Vol 12, No 6 (2022)

Cover Page

Full Issue

REVIEW ARTICLES

Phylogenetic structure of the global population of Helicobacter Pylori

Starkova D.A., Svarval A.V.

Abstract

Helicobacter pylori (H. pylori) is widely considered to be one of the oldest bacteria in the human microbiome. During the co-evolutionary relationships between humans and H. pylori bacterium, spanning at least 100 000 years, a high rate of mutation and recombination events led to extremely high genomic polymorphism of the H. pylori species. Despite this, the large diversity of H. pylori genomes is very well structured, allowing to divide it into different populations associated with the geographic location of H. pylori strains. To date, seven modern H. pylori populations have been determined globally: hpAfrica1, hpAfrica2, hpEastAsia, hpEurope, hpAsia2, hpNEAfrica and hspSahul originated from at least six ancestral populations (ancestral European 1, ancestral European 2, ancestral EastAsia, ancestral Africa1, ancestral Africa2, ancestral Sahul). The global phylogenetic analysis showed that H. pylori is organized into two superlineages: one containing hpAfrica2 and the other containing all other populations in a single monophyletic clade. This indicates that, hpAfrica2 is the most ancient of all H. pylori populations, while the others continued evolutionary development along as mankind spread beyond the African continent. Thus, the H. pylori species populational diversification, which occurred in parallel with paired hosts, allowed us to use H. pylori genetic variants as biological markers, reflecting ethnogeographic migration processes in human history. Moreover, the rapid and dynamic evolution of H. pylori informs about ongoing recombination events enabling use H. pylori as a model both for the co-evolution of pathogenic bacteria and humans as well as for within-individual host pathogen microevolution. This review summarized developments from numerous studies on coevolution process and phylogenetic pattern of the global H. pylori population. The relationships between currently known bacterial populations and subpopulations, related geographical distribution, reconstruction of evolutionary pathway for ancestral and recent populations are detailed. New data on the H. pylori strain populational pattern in Russia, as well as strains circulating in the Northern, Central and South America, are presented. Phylogenetic analysis of the H. pylori population pattern permitted to reconstruct both prehistoric and recent human migrations, demographic processes as well as multilayered evolutionary pathways of H. pylori population.

Russian Journal of Infection and Immunity. 2022;12(6):1009-1018
pages 1009-1018 views

Leptospirosis in Vietnam

Tokarevich N.K., Blinova O.V.

Abstract

Leptospirosis poses a serious public health problem in many countries because about 1 million people suffer annually from this severe, often fatal, infection. At present, its importance has been increasing due to development of integration processes, globalization and intensification of economic activities, inevitable anthropogenic transformation of landscapes as well as rise in number of people with occupational risk of pathogen exposure. The burden of human leptospirosis is expected to rise with demographic shifts and climate change that result in heavy rainfall and flooding. Regarding leptospirosis, Southeast Asia, including Vietnam, is among the most vulnerable global regions. The objective of the review was to analyze available published data on the spread of leptospirosis in Vietnam. More than 100 research articles were analyzed allowing to state that in Vietnam synanthropic rodents (rats), agricultural (buffaloes, cattle, pigs) and domestic animals (cats, dogs) are the main sources of leptospirosis infection in humans. It is essential that rats (cats and dogs also) in Vietnam are used for food. Among all farm animals, pigs are of maximal importance as a source of infection in humans. In Vietnam, Leptospira prevalence in pigs varies widely, up to 73%. It depends significantly on the location, farm size, age and gender of animals, etc. A large variety of Leptospira serovars have been identified in pigs in Vietnam: Tarassovi, Bratislava, Australis, Javanica, Autumnalis, Grippotyphosa, and some others. Official Vietnam reporting of leptospirosis cases based on clinical data does not reflect the real-life incidence rate in humans. However, the available seroprevalence studies reveal that, on average, about 10% of the Vietnamese population are infected with Leptospira. Work in agriculture is the dominant risk factor for acquiring this infection. The highest Leptospira seroprevalence rates were detected in farmers, 63.2%. Serovar diversity is typical for pathogenic Leptospira circulating in Vietnam. In humans, the most frequent are antibodies to Hebdomadis, Wolffi and Icterohaemorrhagiae, but the frequency varied markedly across the country depending on the site, possibly with relation to the environment, as well as with economic activity of the local population. In Vietnam, geographic, climatic and social differences between northern, central and southern regions contribute to the specificity of local leptospirosis epidemiology. This emphasizes the advisability of developing special measures for leptospirosis prevention taking into account regional peculiarities.

Russian Journal of Infection and Immunity. 2022;12(6):1019-1028
pages 1019-1028 views

Epidemiology and course of infectious diseases during the covid-19 pandemic. Report 2. Interference engaged between SARS-COV-2 and acute respiratory viral infections

Boeva E.V., Belyakov N.A., Simakina O.E., Danilenko D.M., Lioznov D.A.

Abstract

Currently, the disease caused by the new coronavirus (COVID-19) and the possibility of co-infection with SARS-CoV-2 and other pathogens in the current epidemic situation continues to be of particular interest. The review, based on the analysis of literature and own materials, outlines the features of the relationship between SARS-CoV-2 and pathogens of acute respiratory viral infections (ARVI). Particular attention is paid to the combined course of COVID-19 and influenza, a comparative characteristic of the severity of the clinical picture. An assessment of the epidemic situation against the backdrop of the COVID-19 pandemic in foreign countries and the Russian Federation (RF) revealed the presence of the phenomenon of SARS-CoV-2 interference with other viral respiratory agents, based on the facts of a sharp suppression of the circulation of influenza viruses, respiratory syncytial virus (RSV) and other ARVI pathogens during the period of active spread of pandemic coronavirus. The main epidemiological indicators of the course of coronavirus infection were compared and the contribution of various pathogens to the etiology of acute respiratory viral infections during the development of the second wave of COVID-19 in the RF was assessed. It was noted that the decrease in the number of new cases by 11.4 and deaths by 2.1 times due to COVID-19 at 6 and 13 weeks in 2022 occurred with unchanged laboratory detection of the influenza virus (0.8%) and an increase in the frequency detection of pathogens of other SARS. The results of observations showed that against the background of a decrease in the incidence of COVID-19, there was no increase in the proportion of diagnosed cases of infections caused by other pathogens, especially influenza. The results obtained confirm the need to ensure effective epidemiological surveillance and additional application of pathogen identification methods for monitoring various ARVI, which can significantly affect the approach to differential diagnosis, patient management tactics and the decision on appropriate preventive measures.

Russian Journal of Infection and Immunity. 2022;12(6):1029-1039
pages 1029-1039 views

ORIGINAL ARTICLES

Disseminated purulent peritonitis outcome affects NKT cell phenotype

Savchenko A.A., Borisov A.G., Kudryavtsev I.V., Belenjuk V.D.

