Vol 11, No 5 (2021)

This article is dedicated to the analysis and generalization of the Russian and foreign research results on natural and climatic factors effect on the intensity of epidemic process manifestations and the natural focal infections pathogens vectors vital activity which are the most widespread in the Russian Federation. Over the past seven years tick-borne infections have been accounting for more than 50 per cent in the natural focal diseases general nosological structure. Among the diseases of this group Lyme borreliosis leads in prevalence and frequency of cases identification. Tick-borne viral encephalitis is still a serious danger for national health. Crimean-Congo hemorrhagic fever epidemiological situation remains unfavorable in the south of the European part of Russia. In addition to the annual patients identification, the demonstrable trend of shifting and expansion of the pathogen’s area in a northerly direction was established. It creates a risk for the spread of the Crimean-Congo hemorrhagic fever virus outside the southern regions of the country. High incidence of the dangerous vector-borne infection — West Nile fever — with the involvement of new subjects in the epidemic process and the emergence of local cases of infection in previously non-endemic territories is registered. Expansion of hemorrhagic fever with renal syndrome natural foci borders, which is the most widespread natural focal zoonosis of viral etiology in the Russian Federation and is the second by the frequency of patients identification after tick-borne infections, is noted. Research data for the dependence of the carriers pathogens number and the dynamics of the natural focal infections incidence on the values of climatic factors, confirmed using various methods of mathematical statistics (time-series analysis, autoregression integrated moving average, logistic regression, correlation analysis, one-way analysis of variance and other) were systematized. It was found that the temperature and humidity of the air and soil, the amount of precipitation, the height of the snow cover are the common abiotic factors for all of investigated infections. The values of these factors can be used for the subsequent epidemiological forecast. The further study of relationship between the incidence rate of the population, the number of arthropod vectors and small mammals with indicators of soil moisture and temperature at different depths, hydrothermal coefficient, normalized relative vegetation index, accumulated values of temperature and precipitation, as well as similar studies on other actual natural focal infections in the Russian Federation will be very promising.

The gut microbiome profoundly affects the body functioning: it participates in host protection against pathogenic microorganisms, metabolic events, inhibition of inflammatory responses, formation of innate and adaptive immune response in the intestinal mucosa. One of the causes altering microbiota community is due to antibiotics. Therefore, the processes of antibiotics interaction together with Salmonella enteritidis and Salmonella typhimurium with representatives of normal intestinal microflora are of particular interest. Materials and methods. The quantitative and qualitative analysis of the wall microbiota composition in rats was evaluated by bacteriological method, the statistical data analysis was performed using the software StatSoft Statistica v.12. Results and discussion. Inoculation of vancomycin and S. enteritidis, S. typhimurium in groups II, III, IV resulted in quantitatively decreased E. coli level by 10-, 7- and 110-fold, respectively (p ≤ 0.05). The count of P. aeruginosa decreased markedly only in the group III (p ≤ 0.05). The count of Bacteroides spp. members was profoundly decreased by several thousand times (group II) as well as 70- and 87-fold (groups III and IV), respectively (p ≤ 0.05). The count of E. faecalis and E. faecium decreased by 861-, 6- and several thousand times (groups II, III, IV), respectively (p ≤ 0.05). The count of Proteus spp. markedly decreased in group II by 27-fold and rapidly increased in group IV (p ≤ 0.05). Group III revealed a sharp decline in level of Enterobacter spp. and Klebsiella spp. by 847- and 150-fold, whereas in group II they were increased by 7- and 46-fold, respectively (p ≤ 0.05). The count of Staphylococcus spp. decreased by 10-fold only in group II. The level of Clostridium spp. decreased by several thousand times (group II) and by 5,500 times (group IV) (p ≤ 0.05). The count of Lactobacillus spp. decreased by several thousand times (group II). The count of Bifidobacterium spp. members significantly decreased by 10.9-fold and by several thousand times (groups III, IV). The level of Peptostreptococcus anaerobius profoundly decreased in all three study groups (p ≤ 0.05). The level of Salmonella spp. increased in group II by 49 times, but markedly increased in groups III and IV (p ≤ 0.05). Inoculation of Salmonella after vancomycin pretreatment caused dramatic change in the microbiota composition in groups V and VI, namely: increased count of E. coli by 65- and 105-fold, markedly increased level of P. aeruginosa in group V and VI — by 3-fold. In addition, these groups also showed decreased level of Bacteroides spp. by 9- and 10-fold (p ≤ 0.05). The count of E. faecalis and E. faecium decreased dramatically only in group V (p ≤ 0.05). The count of Proteus spp. decreased by 17 times in group V as well as in group VI (p ≤ 0.05). A sharp increase in level of Enterobacter spp. and Klebsiella spp. members was observed in groups V and VI (p ≤ 0.05). However, representatives of Peptostreptococcus anaerobius in groups V and VI decreased by 20 and 9 times, respectively (p ≤ 0.05). The count of Salmonella spp. decreased only in group V by 7 times (p ≤ 0,05). Inoculating experimental animals with B. fragilis conditioned with S. enteritidis, S. typhimurium and pretreated with vancomycin resulted in markedly decreased level of E. coli in group VII and VIII by 538 times (p ≤ 0.05). The count of P. aeruginosa in groups VII and VIII decreased profoundly, whereas level of Bacteroides spp. members was reciprocally increased (p ≤ 0.05). The level of Lactobacillus spp. decreased by 10.3 times only in group VI. The count of E. faecalis and E. faecium increased by 10 and 19 times in groups VII and VIII, respectively, whereas level of Proteus spp. decreased only in group VII by 322 times (p ≤ 0.05). In addition, a sharp decrease in level of Enterobacter spp. and Klebsiella spp. members (p ≤ 0.05) was found in groups VII and VIII. The count of Peptostreptococcus anaerobius and Lactobacillus spp. members was markedly increased by 7-, 12-, several thousand-fold and 40 times (groups VII and VIII, respectively) (p ≤ 0.05). The count of S. enteritidis and S. typhimurium in groups VII and VIII decreased rapidly (p ≤ 0.05). Conclusion. Inoculation of B. fragilis can be used in treatment of inflammatory bowel diseases or disorders with impaired gut barrier function.

