypes or allelic proportions in the study group with those in the control group. At the stage of determining the ratio of genotypes of the studied polymorphisms in the reference group, researchers meet a number of problems, which are the subject of the present work. Aim of the work is to provide scientific rationale for the feasibility of creating a national information system comprising genetic data of the relatively healthy population of Russia, incorporating its ethnic diversity. MATERIALS AND METHODS: The study group, total 1020 people, was genotyped for a number of single nucleotide polymorphisms of human genes. A comparative characteristic of the frequency distribution of the studied polymorphisms with those presented in international databases as reference data was carried out using χ2 index. RESULTS: The frequency of SNP rs4986790 of the TLR4 gene significantly differs from the EUR population (p = 0.032) and the CEU subpopulation (p = 0.047). The allele frequencies of the rs1800795 (IL6) and rs1800896 (IL10) polymorphisms in the study population differ from the CEU subgroup (p = 0.030 and 0.012, respectively). The frequency of SNP rs2295119 (HLA-DPA2) in the study group is significantly different from the EUR population (p = 0.034). CONCLUSION: The analysis carried out in this work confirms the need to create a domestic information system containing data on the occurrence of SNP alleles and genotypes for a conditionally healthy population and in subgroups with various pathological conditions.

[Modern views on the role of X gene of the hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) in the pathogenesis of the infection it causes].

The review presents information on the role of hepatitis B virus (Hepadnaviridae: Orthohepadnavirus: Hepatitis B virus) (HBV) X gene and the protein it encodes (X protein) in the pathogenesis of viral hepatitis B. The evolution of HBV from primordial to the modern version of hepadnaviruses (Hepadnaviridae), is outlined as a process that began about 407 million years ago and continues to the present. The results of scientific works of foreign researchers on the variety of the influence of X protein on the infectious process and its role in the mechanisms of carcinogenesis are summarized. The differences in the effect of the X protein on the course of the disease in patients of different ethnic groups with regard to HBV genotypes are described. The significance of determining the genetic variability of X gene as a fundamental characteristic of the virus that has significance for the assessment of risks of hepatocellular carcinoma (HCC) spread among the population of the Russian Federation is discussed.

[Patterns of the SARS-CoV-2 epidemic spread in a megacity].

The purpose of the study is to analyze patterns demonstrated by the COVID-19 epidemic process in a megacity during the increase, stabilization and reduction in the incidence, and to evaluate the effectiveness of the epidemic prevention measures. MATERIALS AND METHODS: The comprehensive study incorporating epidemiological, molecular genetic and  statistical research methods was conducted to analyze the spread of SARS-CoV-2 in Moscow during the COVID- 19 pandemic. RESULTS AND DISCUSSION: It was found that the exponential growth in COVID-19 cases was prevented due to the most stringent control and restrictive measures deployed in Moscow to break the chains of SARS-CoV-2 transmission and due to people who were very disciplined in complying with the self-isolation rules. The  analysis of the dynamics in detection of new COVID-19 cases showed that in a megacity, the impact of social distancing and self-isolation would become apparent only after 3.5 incubation periods, where the maximum length of the period is 14 days. It was discovered that the detection frequency of SARS-CoV-2 RNA in relatively healthy population and its dynamics are important monitoring parameters, especially during the increase and stabilization in the COVID-19 incidence, and are instrumental in predicting the development of the epidemic situation within a range of 1-2 incubation periods (14-28 days). In Moscow, the case fatality rate was 1.73% over the observation period (6/3/2020-23/6/2020). CONCLUSION: The epidemiological analysis of the COVID-19 situation in Moscow showed certain patterns of the SARS-CoV-2 spread and helped evaluate the effectiveness of the epidemic prevention measures aimed at  breaking the routes of transmission of the pathogen.

[EFFECTIVENESS OF PREVENTIVE VACCINE PROPHYLAXIS OF CHICKEN POX IN MILITARY COLLECTIVES].