Abstract

The aim of our study was to investigate the main characteristics of peripheral blood NKT cell phenotype in patients with disseminated purulent peritonitis (DPP) in dynamics of postoperative period, depending on the disease outcome. Fifty-two patients with acute surgical diseases and injuries of the abdominal organs complicated by DPP, and 68 healthy individuals in control group, were examined. Blood sampling was performed before surgery (preoperative period), as well as on the day 7, 14 and 21 of postoperative period. All patients with DPP were divided into two groups depending on disease outcome in postoperative period: patients with favorable disease outcome (n = 34); and patients with unfavorable outcome (n = 18). Study of the phenotype of blood NKT lymphocytes was performed by flow cytometry using direct immunofluorescence of whole peripheral blood samples with monoclonal antibodies. The low relative and absolute level of NKT cells was observed in DPP patients regardless of outcome disease in preoperative period. At the same time, the absolute level of NKT cells returned to normal only in patients with favorable DPP outcome and only by day 21 after surgery. Patients with favorable DPP outcome by the end of examination period had normalized quantity of mature NKT-lymphocytes and significantly decreased level of cytotoxic cells which was apparently associated with migration of such cell subsets to site of inflammation. A reduced level of non-classical (expressing CD8 marker) mature and cytokine-producing NKT cells was detected only in patients with favorable DPP outcome in preoperative period which returned to normal by the end of postoperative period. At the same time, patients with unfavorable disease outcome had reduced quantity of NKT cells of these subsets by day 21 of postoperative treatment. Patients with favorable outcome had high level of mature and cytotoxic CD11b+ NKT cells already in the preoperative period, while patients with unfavorable DPP outcome had increased level of cytotoxic CD11b+ NKT cells only by day 21 after surgery. The proportion of NKT cells expressing activation markers (CD28 and CD57) was reduced in patients in preoperative period that returned to normal immediately after surgery with favorable outcome, while it recovered with unfavorable outcome closer to the end of postoperative examination. The defined features of NKT cell phenotype in patients with unfavorable DPP outcome characterize disturbances in subset ratio and mechanisms of functioning of this cell fraction. This determines a need to develop immunotherapeutic methods aimed at stimulating immunoregulatory activity of NKT cells.

Russian Journal of Infection and Immunity. 2022;12(6):1040-1050
pages 1040-1050 views

Post-Gam-COVID-Vac combined vector vaccine cellular and humoral immune response

Inviyaeva E.V., Vtorushina V.V., Drapkina Y.S., Krechetova L.V., Dolgushina N.V., Khaidukov S.V.

Abstract

Currently, as the SARS-CoV-2 pandemic evolves, there has been increasingly more attention paid to building natural and vaccine-induced immunity against SARS-CoV-2 and related disease known as COVID-19. Widespread preventive vaccination plays an important role in effectively protecting people from viral infections and can reduce national economic costs. Purpose — to study peripheral blood cell subset composition and magnitude of humoral response in vaccinated Gam-COVID-Vac subjects. The prospective study included 352 patients, of which 194 (119 women and 75 men) underwent an immunogram study and assessed level of anti-SARS-CoV-2 antibodies. In patients, the study of the lymphocyte subset composition and estimation of anti-SARS-CoV-2 antibodies was carried out at two time points — prior to vaccination and 90 days after inoculated component 1 of the Gam-COVID-Vac vaccine. In general, vaccination was well tolerated by patients, with no serious adverse events after immunization. The reaction to the vaccine (fever, malaise, headache, local reactions) was short-term (1–2 days) and more often noted after inoculated vaccine component 2. Comparatively analyzed immunogram parameters in females before and after vaccination revealed increased relative level of T-lymphocytes (CD3+), T-helper cell subset (CD3+CD4+), increased absolute and relative level of activated CD3+CD25+ T-lymphocytes, but decreased absolute and relative level of natural killer (CD3CD56+CD16+) and natural killer T-cell (CD3+CD56+CD16+) cell subsets as well as decreased CD147 receptor expression on T-lymphocytes. Similar patterns were also found while examining the immunogram in males exepting increased level of lymphocytes and lowered CD147 expression on both T- and B-lymphocytes. No changes in the parameters of the immune T-cell arm was found. The high efficacy of the vaccine was confirmed by development of SARS-CoV-2-specific class G antiviral antibodies in 97.5% and 92.3% of vaccinated females and males, respectively. The data obtained evidence that: 1) vaccination induces a specific humoral immune response determined three months post-vaccination, and 2) it caused no serious disturbances in the immune system functioning, which could be reflected in the peripheral blood lymphocyte subset composition. Thus, the data presented allow to conclude that Gam-COVID-Vac is effective vaccine against SARS-CoV-2 infection.

Russian Journal of Infection and Immunity. 2022;12(6):1051-1060
pages 1051-1060 views

The non-protein fraction of embryonic stem cell secretome exerts antibacterial effects against antibiotic-resistant bacterial strains

Kaigorodov D.G., Kaigorodova A.D.

Abstract

In recent years, it has been extremely evident to seek out for new antibacterial agents, because the burgeoning problem of antibiotic resistance and the toxicity of many antimicrobial compounds has forced scientists to turn attention to alternative approaches. Investigating stem cell secretomes, including the non-protein portion, to find new antimicrobials is a promising area in the field. We examined an effect of the non-protein portion within the embryonic stem cell secretome on various bacterial strains, including antibiotic-resistant members. The non-protein fraction of the stem cell secretome was obtained by preparative high-performance liquid chromatography. Bactericidal activity was tested against eight museum bacterial strains and 206 clinical strains by comparing the secretome-related effects on growth of bacterial cultures. The museum strains showed some dose-dependent effects at concentrations of 25–100 µg/ml. Some bactericidal activity was shown at a concentration of 100 µg/ml against the clinical strains of Gram-negative microorganisms of different species, but bacterial sensitivity to the secretome fraction varied, with growth stimulation being detected in some strains. Applying non-protein fraction of the stem cell secretome at higher concentrations of 100–1000 µg/ml showed no dose-dependent effect. The clinical strains of E. coli and P. aeruginosa were shown to have reduced bactericidal activity after 24-hour incubation. Thus, this study has shown that the non-protein fraction of the embryonic stem cell secretome exerts bactericidal effects against some bacterial strains. However, more detailed studies are needed to identify a mechanism of action and to determine the most effective dose as well as frequency of administration.

