Review
The issue of antimicrobial resistance continues to be on the first page of the global agenda. The system of factors influencing the growth of antibiotic resistance in bacteria comes from various fields (medicine, veterinary medicine, agriculture and the environment), what requires a One Health approach. Vaccination as one of the most important tools against antimicrobial resistance is considered in detail in this review. Vaccine-induced direct and indirect mechanisms for overcoming antimicrobial resistance are presented, as well as the current evidence base and perspectives for expanding the use of vaccines in the context of this problem. Increased vaccination against both known bacterial pathogens (Pneumococcus, Haemophilus influenza type b, typhoid fever) and viral infections (influenza, rotavirus) would reduce the burden of antibiotic-resistant infections, and thus preserve effective options for treatment and saving lives.
This review summarizes current data on the pathogenetic mechanisms of fibrosis in chronic liver diseases. Controlled inflammation and transdifferentiation of hepatic stellate cells into myofibroblasts is a key element of fibrogenesis, however, further study of the role of each of the macrophage populations is required. The initiation and progression of liver fibrosis is promoted by a complex interaction of different types of liver cells, mediated by cytokines, growth factors, miRNAs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to the pathogenesis of fibrosis. Modern experimental work has proven the role of mesenchymal stem cells in liver regeneration by inhibiting the expression of the proapoptotic BAX gene. The involution of liver fibrosis is associated with monocytes of the prorestorative phenotype LY6Clow. On in vivo models, regression of fibrosis and utilization of the extracellular matrix depot by inhibition of miRNA-221-3p of hepatocytes have been proven.
Original Research
Purpose: to develop a logistic regression model for early differential diagnosis of viral and bacterial community-acquired pneumonia in children.
Materials and methods. A prospective study of the clinical and laboratory features of community-acquired pneumonia (CAP) was carried out in 130 children. A complex approach using bacteriological, molecular genetic, serological diagnostic methods (material – nasopharyngeal swabs, pleural effusion, blood) was used to establish the etiology of CAP. Two etiological groups of CAP were distinguished: viral (n=76), bacterial (n=44). The binary logistic regression method was used to create a differential diagnosis model. Potential predictors of CAP etiology were anamnestic, clinical, laboratory (complete blood count), instrumental (chest x-ray) data. The quality of the constructed regression model was evaluated on a validation set of 42 children with CAP.
Results. A statistically significant (p<0.001) regression model was created, which looks like: y=exp(2.04- 2.87×X1+2.2×X2+0.13×X3+0.12×X4-0.44×X5)/(1+exp(2.04- 2.87×X1+2.2×X2+ +0.13×X3+0.12×X4-0.44×X5)), where “y” is the probability of bacterial CAP in children, X1 – bronchoobstructive syndrome (BOS; no – 0, yes – 1), X2 – age (<4.5 years – 0, ≥4.5 years – 1), X3 – absolute neutrophil count (ANC, *109 cells/l), X4 – relative band count (Band,%), X5 – platelet distribution width (PDW,%). At y≥0.31, bacterial CAP is diagnosed with sensitivity of 81.8% and specificity of 81.6%, at y<0.31 viral CAP is diagnosed. Proposed predictors are widely available in clinical practice, which makes it possible to apply the method in outpatient and inpatient settings. The regression model confirmed the high classificatory ability using cross-validation.
Conclusion. The regression model based on a complex of clinical (age, BOS) and laboratory signs (ANC, Band, PDW) has high statistical significance (p<0.001) and excellent diagnostic ability (84.2%) and can be used for early differential diagnosis viral and bacterial pediatric CAP in different health care settings.
Aim. The aim of the study was to provide clinical and laboratory characteristics of infectious mononucleosis caused by Epstein-Barr virus (EBV) genotype 1 in hospitalized children.
Materials and methods. The material of the study was blood leukocytes and saliva of children aged 1-17 years, hospitalized with a diagnosis of infectious mononucleosis caused by EBV (n=67). For differential detection of EBV-1/ EBV-2, we used an optimized one-round PCR variant with electrophoretic detection of amplification products in agarose gel. Clinical symptoms and laboratory data of patients were analyzed separately and combined into groups of signs. Statistical data processing was carried out using the R programming language and the RStudio environment.
