Dysregulated immune response occurring in chronic hepatitis B prevents the virus elimination and contributes to progression of the infectious process. The aim of the study was to evaluate the effectiveness (biochemical, immunological, virological) of combination treatment with tenofovir and Recombinant interleukin-2 in chronic hepatitis B patients. Material and methods. A comparative analysis of the results from laboratory examination of chronic hepatitis B patients in two comparison groups, comparable in sex, age, stage of fibrosis, viral load, was carried out: group I (n = 27) received tenofovir, according to the accepted recommendations, and recombinant interleukin-2 (rIL-2), group II (n = 25) — tenofovir. Results. Before the onset of antiviral therapy all patients with chronic hepatitis B had increased hepatic transaminases, alkaline phosphatase and gammaglutamyl transpeptidase from 1.2 to 5 norms as well as dysregulated cellular immunity factors with significantly decreased absolute count of CD4+, CD8+, CD16+ and increased CD20+ lymphocytes. After 12 months of treatment, patients in observation groups showed normalized cytolysis and cholestasis with insignificant intergroup differences. The level of absolute count of CD4+, CD8+ T-cells and CD16+ lymphocytes in the I group increased (by 24.7%, 24.1%, 34.5%, respectively, all p 0.001 relative to the initial values), not observed in comparison group. The level of CD20+ lymphocytes in group 1 was decreased by 35.9%, and in group 2 — by 7.9% (pI–II 0.001). In group 1, the level of HBsAg after 12 months of treatment became lower by 52% (p 0.001). Conclusion. The conducted pilot study showed that the combination etiopathogenetic therapy of patients with chronic hepatitis B using tenofovir and rIL-2 improves liver functional state, restores the disturbed balance of immunocompetent cells: by increasing level of CD4+, CD8+ T-lymphocytes, CD16+ lymphocytes and reducing the count of CD20+ cells, and also allows to steadily reduce blood serum HBsAg level.
Opisthorchis felineus invasion in human causes inflammatory and dyskinetic disorders of the gastrointestinal tract accompanied by altered phenotypic characteristics in colon microbiota. The aim of research — study an impact of the Escherichia coli isolate phenotypic characteristics on Klebsiella spp. bacteria, isolated from colonic contents of patients with diagnosed opisthorchiasis as well as E. coli antagonistic activity. Materials and methods. The phenotypic properties of 54 E. coli isolates and 8 genus Klebsiella isolates obtained from colonic contents of patients with diagnosed opisthorchiasis were assessed. Identification of isolates and analysis of proteomic profiles were performed using Maldi BioTyper 3.0 software. 204 co-cultivation datasets were analyzed investigating antagonistic activity of E. coli isolates with varying properties on Klebsiella spp. E. coli and Klebsiella spp. isolates were examined by whole genome sequencing. Results. E. coli bacteria with typical phenotypic characteristics showed significantly more prominent antagonistic activity against Klebsiella spp. A significantly higher level of antagonistic activity against K. oxytoca bacteria vs K. pneumoniae strains. The proteomic bacterial strain profiles were divided into clusters depending on the level of antagonistic activity. E. coli molecular serotyping for O- and H-antigens revealed the genes of enterotoxigenic, enteroinvasive and extraintestinal pathogens in 60.0% of cases. Strains with the highest antagonistic activity index, which are carriers of the genes typical to enterotoxigenic E. coli sequence serotypes O6:H1 and O6:H5, were identified. The genome of such strains consisted of the largest number of virulence gene complexes: adhesins, invasins, toxins, bacteriocins. Multilocus sequence typing and sequence serotyping of E. coli and K. pneumoniae strains established their heterogeneity; K. oxytoca isolates were identified as ST242 and ST176. All strains were characterized by homology of antibiotic resistance markers (oqxA, oqxB, fosA) and a variety of beta-lactam resistance gene variants. Conclusion. It was found that E. coli isolates with typical phenotypic characteristics and carriers of virulence gene complexes exhibited significantly more pronounced antagonistic activity against Klebsiella spp. isolated from colonic contents of patients with diagnosed opisthorchiasis.
