The identification of risk factors for early pregnancy termination is an important aspect in modern obstetrics. The vaginal microbiota plays a significant role in normal pregnancy course affecting the local immune response. Inflammation caused by pathogenic and opportunistic microorganisms activates various immune arms altering expression of innate immunity genes. Molecular genetic determination of the inflammatory response and microbial composition of the vaginal biotope could become an important criterion for predicting pregnancy complications. The aim of the study was to analyze markers of the local immune response and vaginal microbiota composition during pregnancy to predict pregnancy outcomes. Materials and methods. 52 women verified at up to 10 weeks pregnancy were examined. Depending on the outcome of ongoing pregnancy, study participants were divided into 3 groups: group 1 (n = 42) with term birth; group 2 (n = 7) with premature birth; and group 3 (n = 3) with miscarriage. Vaginal discharge was analyzed using a molecular genetic test to evaluate local cytokines and vaginal microbiota profile, sequentially in each trimester. Results. In all patients during the first trimester, the presence of lactobacillus species dominated by L. iners and L. crispatus was detected. L. crispatus prevailed only in group 1 in the first and second trimesters. In group 2, L. iners was most common in both the first and second trimesters, with a significantly higher level in the second trimester compared to group 1. The inflammation index in the first trimester was more often associated with inflammation in groups 1 and 2. In the second trimester, the cytokine profile in group 1 showed no signs of inflammatory response, while in group 2, pro-inflammatory responses were significantly more common. Conclusion. The dominance of L. crispatus in the vaginal microbiota and the low expression of pro-inflammatory cytokines during the second trimester may suggest a high likelihood for successful pregnancy outcome. Assessing cytokine profile along with type of vaginal microbiocenosis opens up avenues for diagnosis allowing to identify women at risk of premature birth.
As part of the 365-day isolation experiment “SIRIUS-23” a relationship between hormone concentrations (estradiol and prolactin) and vaginal microbiota composition in four female participants was assessed. Vaginal swabs were collected 10–14 days before the start of isolation, on days 36, 64, 102, 123, 186, 256, and 339 of isolation study, and 10 days after its cessation. Blood estradiol and prolactin concentrations were measured using an enzyme-linked immunosorbent assay, while microbiological analysis included microbial culture on selective media and identification using MALDI-ToF MS, followed by statistical data processing using factorial and regression analysis, and nonparametric tests (Friedman, Mann–Whitney). The study revealed that estradiol concentrations decreased after the onset of isolation, reaching a minimum level on day 123 (p = 0.05), while prolactin demonstrated an upward trend on day 36, followed by a statistically significant decline on day 64. Factor analysis identified three main factors influencing the “hormone-bacteria” system: i) combined opportunistic microorganisms (OM) and prolactin; ii) included estradiol concentration and its antagonistic relation with some OM number; iii) mirrored competitive interplay between microorganisms. Estradiol concentration correlated positively with protective lactobacilli count (L. aginalis, L. jensenii, L. crispatus) and negatively with OM count, while prolactin concentration was more often positively associated with OM count (S. hominis, S. anginosus, C. amycolatum) and negatively with lactobacilli count. Regression analysis confirmed direct and inverse relationships, such as a positive association between prolactin concentration and E. coli count on day 64 and an inverse association between estradiol concentration and S. anginosus count. Stress factors (resource limitation, psychoemotional stress) exacerbated microbiota imbalance through decreased estradiol and increased prolactin level, which was particularly evident on day 102 of isolation, when OM count peaked in parallel with decreased lactobacilli count. The results highlight the key role for estradiol in maintaining vaginal microbiota balance and the opposite effect of prolactin associated with OM, which justifies a need to monitor hormonal levels and microbiota in women under extreme conditions (e.g., during space flights) and development of personalized probiotic strategies to minimize dysbiosis risks.
The Ob-Irtyshsky focus, which includes the Tyumen region is largest among Opisthorchis felineus invasion sites. The high intensity of invasion spreading in the outbreak underlies a high risk of infection often occurring with acute stage for the residents of the Tyumen region. The aim of this study was to evaluate the immunological parameters in patients with acute opisthorchiasis compared to healthy subjects. Ten patients at the clinic of the Tyumen Research Institute of Regional Infectious Pathology were examined with a diagnosis of acute opisthorchiasis. Immunological examination included lymphocyte phenotyping by flow cytometry. The concentration of immunoglobulins M, G, A, and E and cytokines IFNγ, IL-4, IL-8, IL-10 in blood serum was quantitated by enzyme immunoassay. Neutrophil absorbance was investigated in latex particle test (d = 1 μm). Neutrophil myeloperoxidase enzyme activity was measured spectrophotometrically, concentration of circulating immune complexes — by precipitation with PEG-6000 solution. In patients with acute opisthorchiasis, increased count of leukocytes, eosinophils, monocytes was detected; increased neutrophil scavenging and enzymatic activity; increased absolute number of CD3+ cells, absolute number of T-lymphocytes with CD3+HLA-DR+ marker, relative and absolute number of CD4+ cells were found as well. The concentration of total immunoglobulins G, A, M as well as circulating immune complexes and pro-inflammatory cytokine IL-8 were increased. A positive correlation between IL-8 levels and count of eosinophils, monocytes and percentage of natural killers was revealed in patients but not in control group. Patients have decreased levels of IFNγ and the cytokine IL-10. The level of IL-4 did not differ between patients with opisthorchiasis vs. control subjects. The correlation between IL-4 level and circulating immune complexes, count of eosinophils and natural killer cells was found in patients but not in control group. Thus, patients with acute opisthorchiasis were characterized by activated innate immune response as well as cellular and humoral arms of the adaptive immune response.
