MATERIALS OF THE YII SCIENTIFIC AND PRACTICAL CONFERENCE "TOPICAL ISSUES OF INFECTIVE PATHOLOGY IN THE FAR EAST OF THE RUSSIAN FEDERATION" (OCTOBER 28-29, 2020, KHABAROVSK)
Rise in number of natural and human-induced disasters that can complicate epidemiological situation on a wide range of dangerous infectious diseases. High migration rate, transport connections also gradually increase risks of both local outbreaks and importation of infectious diseases in different territories of Russia from other countries or regions of our country. Current article presents a four-year record of collaboration between scientific research and practice institutions of the Federal service for surveillance on consumers rights protection and human wellbeing (Rospotrebnaszor) of the Far Eastern federal district of the Russian Federation on epidemiological diagnosis and etiological outbreak analysis of number of infections that provided contribution in efforts aimed at strengthening public healthcare and protection of population from external and internal threats rising from emergence of dangerous diseases and infections that have high epidemic potential.
NEW CORONAVIRUS INFECTION (COVID-19)
Continuing COVID-19 pandemic has spread all over Russia including the Far Eastern Federal district. Considering the fact that epidemic process of COVID-19 necessitates evaluation of regional peculiarities of the infection, FBUN Khabarovsk research institute of epidemiology and microbiology of the Federal service on consumers rights protection and human wellbeing conducts regular analysis of epidemiological situation in the Republic Sakha (Yakutia), Kamchatka, Khabarovsk and Primorsky regions, Amur, Magadan and Sakhalin districts, Jewish and Chukotka autonomous districts by order of the Federal service on consumers rights protection and human wellbeing. A comparative analysis of epidemiological situation on new coronavirus infection (COVID-19) was conducted in nine constituent entities of the Far Eastern Federal district during 23rd and 43rd calendar weeks of year 2020. An increase in incidence, mortality and testing coverage was shown. A dynamic in clinical manifestations of new coronavirus disease as well as percentage of recovered and ill patients residing in the Republic Sakha (Yakutia), Kamchatka, Khabarovsk and Primorsky regions, Amur, Magadan and Sakhalin districts, Jewish and Chukotka autonomous districts were presented.
The article presents data of bacterial microflora evaluation of two groups of patients with community-acquired pneumonia («Covid-19+», N=86 and «Covid-19–», N=87). Both groups had high levels of bacterial flora isolation (81.4% и 74.7%) including common pathogens for community-acquired pneumonia as well as notable detection frequency of Candida spp. and microbial associations. The group of «Covid-19+» patients was characterized with a more vast specter of detected pathogens, isolation of poly-resistant gram-negative Enterobacteriaceae producing ESBL, nonfermenting gram-negative poly-resistant bacteria, more excessive manifestation of microbial associations. In the group of «Covid-19–» participants drug-resistant microflora was presented only by MRSA and MRSE staphylococci and others.
The results of studying the course and outcomes of ischemic strokes in 18 patients with COVID-19 are presented. The observation group was dominated by women (72.22%). The average age of women is 74.69 years, of men - 59.6 years. Multimorbidity was noted - a simultaneous combination of 3 to 6 chronic diseases, which increased the severity of the patient's condition and mortality. Atherothrombotic stroke subtype was registered in 55.56% of cases, cardioembolic - in 38.88%, lacunar - in 5.56%. In all patients, the course of stroke was complicated by the addition of polysegmental pneumonia, mainly of moderate severity (50% of cases). The lethal outcome took place in 27.78% of cases.
A brief historical sketch concerning first experience of response to small pox, cholera and plague in the Amur River region in 1881, 1902 and 1910 years was presented. Significance of quarantine measures as well as disinfection and vaccination was described. Dedication of medical workers in response to epidemics was emphasized. Significance of obtained experience concerning current epidemic situation caused by novel Coronavirus COVID-19 was studied.