The aim of this study was to assess the prevalence of occult hepatitis B infection among blood donors in St. Petersburg, as well as to characterize the identified virus isolates. The study material was represented by 2800 blood plasma samples collected in 2019 from blood donors living in St. Petersburg. The ELISA study for HBV marker rate consisted of HBsAg, anti-HBs IgG, anti-HBcore IgG. HBV DNA was analyzed by nested PCR with real-time hybridization-fluorescence detection on three targets allowing to determine virus DNA at low viral load, including HBsAg-negative chronic hepatitis B. Hepatitis B serological markers were detected in 69.43% of those surveyed, HBsAg was found in 0.43% of individuals, and all of which donated blood first time. A significant excess of the anti-HBcore IgG antibodies occurrence among primary donors (15.1%) compared with repeated/regular donors (7.48%) was shown. The prevalence of virus DNA in the group was 3.14%, including 2.71% of cases in HBsAg-negative CHB. Based on phylogenetic analysis of 88 isolates, HBV subgenotypes were determined in the following order: D1 and D2, 40.91% each, D3 and A2, 9.09% each. While determining the serological subtype in detected isolates, the serotype ayw3 (52.27%) vs ayw2 (46.59%) and adw2 (10.23%) prevailed. Drug resistance mutations, including compensatory ones, were detected in six examined patients (6.82%). In all genotype D isolates, multiple amino acid substitutions were identified in the RT, SHB, MHB, LHB, and Core regions; mutations in the preCore region were detected in 21.59% samples. In the MHR of the HBV genotype D genome, twenty-six positions were identified in which amino acid substitutions occurred, and all isolates showed modifications at positions 113, 114, 131, 134, 159, 161, 168, in 76 — at position 122, in 68 — at position 127, in 36 — at position 118, in 24 — at position 128. In HBV A2 isolates, mutations T113S, S143T, Y161F were identified. Nine isolates in the preCore region showed a polymorphism including a stop codon W28*W; in five isolates the W28S substitution was shown in the same position, and the W28*S variant was found in one more sample. The high incidence of HBsAg-negative CHB cases among blood donors, as well as the predominance of HBV isolates that simultaneously carry mutations resulting in diagnostic failure of HBsAg tests and prophylactic failure of immunoglobulin or vaccines and virus reactivation, mutations that contribute to disease progression obviously pose a threat to health and require to be further examined.
Introduction. Since May 2022, an unusually large number of new monkeypox infections-a previously rare viral zoonotic disease, mainly reported from central and western Africa has been reported globally, and the World Health Organization (WHO) declared a global health emergency in July 2022. We aimed to systematically review the monkeypox virus epidemiology, pathogenesis, transmission, presentations, and outcomes. Materials and methods. Our aim is to systematically review the epidemiology, pathogenesis, manifestations, and outcomes of Monkeypox disease. We searched the keywords in the online databases of PubMed, Embase, Scopus, and Web of Science and investigated all English articles until December 2022. In order to ascertain the findings, this study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. In order to optimize the quality, this review study benefits from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. To minimize any probable bias risk, we utilized the Newcastle-Ottawa Scale (NOS) risk assessment tool. Results. The most prevalent symptoms were rash and fever. The infection was accompanied by different complications such as, but not limited to, encephalitis (mainly in children), septicemia, bacterial cellulitis, retropharyngeal and parapharyngeal abscesses, etc. A wide range of hospitalization from 3.7% to 100% has been reported. The mortality rate ranged from 0% to 23%, which mainly occurred in infants and children. High mortality of the monkeypox rate was reported among pregnant women. The mortality rate of monkeypox is lower among women and those who received the smallpox vaccine compared to men and those who did not receive the vaccine. A wide range of the overall second-rate attack was reported, which is more pronounced in unvaccinated patients. Conclusion. In our systematic review of 35 studies on monkeypox, we cast light on the existing evidence on its epidemiology, pathogenesis, manifestation, and outcomes. Further studies are needed to elucidate the natural history of the disease in various patients’ population, as well as detailing the monkeypox attack rate.
Relevance. Due to the large-scale vaccination campaigns against the SARS-CoV-2 coronavirus taking place worldwide, the question arises as to how vaccination may affect complete blood count (CBC) parameters in COVID-19 cases. Research objective: assess differences in complete blood count parameters in COVID-19 patients based on their vaccination status. Materials and methods. A review of publications was conducted describing and presenting the complete blood count parameters in patients with verified COVID-19, by stratifying them into vaccinated and unvaccinated individuals against the SARS-CoV-2 virus-caused disease. Subsequently, a meta-analysis of the results for each CBC parameter was carried out by describing identified differences among patients with mild and moderate COVID-19, lacking comorbidities affecting CBC indicators. Results. The analysis conducted allowed to determine that the complete blood count parameters do not exceed the reference range in most cases in both groups, excepting those of individuals with a severe disease course. The exception is the erythrocyte sedimentation rate (ESR) (42 [20.5–63.5] (∑n = 107, Me [Q1–Q3])) mm/h in unvaccinated individuals. Also, a slightly lower absolute lymphocyte count is observed in vaccinated individuals (0.95 [0.58–1.62] × 109/L (∑n = 441, Me [Q1–Q3])). There is a twofold greater range of leukocyte quartile values in vaccinated individuals compared to unvaccinated individuals: 7.07 [4.07–12.31] × 109/L (∑n = 555, Me [Q1–Q3]) vs 5.68 [4.02–8.34] × 109/L (∑n = 2202, Me [Q1–Q3]). A similar pattern is observed for monocytes. Conclusion. Conducting a meta-analysis of laboratory parameters in COVID-19 cases among vaccinated and unvaccinated individuals allows for determining the effectiveness of vaccination as well as identify the major trends in dynamic changes for essential blood parameters among unvaccinated and vaccinated individuals in general or with certain immunobiological preparations.