Objective was to investigate the SARS-CoV-2 collective immunity status of the population of Belarus within the context of the COVID-19 pandemic. Materials and methods. The work was carried out according to the methodology for assessing SARS-CoV-2 population immunity, developed by Rospotrebnadzor Russia and the Ministry of Health of Belarus with the participation of the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The Bioethics Committee of Belarus and the local ethics committee of the St. Petersburg Pasteur Institute approved the study. Selection of participants was carried out using a questionnaire method and online technology (internet, cloud server). Volunteers were randomized into seven age groups (years of age): 1–17; 18–29; 30–39; 40–49; 50–59; 60–69; and 70+. Regional randomization ensured proportional representation of volunteers from each region, and no more than 30 people were included from one enterprise. In accordance with manufacturer instructions, blood plasma samples were analyzed for: IgG antibodies (Abs) to the SARS-CoV-2 nucleocapsid (Nc) using a quantitative ELISA test system; and IgG Abs to the receptor binding domain (RBD) of the SARS-CoV-2 S (spike) surface glycoprotein using a qualitative ELISA test system. Statistical processing was carried out using Excel 2010 and other software. Statistical differences were designated as significant when p < 0.05, unless otherwise indicated. Results. The level of seroprevalence, in terms of Abs to Nc among the Belarusian population, was 38.4% (95% CI 37.6–45.4). The highest Ab levels were found among individuals in older age groups (50-70+ years old). The lowest were found in children 1–17 years old and in young people 18–39 years old The distribution of seroprevalence across Belarusian regions was relatively homogeneous, with the exception of the Minsk Region, where a statistically significant decrease in the indicator was noted. In terms of profession, the largest share of seropositive individuals was found among transportation workers; the smallest was found in business. The moderate COVID-19 incidence has not led to a dramatic increase in the number of contacts. The base reproduction number (R0) was 1.3. In the Republic of Belarus, there was a moderate level of asymptomatic COVID-19 among seropositive individuals (45.3% [95% CI 44.0–46.7]). This form of infection was observed most often among children aged 1–17 years old (65.0% [95% CI 61.3–68.6]). In parallel with seroprevalence assessment, SARS-CoV-2 vaccination was carried out. We used two vaccines: Gam-COVID-Vac (also known as Sputnik V, developed by Gamaleya National Center for Epidemiology and Microbiology, Russia); and BBIBP-CorV (Sinopharm, PRC). Vaccination against SARS-CoV-2 was accompanied by an increase in the level of anti-RBD Abs (95% [95% CI 94.7–96.7]). Taking into account the vaccination of a subset of the population with BBIBP-CorV, the overall herd immunity, inferred from the analyzed indicators (presence of anti-Nc or anti-RBD Abs), was 47.1% (95% CI 46.3–48.0). Conclusion. COVID-19 in Belarus was characterized by a moderately pronounced course of the epidemic process. The threshold level of herd immunity to SARS-CoV-2 has not yet been reached, as a result of which the conditions for progression of the epidemic remain.