GENETIC ENGINEERING RESEARCH
All known approaches were tested in order to create a vaccine against HIV-1, however currently there is no effective vaccine against this pathogen. Relatively new and perspective approach involves rational design of immunizers aimed at focusing immune response against vulnerable virus regions. It is considered that highly conservative epitopes are located in protein-based regions and are essential for survival of the virus. Such epitopes can be regarded as ideal antigens for vaccine development. Core protein of Hepatitis B virus (HBcAg) that is regarded as a perspective platform for developing highly immunogenic vaccines was utilized as a carrier protein in current research. Because epitopes of a majority of broadly neutralizing antibodies are conformational current study utilized mediator-peptides that were obtained by means of phage display. Recombinant plasmids that contained epitopes and epitope imitators that are recognized by antibodies VRC34.01 and VRC01 respectively were derived on a basis of plasmid coding HBcAg. Electronic microscopy showed that chimeric variant НВсAg-c7cVRC01 forms particles of specific spherical shape. Immunological potency of obtained recombinant proteins was tested on rabbit model. It was revealed that animal serum that was immunized with chimeric variants of HBcAg had neutralizing activity against SF162.LS (subtype B) pseudovirus.
Vaccination is considered one of the most effective means of preventing influenza. However, the variability of the influenza virus allows it to escape from permanent specific immunity. Therefore, an urgent task is to create vaccines capable of inducing an immune response against a wide range of different strains of the human influenza virus. One of the approaches to the creation of a universal vaccine against influenza is the production of mRNA of vaccines encoding genes of artificial immunogens containing conserved fragments of proteins of various subtypes of the influenza virus. The objective of this work was to obtain mRNA vaccines encoding influenza virus antigens using template synthesis. As a template, we used DNA vaccine constructs encoding a conserved fragments of influenza virus hemagglutinin stem and M2 protein. In this work, we optimized the conditions for RNA synthesis using T7 phage polymerase with DNA templates, followed by its capping and polyadenylation.
VIRAL INFECTIONS
Epidemiological and molecular-genetic analysis of enterovirus infection was conducted in constituent entities of the Far Eastern and Siberian Federal Districts (FEFD and SFD) during years 2016-2019. Challenging epidemic situation concerning specified disease conditioned among other things by disease clusters was revealed in the Altai and Sakha (Yakutia) Republics, Amur, Sakhalin and Irkutsk regions. In addition, a substantial increase in cases of meningitis caused by enterovirus was detected in the Krasnoyarsk krai, Tuva and Sakha (Yakutia) Republics during the analyzed period of time. Results of molecular-genetic research evidence that substantial increase in incidence during years 2017-2019 were caused mostly by Coxsackie A-6.
The research paper presents the results of molecular genetic studies of clinical samples from patients with acute gastroenteritis and environmental samples obtained during the investigation of group incidence foci of norovirus infection among children in the Khabarovsk krai, Jewish Autonomous oblast and Amur oblast in 2019.
The urgency of the problem of chickenpox is due not only to the high incidence, the presence of complications and a chronic form of infection, but also to the prospects for the introduction of its vaccine prevention. Modern features of the course of the disease are the involvement of individuals of different age groups in the epidemic process, the development of complications and CNS lesions in initially healthy individuals. The complicated course of chickenpox more often observed in adolescents, adults, and immunocompromised individuals. Pregnant women are a special risk group. Chickenpox is among the leaders in terms of economic damage from infectious diseases in the Russian Federation (2nd rank). The concept of basic reproductive number explains the rapid spread of these infections among new populations. Epidemiological risks of chickenpox are determined by the possibility of introduction into socially significant groups, the occurrence of group and outbreak diseases in organized groups, and epidemic spread among the population of municipalities. Immunization against varicella-zoster virus is a key aspect of epidemiological risk management. Tactics of immunization against varicella may be defined as a selective, post-exposure prophylaxis and universal. Routine universal vaccination against chickenpox is the most effective prevention measure. In anticipation of the national varicella immunization program, it is necessary to implement regional components, which should be aimed at immunizing groups at risk of infection and the development of severe clinical forms of infection and post-exposure prophylaxis in organized groups.
Molecular-epidemiological examination of HIV-infection conducted during years 2015-2019 showed that despite domination of sub-subtype A6 genetic profile of HIV-infection was quite diverse in investigated territories of the district. Ninety HIV-1 recombinant forms isolated from patients residing in the Far Eastern Federal district (FEFD) were identified and their specter was revealed. Total amount of seven types of circulating recombinant forms (CRF) and one unique recombinant form of HIV-1 were identified. Some peculiarities of HIV-infection genetic profile were revealed in the Jewish autonomous district such as high percentage of CRF63_02А1, when sub-subtype A6 was identified only in 40.4% of examined patients.