Until recently, HIV infection does not lose its relevance. In 2022, 630 000 people died and 1.3 million people became infected with the human immunodeficiency virus (HIV). HIV-positive persons develop more infectious diseases than healthy people do; the causative agents are mainly opportunistic microorganisms. Streptococcus pneumoniae is the main causative agent of infection in the lungs in HIV-infected persons. In order to prevent the development of severe pneumococcal infections and to overcome antibiotic resistance, vaccines have been developed. There are polysaccharide (PPV) and conjugate (PCV) vaccines. According to clinical recommendations, vaccination of previously unvaccinated HIV-infected patients is carried out regardless of T-helper cell level. However, no data were found on the effect of PCV13 on immunological memory cells. The purpose of this study is to assess an effect of PCV13 vaccination on the immune system in HIV-infected subjects. Materials and methods. The study included 200 patients with HIV infection, which were divided into two groups: I — received a dose of PCV13 (n = 100) and control group (n = 100). During the first visit, immunological and microbiological studies were carried out. On the second visit, a PCV13 was injected into the deltoid muscle. The third visit was made a year later, where immunological and microbiological studies were repeated. Participants were divided into 4 subgroups depending on CD4+ T cell level. The microbial study was done using a swab collected from the back of the throat. Results. During the immunological examination at visit 1, abnormalities were detected in all examined populations and immune cell subsets. At 12 months post-vaccination, the median levels of CD3+CD4+ and CD45RO+ T lymphocytes in the immunized group were higher than pre-vaccination levels compared to control group, in which the values changed insignificantly. Our data confirm the immunological effectiveness of PCV13 administration in HIV-infected patients. In patients with peripheral blood CD19+ lymphocyte deficiency, had increased microbial detection rate (p = 0.003). Conclusion. As a result, due to the high risk of pneumococcal pneumonia, HIV-infected patients should be immunized with a 13-valent pneumococcal conjugate vaccine.
Purpose of the study: to study the dynamics of developing herd immunity against SARS-CoV-2 in the population of the Republic of Kyrgyzstan during COVID-19. Materials and methods. The work was carried out using the methodology for assessing population immunity developed by Rospotrebnadzor (Russia) as well as the Ministry of Health (Kypgyzstan) and the St. Petersburg Pasteur Institute. The selection of participants was carried out by questionnaire using a cloud (Internet server) service. To monitor population immunity, a cohort of 2421 subjects was formed, who participated in all stages of seromonitoring. Volunteers were randomized according to age groups (1–17, 18–29, 30–39, 40–49, 50–59, 60–69, 70+ years), regional and professional factors. Antibodies (Abs) against SARS-CoV-2 nucleocapsid (Nc) and the receptor binding domain (RBD) of S-glycoprotein were determined by qualitative and quantitative methods. The study was carried out in 3 stages according to a single scheme: 1st stage — 06/28–07/03/2021, 2nd — 21–25/02/2022 and 3rd — 31/10–04/11/2022. Since 2021, Kyrgyzstan has been vaccinating the population against SARS-CoV-2 mainly using inactivated whole-virion vaccines. Results. Population immunity against SARS-CoV-2 was predominantly accounted for by both Ab types (Nc+RBD+). By the 3rd stage, the percentage of such persons reached 99.2%, Nc–RBD– volunteers — up to 0.8%. At the 1st stage, middle-aged people dominated, but age differences were leveled out by the 2nd stage. The greatest impact on seroprevalence was found among medical workers, the smallest — among businessmen and industrial workers. Populational vaccination significantly impacted on the state of herd immunity that reached 25% by the 3rd stage. The refusals of the population in Kyrgyz Republic from vaccination noted at the 2nd and especially 3rd stages did not significantly affect level of herd immunity, which could probably be associated with asymptomatic cases of COVID-19, against which primary vaccination had a booster effect. Conclusion. The dynamics of population humoral immunity against SARS-CoV-2 included a number of changes in the level of circulating antibodies (Nc, RBD), caused by both primary infection and vaccination. The herd immunity formed in population of Kyrgyzstan allowed to reduce the incidence of COVID-19 to almost sporadic level.
Leptospirosis is a zoonotic disease found virtually worldwide. Microscopic Agglutination Test with live leptospira (MAT) is the reference method for the serological diagnosis of leptospirosis. MAT is based on assessing serum potential to agglutinate live reference serovar Leptospira maintained at a reference laboratory. At some laboratories having own collections of isolated and reference Leptospira strains applicable for serological diagnosis, those microorganisms are maintained for many years by repeated subculturing, that increases markedly a chance of strain cross-contamination. The lack of adequate quality control for reference strains may affect data of epidemiological studies. Control of Leptospira spp. reference strains purity and stability of their antigenic composition is very important for diagnosis of leptospirosis. The study objective was to compare the 16S rRNA gene nucleotide sequences of some Leptospira strains from the collection of the St. Petersburg Pasteur Institute to with relevant sequences uploaded to GenBank. In this study, 38 Leptospira strains were investigated. Nucleotide sequences of 36 strains were deposited in the international GenBank database, inconsistencies were revealed in two strains. The study found that the control Leptospira strains from the collection of the St. Petersburg Pasteur Institute had minimal dissimilarities from international control strains. The analysis of the resultant 16S rRNA sequences has shown the presence of point mutations, transitions, deletions and insertions, regardless of the strain species. The open leptospira pan-genome demonstrates high genomic variability in species due to the capability of leptospira for lateral gene transfer in order to adapt to changing environmental conditions. The massive acquisition and loss of genes give rise to an increased species diversity. The 16S rRNA gene is suitable for screening diagnostics; however, high level of the fragment similarity and close phylogenetic relationship between different species put bounds to its use in genotyping. The presence of point nucleotide mutations is most likely associated with the evolutionary mechanisms of leptospira, their ability to horizontal gene transfer and crossing-over, including ribosomal genes, but this assumption necessitates additional research. For specimen genotyping it is necessary to select alternative genes with high specificity and sufficient level of nucleotide divergence. The study shows a need for genetic analysis of collection strains in order to control the purity of cultures.