Laboratory data are important for confirming diagnosis, assessing COVID-19 progression, and determining treatment measures. The aim of this study was to evaluate the associations of hematological, coagulation parameters, and systemic inflammatory markers with COVID-19 severity according to computed tomography data in hospitalized patients. Materials and methods. Clinical blood test parameters were assessed in 356 patients with COVID-19. Results. Patients with severe vs. minimal and moderate lung tissue damage have a significant increase in the absolute leukocyte count, the relative and absolute number of neutrophils, and a decrease in the relative number of monocytes and lymphocytes. These differences are also observed in patients with moderate vs. minimal lung tissue damage, except for the absolute leukocyte count. However, the latter as well as the relative number of neutrophils and lymphocytes in patients with minimal and moderate lung tissue damage, along with the absolute number of neutrophils and the relative number of monocytes in all patients were within the reference range. In COVID-19 patients with severe lung tissue damage, markers of systemic inflammation (neutrophil-lymphocytic index, platelet-lymphocytic index, systemic inflammatory response index, systemic inflammation index and cumulative systemic inflammation index) were higher than in those with the minimum and average volume, and the monocyte-lymphocyte index is higher than in those with the average volume of lung tissue damage. At the same time, in patients with minimal lesion volume, neutrophil-lymphocyte index and systemic inflammation index were at lower level, than in case of average volume of lung tissue lesion. Conclusion. The study revealed an association between the relative count of neutrophils and lymphocytes, neutrophil-lymphocyte ratio, systemic inflammation index, and systemic inflammatory response index, aggregate systemic inflammation index and severe COVID-19 disease based on computed tomography data. These biomarkers provide valuable information about systemic inflammation and immune system activity and can be detected using standard blood tests.
Human herpesviruses 6A and 6B (HHV6A, HHV6B) are ubiquitous pathogens with lifelong persistence in the human body. HHV6A/B infection often accompanies HIV infection, however, data on the interaction between the two viruses are contradictory. The discrepancy in study results on the influence of HHV6A/B on the course of HIV infection may be due to the molecular genetic variability of the betaherpesviruses. The aim of this work was to assess the molecular genetic diversity of HHV6A and HHV6B in HIV-infected adults in the Nizhny Novgorod region. Materials and methods. Blood leukocyte isolates from 138 HIV-infected patients (HIV(+)) and 68 HIV-uninfected (HIV(–)) individuals were studied. HHV6A/B species were identified by PCR with agarose gel electrophoresis. Nucleotide sequences of the U90A (206 bp) and U90B (431 bp) gene fragments were obtained by Sanger sequencing. The intra-species genovariant of the examined betaherpesviruses was determined based on signature nucleotide substitutions of the sequenced sequences and in accordance with the author’s classification. Results. HHV6A/B DNA was detected in 39% of HIV(+) and 46% of HIV(–) examined individuals. HHV6A (genovariant GV3a) was identified in one HIV(+) sample. The remaining samples from both groups contained HHV6B. In the group of HIV-infected patients, dominant genovariants GV1a, GV2b, and GV2e (~30% each) were evenly distributed, and the minor GV2a (7.3%) was also detected. In the group of clinically healthy virus carriers, genovariant GV2e predominated (72.4%), while GV1a and GV2b were less common. The likelihood of detecting GV2e decreased (OR = 0.18 (0.04; 0.76), p = 0.031), whereas that of for GV1a and GV2b variants increased (in both cases OR = 5.48 (1.31; 28.52), p = 0.016) in HIV(+) individuals compared to control group. Analyzing age structure for HHV6B genovariants showed that in HIV-infected patients, the diversity of genovariants declines with decreasing patient age. Сonclusion. The obtained results indicate the need to investigate the molecular genetic diversity of HHV6A and HHV6B for effective diagnosis and interpretation of findings in HIV-infected patients.