The phenotypic and molecular genetic properties of 133 strains of genetically modified (genovariant) Vibrio cholerae O1 El Tor biovar isolated from patients in Dagestan (1993, 1994, 1998), and compared with 246 strains of a typical toxigenic cholera vibrio El Tor biovar isolated in 1970–1990 at the Caucasus Region. It was found that 48.7% of the studied genetically modified strain variants had mixed phenotypic properties of the El Tor and classic biovars that evidences about a need to include the marker genes of the classical biovar (ctxB^Cl+, rtxC–) and the El Tor biovar (ctxB^El+, rtxC+) into the existing biotyping scheme. The genes of the El Tor biovar, isolated from patients in Dagestan, contain in addition to the El Tor ones, the genes of the classical biovar (ctxB^Cl and/or rstR^Cl), as well as the typical toxigenic cholera vibrios of El Tor, islands of persistence (EPI), pathogenicity (VPI-1 and VPI-2) and pandemicity (VSP-I and VSP-II). However, only the El Tor biovar genovariants were found to bear an integrative and conjugative SXT element with antibiotic polyresistance genes. Epidemic cholera outbreaks caused by the El Tor biovar genovariants that occurred in 1993–1998 at the Caucasus Region, correspond to classical (Asian) cholera based on disease severity. The epidemiological features of modern cholera were studied: the main way for transmission via fecal-oral route for typical El Tor cholera vibrio is waterborne, whereas for the El Tor gene variant — household. Primary infections upon water drinking and using domestic water from surface water bodies infected with typical El Tor vibrios occur outside the family hearth. In case of cholera caused by hybrid El Tor variants, infection is transmitted among family members via domestic factors under low sanitary level. The development of laboratory diagnostics and epidemiological surveillance of modern El Tor cholera is based on the development of PCR test systems taking into account the evolutionary genome transformations.

Relevance. Since the beginning of the epidemic in China, there have been reports of nosocomial cases of SARSCoV-2 infection, including among medical workers. Studies of the intensity of humoral immune response to the SARSCoV-2 virus among medical workers who are much more likely to have professional contact with COVID-19 patients than are of particular importance. The aim is to study the seroprevalence and features of the humoral immune response to SARS-CoV-2 among medical workers. Materials and methods. The study included 61 medical workers from a multidisciplinary hospital in Kazan, which was redesigned to provide medical care to patients with new coronavirus infection, using the method of random sampling. The control group consisted of 60 non-medical workers. For the determination of IgG, a solid-phase ELISA was used. Statistical processing of the results was carried out using MS Excel software. The error of the relative value (M±m) was calculated, and the 95% confidence interval of the frequency of occurrence. To assess the significance of differences, the Student’s test (t-test) was used for independent samples. Results. The proportion of those seropositive to SARS-CoV-2 in the study group was 45.9%, compared with 21.7% in the control group. Among medical workers seropositive to the SARS-CoV-2 virus, the proportion of asymptomatic forms was 18.5%, mild forms — 53.6%, moderate forms and severe forms 25%. Two forms of the formation of a humoral immune response among seropositive ones were revealed: the first is characterized by the gradual elimination of specific IgG antibodies to SARSCoV-2 after 8 weeks from the onset of the first symptoms of COVID-19, the second form is an increase in specific IgG to SARS-CoV-2 and a higher value of the coefficient level of IgM positivity to SARS-CoV-2 after 8–10 weeks from the onset of the first symptoms. The group of seropositive, “raising antibodies”, prevailed over the group of individuals “eliminating antibodies”. Among seropositive medical workers, two forms of the formation of a humoral immune response were revealed: synchronous with the parallel elimination of IgG and IgM antibodies and a parallel increase in IgG and IgM. Conclusion. The study of the level of humoral immunity to COVID-19 in medical workers is important in terms of planning both anti-epidemic measures and predicting the effectiveness of the response to vaccination to SARS-CoV-2.