Russian Journal of Infection and Immunity. 2022;12(6):1061-1068
pages 1061-1068 views

The influence of Aspergillus fumigatus micromycetes on immune response regulation in patients with asthma

Kozlova Y.I., Frolova E.V., Kudryavtsev I.V., Uchevatkina A.E., Filippova L.V., Aak O.V., Taraskina A.E., Sobolev A.V., Vasilyeva N.V., Klimko N.N.

Abstract

Introduction. Aspergillus fumigatus is able not only to sensitize patients with atopy, but also to colonize the respiratory tract, remaining a constant source of allergens due to the small spore size and thermal tolerance. Currently, the role of micromycetes in the immunopathogenesis of asthma has been poorly studied. The objective was to evaluate the features of the immune response regulation in patients with allergic bronchopulmonary aspergillosis (ABPA) or asthma with sensitization to A. fumigatus. Materials and methods. There were enrolled 15 patients with ABPA, 10 patients with asthma with sensitization to A. fumigatus, 16 patients with asthma without sensitization to A. fumigatus. The control group consisted of 16 apparently healthy volunteers. All patients underwent a clinical and functional examination. The subpopulations of blood lymphocytes were assessed by flow cytometry. The A. fumigatus allergen was added to peripheral blood samples to evaluate the production of IFNγ, IL-10 and IL-13. The serum cytokine levels in cell culture supernatants, as well as total IgE, A. fumigatus-specific IgE (sIgE) as well as thymus and activation-regulated chemokine (TARC) level were measured by enzyme-linked immunosorbent assay. Results. Significantly higher serum levels of total IgE, A. fumigatus-specific sIgE and TARC were found in patients with ABPA and asthma with sensitization to A. fumigatus compared to patients with asthma without sensitization to A. fumigatus. The results of lymphocyte immunophenotyping revealed significant excess of memory Th2 cells and T-regulatory cells in all patients with asthma compared to the control group. The count of Tfh2 was higher but memory Th17.1 cells were lower in patients with sensitization to A. fumigatus compared to those of apparently healthy volunteers. Patients with ABPA had significantly higher count of memory Th2 cells and TARC level compared to patients with asthma sensitized to A. fumigatus. The increased activity of memory Th2 cells is confirmed by increased secretion of IL-13 and IL-10 following along with decreased IFNγ production in response to specific fungal allergen stimulation of blood cells compared to the patients with asthma and the control group. A positive correlation was revealed between the count of memory Th2 cells and the levels of sIgE, IgE, TARC, a negative correlation — with FEV1. Conclusion. Thus, exposure to A. fumigatus significantly enhances the activity of memory Th2 cells in patients with asthma which can lead to severe disease course and development of allergic bronchopulmonary aspergillosis. The features of the immune response identified dictate a need for a personalized approach to choose therapeutic tactics in such patients.

Russian Journal of Infection and Immunity. 2022;12(6):1069-1080
pages 1069-1080 views

Serogroups and antimicrobial susceptibility of Salmonella isolated from people and food items in southern provinces of Vietnam

Egorova S.A., Truong Q.N., Kaftyreva L.A., Kozhukhova E.A., Makarova M.A., Cuong Q.H., Vu H.N., Huong T.D., Lan T.Q., Tram K.V., Long T.N., Diep T.N., Tu L.K., Thu L.K.

Abstract

This article presents current relevant data on the serogroups and antimicrobial susceptibility of Salmonella strains isolated in the southern provinces of the Socialist Republic of Vietnam. There were examined 189 Salmonella strains isolated from: human feces in acute diarrhea (86 strains); and pork samples (103 strains). Serological O-group identification was performed by slide agglutination with O- and H-antisera and multiplex PCR to detect H phase-1 and phase-2. Antimicrobial susceptibility testing was performed by using the disk-diffusion method according to the EUCAST (version 2019) recommendations. Strains isolated from humans predominantly belonged to O4 group (69.8%). The percentage of other serogroups varied from 1.2% (rare group O16) to 11.6% (O9). About a half of strains (44.7%) isolated from pork samples turned out to belong to the О3,10 serogroup (vs 7.0% of strains from humans). Serogroups О7, О4 and О8 were less frequent (22.3%, 14.6% and 13.6%, respectively). Single strains belonged to serogroups О9, О13, and О18. Regardless of the isolation source, about 80% of Salmonella strains were resistant to antibiotics from different antimicrobial groups (besides carbapenems): 67.0% were resistant to tetracycline; about half were resistant to pefloxacin, ampicillin and chloramphenicol (54.0%, 47.1%, 46.6%); and up to 40% were resistant to trimethoprim/sulfamethoxazole and nalidixic acid. The proportion of strains resistant to ceftriaxone and gentamycin was markedly higher in those of human vs pork origin: 12.8% vs 1.0% and 30.2 vs 1.9%, respectively. Moreover, 62.8% and 43.7% strains of human and pork origin, respectively, showed multidrug resistance (to 3 and more antimicrobial groups). In addition, simultaneous resistance to 6 antimicrobial groups was detected much more frequently in Salmonella strains isolated from humans vs pork samples (15.1% vs 1.0%, respectively). Multidrug resistance (MDR) was observed in strains of different serovars, predominantly S. Typhimurium (36.4%). The predominant MDR (30.3%) phenotype (AMP, TE, QN, C, SXT) was revealed in serovars of S. Typhimurium, S. Bredeney, S. Corvallis, S. Give, S. London, S. Rissen, and S. Meleagridis. Thus, Salmonella strains isolated in the southern Vietnamese provinces featured resistance to fluoroquinolones and cephalosporins. Taking into account simultaneous loss of susceptibility to “old” antimicrobials (ampicillin, chloramphenicol, trimethoprim/sulfamethoxazole), it crucially restricts the list of effective medicines to treat complicated salmonellosis cases.

Russian Journal of Infection and Immunity. 2022;12(6):1081-1090
pages 1081-1090 views

New genetic markers for Burkholderia pseudomallei strains typing

Ledenyova M.L., Tkachenko G.A., Zakharova I.B.