Introduction. H. pylori is a widespread microbe able to long-term persist on gastric mucosa and may cause gastritis, peptic ulcers, and malignant neoplasms of the stomach. It is assumed that the clinical manifestations of the infection depend on pathogen virulence and host response, but the characteristics of the immune response to H. pylori in various morphological forms of gastric lesions have not been sufficiently studied. The aim of the study was to identify peripheral blood antigen-specific CD4+ T cells during H. pylori infection and to evaluate the T cell activation response to H. pylori antigens in infected patients with erosive and non-erosive gastritis. Materials and methods. Peripheral blood monocytes and lymphocytes were isolated from study subjects. The monocytes were incubated with or without H. pylori. Next, lymphocytes were stimulated with syngeneic monocytes, and the CD4+ T cell response to antigens was assessed by expression of activation markers OX40, CD69, and CD25. Results. Antigen-specific CD4+ T cells were easily detected in the blood of patients with non-erosive gastritis by identifying antigen-induced expression of the activation marker OX40. In H. pylori-associated erosive gastritis, stimulation of CD4+ T cells with antigens did not increase OX40 expression and decreased CD69 expression. Evaluation of CD25 expression in combination with CD69 or OX40, as well as analyzing co-expression of these molecules in groups of large and small lymphocytes, allowed to identify antigen-induced changes in the CD4+ T cell phenotype in patients with erosive gastritis. Hence, antigen-induced increase in the number of CD25lowCD69low cells within both large and small CD4+ T lymphocytes most reliably mirrors T-helper activation in these patients. The antigen-induced increase in the number of CD25hiCD69-/low and CD25hiCD69hi large lymphocytes was more pronounced. However, such cells with high CD25 expression levels can be either due to activated T helpers or inducible regulatory T cells. Conclusion. Using an in vitro antigen presentation model, CD4+ T cells specific to H. pylori antigens were detected in peripheral blood samples from patients with H. pylori-associated gastritis. The characteristics of antigen-specific T-cell response in this model varied across different morphological forms of gastric lesions.
Background. Parenteral hepatitis B (HBV), C (HCV), and D (HDV) virus infections pose a global public health problem. It is critical to conduct epidemiological study for planning effective preventive and therapeutic interventions in the Kherson Region during post-crisis healthcare restoration. The study was aimed to comprehensively assess prevalence of population parenteral viral hepatitis markers in the Kherson Region, taking into account infection and vaccination status as well as sociodemographic characteristics. Materials and methods. A cross-sectional randomized study on the representative Kherson Region sample (N = 2806), stratified into 9 age groups was carried out. Anamnestic data on vaccination and former infections were collected. Serological markers (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HDV) were quantitated by ELISA, verified further in case of positive HBsAg and anti-HCV results. Molecular markers (HBV DNA, HCV RNA, HDV RNA) were assessed by PCR, including a highly sensitive method for occult hepatitis B (OBI). Results. Prevalence of HBsAg-positive infection comprised 1.4%, peaking in the 40–49 age group (2.6%). Anti-HBc prevalence progressively increased with age (from 1.7% in under 18 to 21.5% in 70+). Total protective post-vaccination/infection immunity (anti-HBs ≥ 10 IU/L) was low (25.2%), peaking in children aged 1–5 years (58.9%), with sharp decline in adolescents and adults. A key finding: OBI (HBV DNA without HBsAg) dominated over manifest forms. HBV DNA was detected in 4.1% participants, of which 81.6% (3.3% total sample) were referred to OBI. Former iatrogenic interventions served as an OBI risk factor. Self-reported HBV vaccination coverage was 36.5%, but protective antibodies were found in only 31.6% of such vaccinated individuals. Anti-HCV prevalence was 4.1%, increasing with age; HCV RNA was detected in 1.2%. Anti-HDV antibody prevalence was 0.5%, not paralleled with HDV RNA detection. Conclusion. The Kherson Region shows a contradictory epidemiological situation: despite low HBV/HCV infection rates in the younger individuals, a critical issue is posed by insufficient population immunity due to low and ineffective HBV vaccination coverage, OBI dominance resulting in uncontrolled infection reservoir as well as association with iatrogenic interventions. These findings justify a need to strengthen routine immunization, implement catch-up vaccination, and introduce OBI screening in at-risk groups.