Introduction. Features of cytokine production in mononuclear cell cultures from Lyme borreliosis patients based on clinical data remained poorly studied. The study aim was to estimate the patterns of baseline and lipopolysaccharide-induced cytokine-secretory activity of peripheral blood mononuclear leukocytes from patients with erythema migrans form of acute Lyme borreliosis based on clinical parameters. Materials and methods. Groups of 22 and 12 patients with the diagnoses of mild or moderate severity of monoinfection and co-infection with tick-borne encephalitis of Lyme borreliosis with erythema migrans were examined twice: on week 1 after disease onset and day 14. The control group included 17 healthy donors. Basal and lipopolysaccharide-induced IL-6, IL-10, and TNFα secretion levels were assessed in mononuclear leukocyte culture supernatants applying enzyme immunoassay. Statistical analysis was performed by using the Mann–Whitney U-test, Wilcoxon test, and Spearman’s rank correlation. Results. The group of moderate severity patients was clinically distinguished by severer fever and intoxication manifestations. At the disease onset, the basal TNFα, IL-6 and IL-10 secretion levels in the moderate severity patient cultures were significantly higher than in those of the other groups. After antibiotics treatment, the baseline TNFα and IL-10 levels tended to decrease. At the onset, lipopolysaccharide-induced cultures from the moderate severity patients showed significantly suppressed TNFα production and increased IL-10 secretion as compared to the other groups. Lipopolysaccharide-induced IL-6 secretion in the moderate vs. mild severity group supernatants was significantly lower. In dynamics, the induced TNFα levels in the moderate severity patients were increased to the magnitude exceeding that in the controls. Positive correlations between the IL-6 and TNFα basal levels and maximum body temperature or the C-reactive protein serum concentrations were revealed in the patients. Induced TNFα levels showed negative correlations with fever levels or with IL-10 secretion. Conclusions. It was demonstrated that basal TNFα, IL-6 and IL-10 secretion levels in the mononuclear cell cultures of acute Lyme borreliosis patients increased with the increasing disease severity. Suppression of lipopolysaccharide-induced TNFα production in the moderate severity patient cultures was presumably associated with the regulatory cytokine IL-10 effects.
Catalase is a heme-containing enzyme belonging to protection factors that destroys peroxide compounds. The presence of catalase activity is an important ability of microorganisms that allows them to be protected from unfavorable factors as well as adapt to macroorganism conditions. Catalase along with superoxide dismutase plays an important role in pathogen resistance to phagocyte oxygen-dependent bactericidal mechanisms. The aim of the study was to investigate microsymbiont catalase activity from female reproductive tract in normocenosis and candidiasis dysbiosis using the chronobiological approach. The study was conducted on clinical isolates, isolated from female reproductive tract microsymbiocenosis. The catalase activity was determined by spectrophotometry based on 24 hour-long hydrogen peroxide reduction with 3-hours interval in winter season. Dynamic hydrogen peroxide was assessed in 3–5 experiment replicates. In some Lactobacillus spp., catalase was found containing no heme group — pseudocatalase. Chronobiological approach allowed to reveal enzyme activity from all microsymbionts. The dominant and associative microbiota isolated from healthy females was characterized by circadian (24 hours) rhythms of catalase activity early in the morning — 5 a.m. (р 0.05). Hydrogen peroxide decomposes spontaneously or via non-enzymatic catalysts, and microorganisms cope with this situation under such conditions. In microsymbionts characteristic of female reproductive tract dysbiosis, and usually found in large numbers along with decreased Lactobacillus spp. ultradian rhythms with 12- and 8-hour harmonics of catalase activity with acrophase were recorded in the morning (8 a.m.) and evening hours (8 p.m.). The minimum values of enzyme production in all cultures were recorded at 12 p.m. and 5 p.m. Therefore, the contribution of the rhythm of the studied parameter at varying degree of vaginal sterility reflects the adaptive pathogen capabilities to the conditions of existence and can be the basis for studying related regulatory mechanisms. Mesor and amplitude phase stability are universal rhythmometric parameters used to evaluate patient’s condition independent of species assignment.