Human immunodeficiency virus (HIV) is a significant medical and social problem for many developed countries. HIV infection is featured with developing chronic kidney pathology as well as acute renal damage. In some regions, hemorrhagic fever with renal syndrome (HFRS) can contribute somehow to developing renal pathology in HIVinfected subjects. The aim of the study was to identify clinical and laboratory features of HFRS course during HIV infection. A retrospective study was conducted by forming two groups: group 1 consisted of 9 patients suffered from HFRS together with verified HIV infection, group 2 — 53 patients with HFRS but lacking any clinical and epidemiological indications supporting HIV infection. Subjects in both groups were age- and sex-matched. The average age of the patients in group 1 and group 2 was 34 and 31 years, respectively. For statistical analysis, the licensed SPSS 22.0 software was used. A significance level p for statistical criteria was set equal to 0.05. In general, HFRS course in all patients was accompanied by characteristic signs: intoxication syndrome, impaired vision, hemorrhagic rash, pain in the lumbar region, decreased diuresis, thrombocytopenia, proteinuria, polymorphic urinary syndrome and azotemia. HFRS patients with concomitant HIV infection often complain of dry mouth, bloating, visible shortness of breath. Laboratory changes describe more severe kidney damage. A direct strong correlation was shown between leukocyte count and level of blood urea in patients with concomitant HIV infection (r = 0.798; p = 0.01). The combination of HFRS and HIV was accompanied by a milder HFRS course — rate of mild disease was almost 6-fold higher among patients of this group. In this case, no cases of severe hemorrhagic fever with renal syndrome combined with HIV were noted. Our study allowed to obtain unambiguous data. Predisposition of HIV-infected patients to renal pathology may be a determining factor in kidney damage upon emerging HFRS: more prominent rise in creatinine and urea level. Moreover, according to rating scale for assessing HFRS severity, it formally turned out that during concomitant HIV infection patients more often fit to a mild disease severity, even in the presence of more pronounced renal manifestations. The occurrence of acute renal pathology in HIV-infected patients is a life-threatening condition, a factor of deterioration of chronic renal pathology and a predictor of death. Consequently, this patient population requires thorough monitoring both at inpatient and outpatient stages.

The aim of the study was to determine the taxonomic status of a group consisting of atypical strains of Acinetobacter baumannii, outline relevant characteristics and methods necessary for their identification. There were examined 10 strains of A. baumannii (6 of them primary comprised) bearing similar profile of atypical features isolated from clinical samples (urine, sputum) in 2017–2019 at the Military Medical Academy. Сlinical strains of typical A. baumannii (n = 36), Acinetobacter nosocomialis (n = 14), Acinetobacter pittii (n = 9) and 1 strain of Acinetobacter calcoaceticus isolated from the external environment were used in comparative studies. Atypical strains had the characteristics of A. calcoaceticus — A. baumannii (ACB) complex bacteria and were identified as A. baumannii. The utilization of substrates as the only carbon source was studied on a dense synthetic medium added with 0.2 % substrate during incubation for 72 hours at 37°C. Carbohydrate oxidation coupled to acid formation was detected on the Hugh–Leifson medium by using a micromethod. Aromatic amino acid biotransformation was carried out in liquid and dense nutrient media assessed in chromogenic reaction. The rpoB gene was used for strain genetic characterization. Amplification of two 940 and 1210 base pair (bp)-long fragments from the rpoB gene was performed by the routine polymerase chain reaction using primers with previously described sequences. Amplification products were sequenced by Sanger using Big Dye Terminator v3.1 (Applied Biosystems, USA) and capillary electrophoresis on an automatic sequencer ABI PRISM 3130 (Applied Biosystems, USA), followed by using methods for determining the similarity levels of sequenced fragments with the rpoB gene sequences of the reference strain A. baumannii ATCC 17978 (GenBank accession no. CP053098.1). It was found that all strains belonging to atypical A. baumannii spp. had a specific set of features that distinguish them from typical strains of A. baumannii as well as other types of the ACB complex: detected biotransformation of L-tryptophan (via anthranilate pathway) and anthranilic acid under unambiguous lack of such signs in other bacteria; lack of utilized sodium hippurate and L-arabinose being unambiguously evident in other bacteria; lack of utilized L-tryptophan, putrescine, L-ornithine being utilized in the majority of strains of belonging to other bacterial species. Genetic analysis showed that the control strains of typical A. baumannii displayed 99.20–99.21% similarity within the sequenced fragments of the rpoB gene with those from the rpoB gene of the reference strain. All 10 strains of atypical A. baumannii had similar features (99.20–99.21%). At the same time, parameters of control strains from other bacterial species significantly differed: A. nosocomialis (95.10–95.97%), A. pittii (94.63–94.92%), A. calcoaceticus (93.00%). Hence, the strains of atypical and typical A. baumannii are genetically homogeneous and belong to the same species. The data presented allow us to consider this group of atypical A. baumannii strains as a new biovar. We propose the name for this new biovar — tryptophandestruens (tryptophan-destroying) stemming from the Latin word destruens — destroying. Identification of A. baumannii bv. tryptophandestruens bacteria can be carried out in laboratory of any level by using tests for L-tryptophan biotransformation as well as sodium hippurate utilization.