The skin microbiota contains non-diphtheria corynebacteria that can exhibit both pathogenic and beneficial properties. Genomic analysis of clinical isolates of Corynebacterium spp. will provide a more complete picture regarding their pathogenicity or positive effects. The aim of the study was to characterize the role of some clinical isolates of Corynebacterium spp. in shaping the skin microbiocenosis of healthy people based on assessing their genome. Materials and methods. Isolates of C. pseudodiphtheriticum SX1, C. glutamicum SX5, C. variable SX7 from the skin surface of conditionally healthy individuals were identified using mass spectrometry. Whole genome sequencing of bacterial strains and genomic analysis were performed. The virulence of Corynebacterium spp. strains was determined using the Galleria mellonellа larval model. The strains were deposited in the State Collection of Pathogenic Microorganisms and Cell Cultures “GKMP-Obolensk”, the genome sequences were placed in the GenBank database. Results. According to the phylogenetic analysis, the strains C. pseudodiphtheriticum SX1, C. glutamicum SX5 and C. variable SX7 form separate clades, and C. variable SX7 occupies a separate place, having a high phylogenetic proximity to mycobacteria. All isolates contain genes responsible for metabolism, stress protection, synthesis of amino acids, vitamins, and terpenes. Genes of the mntАBС system associated with resistance to hydrogen peroxide, superoxide radicals and the ability to use Mn2+ as an alternative cofactor in case of environmental iron deficiency were found only in C. pseudodiphtheriticum SX1. The ent genes regulating siderophore formation were found in the strains C. glutamicum SX5 and C. variable SX7. The spectrum of AMP resistance genes is wider in C. pseudodiphtheriticum SX1 and C. glutamicum SX5, and the genes presumably associated with AMP resistance are more common in C. variable SX7. Conclusion. C. pseudodiphtheriticum SX1, C. glutamicum SX5 and C. variable SX7 contain genes associated with metabolism, stress resistance, and the ability to survive in the human body. They lack true pathogenicity genes in the presence of polyfunctional genes associated with both metabolism and pathogenicity. Corynebacterium spp. isolates may produce useful substances (amino acids, vitamins, terpenes). This indicates their positive role in shaping human skin microbiocenosis.
Introduction. Post-COVID syndrome (PCS), which develops in 10–35% of cases, is characterized by a spectrum of persistent symptoms sustained for more than 12 weeks post-acute SARS-CoV-2 infection. The aim of the study was to characterize the clinical blood test in patients with varying PCS severity and determine a risk of its development in comorbid pathology while assessing a relation between COVID-19 severity and PCS. Materials and methods. Medical records from 373 patients who underwent an in-depth dispensary examination not earlier than 12 weeks following COVID-19 was conducted at the clinic of the Research Institute of Medical Problems of the North and the Krasnoyarsk Regional Clinical Hospital (Krasnoyarsk). COVID-19 severity was assessed using the WHO Clinical Progression Scale (WHO-CPS). PCS general characteristics were assessed using the Post-COVID-19 Functional Status Scale (PCFS). Comorbidity was assessed using the Age-Specific Charlson Comorbidity Index (ACCI). The type and characteristics of the immune response were assessed using the PROTIST software. Results. The ACCI index in individuals with moderate and severe COVID-19/moderate and severe PCS was significantly higher than in groups without PCS and with mild COVID-19/mild PCS. In patients who had moderate/severe COVID-19, the development of moderate/severe PCS was accompanied by elevated CRP level in 34.5% of cases (20 patients), a peaked rate among all groups. In the group with moderate and severe COVID-19/moderate and severe PCS, the leukocyte level is lower than in group without PCS, but higher than in group with mild COVID-19/mild PCS. The absolute granulocyte level in this group is higher than in other groups. Conclusion. It has been found out that COVID-19 severity is a prognostic factor for PCS development. While assessing immune response types, it was found that more than 50% of patients with moderate/severe PCS show activated innate immunity, while only 25% were non-reactive/normal. The presence of these PCS phenotypes underlies a need for a personalized approach while recommending anti-inflammatory therapy.
Unlike most other mammals, humans have lost the ability to express alpha-1.3-galactosyltransferase (α1.3GT) due to mutations in the GGTA1 gene thereby underlying inability of human cells to synthesize Gala1–3Galb1–4GlcNAc-terminated glycans (αGal), also present in bacterial and viral glycopolymers. The latter are not only highly immunogenic to humans, but also cause an immediate immune response due to pre-existing antibodies to them resulting in local complement hyperactivation followed by an immunoadjuvant effect. Such properties of antibodies against αGal are manifested in hyperacute rejection reactions during xenotransplantation, and are also used to increase the immunogenicity of vaccines against tumors and to develop methods for regenerating nervous system cells. The presence of pre-existing anti-αGal antibodies in human body is commonly associated with protection against bacterial and viral infectious diseases. However, in addition to mediating immune responses, these antibodies have been shown to block activation of the alternative complement pathway, reducing blood bactericidal activity and contributing to development of antibody-dependent enhancement of infection. It is known that blocking activity of anti-αGal antibodies increases blood bactericidal activity against some Gram-negative bacteria. We assumed that this pattern of anti-αGal antibodies could be used for prognostic purposes. Materials and methods. In a pilot study with patients showing sequelae of severe brain damage (n = 70) without clinical signs of pneumonia, plasma samples collected on the day of hospitalization were used to quantitate anti-αGal antibodies using 96-well plates covered with αGal antigen. Results. The presence of high anti-αGal antibody levels in patients significantly predicted a high risk of nosocomial (hospital-acquired) pneumonia. For the first time, the presented results demonstrate the high potential for quantification of anti-αGal antibodies for early stratification of patients at risk of developing nosocomial pneumonia in order to personalize treatment, and also warrant the feasibility of translational studies assessing αGal antibody blockade potential.