Classical reassortment in developing chicken eggs is a well-established technique for obtaining LAIV strains. Naturally generated reassortant vaccine strains are characterized by high reproductive capacity, genetically stable characteristics of temperature sensitivity and cold resistance, which correspond to the characteristics of the MDV involved in crossing with the epidemic virus. Along with antigenic relevance, natural reassortment ensures attenuation of vaccine strains, good reproduction capacity in upper respiratory tract cells and inability to reproduction in the lower respiratory tract. With classical reassortment, the speed and efficiency of obtaining vaccine reassortants largely depend on the properties of epidemic virus, and therefore cannot be stable. The potential of reverse genetics is attractive because it allows to obtain vaccine reassortants quickly and efficiently, reduce the likelihood of spontaneous mutations; however, the vaccine strain is deprived of the advantages of natural selection, in which the most viable clones are selected. This study presents the results of comparatively assessed A(H3N2) LAIVs obtained in parallel by classical reassortment and reverse genetics according to criteria confirming that vaccine strains inherit the necessary properties that guarantee their harmlessness and high reproduction in chicken embryos. Strains for LAIV obtained by both methods retained all attenuating mutations inherited from the MDV, were highly reproductive at the optimal temperature, with temperature sensitivity corresponded to the MDV. However, strains obtained by reverse genetics, was observed to have partial loss of cold resistance in comparison with that of the MDV and classical reassortants. Reduced cold adaptation may negatively affect vaccine effectiveness. It is important that after several additional passages in chicken embryos at low temperature, the cold resistance of the vaccine strain, assembled by reverse genetics, was increased. Credibly that cold resistance is a phenotypic trait, the degree of manifestation of which depends on the temperature conditions of virus multiplication. The selective factor of reduced incubation temperature is missing in reverse genetics. In order for the cold-adapted phenotype to be fully realized, additional passages at low temperature of RG-reassortants are necessary. Thus, the reverse genetics method using plasmid technology allows to effectively prepare reassortant strains for LAIV. An important stage in obtaining vaccine strains using genetic engineering techniques should be the control of their cold-adapted phenotype and its optimization by additional passages at low temperature.
Introduction. Bacterial coinfection and secondary bacterial infection are considered critical risk factors for the severity and mortality of SARS-CoV-2-caused pneumonia. The aim of the study was to analyze a pattern of microbial associations between K. pneumoniae and A. baumannii isolated from the lower respiratory tract discharge and sectional material (lung tissue) of patients diagnosed with pneumonia, and to compare resistance level in monoculture and associations during new coronavirus infection pandemic. Materials and methods. A bacteriological study of 2689 sputum and bronchial washing samples from patients at infectious diseases hospitals, and 1411 lung pathological material samples was carried out. Bacterial isolates were identified by mass spectrometry. Antibiotic sensitivity for isolates was determined by the disk diffusion method. Genetic determinants of resistance to beta-lactam antibiotics were detected by PCR. Statistical data processing was performed using SPSS version 22 software. Results. K. pneumoniae and A. baumannii isolates were predominantly found in two- and three-pathogen associations. It was established that the resistance level of K. pneumoniae isolates in association with A. baumannii is significantly higher compared to that in monoculture for all antimicrobial drugs studied. At the same time, K. pneumoniae in combination with Candida spp. vs monoculture showed significantly lower level of resistance to ciprofloxacin, amikacin, cefotaxime, ceftazidime and amoxicillin/clavulanic acid. K. pneumoniae isolates carried resistance determinants to extended-spectrum beta-lactamases: OXA-48 — (22.5%), OXA-51 — (5.6%), OXA-23 — (4.2%), KPC — 70.9%, NDM — 7%. Of these, 14.1% of strains had the ability to co-produce serine carbapenemases OXA-48 and KPC. Sputum and lung tissue A. baumannii isolates exhibited extremely high multiple resistance regardless of their associations with other microorganisms. Microbiome species similarity in the lower respiratory tract and lung tissue discharge was revealed. The proportion of lung tissue vs sputum resistant strains of K. pneumoniae and A. baumannii was significantly higher. Conclusion. The detection of of multiple drug resistant K. pneumoniae and A. baumannii isolates as well as their associations may indicate aggravated pneumonia severity.