Epidemiologic surveillance over HIV-infection and viral hepatitis B and C is necessary in order to take timely and effective preventive measures in order to provide population wellbeing. Conducted analysis revealed an increase in prevalence and mortality rates among HIV-infected citizens of nine constituent entities of the Far Eastern federal district (FEFD) during years 2006-2019. HIV incidence downward trend was detected in FEFD as well as in Russian Federation in general. Considerable growth of mortality rates was due to registration of 79.9±1.1% of all fatal cases in FEFD among HIV-infected people living in the Primorsky region in 2019. Percentage of chronic viral hepatitis B had an increasing tendency when fraction of viral hepatitis C was relatively stable during years 2006-2019. Prevalent genotype of hepatitis B virus was genovariant D and for hepatitis C virus – subtypes 3a and 1b.
The research presents preliminary results of the first phase of sociological survey carried out in 2019-2020 years among professionals of health care and social welfare institutions of four constituent entities of the Russian Far East. The objective of the research was to examine their awareness on issues of HIV/AIDS, risk of being infected with HIV as well as stigmatization level towards people living with HIV. Results of the survey showed certain lack of knowledge on the issue of HIV/AIDS. This fact necessitates extension of the study in order to plan events targeted at improving competence level of social welfare professionals on the matter.
Along with medical aspects of epidemiology, diagnosis and treatment an issue in question is implementation of effective preventive programs in order to lower spread of HIV-infection among youth. Application of monitoring awareness levels on transmission routes, self-perceived risk and HIV/AIDS related sources of information could help planning key priorities of awareness-raising and educational activities.
BACTERIAL INFECTIONS
Results of the investigation of four bacterial food poisoning outbreaks with number of cases totaled 14 people, located in the Republic Sakha (Yakutia) in August of year 2018 caused by consumption of fish preserves were presented. Bacterial food poisoning was caused by Staphylococcus aureus, Klebsiella pneumoniae, Raoultella ornithinolytica that were isolated from patients and fish preserves. Basis for etiological diagnosis were results of wide-ranging bacteriological examination of samples collected from patients and fish preserves by appealing to molecular-biological methods, that revealed presence of sea and seb S. Aureus enterotoxin genes and single genotype of Kl. pneumoniae strain.
The research included evaluation of express-diagnosis capability of immunochromatographic assay (ICA) Binax NOW (Alere, Inc., США) for diagnosis of the rhinosinusitis caused by to detect the Streptococcus pneumoniae antigen directly in clinical samples. The unique feature of the method included obtaining samples with an electric suction machine in order to evaluate aspirate from deep parts of the nasal cavity. Diagnostic capability of the Binax NOW was determined in a comparative study using classical bacteriological method in 100 clinical samples. Pneumococcus was isolated in 16 patients (16±3,7%) via bacteriological method. ICA utilization allowed to reveal pneumococcal antigen in 20 cases (20±4,0%). ICA test sensitivity equaled 87,5%, specificity – 92,9%. Obtained results allow us to recommend ICA for identification of pneumococcal infection in patients with sinusitis for practicing physicians. The advantages of the evaluated method were fast results (for up to 15 min) and possibility of non-invasive sampling technique of clinical specimens.
NATURAL-FOCAL INFECTIONS
The spread of natural foci and infectious diseases of bacterial etiology in Siberia and the Far East requires mandatory actions to ensure sanitary and epidemiological welfare of the population. The article provides the results of epizootological and epidemiological monitoring of natural foci of natural and chozoonotic infections of bacterial etiology in the period from 2014 to 2018.
The ratio of cyclic adenosine monophosphate / cyclic guanosine monophosphate and pathological changes in immunocompetent organs (thymus, spleen) of white mice infected with Bacillus anthracis with different plasmid composition were studied. Differences in the action of B. anthracis on the functional state of cells of the immune system (differentiation and proliferation of cells), which depend on the plasmid composition of the sibyl ulcer microbe, were revealed. The presence of morphological changes in the immunocompetent organs of laboratory animals during experimental anthrax infection, manifested by varying degrees of severity of the pathological process and activation of the immune response, caused by the pXO1 + plasmid, was established.