AIM: Study the effectiveness of preventive vaccine prophylaxis of chicken pox in military collectives. MATERIALS AND METHODS: In the focus of chicken pox, 200 servicemen of the new addition by conscription were immunized once against chicken pox; 97 servicemen by conscription of the new addition (comparison group) were not vaccinated. Epidemiologic and immunologic effectiveness of conduction of preventive vaccine prophylaxis in chicken pox focus were studied. RESULTS: In the group of 200 soldiers, that were present in the focus of infection and were immunized once against chicken pox, only 2 cases of this disease were registered (10 per thousand). In the comparison group, that consisted of 97 unvaccinated servicemen, chicken pox disease was registered in 7 individuals (72 per thousand). Epidemiologic effectiveness of preventive vaccine prophylaxis of chicken pox amounted to 86%. Immunologic effectiveness of vaccination 2-3 weeks after the immunization was 42%, and 2 months after--44%. Local reactions in the form of hyperemia (up to 1.5 cm) and edema were noted in 10% of the vaccinated at the location of preparation administration; in 1.7%--general reaction in the form of temperature increase to 37.8°C was observed. Post-vaccinal complications in the immunized group were not detected. CONCLUSION: Preventive vaccination of servicemen allows to minimize the spread of chicken pox, however can not serve as means of complete elimination of the infection from military collectives.

[Comparative evaluation of effectiveness of traditional serologic and modified methods of herpes zoster laboratory diagnostics].

AIM: Comparative evaluation of effectiveness of traditional serologic and modified diagnostic methods of disease arising due to varicella and herpes zoster virus (VZV) reactivation. MATERIALS AND METHODS: 2 groups of patients were examined. The main group consisted of 39 patients with manifest form of herpes zoster (HZ), control--20 healthy donors. Sex composition of the groups did not differ. Traditional method of serologic diagnostics included determination of anti-gE VZV IgG and anti-VZV IgG and anti-IgM in patient and donor blood sera by using EIA. Modified methods consisted of isolation in density gradient and cultivation for 48 hours of peripheral blood mononuclears (PBMC) in RPMI-1640 complete culture medium containing 10% of fetal bovine serum, 4 mM L-glutamin and gentamycin. Concentrations ofanti-VZV IgG and IgM were then determined in culture medium by using EIA. RESULTS: In all the examined HZ patients and healthy donors anti-VZV IgG were detected in blood. Only in 26 (67%) of 39 HZ patients anti-gE VZV IgG and anti-VZV IgM were determined in blood sera. Among donors false positive results for these markers were detected in 10% and 5% of cases, respectively. During simultaneous determination of anti-gE VZV IgG and anti-VZV IgM the specificity of the method increased to 100%, sensitivity of the diagnostic method based on simultaneous determination of anti-gE VZV IgG and anti-VZV IgM was 59%. During analysis of spontaneous production of anti-VZV antibodies by PBMC in 38 (97.4%) of 39 patients anti-VZV IgG were determined in PBMC culture, anti-VZV IgM production was observed only in 4 patients. In control group false positive results of anti-VZV IgG and IgM production by PBMC was not detected by the modified method (100% specificity). At equal specificity level sensitivity of the modified method based on determination of spontaneous anti-VZV IgG production by PBMC culture was significantly higher than effectiveness of the traditional serologic diagnostics (97.4% and 59%, p < 0.0001). CONCLUSION: The data obtained allow to recommend during diagnostics of manifest and atypical VZV infection forms arising due to endogenous virus reactivation the new modified method of laboratory diagnostics of the disease as having higher sensitivity compared with traditional serologic method.

[Problems of diagnosis of the hepatitis B virus].

The recent data on the genetic variability of the hepatitis B virus and problems of serological ELISA-mediated detection of this virus are discussed.

[Some epidemiological aspects of respiratory diseases in in-country forces of the ministry of internal affairs of the Russian Federation in 1998-2011].

The authors analyzed the rate of respiratory diseases among the contingent of the in-country forces of the Ministry of Internal Affairs of the Russian Federation for the last 14 years. It was noted that the rate of respiratory diseases in 2009-2011 is higher than in 1998-2007. It is concerned with cold aggression and factors of intermigling of contingent, and also with mistakes of prevention actions. Improvement of life quality during all types of military service, improvement of prevention measures is necessary for the complex prevention of respiratory diseases.

[Heterogeneity of hepatitis B virus and diagnostic potential of modern test systems for the detection of HBsAg].