Abstract

Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease in humans and animals that may be asymptomatic long-term and quickly develop to pneumonia and septicemia in immunocompromised state and due to predisposing factors. Melioidosis is endemic in countries with tropical and subtropical climates, where B. pseudomallei is a part of the soil and water microbiota of stagnant water bodies, as well as the plant rhizosphere. The recording of imported melioidosis cases in countries with temperate climate zone, along with the continued threat of using this pathogen as a bioterrorism agent, indicate the relevance of research aimed at developing modern methods for its diagnosing and typing. Current research in the intraspecific differentiation of pathogenic strains of infectious diseases tends to use two or more types of molecular markers. A promising direction for the B. pseudomallei strains genotyping is based on using a combination of VNTR loci, which provides a high discriminating ability of the method of multi-locus variable tandem repeat number analysis (MLVA), and slowly evolving single nucleotide polymorphisms (SNPs). The aim of this work was to identify new VNTR and SNP loci suitable for use as genetic markers in molecular typing of the melioidosis causative agent. 20 strains of B. pseudomallei from the collection of the Volgograd Plague Control Research Institute and whole genome sequences of 85 B. pseudomallei strains from the GenBank NCBI database were analyzed. While typing melioidosis causative agent strains from the GenBank NCBI database for 4 VNTR loci, 74 genotypes were identified, of which 64 were unique (Hunter–Gaston index 0.997). It was found that the high allelic polymorphism of VNTR loci limited a potential to determine the geographical and phylogenetic relationships of B. pseudomallei isolates by using the MLVA-4 scheme, and the identified null alleles increased the risk of homoplasia. In this regard, the MLVA-4 scheme was supplemented with a VNTR marker in the BPSS1974 locus encoding a collagen-like protein as well as with SNP markers in the genes of lipid A biosynthesis lauroyl acyltransferase, RNA polymerase sigma factor RpoH, and glutamine amidotransferase. For amplification of the select loci, primers and probes were designed as part of the developed scheme, which were tested in the typing of B. pseudomallei collection strains. According to the results of a cluster analysis for 105 strains of the melioidosis causative agent, an integrated approach turned out to be optimal, allowing differentiation of strains within SNP groups based on VNTR profiles. The methodological approach developed for B. pseudomallei genetic typing, based on a comprehensive analysis of 4 SNP- and 5 MLVA-markers in our modification, allowed to differentiate strains according to the geographical regions of their origin and establish the clonal origin of isolates upon revealing cases of melioidosis.

Russian Journal of Infection and Immunity. 2022;12(6):1091-1102
pages 1091-1102 views

Genotyping of tick-borne pathogens and determination of human attacking tick species in Novosibirsk and its suburbs

Kartashov M.Y., Krivosheina E.I., Svirin K.A., Tupota N.L., Ternovoi V.A., Loktev V.B.

Abstract

The south of Western Siberia traditionally belongs to the regions with unfavorable epidemiological situation for tick-transmitted infections. In Novosibirsk and its suburbs, approximately 20 thousand people annually seek for medical care after tick bites. The purpose of this work was to determine human-attacking tick species composition in the territory of Novosibirsk and its suburbs by identifying nucleotide sequence of tick mitochondrial gene cytochrome oxidase COI fragment during the 2018 spring-summer season, determination of infections of individual ticks with viral and bacterial tick-borne infections, followed by genotyping identified pathogens by PCR methods, by determining nucleotide sequences and phylogenetic analysis. It is established that ticks of five species attack the humans: Ixodes persulcatus, Ixodes pavlovskyi, Dermacentor reticulatus, Dermacentor marginatus, Dermacentor nuttali in the Novosibirsk metropolis. The majority of tick attacks on humans are associated with I. pavlovskyi (43.6%) and D. reticulatus (41.2%) ticks. The genetic material of the tick-borne encephalitis virus was detected in 3.6%, borrelia — 13.8% and Rickettsia — 23.1% individual ticks collected from humans. Genotyping of the tick-borne encephalitis virus (TBEV) in the collected ticks showed the presence of TBEV Siberian and Far Eastern genotype in 83% and 17% cases, respectively. The Kemerovo virus could not be detected. Genetic material from Borrelia spp. and Rickettsia spp. has been detected in all five tick species attacking the local human population. The bulk of the identified Borrelia spp. isolates were genotyped as Borrelia garinii (86%) and 13% of the isolates as Borrelia afzelii species. The genetic material of Borrelia miyamotoi was found in one individual tick. Ticks of the genus Dermacentor have been found to be infected by Rickettsia raoultii, and ticks of the genus Ixodes were largely infected with Rickettsia tarasevichiae, and I. persulcatus tick was infected by Rickettsia helvetica in a single case. Thus, the human population of Novosibirsk and its suburbs is attacked by five species of ixodid ticks dominated by I. pavlovskyi and D. reticulatus ticks. The genetic material of the following tick-borne pathogens was found: Siberian and Far Eastern TBEV genotype, B. garinii, B. afzelii, B. miyamotoi, R. raoulti, R. tarasevichiae and R. helvetica in the individual ticks collected from humans.

Russian Journal of Infection and Immunity. 2022;12(6):1103-1112
pages 1103-1112 views

Dynamics of clinical symptoms and secretory immunoglobulin a in COVID-19 convalescent patients

Khasanova A.А., Kostinov M.P., Soloveva I.L., Nikitina T.N., Khromova E.A.

Abstract

The post-COVID-19 recovery period is characterized by persistence of some symptoms, with immunological alterations being of great importance. Development of preventive measures to normalize mucosal immunity after a coronavirus infection determines the relevance of the current study. The aim was to study dynamics of clinical symptoms and level of secretory immunoglobulin A in individuals after a novel coronavirus infection as well as evaluate effectiveness of using IFNa-2b. Materials and methods. A study was conducted with patients aged 18 to 60 years old (n = 130), surveyed 1 to 9 months after post-infection, as well as in apparently healthy individuals lacking COVID-19 (n = 15). Previous novel coronavirus infection and post-COVID manifestations were verified based on medical documentation, complaints, anamnesis data, physical examination and questionnaires. The concentration of salivatory and nasopharyngeal mucosal sIgA was measured dynamically prior to and after administration of local therapy with IFNa-2b (gel applied intranasally twice a day for 30 days). Results. The acute period of COVID-19 was characterized by fever, anosmia, severe asthenia (fatigue and weakness), muscle and joint pain. Among the post-COVID manifestations at early period (1–3 months), pain in the joints and muscles (75.0%) as well as elevated body temperature (21.2%) were reliably detected, whereas in the long period (6–9 months) there were revealed dominance with the same frequency of shortness of breath, muscle and joint pain (75.8%, respectively). Based on examination data in healthy subjects, there was determined an arbitrary normal range of secretory IgA in saliva — 6.45±1.81 mg/ml and nasal swabs — 13.43±3.24 mg/ml. In the group of patients 1–3 months post-infection, therapy with IFNa-2b one month later resulted in significantly increased level of secretory IgA in saliva (from 1.84±0.28 to 5.78±1.96 mg/ml) and in nasal swabs (from 28.61±3.0 to 39.83±3.85 mg/ml) by more than 3- and 1.5-fold, respectively. In the group of patients without therapy was featured with stably sustained decline in sIgA level up to 9 months after COVID-19. In particular, the level of saliva sIgA ranged from 2.36±0.56 down to 2.16±0.66 mg/ml, and in nasal smears — from 15.66±1.32 to 10.23±1.07 mg/ml that differed insignificantly compared to baseline level. The rate of respiratory diseases prevailed in this group (27.6% of cases), which fully lacked in the group of topically administered IFNa-2b. Conclusion. In the post-COVID period, multiple organ disorders persist and reduced sIgA level is registered. Intranasally applied IFNa-2b made possible to normalize sIgA level and prevent accumulation of respiratory infectious pathologies.