Seroepidemiological studies are essential for epidemiological surveillance of vaccine-preventable airborne infections prevented in children through using combination vaccines. The aim of the study was to assess post-vaccination immunity to diphtheria, pertussis, measles, rubella and mumps in children and adolescents living in the Republic of Karelia. Materials and methods. Results of seromonitoring in study groups of children and adolescents in the Republic of Karelia in 2019–2024 were retrospectively analyzed. Results. A high level of immunological protection was established only for diphtheria (0.7% seronegative among children 3–4 years and 1.0% among adolescents 16–17 years) and rubella (3–4 years — 1.7%, 9–10 years — 0.9%, 16–17 years — 2.2%). A total of 2.4% of children aged 3–4 years had no protective antibody titer to pertussis microbe in 2019–2021 and 67.9% in 2022–2024. The increase in the frequency of seronegative children coincided with increased incidence of infection and the beginning of using acellular vaccine. The agglutination test allows the detection of antibodies to the microorganism, but not to toxoid. The percentage of measles and mumps seronegative children aged 3–4 years was 9.1% and 19.5%, 9–10 years — 17.6% and 8.8%, among adolescents — 36.5% and 17.4%. An analysis of the epidemiological situation showed that seromonitoring data mirrored the state of post-vaccination immunity. The presence of antibodies to rubella in children seronegative to measles and mumps, and antitoxic antibodies to diphtheria at a high level in children seronegative to pertussis, excludes falsification of vaccination data or loss of vaccine immunogenicity due to violation of storage temperature conditions as potential causes of negative results. Conclusions. Our results demonstrate the importance of assessing antibodies to all simultaneously administered antigens and a need to expand a search for causes behind substantial level of seropositivity among children.
Tetanus is a rare but highly dangerous vaccine-preventable disease with a high mortality rate. Previous tetanus infection does not protect against reinfection, and antitoxin immunity must be maintained throughout life through routine immunization, which is often overlooked by adults, while children are sometimes deprived of protection against tetanus due to the actions of their parents. The objective of the study was to analyze the causes of tetanus in children, identify problems associated with diagnosis and treatment, and assess the level of vaccination in the country to improve primary and secondary prevention of the disease. Materials and methods. To study the level of vaccination in Kyrgyzstan, we used data from reports of the Republican Center for Immunoprophylaxis of the Kyrgyz Republic (RCI KR), information posted on the websites of the WHO, the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). To examine the clinical and epidemiological data of two clinical cases, we reviewed the medical records of patients who were treated in infectious disease hospitals (Bishkek and Osh). Results. In Kyrgyzstan, coverage with the third dose of DPT vaccine under the National Immunization Schedule has fallen below the target of 95% since 2019, fluctuating between 86–90% over the past three years. In 2023, the number of children who did not receive immunization increased by 31.8% compared to 2019. Most parents refuse to vaccinate their children for religious reasons (50–62%), with doubts about the safety of the vaccines themselves coming second. With the non-immune segment of the population expanding, especially among children, the resurgence of nearly forgotten vaccine-preventable diseases is inevitable. The example of two clinical cases of generalized tetanus in children demonstrates the healthcare system’s unpreparedness to deal with a long-forgotten disease. Conclusion. The only reliable way to protect against tetanus is timely routine vaccination of children and adults according to the National Immunization Schedule and complete primary and secondary surgical treatment of wounds. Early diagnosis of tetanus, knowledge of its symptoms, and collection of an epidemiological history are essential. Every infectious disease hospital should have a supply of at least 100.000 IU of tetanus vaccine for one patient.
Viral hepatitis holds a leading place among infectious diseases. The morbidity rate of chronic hepatitis C (HСV) among children in the Russian Federation is 1.29 per 100 000 population. Increasing access to antiviral therapy in childhood contributes to achieving the global health goal on HСV elimination. The aim of the study was to summarize the epidemiological characteristics, clinical features of chronic hepatitis C in children, and to evaluate the effectiveness of direct-acting antiviral (DAA) treatment in the pediatric cohort of the Tomsk Region. Materials and methods. The study included all children under 18 years of age diagnosed with chronic HCV and recorded in medical organizations of the Tomsk Region. All children underwent standardized screening and were treated with DAAs according to the “Clinical guidelines for chronic viral hepatitis C in children (ID: 824)”. Results. HCV was first diagnosed in children aged 0 to 3 years in 94.4% of cases (n = 34). The median disease duration was 5 [3;8] years; 4 children were diagnosed within one year. Alanine aminotransferase activity levels did not exceed age-specific reference values; in 4 patients, mild cytolytic activity within five age-specific reference values was observed. Minimal viral load was found in 55.6% of patients, while 25% subjects exhibited high viraemia. Correlation analysis revealed a positive relationship between viremia level and disease duration (r = 0.46, p 0.05). HCV genotypes 1 and 3 were found at similar frequencies (48% and 44%, respectively). All patients treated with DAAs achieved undetectable HCV RNA levels and showed normalized ALT levels post-therapy, demonstrating sustained virological response. Conclusion. Expanding access to treatment and use of DAAs in children enabled HCV micro-elimination in the pediatric population within two years.