Introduction. Chikungunya virus infection (CKV) may lead to chronic arthritis in up to 40% of the patients. There are previous data regarding positive auto antibodies in CKV. Objective is to systematically evaluate the prevalence of auto antibodies in CKV patients. Methods. All study participants had clinical manifestations being CKV positive at least serologally or by RT-PCR data. The following autoantibodies were assessed: antinuclear antibodies (ANA), anti-dsDNA, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-U1RNP, IgG and IgM anticardiolipin, anticyclic citrullinated peptide (antiCCP), rheumatoid factor (RF), antiribosomal P protein, lupus anticoagulant, anti-Jo-1 and anti-Scl-70. CH100, C3 and C4 complement components, serum levels of immunoglobulins, C-reactive protein, erythrocyte sedimentation rate, alpha1-acid glycoprotein, antithyroglobulin, antithyroperoxidase, TRAb, 25 hydroxyvitamin D (25OHD), dengue and zika IgG and IgM antibodies were also measured. Results. 30 CKV patients were included. Mean age was 59.1±15.7 years, 85% females and 77% Caucasian subjects. Disease duration comprised 4.9±4.0 months. Oligoarthritis was observed in 93% cases. Mean C-reactive protein levels were 10.1±6.8 ng/dL, erythrocyte sedimentation rate — 34.2±19.9 mm/1^st hour and alpha1-acid glycoprotein 115.5±52.6 mg/dL. Intramuscular betamethasone depot single dose injection was administered in 54%, prednisone — in 15% and methotrexate — in 23% cases. Importantly, 1/30 (3.3%) cases was positive for ANA, 4/30 (13.3%) — for RF and none was positive for anti-CCP or any other autoantibodies. Complement and immunoglobulin levels were all within the normal range. Low levels of 25OHD were observed in 88% cases.

The epidemiological significance of combined forms of especially dangerous infections has not been studied enough, unlike mono-infections. Currently, there is a tendency towards an increase in the incidence of multidrug-resistant tuberculosis. The formation of severe forms of the disease is caused by other widespread infections, such as chronic viral hepatitis and HIV. Polymorbid conditions distort the clinical manifestations of tuberculosis, reduce the effectiveness of anti-tuberculosis therapy and worsen the prognosis of the disease. Risk factors among patients in this category need analysis to carefully monitor patients and ensure infection control. Objective is to analyze the factors affecting the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis. Materials and methods. Cases of the combined pathology of multiresistant tuberculosis, HIV infection and viral hepatitis with a dominant diagnosis of tuberculosis are analyzed. Results and discussion. The influence of the immunological status on the course of combined pathology was revealed. Since all the patients under study had clinical stage 4 of HIV infection, tuberculosis developed as an opportunistic infection. Severe immunosuppression (CD4 < 200 cells/ml) contributed to the progression of the generalized tuberculosis process. Long-term immunodeficiency was an unfavorable factor; in the overwhelming majority of cases, antiretroviral therapy was prescribed only after tuberculosis was detected. The dependence of the clinical form of tuberculosis on the level of CD4-lymphocytes was noted: isolated lesion of the chest organs prevailed in patients with a level of CD4-lymphocytes more than 200 cells/ml, generalization of TB process — with CD4 less than 200 cells/ml. Patients with miliary tuberculosis had a higher mortality rate compared to patients with other clinical forms, regardless of antiretroviral therapy. It was revealed that socially disoriented young people with viral hepatitis C prevailed in the structure of patients, the prevalence of which was due to the influence of aggravating factors, such as alcohol and drug abuse, and stay in prisons. Against the background of combined treatment, there was no significant effect of viral hepatitis on the course of polymorbid conditions and the effectiveness of the therapy.