Vol 15, No 1 (2025)

Here, we review summarized epidemiological data and analyze the situation on infectious diseases in the countries of the Indo-West-Pacific region that require measures for sanitary protection of the territory of the Russian Federation. The main source of relevant information was the official websites and periodicals of the WHO, Ministries of Health of the respective countries. The data from other international organizations (Food and Agriculture Organization of the United Nations, World Organization for Animal Health), electronic aggregators of operational information (ProMED-mail, EpiSouth, arbo-zoonet, etc.), data from articles published in peer-reviewed journals covering epidemiological issues were used. In recent years, due to a set of reasons, the risk of infectious diseases entering Russia from the Indo-West-Pacific region has increased manifold: actively developing tourism to Asian countries, higher number of trade and economic ties, increased number of direct flights with the countries of the region. The paper systematizes data on morbidity and territorial distribution of diseases in the Western Pacific and South-East Asia regions by assessing potential risks for persons visiting it. During the analysis, it has been established that the epidemiological situation currently developing in the Indo-Pacific region poses a significant threat to the sanitary and epidemiological welfare of the population primarily due to the increasing risks for spread of dangerous infectious diseases into the territory of the Russian Federation. The most probable is the risk of spreading of infectious diseases such as cholera, malaria and dengue fever, the unfavorable epidemiological situation on which has developed in recent years in the region. At the same time, the presence of direct transportation links between Russian regions and a number of countries in the region (Thailand, Sri Lanka, Vietnam, Maldives, India, Mongolia, China, Myanmar) multiplies the risk of spreading for such diseases. According to the previously developed methodology for calculating the risk of infectious diseases entering the territory of the Russian Federation, it was established that there is a high risk of dengue fever entry from Laos, Malaysia, Nepal, Thailand and the Philippines.

Candidiasis is a mycosis caused by opportunistic pathogenic Candida spp. fungi. The infectious process can manifest as superficial forms affecting the skin and mucous membranes, as well as invasive variants. Since Candida spp. are commensals, a related disease development implies an imbalance between the pathogenic fungal factors and human immune system. Research in the field of immunotherapy of fungal infections is particularly relevant due to the increasing resistance to antifungal drugs. Based on the analyzed publications investigating candidiasis immunotherapy retrieved from the databases PubMed, ClinicalKey, and e-library, we have assessed the main directions and achievements in immunotherapy of infections caused by Candida spp., described emerging issues, and outlined future prospects. The development of live vaccines based on attenuated, genetically modified, and mutant Candida strains began in the 1980s and continues to the present day. However, creating vaccines based on Candida recombinant proteins, adhesins, and enzymes represents a safer alternative to live vaccines. A promising direction is the development of conjugate vaccines, in which the fusion of weaker antigens (cell wall glycans) with carrier immunogenic proteins leads to the formation of immunogens capable of eliciting a robust immune response. In experiments, vaccines based on inactivated C. аlbicans along with a genetically Escherichia coli-derived modified heat-labile toxin as an adjuvant have also been studied. The experience of creating combination therapies aimed at combating recurrent bacterial and fungal urogenital tract infections is promising, e.g., the combination of sublingual inactivated polyvalent bacterial vaccine MV140 and sublingual preparation of inactivated Candida albicans V132. An interesting approach involves the use of inactivated S. cerevisiae yeasts, providing cross-protection against infections caused by C. аlbicans, Aspergillus fumigatus, and Coccidioides posadasii. A search for immunotherapy targets continues, with numerous studies aimed at a deeper understanding of crosstalk between C. аlbicans and human host. Currently, two recombinant vaccines (PEV7 and NDV-3) have successfully completed Phase I/II clinical trials, raising hopes for their clinical use in the near future.