AIM: Study heterogeneity ofhepatitis B virus in adult patients with chronic hepatitis B and determination of diagnostic potential of modern test systems with the detection of HBsAg with amino acid substitutions in the main hydrophilic region (MHR). MATERIALS AND METHODS: In 27 hepatitis B virus samples isolated from patients with chronic hepatitis B virus infection living in Vladimir, nucleotide sequence ofgenome region corresponding to preS1/preS2/S genes was determined. RESULTS: In all of the 27 isolates genotype D virus presented by 3 subgenotypes D1, D2, D3 was detected in 18%, 26% and 56% respectively. Based on the distribution of nucleotide substitutions in the compared functional regions of hepatitis B virus (virus entry into the cell coding site (2875 - 2991 n.b.), pre-S2/S promoter region (2994 - 3171 n.b.), 5'-end pre-S2 and S-genes sequences (3172 - 154 n.b. and 155-455 n.b.), MHR (455 - 635 n.b.) and 3'-end S-gene sequence (636 - 835 n.b.), substitutions are mostly concentrated in the promoter region of the S2/S-genes (30.8%). HBsAg serotypes were determined in 24 of 27 cases by using the predicted amino acid sequence, and in 17 cases HBsAg belonged to ayw2 (71%) serotype and in 7 cases - to ayw3 serotype (29%). Amino acid substitutions G145A, M133I, S132T localized in the main hydrophilic region and P217L, S207N, V184A localized in the C-end of the protein C that are connected with diagnostic and vaccine escape were identified in 5 isolates. CONCLUSION: Diagnostic potential of test systems with the detection of HBsAg with known amino acid sequence of the MHR region were studied. Approximately equal potential of 6 test systems to detect HBsAg with amino acid substitutions G145A, M133I and S132T localized in the MHR region were shown.

[Molecular and epidemiology studies of HIV-1 prevalence in the Republic of Sakha (Yakutia)].

The gag, pol, and env genomic regions of HIV-1 variants currently circulating in the Republic of Sakha (Yakutia) were analyzed. The results of the study indicated that in this area there were HIV-1 variants belonging to two subtypes: A (IDU-A) and B, the former being predominant in this area and in the Russian Federation. The IDU-B-East strain was first isolated from a heterosexually infected patient, which suggests that the strain is outside the risk group of injection drug users. No cases of primary infection with resistant variants were notified during the study.

[Hepatitis virus genotype structure in patients with chronic hepatitis C].

AIM: Studies of hepatitis C virus (HCV) genotype and subtype structure in patients with chronic hepatitis C in 3 regions of the Central federal district of Russia. MATERIALS AND METHODS: Hepatitis C virus genotype and subtype structure was determined in patients with chronic HCV infection in Moscow (1993 - 1995 and 2005), Moscow region (2008) and Vladimir region (1993 -1995, 2005-2007). HCV genotype was determined by using A. Widell et al. (1994) technique, PCR (AmpliSens diagnostic kits), Genotype C test system. RESULTS: In all studied regions and during all the time periods the first position in rating belonged to HCV 1b subtype. In 1993 - 1995 and 2005 - 2007 period changes in HCV genotype and subtype structure were registered that consisted of relative weight of 1b subtype decrease and 3a subtype increase. Subtype 1b in females with chronic hepatitis C was registered more often than in males. In Vladimir region 3a subtype in males was detected more often than in females. In males older than 30 years the first rating position belongs to 1b subtype and in males younger than 30 years--subtype 3a. In females older than 30 years in Moscow region and Vladimir region, as well as in females younger than 30 years in Vladimir region subtype 1b was detected more often, while in Moscow region HCV subtypes 1b and 3a were detected with the same rate of 47.6%. CONCLUSION: Currently there is an urgent need to include mandatory monitoring of hepatitis C virus genetic variants into the system of hepatitis C epidemiologic control in Russia. This approach will allow for a significant increase in quality of hepatitis C serological diagnostics, and can be used in the prognosis of evolution of the epidemic process of this disease.

[Epidemiological characteristics of acute tonsillitis in military draft personnel from troops of the Ministry of Interior of Russia].

Studied the incidence of angina conscripts in the Russian Interior Ministry troops in the period from 2000 to 2009, given its epidemiological characteristics, calculated rates of changes for the troops in general and regional commands. The incidence of angina tended to moderate growth with an average rate of 4.5% per year. The greatest increase in the frequency of sore throats was registered in 2009 during the reform period of Interior troops, when their share in the overall incidence of conscripts reached 5.9%. The structure of the monthly incidence of maximum values were recorded twice a year--in January and July (the first few months of winter and summer periods of study).

