EPIDEMIOLOGICAL FEATURES OF CHRONIC VIRUS HEPATITIS B AND C IN THE REPUBLIC SAKHA (YAKUTIA).

High disease burden of chronic virus hepatitis B and C of population in the Republic Sakha (Yakutia) is subject to referring it to endemic territories due to these infections. For a 15-year-old period the disease has been registered at higher rates in the Russian Federation.

[Frequency of antibodies against surface and nuclear antigens of hepatitis B virus in population of St. Petersburg in 2013].

AIM: Determine the frequency of antibodies to surface (anti-HBs) and core (anti-HBc) antigens of hepatitis B in population of St. Petersburg of various age for evaluation of protective herd immunity against hepatitis B virus (HB). MATERIALS AND METHODS: Blood sera of 970 individuals (491 males, 479 females) of 10 age groups from 0 to 50 years and older were examined for the presence of anti-HBs and anti-HBc IgG by enzyme immunoassay using commercial diagnostic test-systems. RESULTS: In general anti-HBs at the level of 5 mIU/ml and above were detected in 603 of the examined individuals (62.2%). Anti-HBs at the level of 10 mIU/ml and above were detected in 53.9%. The frequency of anti-HBs in protective titers in males and females in general turned out to be similar (52.6% and 55.2%, respectively). Juxtaposition of age-specific parameters of seroprotection and acute HB morbidity in St. Petersburg revealed an inverse correlation of medium strength (r = - 0.54). CONCLUSION: Results of the study confirm high effectiveness of the program of HB vaccine prophylaxis in St. Petersburg and emphasize the necessity of further implementation of broad measures of population immunization against HB.

[Vaccination against hepatitis A among occupational risk groups].

The study was aimed to evaluate vaccine prevention of hepatitis A in occupational risk groups in Russian Federation over 2011-2013. Epidemiologic analysis method was used. Data array for the analysis included information about 1,162,619 individuals vaccinated against hepatitis A throughout the country. Findings are that during the studied period a total of 470,278 adults over 18 years were vaccinated (i.e., 0,4% of all population of this age). Among occupational risk groups subjected to anti-hepatitis A vaccination within immunization calendar on epidemic indications, major (29%) share was presented by catering enterprises workers and individuals engaged into food trade and supply. Other occupational risk groups (workers maintaining water supply systems and sewerage system, medical staff, preschool institution teachers, etc) demonstrated significantly lower levels of being vaccinated. Vaccination against hepatitis Ain occupational risk groups should be in a focus of prophylactic measures, as will help to control over hepatitis A spread.

[Molecular epidemiology of hepatitis C in centers of hemodialysis in St. Petersburg].

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. ,

[Biodiversity and evolution of circulating bacteria and virus populations. Novel problems of medical microbiology].

Biodiversity and evolution of circulating bacteria and virus populations is a serious scientific problem, solving this problem is necessary for effective prophylaxis of infectious diseases. Principal trends of development in this field of science are described. Results of studies that were carried out and investigated biodiversity of principal pathogens in Russia and St. Petersburg in particular are presented. Risk of infectious security of society caused by increasing diversity of pathogenic microorganisms is described, and priority trends of research development in this field are specified.

[Genotyping and molecular marking of bacteria and viruses in epidemiological surveillance of actual infections].

AIM: Determination of genetic and molecular features of pathogens circulating in Russia, in the northwest of the country and in St. Petersburg to resolve the problems of spread of diseases caused by these pathogens. MATERIALS AND METHODS: Complete and limited gene sequencing, DNA restriction fragment length polymorphism analysis, spoligotyping, VNTR-typing, resistotyping and other methods were used. RESULTS: Data on population structure and dominant genotypes of tuberculosis mycobacteria, corynebacteria, helicobacteria, hepatitis A, B, C, human papilloma viruses circulating in Russia, in the northwest of the country and in St. Petersburg were obtained. Genetic divergence of rubella virus and poliovirus vaccine strains under mass vaccination conditions was detected. Evidence of higher effectiveness of pathogen genotyping methods in epidemiologic diagnostics compared with traditional epidemiological investigation was obtained. CONCLUSION: Microorganism genotyping methods were helpful in resolving strategic problems of contemporary epidemiology. Perspectives of further development of these methods are related to obtaining data on circulating genotypes in all regions of the world, establishment of complete databases on circulating genotypes and integration of this methodology into daily diagnostics and epidemiological surveillance.