The aim of the work was to determine the safety of oral commercial colloidal nanosilver preparations during mouse pregnancy by assessing microbiota and local colonic nonspecific resistance; pregnancy course and outcome; morphology of vital organs — kidneys, liver, brain in pregnant mice and paired offspring. Microbiological, biochemical, and histological research methods were used in the work. Empirically selected commercial colloidal nanosilver preparations (“Ajenta”, “Vitargol”) recommended for internal use in humans at a therapeutic dose were used in an in vivo experiment by 30-day watering of pregnant mice. As a result, the large intestine microbiome balance was restored due to decreased in number of pathogens: enterobacteria, Staphylococcus and Candida. In the coprofiltrates of both groups of mice receiving both “Adjenta” and “Vitargol”, the state of local nonspecific resistance showed impaired local antiradical protection. If after “Adjenta” therapy there was an imbalance in antioxidant enzyme system, when the activity of superoxide dismutase was 1.5 times higher than control level, and catalase activity was 2 times lower contributing to higher level of peroxidation product — malondialdehyde by 2.6 times, then after “Vitargol” therapy activity of superoxide dismutase and catalase was only 43% and 25%, and the amount of malondialdehyde peaked reaching 431%. Microscopic examination of all organ biopsies from mice receiving commercial colloidal nanosilver preparations “Ajenta” and “Vitargol” revealed no fundamental differences. At the same time, morphological changes in tissues were found in all animals: granular dystrophy of hepatocytes, nephrocytes of the proximal and distal tubules, perinuclearly in liver preparations there is a cytoplasm enlightenment in some liver cell types. In all brain samples, there is moderate perivascular-pericellular edema, vascular fullness, neuron dystrophy. However, breast-fed mouse pup liver histological examination from paired female mice after oral Vitargol intake revealed no negative changes. Despite the fact that the processes of gestation and childbirth in mice proceeded normally, the results of the study indicate insufficient safety of the selected drugs for oral use during pregnancy.

Introduction. High genome variability of the 7th cholera pandemic agent, V. cholerae El Tor, led to emergence of genovariants with distinct set of altered genes. The aim of the work was to analyze the dynamics of changes in pathogenicity, epidemicity as well as drug resistance and phylogeny in toxigenic strains of V. cholerae El Tor isolated in Russia and endemic regions during three waves of ongoing pandemic. Materials and methods. We used whole-genome nucleotide sequences of 155 strains, obtained by us (42) and taken from the NCBI Genbank (113). DNA sequencing was performed on Ion PGM platform. Phylogenetic relations were determined based on the Bayesian analysis of core SNPs obtained using Snippy 4.6 software package. Antibiotic resistance was assessed applying disk diffusion test. Results. SNP data revealed that the studied strains (1970–2023) might be divided into three clusters. A clear correlation between each-cluster strain genotype and relevant isolation timing was observed. Separation of genetically altered cluster II and III strains isolated during the 2nd and 3rd waves of the pandemic from typical cluster I strains is associated with acquisition of new DNA regions and mutations in pathogenicity and drug resistance genes. Due to different combination of mutations, cluster III strains are genetically heterogeneous. Genome comparison showed that this diversity increased dramatically during the 3rd wave, which led to emergence of new genovariants with higher pathogenic and epidemic potential. It is demonstrated that antibiotic resistance in strains both from endemic regions and Russia over the past 30 years (1993–2023) has undergone significant changes. Thereat, the changing drug resistance clearly correlated with the occurrence of mutations in various pathogenicity genes. Conclusion. It is shown that over the past two decades the agent genome underwent a rather rapid change resulting in emergence of various genovariants. A change in the pathogen variants in Russia has been established. Strains combining genetic markers of hyper-virulence and multiple drug resistance are of particular concern. Genome variability of the strains identified in points at a need for constant genomic surveillance to obtain data on altering epidemically important properties for timely generation of new diagnostic and preventive means.

Introduction. Currently, a role for human herpes viruses (HHV) in development of ocular oncopathology remains one of the poorly explored issues. An important factor contributing to neoplastic progression is impaired immunosurveillance particularly alterations in quantitative and qualitative composition of the hallmark peripheral blood lymphocyte subsets. The aim of the study was to determine and analyze peripheral blood lymphocyte subset composition in patients with uveal melanoma (UM) assessing human herpes viruses (HHV) infection in tumor material. Materials and methods. Biomaterial from 99 patients with uveal tract tumors was examined by real-time polymerase chain reaction (rt-PCR) for DNA presence coupled to herpes virus type 1 and 2 (HSV-1,2), Varicella Zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpes virus types 6 and 8 (HHV-6, HHV-8). A total of 231 test samples (tumor tissue (n = 99), blood (n = 132)) were examined. Commercial test-systems of “Vector-Best” (Russia) were used for rt-PCR staging. Peripheral blood lymphocyte subset composition in all patients was studied by laser cytofluorometry on “BD FACSCanto II” flow cytometer. The control group included 33 healthy donors. Statistical data processing was performed using “Biostatd”, “Excel” (t — Student’s t-test, level of statistical significance: p < 0.05) software. Results. HHV DNA was detected in the tumor material from 11.3% of patients (n = 11): in 72.7% of cases EBV, in 18.2% — HHV-6. Co-infection with EBV and HHV-6 was detected in 1 case (retinal pigment epithelium adenocarcinoma). According to the PCR data, patients were divided into 2 groups based on tumor infectivity: Group 1 — HHV+ and Group 2 — HHV–. Patients from HHV+ group had significantly increased and decreased total T-cell (CD3⁺) and NK-cell count, respectively, compared with patients lacking HHV DNA in tumor tissue and control group. Individual analysis of frequencies deviating from normal range showed that HHV+ group had 3-fold more often increased percentage of CD3⁺ lymphocytes, 2-fold more often absolute count of CD3⁺CD4⁺CD8⁺ cells, 2.3-fold more often rise in CD4⁺/CD8⁺ ratio. Conclusion. The obtained data suggest that viruses may be involved in maintaining immunological resistance in tumor patients.