[Nonspecific prophylaxis of tonsillitis in military drafted personnel of internal troops of Ministry of Internal Affairs of Russia].

The morbidity of tonsillitis in military drafting personnel of internal troops of Ministry of the Interior of Russia was high and had the up trend during 2000-2007. In 2008-2009 took place new increase of these diseases. The most unfortunate was the Second training center. Overcrowded accommodation of cadets in kasernes and complete rotation 2 times per year promoted this increase. The conditions of accommodation of cadets ware improved in 2010, preventive prophylaxis of tonsillitis was provided with the help of Bitsillin-5. As a result, the amount of ill in the Second training center during the summer 2010 was 5, 6 times lower than in the same period of 2009. It shows that the best antiepidemic effect can be achieved with combination of measures against the carry-over of causative agent and medicated prophylaxis.

[Assessment of effectiveness and immunogenicity of hepatitis A vaccination in servicemen of Internal Forces of Ministry of Internal Affairs of Russia].

AIM: Comarative assessment of immunological and epidemiological effectiveness of hepatitis A vaccination and duration of immunity after immunization in servicemen. MATERIALS AND METHODS: During 1996-2003, immunogenicity and epidemiologic effectiveness of 3 vaccines against hepatitis A--Havrix 1440 (GlaxoSmithKline, Belgium), Hep-A-in-Vac (Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russia), and Avaxim (Sanofi Pasteur, France)--were evaluated. More than 15,000 servicemen were immunized during that time. In all cases one-dose vaccination without booster was performed. RESULTS: Several cases of acute hepatitis A were registered 12 months and 6-8 months after vaccination in military communities immunized with Havrix 1440 and Hep-A-in-Vac vaccines respectively. Usage of Avaxim vaccine as a single dose in field trials allowed to exclude new cases of acute hepatitis A during time of military service. It was shown that 5 years after single vaccination with Avaxim protective anti-HAV antibody level (20 IU/l) persisted in 90% of Internal Forces servicemen. CONCLUSION: On the basis of performed complex of studies, system of antiepidemic measures was developed, which leads to decrease of hepatitis A incidence. Selective immunization is proposed.

[Impact of changes in the amino acid sequence of the "a" determinant on the diagnostic capacities of test systems for the detection of HBsAg].

The diagnostic capacities of 4 commercial test systems were comparatively estimated for the detection of HBsAg, by applying a panel of samples with the established amino acid sequence of the "a" determinant of HBsAg. The Roche Elecsys HBsAg test system demonstrated the highest sensitivity - the maximum HBsAg concentrations were found in 19 of 31 cases. Escape mutations in the major hydrophilic region (MHR) of HBsAG (P120S, M133T) were responsible for differences in the sensitivity of 4 test systems by 10- to 40-fold. There were also samples that showed differences in the diagnostic capacities of the test systems to detect HBsAg, but without amino acid replacements in the area of the "a" determinant, which seems to be associated with amino acid replacements in other regions of HBsAg.

[Molecular genetic characteristics of HIV-1 variants circulating in Cherepovets, Vologda region: the second case of the epidemic outbreak caused by the recombinant gagAenvB].

HIV-1 variants circulating in the town of Cherepovets, Vologda Region, were genetically analyzed. It was shown that that were predominantly two HIV-1 variants: IDU-A (19%) and the recombinant strain UDU-AIB (77%) that circulated in the region. Amongst the IDU-A strains, there were genotypes containing characteristic secondary drug resistance mutations in the pol gene of V771 and A62V, as well as variants of the wild type. Amongst IDU-AIB strains, only one variant of the virus had genotype V771. The recombinant form of HIV-1 was more common in injective drug users while a group of heterosexuals had both recombinant virus and the variant IDU-A, that is typical of other regions of Russia. Thus, the epidemic outbreak due to the recombinant HIV-1 strain IDU-AIB was first registered in Russia, outside the Kaliningrad Region.

[Evaluation of the efficiency of external assessment of the quality of determining antibodies to hepatitis C virus in the network of screening laboratories].