Introduction. Diarrheal diseases are a global public health issue and cause 15% of deaths in children under 5 years old, of which about 80% occur in the regions of Africa and Southeast Asia. According to the Global Enteric Multicentre Study (GEMS) conducted in a number of African countries, one of the leading pathogens of high risk of death in infants and young children is diarrheagenic E. coli (DEC). In recent decades, antimicrobial resistance (AMR) has become globally ubiquitous. The Republic of Guinea urgently needs large-scale studies devoted to assessing DEC distribution and antibiotic resistance. The purpose of the study is to assess the pattern of E. coli infections and to test the susceptibility to antibiotics in strains of diarrheagenic E. coli sampled from individuals residing in the Republic of Guinea. Materials and methods. From 2019 to 2022, we studied 724 samples of faeces of patients with acute diarrhea, among them 72 (9.9%) children aged 1–5 years, 128 (17.7%) children aged 6–17 years, and 524 (72.4%) people aged 18 years and older; a method of polymerase chain reaction (PCR) was applied with the use of the AmpliSense® Escherichioses-FL reagent kit to identify the genetic determinants of DEC: EPEC, EHEC, ETEC, EIEC, and EAgEC (Central Research Institute of Epidemiology of Rospotrebnadzor, Russia). Susceptibility to 15 antimicrobial agents was found by the disc-diffusion method using Mueller–Hinton agar (Russia) and Oxoid discs (UK). Results were interpreted according EUCAST criteria, versions 2019–2022 (https://www.eucast.org/ast_of_bacteria/previous_versions_of_documents). Results. For the period from 2019 to 2022, the percentage of E. coli infections in the etiological pattern of acute intestinal infections amounted to 51.7%. In the age-related manner, DEC was significantly more common in young children aged 0–5 (96.9%, p 0.05) as compared to school age children aged 6–17 (53.9%) and adults (45.6%). In all years of observation, EAgEC strains prevailed, accounting for 38.4%. Other DEC pathotypes, EPEC, ETEC, EIEC and STEC, accounted for 27.2%, 17.5%, 11.8%, and 5.1%, respectively. DEC strains are susceptible to meropenem, amikacin, and nitrofurantoin. The activity of other antibiotics ranged from 11.3% for ampicillin, 28.3% for trimethoprim-sulfamethoxazole, and 34.0% for tetracycline to 73.6% for cephalosporins, 84.0% for aminoglycosides, and 98.1% for fluorinated quinolones. Conclusion. To reduce the burden of diarrheal diseases in the Republic of Guinea, it may be necessary to conduct targeted epidemiological and microbiological studies to identify DEC and monitor the development of antimicrobial resistance of E. coli infection pathogens in the population.
The official history of the discovery of human coronaviruses dates back to 1965, when the first coronavirus B814, which has now been lost, was isolated on the human embryonic tracheal organ culture from the nasal swabs of a patient with acute respiratory disease. However, this time point can only be an intermediate stage on its long evolutionary path. Paleovirological studies have shown that coronaviruses could have appeared as early as in the Stone Age — in the Upper Paleolithic era, and East Asia is considered as their place of origin — a region that is well known to virologists as the source of many highly pathogenic influenza viruses and new coronaviruses, such as SARS-CoV, MERS-CoV, and SARS-CoV-2. This makes us take a different look at the seeming “innocence” of seasonal coronaviruses that circulated before 2002, when a human pathogenic virus appeared that caused SARS. This also fits well into the assumption about the coronavirus nature of the 1889 Russian flu pandemic. Today, four seasonal and three new, pathogenic for human coronaviruses are known. Two seasonal coronaviruses (229E and NL63) belong to the genus Alphacoronavirus, 2 others (OC43 and HKU1) and three new coronaviruses (SARS, MERS and SARS-CoV-2) belong to the genus Betacoronavirus. In this review, we have focused on the “extreme points” — seasonal coronaviruses and pandemic SARS-CoV-2. We attempted to draw an analogy between them and identify their main distinguishing features. From the viewpoint of epidemiology and clinic, common what they have is only the airborne transmission route, characteristic of all respiratory viruses, and the ubiquitous distribution, the nature and intensity of which were not markedly affected by the influenza epidemics/pandemics. Seasonal coronaviruses continued to circulate even during the COVID-19 pandemic, when the majority of other respiratory viruses had largely disappeared. Significant differences between seasonal coronaviruses and SARS-CoV-2 can be traced in the symptoms, severity and pathogenesis of the diseases they cause. At the structural level, they have a lot common features including taxonomic proximity, morphology, structure, physicochemical properties of virions, genome organization, the main stages of virus replication, etc. What made SARS-CoV-2 such aggressive? The few differences in the size of viral particles and viral genome that have been identified to date, the use or not of hemagglutinin esterase to penetrate into a sensitive cell, attachment to different cell receptors cannot underlie a prominent difference in severity of the infection caused by seasonal or pandemic coronavirus. Most likely, that these differences are based on delicate molecular mechanisms that have yet to be discovered.
The aim is to examine dynamics of avidity maturation of IgG antibodies against SARS-CoV-2 RBD depending on the type of immunization (vaccination or infection), as well as on the duration and frequency of immunization. Materials and methods. The study was performed on two sample cohorts collected at two time points during COVID-19 pandemic. The first cohort (group No. 1) consisted of 87 samples of blood sera obtained from COVID-19 convalescents in the period from March to September 2020. The second cohort included 204 samples obtained in September 2021 from two patient groups. Group No. 2 (n = 64) patients immunized with a full course of Gam-Covid-Vac, group No. 3 (n = 140) COVID-19 convalescent patients and subjects vaccinated with Gam-Covid-Vac (hybrid immunity). Results and conclusion. The dynamics of avidity maturation for SARS-CoV-2 RBD IgG antibodies depending on the method and frequency of immunization, showed that the most effective immunity was formed in COVID-19 convalescent patients and subjects vaccinated with a full course of Gam-Covid-Vac. The hybrid immunity showed not only a significantly higher (compared with groups No. 1 and No. 2) level of IgG antibodies (median 228 BAU/ml vs 75 or 119 BAU/ml, p 0.001), but also a higher level of avidity (IA 90.5% vs 54.5 and 76.6, respectively, p 0.001, 4M urea). In the test for assessing the avidity index with the denaturing agent 8M urea in patients with hybrid immunity, the median level of IA was 25% versus 14.8% and 16% in COVID-19 convalescents and vaccinated subjects (p 0.001), only in 8 patients IA was higher than 50%. While comparing a single infection of COVID-19 with a full course of Gam-Covid-Vac, it was shown that vaccination leads to higher IgG levels (median values in groups 119 and 75 BAU/ml, p 0.001) and to a higher avidity index (median 76.6% vs 54.5%). Thus, the more rapid induction of high-avidity antibodies was in vaccinated individuals at early stages of immunization (up to 4 months), during the period when IgG avidity maturation has not yet been completed. Our results showed that during this period vaccination leads to production of antibodies with avidity index at median level of 82% versus 36% in COVID-19 convalescents at similar time point.