Rheumatoid arthritis (RA) is an joint autoimmune inflammatory disease characterized by systemic destructive and progressive inflammatory synovitis caused by chemokines, reactive oxygen species, and proinflammatory cytokines produced by neutrophils and macrophages in the synovial membrane. The objective of the work was to study indicators of leukocyte phagocytic activity and factors of leukocyte oxygen-dependent bactericidal activity in patients with rheumatoid arthritis receiving methotrexate (MTX) and tofacitinib (TOFA), vaccinated with pneumococcal conjugate vaccine (PCV13). Materials and methods. The study included 151 patients with RA (78.1% women and 21.9% men aged 26–69 years). PCV13 vaccination was carried out once in a dose of 0.5 ml intramuscularly in subjects receiving TOFA and MTX; TOFA was initiated 10–14 days after vaccination; those in comparison groups received same drugs. At the time of inclusion in the study, and during control visits 3 months and 12 months later, leukocyte phagocytic activity and NBT test were carried out. Results. Before the study, patients had minor quantitative and functional changes in leukocyte phagocytic activity and a decrease in the reserve capacity of oxygen-dependent bactericidal activity. In PCV13 vaccinated patients receiving TOFA (Group II), a minor decrease in the phagocytic activity of neutrophilic granulocytes was determined. In unvaccinated patients from group V receiving TOFA therapy, an increase in monocyte absorptive activity was observed both 3 months and 12 months later. In PCV13 vaccinated RA patients from group II receiving TOFA, similar changes were noted. Methotrexate therapy in PCV13 vaccinated and unvaccinated patients did not affect leukocyte phagocytic activity. Conclusion. In patients with RA, PCV13 caused a slight decrease in neutrophil absorptive capacity, which was restored one year post-vaccination accompanied by higher leukocyte oxygen-dependent bactericidal activity in the form of ROS production, which helps to strengthen immune defense in patients encountering potential pathogens.

Background. Routine pre-operative testing for Human Immunodeficiency Virus (HIV) and other blood-borne viruses, Hepatitis B Virus, Hepatitis C Virus (HBV, HCV) has been stated as a strategy to reduce the risk of healthcare workers’ infection by preventing and reducing their infection. However, the argument that screening is essential or not is strong. This study aims to determine the incidence of HBV, HCV, and HIV infections identified during pre-operative screening in a cohort of Egyptian individuals, along with the associated risk factors and the subsequent testing costs. Materials and methods. This study comprised 138 patients, with 92 (66.7%) males and 46 (33.3%) females. All patients scheduled for surgical procedures underwent testing for HCV Ab, HBsAg, and HIV Ag/Ab by chemiluminescent microparticle immunoassay conducted with the “ARCHITECT i2000SR Immunoassay” (Abbot Japan CO., Ltd, Tokyo, Japan). Among the participants, 23 out of 138 (16.7%) tested positive for HCV, while 5 out of 138 (3.3%) showed equivocal results for HCV, and 110 out of 138 (79.7%) tested negative for HCV. Additionally, 2 out of 138 (1.4%) were positive for HBsAg, while 136 out of 138 (98.6%) tested negative for HBsAg. Furthermore, 1 out of 138 (0.7%) was found to be HIV-positive, while 137 out of 138 (99.3%) tested negative for HIV. Results. The prevalence of each infection detected through pre-operative testing of HCV, HBV and HIV and a questionnaire was compared. Furthermore, we calculated the screening cost per confirmed infection by assessing the incidence of infections linked to different risk factors, ages, genders, and levels of HBV vaccination. Conclusions Age markedly impacted HCV and HBV rates. There was no link between viral infections and gender. The expenses associated with each affirmative result were 1763 LE for HCV, 5520 LE for HBV, and 22 080 LE for HIV. While self-assessment through questionnaires can be partially efficacious, it lacks sufficient screening accuracy.