Russian Journal of Infection and Immunity. 2022;12(6):1113-1122
pages 1113-1122 views

Evaluating the iatrogenic effects of polypharmacy and drug interactions in HIV-positive patients admitted to the intensive care unit: a single-center retrospective study

Emerole K.C., Voznesenskiy S.L., Samotolkina Е.S., Kozhevnikova G.M., Klimkova P.V.

Abstract

Background. Polypharmacy and drug interactions are of particular concern in people living with HIV/AIDS, especially those who receive antiretroviral therapy (ARVs). Polypharmacy and drug-drug interactions (DDIs) can impact the efficacy and toxicity of HIV treatment. ARVs used in HIV treatment are often prone to drug interactions if administered with other non-ARV drugs because many of them are metabolized through the cytochrome P450 system. The pharmacological management of HIV patients in the intensive care unit (ICU) is usually complex and typically involves the administration of several classes of drugs. This patient group may be at higher risk for potential DDIs due to polypharmacy in the ICU. The main objective of this study was to assess the iatrogenic effects of polypharmacy in HIV patients treated in the ICU and to describe the DDI profile between ARVs and other non-ARV medications prescribed in the ICU. Methods and materials. Between 2018 and 2020, we conducted a single-center, retrospective study evaluating the medical records of 59 HIV patients admitted to the ICU for more than 24 hours at the Infectious Disease Clinical Hospital No. 2, Moscow, Russia. We evaluated the impact of polypharmacy on renal, hepatic and haemopoietic function. The Liverpool HIV Drug Interaction database was used to identify DDIs in ART-treated HIV patients. Results. All patients received more than 5 different medications matching the definition of polypharmacy. The average number of concurrent medications prescribed was 15±6.713 (maximum — 40, minimum — 6). All drug interactions recorded were between ARVs and antibiotics: 30 cases of potential interactions in 65.5% patients who received ARV. Of such patients, 94% were exposed to at least two potential interactions. Tenofovir (TDF) and the antibiotic vancomycin underlaid the most common potential interaction (49.2%), followed by lopinavir ritonavir (LPV/RTV) and ciprofloxacin (30.3%). A significant difference in average creatinine levels was found in patients with TDF/vancomycin potential interactions (p < 0.05). Conclusion. This study demonstrated that potential DDIs frequently occur in ICU patients in line with previous investigations. It is necessary to implement collaborations among clinical pharmacologists and infectious disease/HIV specialists, as well as frequent clinical and laboratory monitoring, aimed at developing effective and actionable strategies that could reduce potential DDIs in HIV patients in the ICU.

Russian Journal of Infection and Immunity. 2022;12(6):1123-1128
pages 1123-1128 views

A 24-hour Сandida sp. biofilm formation dynamically assesed with modified macrometric method

Nikolenko M.V., Baryshnikova N.V., Malishevskaya O.I., Enoktaeva O.V., Vaseva E.M.

Abstract

The aim of the study was to study the dynamics of 24-hour Candida spp. biofilm formation by using a modified macrometric method. The proposed macrometric method solves the problem of accelerating and simplifying the quantitative assessment of the biofilm formation process, increases sensitivity due to allowing to avoid mistakes related to applied polystyrene material. The ease of implementing such a technique makes it accessible to any laboratory. Reference strains from the American Type Culture Collection (ATCC) and clinical isolates of Candida spp. isolated from the female reproductive tract with candida dysbiosis were used for the study. Biofilm formation of Candida spp. studied according to the O’Toole G.A. et al. method modified by us. The biological activity of Сandida sp. biofilm formation was monitored for 48 hours with 4-hour intervals, in winter season, the IV phase of the moon. A 48-hour fungal culture corresponding to relevant maximum adhesion on glass surface was used. The study chrono-design implied obtaining 6 diurnal measurements for the function evaluated with a 3–5-repetits of the experimental conditions. Amplitude-phase characteristics of the studied biorhythms were graphically represented using cosinor analysis serving as the basic method to identify and model cyclic processes in biological systems. The study proved that the ability of micromycete cells to adhere is significantly higher in the stationary vs. logarithmic growth phase (p < 0.05). The chronobiological technique used here allowed to reveal the presence of diurnal fungal film-forming activity (p < 0.05) and reveal the general patterns of manifestated properties in representatives of all candida species examined. It has been experimentally established that the sequence and consistency of the biological properties of clinical Сandida sp. isolates over time were not fundamentally dependent on the type of fungus. During the study, rhythmometric markers of the strain-related pathogenicity was established reflecting contribution of rhythm and the amplitude-phase characteristic. It has been proven that the activity of biofilm formation increases along the “reference strains — clinical isolates” axis. For С. albicans the Mann–Whitney test data was 29, for C. tropicalis — 26, and for C. krusei — 30 (p < 0.05). We believe that chronobiological method opens up new perspectives in the studying physiology of Candida spp. because it allows to dynamically predict state of microorganism and take into account features of urgent and long-term adaptation to various environmental factors. Identifying diurnal rhythms in biofilm-forming activity of various Сandida sp. strains opens up an opportunity to control viability of bacterial-fungal associations and predict related resistance to diverse antimicrobial agents.

Russian Journal of Infection and Immunity. 2022;12(6):1129-1135
pages 1129-1135 views

A correlation between LP-PLA2 and monocyte levels in atherosclerosis risk subjects

Kumboyono K., Chomsy I.N., Vijayadas D., Wihastuti T.A.

Abstract

Background. Cardiovascular disease (CVD) is the most significant cause of death worldwide. More than 17.9 million people died from CVD, of which 85% deceased due to heart disease. On the other hand, atherosclerosis is one of the most dominant CVD in most developing countries and developed countries. Lp-PLA2 is an enzyme produced by inflammatory cells and a pro-atherogenic protein in atherosclerosis. In the process, monocytes will produce Lp-PLA2 so that it may hydrolyse oxidized low density lipoprotein (oxLDL) into lysophosphatidylcholine (lysoPC) and oxidized fatty acids (oxFA), atherogenic proteins involved in atherogenesis. A chronic inflammatory process that occurs in atherosclerosis requires early detection to avoid CVD severity. The research aims to determine the correlation between Lp-PLA2 concentration and monocyte count as well as percentage in cohorts linked to risk of atherosclerosis. Materials and methods. This study was a descriptive correlational analysis of the population with conditions at risk of atherosclerosis. The total number of respondents sampled in this research was 86. We used the ELISA method to measure Lp-PLA2 concentration and the Hematology Analyzer method to measure monocyte count and percentage. Results. The relationship between monocyte and Lp-PLA2 level accounts for a probability value of 0.028. The correlation coefficient of 0.789 is categorized as very strong. Conclusion. Increase in the concentration of Lp-PLA2 correlates with monocyte count and percentage in a population with conditions at risk of atherosclerosis.