A regional external quality assessment (EQA) system for determining anti-hepatitis C virus (HCV) was developed and introduced. For this, a control panel comprising 14 samples with anti-HCV and 6 samples without anti-HCV was tested in the reference laboratory of Moscow Infectious Hospital One. A total of 6 sessions were conducted with the participation of 8 laboratories. The regional EQA system covering a limited number of laboratories was shown to significantly improve the quality of detection of hepatitis C virus antibodies. The optimal multiplicity of sessions for the developed EQA system was ascertained to be once fortnight. It is possible to define the current rating of screening laboratories in the sensitivity criterion and to elaborate address organizational-and-methodic measures according to the results of control tests.

[Blood levels of HbsAg in patients with different variants of chronic HBV-infection].

AIM: To estimate HbsAg in patients with different variants of chronic HBV infection. MATERIAL AND METHODS: Assay of HbsAg (IU/ml) in blood serum was made in 156 patients with chronic HBV infection (70 males and 86 females, age 19 to 78 years) using the test-system HbsAg Architect Lot 59665LF00 (Abbott) on the automatic analyzer Architect with construction of 4-parameter logistic curve. RESULTS: There are significant differences in the levels of HbsAg depending on the course of chronic HBV-infection: inactive carriers of HBV (12,884.14 +/- 5,512.26 IU/ml) had much lower blood levels of HbsAg than patients with HbeAg-negative (66,992.28 +/- 25,908.74 IU/ml) and HbeAg-positive chronic VHB (135,039.3 +/- 48,127.06 IU/ml) patients with chronic mixed hepatitis (82,783.12 +/- 21,001.34 IU/ml) and cirrhosis of HBV-etiology (67,477.86 +/- 24,081.9 IU/ml). No significant differences were found between two subgroups of pregnant women with or without viremia by HbsAg concentration in the blood. Maximal mean content of blood HbsAg was registered in patients with HbeAg-positive chronic hepatitis B. CONCLUSION: Significant differences in blood serum levels of HbsAg exist between patients with chronic viral hepatitis B and inactive carriers of HBV.

[The spread of hepatitis B and C viruses and the structure of HBsAg subtypes in Kabardino-Balkaria].

A seroepidemiological study of the spread of hepatitis B and C viruses (HBV and HCV) was conducted among some population groups in Kabardino-Balkaria. The structure of HBsAg subtypes was also studied in the residents of the republic. The presence of viral hepatitis B markers among the test groups of the healthy population corresponds to the parameters of moderate activity of an epidemic process. The analysis of the immunological structure of the population leads the author to assign Kabardino-Balkaria to highly HBC endemic areas. The occupational factor is demonstrated to be actively involved in the spread of HBC and it is practically of no significance for HCV. An examination could reveal the HBsAg subtype adrq+ that is uncharacteristic of this area.

[Natural immunity and herpes infection].

The review details natural immunological factors that are the first-line protection from herpes simplex virus. These reactions may be conventionally divided into 3 active phases. In Phase 1, the virus is attacked by proteins, such as complement of precursors of natural class M (IgM) antibodies and antimicrobial peptides. In Phase 2, the interferons produced by infected epithelial and resident dendritic cells go into action. And, finally, in Phase 3, effector cells, such as neutrophils, macrophages, and natural killer cells, show antiviral activity.

[Prevalence of HBV and HCV markers in patients of specialized medical institutions].

240 medical histories of patients admitted to Moscow clinical narcological hospital No. 17 with "opium addiction" diagnosis in 2000 and 2003 (120 histories for each year) were analyzed. From 1997 to 2003 4220 patients registered in narcological dispensary of Cherepovets city (Vologda region) were tested for HBsAg and anti-HCV. It has been shown that in new injection opiate drug users young patients (15 - 19 y.o.) predominated (41.7%). Tendency to development of drug addiction in younger age was revealed - in 2003 compared to 2001 percent of new injection drug users aged 11 - 14 years admitted to hospital raised in 1.5 times. In 2000 and 2003 in Moscow markers of HIV and/or HBV/HCV infection were detected in 84.2 and 91.7% of injection drug users respectively. Maximal rates of HBV and HCV infection in injection drug users in Cherepovets city were detected in 2001 - 11.7 and 83.1% respectively. Leading role of injection drug users in maintenance of HBVand HCV epidemic process activity in Russia was established.