The objective of the study was to identify a leading link in local and lung neuroendocrine immune during tuberculoma. Materials and methods. 60 cases of stable and progressive tuberculoma were studied. The study was conducted in 2 anatomical zones: tuberculoma capsule and adjacent areas. A comparison (apparently healthy) group contained resected samples of the upper lobes in the right lung collected from 10 men died in an accident lacking tuberculosis over lifespan. An immunohistochemistry with monoclonal antibodies against CD8 and CD4 markers was used to assess local immune response. Lung catecholamine level was analyzed by the Falk–Hillarp luminescent histochemical method. Results. When assessing localized lung expression of the studied markers in “apparently healthy” group, the number of CD4⁺ and CD8⁺ cells was observed mainly in the interstitial space: the former prevailed over the latter. In stable tuberculoma, higher lymphocyte number in the capsule was revealed that dominated by T-killers vs T-helpers. In the perifocal zone of stable tuberculoma vs apparently healthy group, the number of immune cells decreased, but at the same time zones where CD4⁺ lymphocytes form contacts with interstitial macrophages were detected. In the capsule of progressive tuberculoma, the number of CD4⁺ and CD8⁺ cells increased, containing more T-killers than T-helpers. In the perifocal zone, there is a decrease in CD4⁺ T lymphocyte number paralleled with increase in CD8⁺ cells. The number of intraalveolar and interstitial macrophages sometimes contacting CD4⁺ lymphocytes increases. Cytotoxic lymphocytes concentrate around blood vessels. When studying catecholamine level, it was found to increase in mast cells in all studied areas during stable and progressive tuberculoma. In macrophages, the catecholamine level decreases in stable disease, and increases sharply in progressive progressive course. Conclusion. The regulation of the phases of tuberculous inflammation course is carried out by various cellular interactions, depends on mycobacteria load in lung tissue and macrophage catecholamine level.

Trichosporon asahii, a fungus found in nature and human microbiota, has recently emerged as the most common cause of disseminated and deep-seated trichosporonosis, particularly in immunocompromised patients. Biofilm formation, one of the important virulence factors of T. asahii, facilitates its colonisation and proliferation, providing the fungus with antifungal and environmental stress’s resistance. In this study, we aimed to develop a reproducible T. asahii biofilm model for our future research by optimising the inoculum concentration, adhesion-time, biofilm maturation-time, static and shaking parameters. Materials and methods. We included two clinical isolates obtained from urine samples and a reference strain in the study. For each strain, we applied 36 different experimental parameters, including, 10⁵, 10⁶ and 10⁷ CFU/mL inoculum consentrations, 60-, 90-, and 120-minutes adhesion-times, 48- and 72-hours maturation-times, and static versus shaking. We determined the biofilm formation of fungus using the most commonly used crystal violet method. We determined standard deviation values with three replicates within each experiment, and we compared all the graphs obtained by repeating these experiments twice. Results. After applying 36 different experimental parameter combinations, we determined the most optimised and reproducible parameters as 10⁷ CFU/mL inoculum concentration, 120-minute adhesion-time, 72-hour maturation-time and static. Conclusion. In optimisation studies conducted worldwide on this subject, it has been reported that biofilms formation varies in terms of quantity and duration across different countries, but there isn’t any optimisation study in Turkey. We believe that the optimisation conditions we have firstly identified in our country will shed light on our future research and other studies to be conducted in the future.

Influenza A is a subtype of the influenza virus that primarily infects birds and mammals, causing respiratory illness. It is characterized by its ability to mutate rapidly, leading to various strains and occasional pandemics. Objective. This paper is dedicated to studying the distribution behavior and predicting confirmed cases of Influenza A within the Algerian context, a highly infectious dis- ease that causes widespread illness and deaths both in Algeria and globally. Materials and methods. To predict confirmed cases of Influenza A, we implemented several statistical models, including ARIMA, Seasonal ARIMA (SARIMA), ETS, BATS, and the machine learning technique RNN, which is widely recognized in the literature. We then conducted a comparative study using performance measures to evaluate these models. Results. We used RMSE to determine the best-performing model. Our findings indicate that RNN outperformed the others due to its ability to handle complex patterns, including seasonal components and memory. SARIMA and BATS also performed well, thanks to their capacity to manage seasonal patterns. In contrast, ARIMA and ETS showed the poorest performance. Conclusion. This study employed a comprehensive approach to develop a model for predicting confirmed cases of Influenza A in Algeria. The results enhance our understanding of the potential future behavior of this disease and contribute to effective risk management strategies.