Russian Journal of Infection and Immunity. 2022;12(6):1136-1142
pages 1136-1142 views

The efficacy and safety of three 30-day courses of albendazole in patients with neurocysticercosis

Sinh C.T., Thang T.T., Thang T.D., Loi C.B., Anh L.T.

Abstract

Albendazole is one of the drugs indicated for the treatment of neurocysticercosis. However, data on the treatment outcome of a long course of this drug is scarce. This study aims to investigate the efficacy and safety of three 30-day courses of albendazole in patients with neurocysticercosis. Materials and methods. The diagnosis of neurocysticercosis was based on epidemiological, clinical and laboratory criteria as guided by the Vietnamese Ministry of Health. Sixty patients with a mean age of 50.17±10.03 years old, with 86.7% (95% CI: 77.8–95.5%) men, were involved in this study. Patients received three 30-day courses of albendazole with an intermittence of 20 days. Additional treatment included steroids, anticonvulsants or analgesics. Based on brain magnetic resonance imaging 6 months after the therapy, the efficacy was classified as cure (viable cysts not discernible), improvement (50% or more cysts disappeared or calcified) or inefficacy (changes in less than 50% of the cysts). The safety was determined based on the changes of biochemical parameters after each treatment course. Results. The most common clinical presentations were headache (90.0%, 95% CI: 82.2–97.8) and/or seizure (68.3%, 95% CI: 56.2–70.4), followed by other symptoms such as fainting, memory loss, and limb numbness. Active cysts were discovered in all cases and located mainly in the parenchymal region. After therapy, the rates of cure, improvement or inefficacy were 43.3% (95% CI: 30.4–56.2%), 51.7% (95% CI: 38.7–64.7%) and 5.0% (95% CI: 0–10.7%), respectively. Liver enzymes were slightly higher compared to those before therapy and mostly returned to normal ranges after drug interruption. Alanine aminotransferase levels before the 3rd course were higher than values before the first and second courses. No abnormalities in blood urea or creatinine after therapy were reported. Conclusion. Three 30-day cycles of albendazole appear to have good efficacy and tolerability in patients with neurocysticercosis.

Russian Journal of Infection and Immunity. 2022;12(6):1143-1148
pages 1143-1148 views

Assessing implementation of prevention and infection control programs in armenian hospitals during the COVID-19 pandemic

Palozyan G.H., Avetisyan S.M., Abovyan R.A., Melik-Andreasyan G.G., Vanyan A.V.

Abstract

Aim of the study was to assess the current state of implementating key aspects of infection prevention and control (IPC) in Armenian hospitals, defined by the main WHO components, using the survey tool IPCAF (Infection Prevention and Control Assessment Framework). Materials and methods. 113 hospitals were involved in the study. All participants filled out the IPCAF questionnaire, consisting of 8 sections (each rated up to 100 points) devoted to various IPC aspects. Depending on the total final score, IPC programs were divided into the following categories: advanced (601–800 points), intermediate (401–600 points), basic (201–400 points) and inadequate (0–200 points). The study conducted a descriptive analysis of the overall IPCAF score as well as score evaluation of the relevant core components and some selected questions of particular interest. Results. The 2021 total average score for all IPCAF components for all hospitals in Armenia is 578.0±7.9 points, which is currently regarded as an “intermediate” level. At the same time, 47 (41.6%) hospitals were assigned to the advanced category, 63 (55.7%) — to the average category and 3 (2.7%) — to the basic category. Analysis of the main IPC components (CC, Core component) revealed that the maximum average scores were obtained for the components CC2 (IPC Guidelines) — 80.8 points, CC8 (Creating a safe environment in medical premises, as well as materials and equipment for IPC) — 75.5 points and CC7 (Workload, staffing and number of beds) — 75.2 points. The lowest average scores were obtained for the key components: CC4 (Surveillance for healthcare-associated infections) with 54.7 points and CC3 (IPC education and training) with 59.5 points. Conclusion. Legislative and practical changes implemented in the real world during the novel coronavirus infection (COVID-19) pandemic have significantly contributed to improved scores for many key components of IPC programs. The study found that the IPCAF is a useful tool for assessing IPC standards and identifying gaps, regardless of a country economic development level. In our opinion, the re-use of IPCAF in all medical institutions should be encouraged, which is important for monitoring changes and trends in IPC, as well as proposing individual strategies in the development and improvement of IPC.

Russian Journal of Infection and Immunity. 2022;12(6):1149-1155
pages 1149-1155 views

SHORT COMMUNICATIONS

Molecular genetic characteristics of Vibrio cholerae nono1/nono139 strain, the causative agent of a new case of acute intestinal infection in Rostov-on-Don

Monakhova E. ., Kruglikov V.D., Vodop'yanov A.S., Selyanskaya N.A., Ezhova M.I., Noskov A.K.

Abstract

During more than 50 years, a heterogeneous population of Vibrio cholerae non-O1/non-O139 (NAGs) exists in Rostov region of Russia, whose representatives periodically cause acute human intestinal infections; the last case was registered in 2018. In 2022, a sick child was again revealed in Rostov, from whom 2 NAG subcultures were isolated. Aim of the study: bioinformatics analysis of whole genome sequences (WGSs) of the 2022 clinical NAG isolates, genetic determinants of pathogenicity factors and relevant products. Materials and methods. Isolation, identification of cultures, as well as antibiotic sensitivity were carried out according to the MUK 4.2.3745-22. SNP analysis of WGSs obtained on the MiSeq Illumina platform were analyzed by means of designed software; BioEdit 7.2.5, Vector NTI Advance 11 package, CARD database were used to identify and analyze genes and relevant deduced products. Results. The isolated cultures with identical phenotypic features, PCR-genotypes and results of SNP analysis, were identified as a non-toxigenic NAG. The agent showed sensitivity to chloramphenicol, ceftriaxone, streptomycin, gentamicin, nalidixic acid, ciprofloxacin, ampicillin, amikacin and intermediate resistance to tetracycline, doxycycline, furazolidon and co-trimoxazole. WGSs lacked CTX and preCTX prophages, pathogenicity island VPI, thermostable and cholix toxin genes, pandemic islands VSP-I and VSP-II. The determinants of the type 6 secretion system (T6SS) were not presented completely, which evidenced in favor of the loss of its functionality. An intact T3SS cluster was revealed, which was adjacent to the nan-nag region of the VPI-2 pathogenicity island in the absence of the proximal and distal parts of the latter. Other determinants of pathogenicity factors were revealed: RTX cluster responsible for synthesis of MARTX cytotoxin, genes for hemolysin HlyA, cytotonic toxin Cef, several serine and metalloproteases. The nucleotide compositions of most determinants differed from the prototypes, but their putative products preserved characteristic active domains. The adhesive activity might be provided by mannose-insensitive MSHA-like pili, since the msh-cluster included all the genes necessary for their production, as well as flagella, as both clusters responsible for their assembling were 99% identical to the prototype. From antibiotic resistance determinants only β-lactamase VarG gene was found. Conclusion. The NAG strain examined here contains a sufficient set of intact virulence-associated genetic determinants, expression of which could contribute to the development of the disease.