Natural killer (NK) cells are innate lymphocytes acting as the key effector cells capable of recognizing and eliminating infected and transformed cells without prior sensitization. Their role in antibacterial defense, inflammatory response regulation and modulation of reproductive processes has been attracting increasing attention. In this regard, of particular interest are opportunistic bacteria of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) characterized by high virulence, a prominent potential for developing multiple antibiotic resistance, being a lead cause of severe nosocomial infections, especially in immunocompromised patients. Pathogens of the ESKAPE produce a wide range of cell wall structural components (lipopolysaccharides, peptide glycans, lipoteichoic acids, capsular polysaccharides) as well as secreted virulence factors (pore-forming toxins, proteases, superantigen-like proteins, extracellular membrane vesicles) that can directly modulate immune cell functional activity. This review systematizes current literature data regarding the mechanisms underlying interplay between products of ESKAPE pathogenic bacteria as well as NK cell receptor apparatus and effector functions. Intracellular signaling pathways (NF-κB, MAPK, JAK/STAT) activated upon binding of bacterial ligands to pattern recognition receptors (TLR2, TLR4, TLR9, NOD1/NOD2) and their impact on NK cell cytotoxic potential, cytokine secretion profile (IFNγ, TNFα, IL-1β), and survival are primarily delineated. In addition, the immunomodulatory mechanisms mediated by bacterial metabolites on dendritic cells and macrophages subsequently affecting NK cell activation are discussed as well. Understanding the complex network of molecular crosstalk between ESKAPE pathogen metabolites and NK cells is fundamental for developing novel immunotherapy strategies for drug-resistant infections, designing adjuvant drugs based on bacterial components as well as correcting immune disorders in critical conditions. Altogether, it opens up a new avenue to a personalized treatment approach for patients with severe nosocomial infections.
COVID-19 pandemic has caused the deaths of more than 7 million people worldwide and revealed the weakness of the global health system in the face of such challenges. In conditions of low effectiveness for disease specific prevention, an important task is to develop drugs acting to stimulate innate immunity for emergency non-specific prevention of coronavirus diseases. The aim of the study was to evaluate the effectiveness of preventive administration of an immunostimulating drug based on antigens complex of opportunistic bacteria (ACOPB, the drug Immunovac-VP-4) in protecting against SARS-CoV-2 infection. Coronavirus pneumonia was modeled by infecting golden Syrian hamsters with the Wuhan-like SARS-CoV-2 Dubrovka strain, assessing indicators such as weight dynamics, viral load and pathomorphological changes in the lungs. Preventive administration of ACOPB to hamsters in the form of a spray and by inhalation helped protect them from SARS-CoV-2 infection and its pathogenic effects. The efficacy of the drug was manifested in protecting hamsters from weight loss, a decrease in viral reproduction in the lungs and the absence of pathological morphology changes in lung tissue. Thus, animals treated with ACOPB in the form of a spray or by inhalation on day 3 post-infection gained weight, average of 4.2±3.0% (p 0.05) and 8.8±1.3% (p 0.001), while the animals of the viral control lost 5.6±2.8% weight. The use of ACOPB reduced virus titer in the lungs of animals by more than 2.5 lg. In addition, in patients with moderate COVID-19, the clinical effect and effect of ACOPB on the level of secretory immunoglobulin A (sIgA) in the upper respiratory tract were studied. The use of ACOPB as part of the complex therapy of patients with COVID-19 was associated with increased sIgA level in the nasal and pharyngeal areas of the upper respiratory tract from day 1 to day 30 follow-up as well as improved patient clinical condition. Thus, the mucosal immunity formed with the use of ACOPB suppresses virus reproduction in the lungs and promotes recovery of COVID-19 patients. The results showed that the ACOPB is of interest for further research as a means of emergency prevention and treatment in new coronavirus infection.