Specific stimulation of receptors of the innate immune system by their purified ligands is commonly used in basic studies of inflammation and in the development of anti-inflammatory drugs. Based on location, receptors of the innate immunity can be classified into two groups: i) cell plasma membrane and on membranes of endosomes (Toll-like receptors (TLRs) and C-type lectin receptors), and recognizing the presence of pathogens in the extracellular space; ii) cytoplasmic sensors playing a special role in the recognition of intracellular pathogens (NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), bacterial DNA sensor cGAS, and Aim2 (absent in melanoma 2). Many experimental models of inflammation use bacterial lipopolysaccharides (LPSs) or other purified microbial molecules to simulate the innate immune response to microbes. In the present study, the response of human blood leukocytes to stimulation with soluble, highly purified LPS from gram-negative bacteria was compared with that induced by formalin-fixed, corpuscular E. coli. The data obtained demonstrate that LPS and bacteria induce similar levels of TNF and IL-6 by plastic-adherent leukocytes, whereas neither LPS nor whole bacteria induce a measurable IFNγ production. The LPS- and bacteria-induced cytokine production, however, drastically differed in the sensitivity to a broad-spectrum TLR inhibitor, peptide 5R667. The LPS-stimulated human leukocyte cytokine production, as expected, was highly sensitive to inhibition by the peptide, whereas production stimulated by corpuscular bacteria was not. The TLR-blocking peptide did not affect the ability of blood leukocytes to phagocytose E. coli as shown by flow cytometry data obtained using FITC-stained fixed bacteria. Because peptide 5R667 blocks several TLRs, including TLR4, TLR5, and TLR9, the differential sensitivity of LPS- and bacteria-induced cytokine production to 5R667 suggests that the intracellular pathogen sensors, most likely NOD1 and/or NOD2, essentially contribute to the bacteria-induced cytokine induction. These results show that LPS and phagocyted bacteria induce cytokine production via different mechanisms and also suggest that the models with corpuscular bacteria for simulating bacterially induced inflammation complement the models that using soluble TLR ligands; therefore, both models should be applied to properly reflect anti-bacterial immune response.

COVID-19 convalescent plasma (CCP) is considered as an important element of therapy for patients in the initial stages of the disease.The main therapeutic effect of CCP is associated with the presence of specific antiviral antibodies. Additionally, the immunomodulatory effect of CCP is considered as therapeutic where cytokines represented one of the main factors. The aim of the study was to evaluate the importance of cytokines and cytokine ratio of transfused CCP for the outcome of the disease in patients who received it during inpatient treatment of COVID-19. Materials and methods. The study included data from 111 patients with COVID-19 who received CCP. The cytokine content in the CCP was measured by enzyme immunoassay Results. It was found that elevated levels of interleukin-6 (IL-6) and interferon-gamma (IFNγ), but not IL-1β, IL-8, IL-10, IL-15, IP-10/CXCL10, MCP-1/CCL2 were detected in CCP transfused mainly to patients who had an unfavorable (fatal) outcome of the disease. Values of cytokine ratios of IFNγ/IL-10, IFNγ/IP-10, IFNγ/MCP-1, IL-6/IL-8, IL-6/IL-10, IL-6/IP-10, IL-6/IL-15 were also significantly increased in these CCP series as compared to CCP samples transfused to patients of the recovered group. Low levels of IL-6 and IFNγ, reduced level of cytokine ratios of IL-6/IP-10, IL-6/IL-15, IFNγ/MCP-1, IFNγ/IP-10, IFNγ/IL-15 were characteristic of CCP, which was transfused to patients, subsequently recovered. The level of IL-6 in the CCP samples transfused to the patients of the recovered group had a strong direct correlation (r = 0.9) with the cytokine ratios of IL-6/IL-10 and IL-6/IP-10, while in the group of the deceased patients there was no strong association (r = 0.6). IFNγ levels in the CCP showed a strong direct correlation with the values of all analyzed cytokine ratios (IFNγ/IL-10 (r = 0.9), IFNγ/IP-10 (r = 0.9), IFNγ/MCP-1 (r = 0.9)). The level of INF-γ in the CCP transfused to patients of the recovered group had a positive correlation with the cytokine ratios of IFNγ/IL-10 (r = 0.78), IFNγ/IP-10 (r = 0.9), IFNγ/MCP-1 (r = 0.75). The level of INFγ in the CCP transfused to patients of the deceased group had higher values of positive correlation with ratios of IFNγ/IL-10 (r = 0.96), IFNγ/IP-10 (r = 0.92), IFNγ/MCP-1 (r = 0.92). Conclusion. The level of cytokines IL-6 and IFNγ, the cytokine ratios based on them in the CCP may affect the outcome of COVID-19 in patients treated with CCP.