A retrospective analysis of epidemical situation on tick-borne infections in Khabarovsk region during 2010-2019 years was conducted. Data including elevation of people noticing attached ticks appealability, removed ixodic ticks infectious rate, incidence of tick-borne infections among population of the region was analyzed. The Khabarovsk krai territory has a setting for high risk of human contact with ixodic ticks in natural surroundings. Four species of ixodic ticks are relevant carriers of tick-borne encephalitis and other tick-borne infections. However, number of tick typhus cases annually exceeds the number of registered cases of other tick-borne infections.
The article presents results on infection rate evaluation of fed ixodic ticks of different species with Borrelia burgdorferi sensu lato detached from humans in the Khabarovsk Territory during 2017-2019 years. The dynamics of tick-borne borreliosis during 2010 – 2019 years on the territory of the Khabarovsk krai was analyzed and compared with statistical indices of the Russian Federation in general. The dynamics of tick activity during the epidemic season of 2017 – 2019 years was analyzed on the territory of the Khabarovsk krai. The main reservoir of tick-borne borreliosis in the Khabarovsk krai was Ixodes persulcatus.
The article presents a case of a patient, who underwent a focal form of tick-borne encephalitis, Lyme arthritis with repeated alimentary infection. Secondary (virus-mediated) immunodeficiency is considered as a possible cause of this condition. Migratory arthralgias in the patient were long regarded as a consequence of muscle tension, and Lyme arthritis was diagnosed only eight years after the onset of symptoms. The issue of the importance of the life history and medical history in the process of differential diagnosis of residual phenomena of tick-borne encephalitis and the syndrome of undifferentiated connective tissue dysplasia is discussed.
PARASITIC INFECTIONS
Natural foci of endemic for Priamurye territory trematodiasis with human and animal hosts such as clonorchosis, nanofietosis and metagonimosis are localized in the Khabarovsk krai and Jewish autonomous territory. The goal of the epidemiological surveillance is maintaining wellbeing concerning trematodiasis incidence in the territories that have active reservoirs of infection. Sanitary-parasitological evaluation of fish is one of priorities in the system of preventive measures. Extensive studies in terms of parasitological assessment of fishery water bodies of the Khabarovsk krai, Jewish autonomous district and Amur oblast were conducted during 2010-2018 years with the participation of the Federal service for consumers rights protection and human wellbeing (Rospotrebnadzor) institutions and Khabarovsk branch of the Federal State Budget Scientific Institution “Russian Federal Research Institute of Fisheries and oceanography”. The results of the research provided basis for a number of scientific papers and guidelines.
The paper presents the results of a sero-epidemiological examination of the population of the southern territories of the Russian Federation and residents of the Khabarovsk Territory, the Amur Region and the Jewish Autonomous Region for the presence of antibodies to the antigens of Echinococcus granulosus, Toxocara canis, and Trichinella spiralis. Discrepancies in seropositivity indicators among the population living in these territories were revealed. The possibility of discrepancy between the levels of registered and actual morbidity of the population with these helminthiases is shown.
The pressing issue of echinococcosis is relevant for Russian Federation in general and for Far Eastern Federal district as well. The obtained results indicate on contradiction between the registered and actual echinococcosis incidence of population. The crucial part of the epidemiological surveillance over cystic echinococcosis is immunoepidemiological surveillance. Due to asymptomatic course of the cystic echinococcosis on the early stage of the disease, it is proposed to expand the population undergoing serological screening.
Active natural foci of clonorchiasis, metagonimosis and nanofietosis that are human and animal trematodosis endemic for the Amur River basin region were localized in the Khabarovsk krai. Main transmission factor of these causative agents is freshwater fish – an integral part of local peoples diet. Current article presents data on indigenous people infection rate with Сlonorchis sinensis, Metagonimus spp. and Nanophyetus salmincola schikhobalowi in the Dada village of the Nanaysky district.
Anisakodosis is a larval zoonotic biogelminthosis. Factor of its transmission are different species of seawater fish as well as cephalopods. The research presents survey results of the Khabarovsk region population who applied in medical organizations regarding dyspeptic disorders and those that had in their anamnesis consumption of undercooked seawater fish and seafood. Anisakidosis diagnosis can be problematic due to polymorphism of clinical manifestations this is why majority of disease cases are undetected. Enzyme-linked immunosorbent assay (ELISA) can be an additional diagnosis method that allows to characterize spread of anisakidosis causative agent among population. ELISA combined with epidemiological anamnesis can be an effective tool in diagnosis of intestinal localization of anisakidosis as well as its chronic form.