Russian Journal of Infection and Immunity. 2022;12(6):1156-1162
pages 1156-1162 views

Immunochemical activity of Yersinia pseudotuberculosis ompF and ompC porins evaluated by optical trapping

Konyshev I.V., Novikova O.D., Portnyagina O.Y., Byvalov A.A.

Abstract

Introduction. Study of features for interacting “antigen-antibody” system is of great importance for developing new modern tools for diagnostics and therapy of infectious diseases. In this regard, it is of great interest to study the rupture force between bacterial antigens and antibodies using modern biophysical methods including optical trapping. The importance of surface antigens in the immunochemical activity of Yersinia pseudotuberculosis assessed by such method has not been evaluated yet. In this work we examined an opportunity to evaluate the interaction of hydrophobic Y. pseudotuberculosis porins OmpF and OmpC with specific antibodies using optical trapping method. Materials and methods. Polystyrene microspheres (d = 1 μm) were coated by passive adhesion with purified preparations of OmpF and OmpC porins; microsphere sensitization was verified by enzyme immunoassay. Antibodies from mouse sera were adsorbed onto the glass surface by chemical linking. The rupture force in the “porins-antibodies” system was determined using a laser trap according to the previously developed algorithm. Results. Using a model system including polystyrene microspheres sensitized with the proteins and aminated glass substrate coated with immune or nonimmune serum, significant differences in binding strength of OmpF and OmpC porins to homologous immune versus nonimmune sera were detected. The average forces of interaction with immune sera was 60 pN for OmpF microspheres (control — 40 pN) and 69 pN for OmpC microspheres (control — 49 pN). The proportion of irreversible substrate binding of the microspheres coated by the antigens to the treated with immune vs. non-immune sera was significantly higher. The results of assessing the average interaction force, as well as the predominance of the proportion of irreversible binding of antigen-coated microspheres with sera-treated substrates, indicates that specific interactions contribute significantly to the force of interaction. The aforementioned method can be used to evaluate the forces of intermolecular interaction in similar model systems using other microbial antigens.

Russian Journal of Infection and Immunity. 2022;12(6):1163-1168
pages 1163-1168 views

Features of the Candida genus community pattern in the intestinal biotope of patients with tuberculosis

Kholodov A.A., Zakharova Y.V., Otdushkina L.Y., Bryukhacheva E.O., Pyanzova T.V.

Abstract

Fungi are opportunistic microorganisms that colonize all biotopes of the human body, including intestinal. In case of emerging adverse environmental factors (HIV infection, other immunodeficiencies, antibiotic therapy), these microbial representatives begin active reproduction, which might require prescribing antimycotics. Frequent use of the latter in clinical practice induces the development of drug resistance to antifungal drugs, which may impact on effectiveness of both the treatment of fungal infections and other diseases. The purpose of the study was to assess the pattern and spectrum of drug resistance of Candida genus in the intestinal biotope of patients with respiratory tuberculosis and identify risk factors for developing total fungal drug resistance to antimycotic drugs. Material and methods. There were enrolled 21 patients with respiratory tuberculosis. Pattern of the fungal species diversity for the Candida genus isolated from faeces was evaluated, and the spectrum of relevant drug resistance to antimycotic drugs was determined. Patients (n = 21) were divided into 2 groups: with (n = 10) and without (n = 11) total resistance to antimycotics, after which the main risk factors for its development were identified. Results. Members of the Candida genus were isolated from all patients examined, wherein pure cell cultures were characterized by high level of antimycotics resistance. Resistance to three drugs was noted in 1 culture (4.8%), to four — in 10 cultures (47.6%), also found in 10 cultures to the entire drug panel (47.6%). During statistical processing, the data were obtained on affecting formation of total resistance to antimycotics of concomitant pathology of the gastrointestinal tract, the presence of a clinically significant dyspeptic syndrome, a history of antimycotic therapy, HIV infection with severe immunodeficiency, and some decrease in the peripheral blood CD4+ lymphocyte count. Conclusion. Fungi of the Candida genus isolated from tuberculosis patients were characterized by high level of resistance to antimycotics. Total resistance was observed in 47.6% of patients. In addition, the major fungi colonizing the intestines of tuberculosis patients were found to be Candida albicans species. The risk factors for the development of total antifungal resistance included: chronic enterocolitis, dyspeptic syndrome, peripheral blood CD4+ lymphocyte count lower than 350 cells/µl, and history of antimycotic therapy.

Russian Journal of Infection and Immunity. 2022;12(6):1169-1174
pages 1169-1174 views

The oral cavity as a site for developing a heterogeneous bacterial population in patients with cystic fibrosis

Kondratenko O.V., Saburova M.S.

Abstract

Cystic fibrosis is an important medical and social problem. Despite significant advances in modern science and practice, bacterial complications are still among the main causes of patient mortality. One of the crucial bacterial pathogens in cystic fibrosis is Pseudomonas aeruginosa, which can lead to rapidly decreased pulmonary function. At the same time, the lungs are not the only site for microbial colonization. The oral cavity can also serve as a reservoir for initial entry and adaptation of microbial strains, which, however, were only sparsely investigated. A clinical case of isolated heterogeneous microbial population of P. aeruginosa from various loci of the oral cavity and sputum of a patient with cystic fibrosis is described. A proteomic mass-spectrum analysis obtained from eleven isolates as well as their mutual comparison with the control strain of P. aeruginosa ATCC 27853 visualized with CCI matrix was performed. As a result, a high level of heterogeneity of the studied population was revealed, while high CCI Score values were obtained only for individual pairs of isolates. It was shown that the bacterial strains isolated from the patient sputum turned out to be more homogeneous in protein profiles than cultures detected from various oral sites. At the same time, in case of isolated several morphotypes of P. aeruginosa from single oral site, no closely related strains were found. Thus, it is shown that the oral cavity is more important viewed from microbial dissociation in cystic fibrosis, which may be due to more diverse microecological conditions. Representatives of the microbiological community can recolonize the tracheobronchial tree through microaspiration, thereby contributing to the maintenance of infectious inflammation in the lower respiratory tract and partially accounting for ineffectiveness of nebulized antibacterial therapy. At the same time, clones adapted to the lung tissue upon coughing up sputum are able to colonize oral sites. The data obtained actualize the question of the need for a comprehensive microbiological approach while examining patients to increase effectiveness of eradication measures in cystic fibrosis.