[Seroepidemiology of hepatitis A in Saint-Petersburg in 2009].

AIM: To determine immune structure of different population groups in Saint-Petersburg to hepatitis A virus in 2009 in order to study trends of epidemic process dynamics and planning of prophylactic measures. MATERIALS AND METHODS: Nine hundred and three citizens of Saint-Petersburg aged 3 months to 60 years were tested for anti-HAV by ELISA in 2009. Results were compared with data of previous study conducted in Saint-Petersburg in 1999. Two hundred injection drug users (IDUs) aged 14 - 29 years were tested additionally. RESULTS: In total in 2009, anti-HAV were detected in 32.5 +/- 1.6% citizens of Saint-Petersburg that is 2-fold lower than in 1999 (60.2 +/- 1.5%). Especially sharp decrease of anti-HAV prevalence in 2009 compared to 1999 was observed in age groups 15 - 19 years (by 2.6-fold), 20 - 29 years (by 3.1-fold), and 30 - 39 years (2.8-fold). Anti-HAV were detected in 58.5 +/- 3.5% of tested IDUs that 2.8-fold higher of that value observed in persons 14 - 29 years old from population sample (21.7 +/- 2.4%). CONCLUSION: Decrease of immunity to HA in population of Saint-Petersburg is very unfavorable prognostic factor pointing to strong possibility of HA outbreaks onset during worsening of epidemic situation. In such circumstances, active immunization against HA of wide strata of population should become important prophylactic measure.

[Molecular-epidemiologic characteristic of hepatitis A outbreak among workers of food stores network].

Investigation of hepatitis A (HA) outbreak developed in 2005 among workers of food stores networkwas performed using conventional epidemiologic diagnostics as well as methods of molecular epidemiology. In 14 of 15 ill persons, using polymerase chain reaction, HAV RNA was detected by PCR in serum obtained on 2 - 25 day of illness (mean - 9.3 days). In 10 cases it was possible to determine nucleotide sequence of VP1/VP2 region of HAV genome and perform phylogenetic analysis of obtained isolates. It was determined that all isolates belonged to subgenotype IA, had high degree of homology and grouped in one cluster. These findings demonstrate their descendance from one source of infection, which, with high degree of probability, was the cook who made salads from fresh vegetables. HAV strain, which caused this epidemic outbreak circulates in Saint Petersburg for a long time and was already detected in 2004. Importance of vaccination against HA for persons working in manufacturing and distribution of food and use of molecular epidemiologic methods of surveillance for this infection is underlined.

[Duration of viral RNA circulation in blood of patients with hepatitis A].

Duration of hepatitis A virus (HAV) RNA circulation in blood of patients with HA was assessed and compared with intensity of cytolytic syndrome. Detection of viral RNA was performed by RT-PCR method with specific primers to VP1/P2A region of HAV genome. 54 blood serum samples from 40 patients were prospectively studied on the presence of HAV RNA. The latterwas detected in 53.7% of serum samples. The greatest number of positive results of HAV RNA detection in blood of the patients with HA was obtained from 8th to 21st day of illness (77.4%). Prolonged viremia (42+/-9 days) was observed in more than 20% of the patients. The maximal time of HAV RNA daetection in blood serum amounted 74 days (period of follow-up). HAV RNA was present in almost all patients with AIAT activity higher than 500 U/l regardless of duration of illness.