Introduction. As the COVID-19 pandemic continues to pose a significant challenge to global health, effective therapeutic options for preventing and treating the disease have become increasingly important. We aimed to provide an update on current treatments and therapeutic options for COVID-19 patients.Materials and methods. The purpose of this umbrella review is to explore the current treatments and therapeutic options for COVID-19 patients. Keywords and their combinations were searched across online databases in Embase, PubMed/MEDLINE, Web of Science, and Scopus spanning from July 1, 2020, through March 3, 2023. Publications were selected for data extraction in two steps based on the study inclusion/exclusion criteria. The study adheres to the PRISMA checklist as well as NIH bias risk and quality assessment tool.Results. In this review, 28 relevant articles were selected for the final qualitative synthesis. The majority of included studies had reported on the efficacy of Lopinavir/Ritonavir (n = 4), Ivermectin (n = 3), Baricitinib (n = 2), Tocilizumab (n = 2), Remdesivir (n = 2), ACEI/ARB (n = 2), Vitamin D (n = 2), Molnupiravir (n = 2), Traditional Chinese medicine (TCM) (n = 2), Convalescent plasma transfusion (CPT) (n = 2) and hydroxychloroquine (n = 2) in treating COVID-19. It appeared that Baricitinib, Remdesivir, ACEI/ARB, TCM, and CPT may have beneficial effects on reducing mortality, hospitalization duration, and disease severity in COVID-19 patients. Other interventions, such as Lopinavir/Ritonavir, Ivermectin, Vitamin D, and Hydroxychloroquine did not show clear benefits or had inconclusive results.Conclusion. This umbrella review provides a comprehensive overview of the current evidence on the effectiveness and safety of various pharmacological and non-pharmacological interventions for COVID-19. These results provide an updated overview of the current landscape for COVID-19 treatments, highlighting potential avenues for further research and clinical practice. It is crucial to continue monitoring emerging evidence and conducting rigorous studies to guide the development and optimization of therapeutic strategies against COVID-19.
B-cell receptors can interact with antigen epitopes on various objects: macromolecules, microorganisms or on the surface of other cells, e.g., follicular dendritic cells. Accordingly, B cells, on the one hand, have the ability to evaluate the location of pathogen surface epitopes, and, on the other hand, they must adapt their receptor apparatus to different epitope locations and antigen-bearing surface properties. Indeed, B-cell receptors and antibodies better bind objects with regular and dense epitope arrangement characteristic of many pathogens. As a result, such epitope arrangement can be recognized as a pathogen-associated geometric pattern, but the conditions for such recognition depend on the isotype of membrane immunoglobulin and the degree of B cell maturity. Young B cells express membrane IgM, which is involved in B cell development and the selection of their repertoire. Receptors with IgM do not impose strict requirements on epitope location and can activate B cells even upon binding a monovalent antigen. Receptors with membrane IgD are expressed later and predominate on naive B cells before entering the immune response. These receptors are optimized for two-point antigen binding and strictly require this type of interaction to induce an activation signal. Before contact with antigen, B-cell receptors are grouped in discrete membrane zones — nanoclusters, due to close interactions with the actin cytoskeleton. Contact with the antigen leads to the detachment of receptors from the cytoskeleton, rise in their mobility and the combining nanoclusters into microclusters — large clusters enriched with signaling molecules. The most dynamic changes are observed upon contact with an antigen fixed on the membrane of adjacent cell. In this case, free actin moves to the periphery of the intercellular contact zone, where it forms the cytoskeleton of the processes carrying receptor clusters. The processes spread across the surface of the partner cell and then contract, moving the antigen-binding microclusters to the center of the contact zone. Finally, the microclusters combine into a central cluster of the immune synapse, the intensity of the activation signal drops, and the cell prepares for endocytosis of antigens grouped at the local site. Thus, the structure of B-cell receptors can contribute to the response of the B-lymphocyte to antigens with a characteristic spatial location, while the dynamic interaction between B-cell receptor apparatus and the cytoskeleton allows optimizing the binding of antigens presented on various carriers. Knowledge on spatial aspects of antigen recognition may be useful for the construction of vaccines based on virus-like particles or antigens on other artificial carriers.