Russian Journal of Infection and Immunity. 2022;12(6):1181-1185
pages 1181-1185 views

An impact of activated Epstein–Barr Virus and HHV-6 on the course and control of bronchial asthma in children of the Amur Region

Suprun E.N., Suprun S.V., Vlasova M.A., Kuderova N.I., Evseeva G.P., Lebed'ko O.A.

Abstract

The role of viral infection in bronchial asthma (BA) is well-known being reflected particularly in GINA. An effect of pneumotropic intracellular persistent herpesviruses on the course of BA is of particular interest. The most common viruses of this group are cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human herpesvirus 6 (HHV-6). The CMV role has been discussed in our previous publications allowing us to focus here on EBV and HHV-6. We examined 167 children with BA that was diagnosed and clinically assessed in accordance with the current national clinical guidelines. Patients with controlled asthma (70 patients), partially controlled and uncontrolled asthma (97 patients) were stratified into several groups. The detection of EBV and HHV-6 DNA was carried out in throat swabs by PCR; the level of total and virus-specific IgA, IgM, IgG, IgE as well as serum level of IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-8 and TNFα was assessed by enzyme linked immunosorbent assay; lymphocyte subpopulations were analyzed by flow cytometry. The dose of topic GCS was taken into account with reference to the fluticosone equivalent; the function of external respiration was studied by spirometry. It was revealed that EBV DNA was found in 14.2% of cases, whereas HHV-6 — in 19.0% of cases, but 14.4% and 52.4% of patients, respectively, shed no pathogen-linked DNA. At the same time, patients with uncontrolled BA are significantly more likely to shed the pathogen DNA, so that EBV is released in 17.1% vs 4.5% of patients with controlled BA, HHV-6 — in 19.5% vs 13.6%. On the contrary, children with controlled BA were significantly more often (63.6% vs 51.2%) negative for viral DNA shedding. Moreover, virus shedding was paralleled with higher levels of IL-5: it was as high as 0.91 pg/ml and 0.29 pg/ml for EBV and HHV-6, respectively; those shedding DNA of both pathogens vs no shedding had IL-5 at level of 0.25 pg/ml vs 0.11 pg/ml. Similar pattern was observed for higher total IgE: 184.5 IU for EBV, 113.1 IU — for HHV-6, and 371.7 IU –shedding both viruses vs 95.2 IU in without DNA pathogen shedding; lower level of FEV1: EBV — 96.6%, HHV-6 — 98.8%, and 106.2% in patients shedding both viruses vs 109.8% in patients not shedding the pathogen DNA. Patients shedding EBV DNA require higher doses of topic GCS to achieve disease control: EBV — 325.0 mg, HHV-6 — 186.4 mg; shedding both viruses — 328.1 mg of topic GCS vs 198.6 mg in patients without pathogen DNA shedding. Thus, activation of both EBV and HHV-6 worsens BA control and aggravates its course, but EBV persistence has a more pronounced effect on the course and control of the disease.

Russian Journal of Infection and Immunity. 2022;12(6):1175-1180
pages 1175-1180 views

Artificial intelligence in the immunodiagnostics of chronic periodontitis

Mudrov V.P.

Abstract

Artificial intelligence is used to diagnose various diseases of the oral cavity. In the field of clinical laboratory diagnostics, machine learning algorithms are used in the interpretation of complex biochemical data. The purpose of this study was to search for significant infectious-immunological clinical and laboratory data based on a machine learning algorithm for chronic periodontitis. To do this, 124 patients aged 40 to 70 years diagnosed with chronic periodontitis were examined by real-time PCR to detect the periodontal pocket DNA of human herpes viruses and bacterial periodontopathogenic microflora Fusobacterium nucleatum, Treponema denticola, Porphyromonas endodontalis etc., and Porphyromonas gingivalis. Matrix RNAs of proinflammatory cytokines and other markers of chronic inflammatory process were also studied: IL-1β, IL-10, IL-18, TNFa, TLR4, GATA3, CD68. TNFa, IFNg, IL-1β, IL-4, IL-6, IL-10, IL-18; VEGF were determined in a dentoalveolar fluid. Immune cells of the oral cavity were evaluated by analyzing level of CD3+, CD4+, CD8+, CD3+HLA-DR+, CD64+16+14, CD4+25+127+low, CD3+CD16+CD56+, CD3CD16+CD56+, CD14+, CD14+HLA-DR+, CD19+HLA-DR+, CD19+CD5+B27, CD19+CD5B27, CD19+CD5B27+ cells. Random forest machine learning was used to evaluate the data. A relationship between pathogenic microflora and modality of immune response was revealed. The proinflammatory component reflected in the expression of IL-1β, TNFa, and IFNg mRNA, prevailed in the immune response against aggressive periodontal pathogens: T. denticola, F. nucleatum, etc. The random forest machine learning algorithm selected correlation ratios r ≥ 0.5 (both positive and negative) from a set of data for further analysis by the operator. The random forest machine learning model showed the following significant combinations of data by 10% with a teacher: VEGF, CD3+, CD14+HLA-DR, CD19+CD5CD27+, as well as TLR4, IL-1b, IL-10, TNFa, and IL-18 mRNA. The development of the applied “random forest” machine learning model with a teacher has already shown a 25% difference: P. endodontalis, GATA3, CD3+, CD14+, CD19+CD5CD27+, as well as TLR4, TNFa, IL-1b, IL-10, and IL-18 mRNA. The search for significant infectious-immunological clinical and laboratory data based on a machine learning algorithm for chronic periodontitis has shown the importance of proinflammatory cytokines, monocytes, T-lymphocytes and memory B-cells in the development of osteodestructive inflammatory process of mRNA to reveal non-evident causality factors.

Russian Journal of Infection and Immunity. 2022;12(6):1186-1190
pages 1186-1190 views

Pathomorphological features of acute respiratory distress syndrome in competing lung diseases: COVID-19 and sarcoidosis

Vorobeva О.V., Gimaldinova N.E., Romanova L.P.

Abstract

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome.

Russian Journal of Infection and Immunity. 2022;12(6):1191-1196
pages 1191-1196 views


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