[Characteristics of the manifest and latent components of the hepatitis A epidemic process in cities of Russia]. / Kharakteristika manifestnogo i skrytogo komponentov épidemicheskogo protsessa gepatita A v gorodakh Rossii.

Seroepidemiological study of hepatitis A (HA) morbidity was carried out in three Russian cities, with different levels of HA morbidity. The study included the analysis of HA morbidity for 22 years, the determination of antibodies to HA virus (anti-HAV) in 2,958 healthy persons aged 0-12 months to 40 years and older. In one of the cities 7 isolates of HA virus were obtained from unrelated sources and the genotypes of the virus were determined. The study revealed that the frequency of seropositive cases among persons of different ages correlated with the level and prolonged dynamics of HA morbidity. According to the occurrence of anti-HAV, such cities as St. Petersburg, Rostov-on-Don and Yakutsk may be at present classified as territories, moderately endemic in HA. At the same time in the 90 s the epidemic situation in HA was more favorable in Rostov-on-Don than in two other cities. The suggestion was made that a high proportion of seropositive persons among the population of St. Perersburg was linked with an almost twofold rise in HA morbidity in 1993-1995 caused by genotype 1 of the virus. Seroepidemiological studies in HA during the period of a drop in morbidity acquire special importance in the surveillance and control system of this infection.

[The theoretical bases of the epidemiology of viral hepatitis B]. / Teoreticheskie osnovy épidemiologii virusnogo gepatita B.

In this article the development of the concepts concerning the sources of hepatitis B virus in the second half of the XXth century is analyzed and the importance of patients with manifest and latent forms of chronic infection as the main reservoir of the infective agent is substantiated. The scheme of the mechanisms and paths of the transmission of hepatitis B virus is proposed, the mechanism of transmission understood only as the natural ways of the spread of the infective agent which result from its evolutionary development and can be only slightly controlled at present. The study revealed that the present decrease of morbidity rate is greatly determined by measures of the social character, aimed at the elimination of the artificial paths of virus transmission.

[The prospects for using the genetically engineered surface antigen of the hepatitis B virus (HBsAg) expressed by recombinant poxvirus strains as the basis for vaccines against hepatitis B]. / Perspektivy ispol'zovaniia genno-inzhenernogo poverkhnostnogo antigena virusa gepatitia B (HBsAg), ekspressiruemogo rekombinantnymi shtammami poksvirusov, v kachestve osnovy vaktsin protiv gepatita B.

The use of a recombinant poxvirus (RPV) strain, expressing HBsAg in the process of reproduction in different bioreactor systems under stationary and bioreactor conditions of cultivation, made it possible to obtain highly purified HBsAg. The identity and purity of HBsAg was confirmed by the analysis of its amino acid composition, SDS electrophoresis in polyacrylamide gel, electron microscopy and high-performance liquid chromatography. Good prospects of the use of RPV-expressed gene engineering HBsAg as the basis vaccines against hepatitis B was demonstrated in 10 experimental batches of vaccine. All batches of the preparation had pronounced immunogenicity and were safe and nontoxic in animal experiments. The ID50 of experimental batches did not exceed 211 ng/ml, which, according to the data of comparative experiments, was lower than, or equal to, corresponding values of analogous foreign commercial preparations, based on plasma or yeast HBsAg.

[The morbidity and immunological structure of the population in viral hepatitis A at different phases in the development of multiyear epidemic cycles]. / Zabolevaemost' i immunologicheskaia struktura naseleniia pri virusnom gepatite A v raznye fazy razvitiia mnogoletnikh épidemicheskikh tsiklov.

For the first time population immunity to virus hepatitis A has been studied during three different phases of prolonged morbidity cycles of this infection, and the results of this study have been compared with the data on morbidity in different age groups. Pronounced variability of the immunological structure of the population in different age groups, found to be related to the dynamics of hepatitis A morbidity, has been established. Fluctuations in immunity level are most pronounced among children aged 1-6 and 7-14 years, having the least proportion of seropositive persons. A new epidemic cycle is started among these groups of the population, and at the first stage this cycle is manifested by an increase in the intensity of the latently developing epidemic process. This is followed by the activation of registered morbidity among the whole of the population. Seroepidemiological study may be used both for prognostication purposes and in the system of surveillance on this infection.