Difficulties identified in recent years while preparing reassortant live influenza vaccine (LAIV) strains related to the specific biological properties of currently circulating epidemic influenza viruses, necessitate the search for alternative development pathways that guarantee the rapid and stable production of LAIV candidates. It was shown previously that genetically engineered reassortant LAIV candidates (LAIV-RG) exhibited reduced cold adaptation in developing chicken embryos compared to the A/Leningrad/134/17/57 (H2N2) master donor virus and vaccine candidates obtained by classical reassortment (LAIV-NR). Concerns that reduced cold adaptation could negatively impact vaccine quality led to implement the objective: to conduct a comparative study of the humoral immune response in laboratory animals to immunization with RG- or NR-LAIV candidates. Materials and methods. In vivo studies involved pairs of LAIV-RG and LAIV-NR strains based on seasonal influenza A(H3N2) viruses and master donor virus for live influenza vaccine. Results. In mouse studies, LAIV-RG candidates demonstrated similar humoral immune response performance to classical reassortants. A slight reduction in the cold-adapted phenotype of LAIV-RG strains did not result in a decrease in their attenuation level. They are as safe for laboratory animals as classical reassortants suggesting that LAIV quality remains unchanged, regardless of the methods used to produce vaccine reassortants. Interestingly, the adaptive Thr-Ile amino acid substitution at position 203 of HA1, identified in three LAIV-NR A(H3N2) candidates belonging to clades 3C.2a1 and 3C.2a2, had a positive effect on increasing the thermal stability of hemagglutinin and their immunogenicity in guinea pigs. Conclusion. Classical and genetically engineered reassortment methods are equally applicable for producing attenuated LAIV candidates, and the quality of vaccine preparations may be improved by targeted introduction of well-characterized favorable mutations into the genome of LAIV-RG strains, such as the mutation in HA1 with the amino acid substitution Thr-203-Ile, which contributes to increased stability and immunogenicity of vaccine strains based on the influenza A(H3N2) viruses of clades 3C.2a1 and 3C.2a2. This should not conflict with regulatory requirements for LAIV.
Introduction. Bacteria of the genus Aeromonas are widespread in the environment, including marine and freshwater ecosystems, therapeutic mud, and wastewater. In recent years, human diseases caused by Aeromonas spp. have been increasingly reported, especially in individuals with weakened immune system. Being resistant to multiple drugs, these bacteria isolated from water bodies, fish, and seafood on fish farms pose a potential threat to aquaculture production and their spread throughout the environment. This review on study results assessing biological properties of Aeromonas bacteria, systematizing data on the phenotypic and molecular genetic mechanisms of their pathogenicity, defines a strategy for an interdisciplinary approach to diagnose and prevent Aeromonas infection. The objective of this review is to summarize and analyze data on the biochemical and molecular genetic characteristics of Aeromonas bacteria and determine their clinical and sanitary-epidemiological significance. Materials and methods. Literature sources for this review were selected from the PubMed and Web of Science databases, and the eLIBRARY.ru scientific electronic library website. Initially, 98 scientific articles published between 2019 and 2025 were included in the work, covering the results from studies on the biological properties and prevalence of Aeromonas bacteria in patient biomaterials with bacterial infections, as well as their prevalence in environmental objects. The final version of the review included 65 references. Results. The scientific data presented here indicate a high frequency of detection of Aeromonas spp. in various environmental objects and those possessing pathogenicity factors. The presence of virulence and antimicrobial resistance determinants confirm their role in the development of human and animal as well as aquatic infections. Due to their ubiquitous distribution, metabolic and genetic characteristics, Aeromonas bacteria have been currently acquiring the status of a new pathogen and an indicator of resistance and virulence genes. Conclusion. The conducted analysis assessing results of studies on issues of identification, determination of phenotypic and genotypic characteristics, including antibiotic resistance underlying pathogenic potential of bacteria of the genus Aeromonas, suggests a need to further investigate these bacteria in the fields of healthcare, fish farming and agriculture.
Total arthroplasty is a key method for treating degenerative and dystrophic diseases of large joints. The most serious complication related to endoprosthesis is periprosthetic infection, the treatment of which involves significant economic costs and a high risk of recurrence. Therefore, during endoprosthetics, it is necessary to conduct a preliminary microbiological examination, which allows to choose the most effective etiotropic therapy especially important in case of antibiotic-resistant microorganisms, fungi and mixed infections. The aim of the study was to analyze the pattern of microorganisms isolated from synovial fluid in patients with chronic orthopedic infection of large joints of the extremities. The study included 79 patients with suspected periprosthetic infection and 15 patients with chronic arthritis combined with osteonecrosis. Synovial fluid samples were delivered to the microbiological laboratory of SamSMU Clinics, where positive samples were cultured and microorganisms were identified using MALDI-ToF mass spectrometry (Bruker, Germany). The study found that among Gram-positive pathogens, S. aureus was the most common — 45.9% (56 strains), S. epidermidis — 29.5% (36 strains) and C. striatum — 13.1% (16 strains) of cases. Among S. aureus, 17.9% were methicillin-resistant. K. pneumoniae was the dominant Gram-negative species (50%), E. coli was the second most common, with 33.2%. 9 strains of K. pneumoniae produced beta-lactamase, and carbapenemases were detected in 4 cases. All E. coli strains were producers of extended-spectrum beta-lactamases. In patients with chronic arthritis and osteonecrosis, Gram-positive pathogens were mainly isolated (73.3%), including methicillin-resistant S. aureus (25%). Gram-negative pathogens accounted for 26.7%, and extended-spectrum beta-lactamase producers prevailed. Hence, Gram-positive bacteria predominate in the pattern of pathogens, especially S. aureus and coagulase-negative Staphylococcus spp. Gram-negative microorganisms act as an etiological agent much less frequently, however, the frequency of prevalence for strains with multiple antibiotic resistance is increasing among them. Thus, conducting a preliminary microbiological examination to determine antibiotic sensitivity becomes a necessary step during endoprosthetics.