Results. In all children, only one type of virus (EBV-1) was detected in blood leukocytes and saliva. The first data on clinical and laboratory signs of EBV-1 infectious mononucleosis, characterized by a typical symptom complex, have been obtained. The age criterion for dividing patients into groups of younger (1–5 years) and older (6–17 years) age, which were characterized by the most pronounced differences in the manifestations of overt EBV-1 infection, was determined. In young children, the leading was the syndrome of intoxication, in older children, signs of cytolytic syndrome were more pronounced. According to laboratory data, in the age group of 1–5 years, monocytopenia and a decrease in hemoglobin were more often observed, and in children of 6–17 years, lymphocytosis, monocytosis, elevated levels of hepatic transaminases and hemoglobin.
Conclusion. For the first time, EBV typing was performed in children with infectious mononucleosis. The dominant genotype of the virus in infectious mononucleosis in children living in the territory of a large city in the European part of Russia is EBV-1. For the first time, the characteristics of EBV-1 infection are given. The data obtained on the different severity of clinical and laboratory signs of the disease are prerequisites for continuing research aimed at finding the relationship between the characteristics of the clinical course of the infection and the genetic heterogeneity of the EBV population.
The aim of the study was to evaluate the effect of antiviral therapy prescribed at the outpatient stage on the course and outcomes of COVID-19 in hospitalized patients.
Materials and methods. The retrospective study included 182 hospitalized patients with COVID-19 of moderate severity who received various initial therapy in the period before hospitalization. In the main group (91 patients), therapy included antiviral drugs: favipiravir or umifenovir, in the comparison group (also 91 patients), the treatment regimens did not contain etiotropic drugs against SARS-CoV-2. The groups were comparable in age, gender and severity of the disease. All patients received antipyretic drugs (paracetamol), vitamin therapy, according to indications – local antiseptics, mucolytics, antiplatelet agents and antibacterial drugs. The effectiveness of treatment was evaluated on days 7 and 14.
Results. The presence of the virus was significantly less frequently detected on day 7 – in 15.38% and on day 14 of the disease – in 2.20% among patients receiving antiviral therapy, 82.42% and 39.56%, respectively in the comparison group. The average duration of the disease was more than 5 days less – 8.28 ± 3.74 days. The proportion of patients with a deterioration in their clinical condition to 3-4 points was significantly higher in the group that did not receive antiviral drugs – 61.54%, and with the use of favipiravir or umifenovir – 2.2%.
Conclusions: 1. Timely administration of antiviral therapy for COVID-19 at the outpatient stage prevents the increase in severity, the development of complications, promotes earlier elimination of the virus and shortens the duration of the disease during hospitalization of the patient. 2. The absence of antiviral therapy with moderate severity of COVID-19 at the outpatient stage significantly increases the risk of deterioration of the patient’s condition.
Aim: To assess the current epidemiological situation and establish the dominant clinical profile of patients with chronic hepatitis C, taking into account the stage of the disease and the molecular genetic characteristics of the virus in the Republic of Tyva.
Materials and methods: Based on the annual reports of the dispensary observation office of the Infectious Hospital of the Republic of Tyva, an electronic database was developed using the licensed Office Excel 2016 program, which included results on the health status of patients, clinical, laboratory and instrumental data, including molecular biological data with the determination of HCV genotypes. The analysis of the data of the state statistical reporting of infectious morbidity in the Russian Federation (form №2 “Information on infectious and parasitic diseases”) was carried out. Analytical tables developed by specialists of the Scientific and Methodological Center of the Saint-Petersburg Pasteur Institute for the period 2012-2022. The data of the Reference Center for Monitoring Viral Hepatitis of the Federal State Budgetary Institution “Central Research Institute of Epidemiology” of Rospotrebnadzor were used.
Results. Over the past two years, the decrease in incidence in the Republic of Tyva is likely due to a decrease in the number of examinations, a decrease in patients seeking outpatient care, and insufficient screening in the context of the COVID-19 pandemic. Clinical, laboratory and instrumental examination of patients with HCV revealed the predominance of HCV-infected genotype 1 (49.4%), with F0-F2 fibrosis in 79% of cases. The clinical profile of typical patients with chronic hepatitis C was established; whose share in the total structure of the examined was 38.4%.