[Viral infection markers in foci of chronic hepatitis B]. / Markery virusnoi infektsii v ochagakh khronicheskogo gepatita B.

The intensity of detection and time course of the main markers of virus infection were studied in subjects who had contacts with patients in 74 foci with chronic active hepatitis, 52 with chronic persisting hepatitis and 41 with chronic hepatitis of unknown etiology. A high (up to 80.7%) frequency of detection of HBsAg, anti-HBs, anti-HBc was established in contact subjects which showed a trend of growth with the increase of the time of their contact with the source of infection.

[Monthly dynamics of the epidemic process in viral hepatitis B]. / Pomesiachnaia dinamika épidemicheskogo protsessa pri virusnom gepatite.

Monthly fluctuations in the number of registered cases of acute viral hepatitis B and HBsAg carriership have been studied. The study has revealed that, similarly to other infectious diseases, viral hepatitis is characterized by monthly fluctuations in the intensity of the epidemic process. Such fluctuations are characteristic of all known clinical forms of this infection; they are determined by the specific pathogenetic features of the process and by the ways of the transfer of the virus. The vernal rise of the infection is explained by activation of the manifest and asymptomatic chronic variants of the infectious process and, as the consequence of a rise in the number of asymptomatic cases, by a higher incidence rate of post-transfusion hepatitis infection. The autumnal rise of the infection results from the action of natural factors contributing to the transfer of the virus. Both rises are interrelated and interdependent. The seasonal fluctuations of the epidemic process should be taken into consideration when planning and implementing prophylactic and epidemic-control measures.

[Patients with chronic viral hepatitis as sources of infection]. / Bol'nye khronicheskim virusnym gepatitom kak istochniki infektsii.

Dynamic observation on 126 foci of infection formed by patients with manifest forms of chronic hepatitis B, 41 foci of chronic hepatitis of unknown etiology, and 37 foci formed by chronic "healthy" carriers was made. In the foci of type 1 the epidemic process developed intensively and was manifested mainly by HBsAg carriership in persons having had contacts with the patients. During the period of observation 43.0% of new cases of infection were detected. In the foci of types 2 and 3 the frequency of contacting infection was not different from that in the control group of the population.

[Characteristics of the epidemic process manifested as chronic viral hepatitis]. / Osobennosti épidemicheskogo protsessa, proiavliaiushchegosia khronicheskim virusnym gepatitom.

The incidence rates of chronic viral hepatitis in Leningrad over the period of 1962-1984 were studied. The tendency towards a rise in total morbidity because of increased incidence of chronic hepatitis B was shown to appear in recent years. This increase in morbidity was mainly due to its rise among adult males and children, which led to the shift of morbidity to younger age groups. The seasonal rises of morbidity in winter and spring were found to be characteristic of viral hepatitis.

[Use of highly sensitive methods of detecting hepatitis B virus markers for studying epidemic foci of hepatitis B]. / Ispol'zovanie vysokochuvstvitel'nykh metodov obnaruzheniia markerov virusa gepatita B dlia izucheniia épidemicheskikh ochagov étoi infektsii.

Passive hemagglutination test (PHA) was found to detect HBsAg in the population living outside the hepatitis B virus foci 1.5-fold as frequently as counter immunoelectroosmophoresis technique, and anti-HBs by enzyme immunoassay 14-fold as frequently. As compared with normal population, the contacts in foci had 4-fold higher levels of HBsAg carrier state and twice as high rates of detection of anti-HBs. The total index of HBV infection in foci was 27.7%. The above materials considerably extend the concepts of HBV epidemiology. The regularity of the results obtained indicate the specificity and high sensitivity of PHA and EIA tests and suggests that they be used on a wider scale.