Seasonal influenza A viruses including A(H1N1)pdm09 and A(H3N2) subtypes infect over 5–15% of the global population annually. According to epidemiological data, influenza A(H3N2) viruses are associated with more severe disease progression and the development of hemorrhagic syndrome as well as different thrombotic complications associated with activated vascular endothelial cells. The aim of the study was to investigate the effect of influenza A(H3N2) virus on the morphofunctional properties of blood vessel endothelium during the acute phase of infection. Materials and methods. Wistar rats were intranasally infected with influenza A virus A/Port Chalmers/1/1973 (H3N2) in a volume of 0.1 ml and subsequently euthanized at 1- and 4-days post infection (d.p.i.) (n = 5). Animals in control group were intranasally administered DMEM medium (0.1 ml). After necropsy, lung and mesentery tissues were collected to assess viral infectious activity titer. Additionally, severity of histopathological alterations in lung blood vessel endothelium and mesentery was assessed, the expression level of endothelial nitric oxide synthase (eNOS) in pulmonary and mesentery vascular endothelium was measured by immunohistochemical analysis, and the parameters of vasomotor activity in mesenteric arteries using wire myography was assessed. Results. Influenza A(H3N2) virus induced morphological changes in lung blood vessels on days 1 and 4, decreased eNOS expression levels in lung vessel endothelium at 1 d.p.i., and in mesenteric blood vessel endothelium at 1 and 4 d.p.i. Furthermore, the response of mesenteric blood vessels to median phenylephrine concentrations on day 4 vs day 1 d.p.i. was 87.13% higher (p 0.05), while the vascular response to premaximal acetylcholine concentrations on day 4 was 26.15% lower (p 0.05) compared to control. Conclusion. Influenza A virus subtype H3N2 impairs the morphofunctional properties of the blood vessel endothelium in rat lungs and the functional properties of the vascular endothelium in the mesentery during the acute phase of infection, suggesting activation of endothelial cells at both local and systemic levels.
Background. Southern Vietnam is hyperendemic for Hepatitis B virus (HBV) infection, yet comparative data on the full spectrum of HB serological and molecular profiles — including susceptibility and occult infection — between HIV-infected and healthy adults in this setting remain limited. The aim of this study was to comprehensively evaluate and compare the serological and molecular markers and profiles of Hepatitis B virus infection between HIV-infected patients and apparently healthy adults in Southern Vietnam. Materials and methods. A comparative cross-sectional study was conducted on 713 participants (316 HIV-infected and 397 healthy adults). Blood plasma samples were screened for HBsAg, anti-HBs IgG, and anti-HBc IgG markers. HBV DNA testing was performed using a high-sensitivity in-house PCR. Multivariable logistic regression and interaction analyses were employed for comparative analysis. Results. HBsAg prevalence was comparably high in both the healthy (17.6%) and HIV-infected (16.1%) cohorts, reflecting early-life exposure. However, the HIV cohort exhibited a significantly higher rate of seronegativity for all markers (43.0% vs 16.1%; p 0.001). The burden of OBI was two-fold higher in the HIV group (17.1%) compared to healthy controls (9.3%; aOR = 2.00). Notably, 6.65% of seronegative HIV patients (“triple-negative”) tested positive for HBV DNA, a prevalence 13-fold higher than in controls (0.50%). Age-trend analysis revealed that while healthy adults accumulated immunity with age, HIV-infected individuals exhibited “immune erasure” and seroreversion, leading to the loss of protective antibodies and increased risk of occult infection in older age. Conclusion. Our study documents important differences in HBV serological and molecular profiles between HIV-infected patients and healthy adults in a hyper-endemic setting. Our cross-sectional data are consistent with HIV-associated perturbation of humoral immunity, manifested by higher rates of seronegativity. The detection of triple-negative occult HBV infection highlights a limitation of serology-only screening. In endemic settings, clinicians and public health programs should therefore consider risk-stratified approaches that incorporate molecular testing, particularly for high-risk subgroups where universal screening is not feasible.