Measles is a highly contagious, vaccine-preventable anthroponotic infection. Despite the policy of active measles vaccination for entire global population, measles has not completely disappeared, it wanes and waxes in outbreaks. It has been shown that not only the unvaccinated but also the vaccinated, which is quite understandable, subjects are involved in measles progression. The study was aimed at assessing features of the immune response in adult measles patients at rise in disease incidence upon its eradication. 1.158 blood sera from measles patients aged 18 to 70 living in Moscow and the Moscow region were studied by ELISA (Euroimmun, Germany). The vast majority of subjects were aged 1840 years comprising 72.36% cases. 69 sera collected at a later timepoint (1020 days from rash onset) were excluded and analyzed separately. According to anti-measles IgG and avidity level, the data were stratified as follows: group 1 with a primary type of immune response 582 sera (53.44%), not vaccinated in childhood; group 2 (secondary response) 446 sera (40.96%), vaccinated in childhood, but lost anti-measles antibodies; group 3 with intermediate level of parameters 61 sera. To clarify the type of immune response in group 3, an additional analysis of the spectrum of anti-measles antibody subclasses was carried out. It was shown that a mixed type of response was detected in this group: 31 subjects mainly had primary immune response, and 30 subjects secondary immune response. At the same time, 40 out of 61 subjects were vaccinated against measles 13 months prior to disease onset, i.e., it was overlapped on arising post-vaccination immunity. Thus, the previously identified trend towards the loss of post-vaccination immunity among older schoolchildren and young adults vaccinated in childhood who are involved in the epidemic process continues to worsen.
Aim. The aim of our work was to assess the mutations prevalence in the HCV drug resistance in the NS3, NS5A, NS5B genes in HIVinfected patients. Materials and methods. The material of the study was 157 blood plasma samples from HIV patients living in the Leningrad Region, with virological inefficiency of antiretroviral therapy. Samples were examined for the presence of anti-HCV antibodies and HCV RNA. In the case of detecting HCV RNA, amplification was carried out using a set of primers co-flanking the NS3, NS5A, and NS5B genes. After sequencing the nucleotide sequences of these genes, the virus subtype was determined and drug resistance mutations were detected. Results and discussion. The age of the patients varied from 18 to 65 and averaged 34.3 7.27 years. The number of men in the group prevailed compared to women - 71% and 28%, respectively. Antibodies to HCV were detected in 94.2% of HIV-infected persons. HCV RNA was detected in 98 (61.7%) patients. The distribution of HCV genotypes in this group was as follows: 1a 7% (n=7), 1b 53% (n=52), 2 2% (n=2), 3a 38% (n=37). The results of determining the viral load varied from 5.3x103 to 2.3x108 IU/ml. The nucleotide sequence of all three regions NS3, NS5A, NS5B was determined in 73 samples. In the study group, mutations associated with resistance of the hepatitis C virus to direct antiviral drugs in all regions were found in 16.6% of cases (n=26). There are 6 significant amino acid substitutions in the NS3 region, 15 and 10 significant amino acid substitutions in the NS5A and NS5B regions, respectively.
COVID-19 is a highly transmissible disease with severe course especially in patients with nephrogenic hypertensive disease and chronic kidney disease due to a higher incidence of all-type infections than in the general population. The aim of the study is to describe a clinical case of SARS-CoV-2 infection complicated by nephrogenic pulmonary edema and COVID-associated pneumonitis, alveolitis. Description of the case. Patient K.S., born in 1975, was hospitalized 24 hours after symptom onset at emergency hospital due to complaints of increased blood pressure up to 180200/110120 mm Hg, temperature up to 38.7C, dry cough, feeling of heaviness in the chest, change in urine color. PCR smear for SARS-CoV-2 was positive. Computed tomography revealed a pattern of bilateral COVID-associated pneumonitis, alveolitis, with 75% involvement. The electrocardiogram revealed signs of left ventricular myocardial hypertrophy. Ultrasound examination showed numerous cysts in the kidneys. Urinalysis at admission: leukocytes 499, erythrocytes 386. Glomerular filtration rate (CKD-EPI: 29 ml/min/1.73 m2) and corresponds to stage IV of chronic kidney disease. Coagulogram: fibrinogen: 32.3 (1.64.0) g/l, D-dimer: 663 (0250). Despite the treatment, the patients condition worsened, the phenomena of cardiopulmonary and renal insufficiency increased, which led to a fatal outcome. During a virological study of sectional material: SARS-CoV-2 coronavirus RNA was found in the lung and kidneys. Signs of bilateral COVID-associated pneumonitis, alveolitis with diffuse cellular infiltrates in combination with changes in the alveolar apparatus, signs of pulmonary edema were revealed. Heart-related signs swelling of the interstitium, fragmented muscle fibers, some of them hypertrophied, a wave-like deformation of cardiomyocytes, blurring of the transverse striation. Arteries with thickened sclerosed walls. In the kidneys diffuse damage to the proximal tubules of the nephron with areas of cortical and proximal necronephrosis, areas of fibrinoid swelling. Conclusion. The cause of death of a 45-year-old patient was a severe course of bilateral COVID-associated pneumonitis, alveolitis, which contributed to the development of renal medullary hypoxia and type 1 cardiorenal syndrome, which led to early nephrogenic pulmonary edema.