Conclusion: There is a tendency to reduce the incidence of chronic hepatitis C in the Republic of Tyva. Based on the clinical information base, the most typical characteristics of chronic hepatitis C patients living in the Republic of Tyva have been established.
Helminthiases are found in the group of the most common and socially significant human infectious diseases. According to current data, at least 1 billion people are infected with helminths or pathogenic infections. One of the most important and widespread human biohelminth parasites in the Russian Federation is the broad-spectrum tapeworm (Diphyllobothrium latum). The absence of specific clinical diagnosis, as well as the predominance of latent forms, determines the presence of diphyllobothriasis disease. The aim of the study was to summarize current data on the epidemiology, pathogenesis, clinical and laboratory manifestations and therapy of diphyllobothriasis.
Materials and methods. Clinical cases of diphyllobothriasis were analyzed among patients who were treated in January to November 2022 in the departments of the daytime period of clinical observation of the infectious diseases hospital named after S.P. Botkin, as well as the department of incidents detected and the clinical diagnostic center of Pediatric Research and Clinical Center for Infectious Diseases. Cases of the use of diseases, data from laboratory and instrumental studies, and therapy were evaluated. The most informative of them is given as a clinical example. The article also describes in detail the current biological and epidemiological features of Diphyllobothrium latum, the characteristic clinical picture of diseases and the most frequent complications.
Results. Diphyllobothriasis still remains one of the most vulnerable biohelminthiases in Russia, typical for some patients of different ages. Verification of the diagnosis of “diphyllobothriasis” can be of the nature of an “accidental finding” during screening scatological or instrumental studies; upon admission, patients themselves begin to suspect helminthiasis when fragments of the strobila worm are found in the feces. To identify a conditional diagnosis of the pattern of clinical and laboratory infection (exclusion of a complicated course of diseases, helminthiases of a different etiology) and to determine risk factors for the transmission of diseases for the prevention of infections.
Aim: To identify the signs and reasons why listeriosis can be classified as opportunistic infections in HIV infection, requiring timely diagnosis and treatment to prevent the development of a severe course of the disease and minimize the risks of death.
Materials and methods: 38 hospitalized patients with listeriosis meningitis/ meningoencephalitis were examined. All patients were hospitalized in the boxed departments of neuroinfections (the diagnosis of HIV infection was not known) with a directional diagnosis of meningitis of unclear etiology, where, according to the Meningitis program, a PCR examination for L. monocytogenes was included. The comparison group consisted of patients with other most common bacterial pyogenic meningitis (BPM) – meningococcal, pneumococcal and patients with listeriosis meningitis/meningoencephalitis without HIV infection.
Results: Studies have shown that patients with HIV infection accounted for the majority – 26% (out of 38 hospitalized). Men predominated among the patients – 60 %, the average age was 34.9 ± 2.2 years (29 – 41), which differs from the well–known age status, where the risk group is primarily male patients over 70 years of age.
Conclusion: Polymorphism of clinical manifestations of neuro listeriosis in some cases presents diagnostic difficulties for primary care physicians. CNS listeriosis in patients with HIV infection belongs to the category of opportunistic infections, which clinically and in the study of cerebrospinal fluid presents difficulties for early diagnosis, which directly affects the timing of the initiation of etiotropic therapy and the further outcome of the disease.
Aim. To evaluate the immune response in patients with COVID-19 and to track the dynamics of changes in immunological parameters 2-3 weeks after the onset of the disease.
Materials and methods. The study included the results of a survey of 55 people aged 19 to 55 years with a new coronavirus infection (NCVI, COVID-19) in 2020. 27 of them were re-examined. The first sample (n=55) was taken on average 4.3 ± 0.49 days from the onset of the disease, the second (n=27) – 12.7 ± 1.12 days. The control group consisted of practically healthy individuals (n=41). The following indicators were determined in all patients: the presence of SARSCoV-2 RNA, the parameters of the general blood test, the main subpopulations of lymphocytes, the level of total immunoglobulins (IgM, IgG, IgA), the number of CEC, the absorption and bactericidal activity of leukocytes, the level of specific IgM and IgG to SARS-CoV-2.
Results. At the onset of the disease, a statistically significant decrease in the level of lymphocytes (p<0.001) and their subpopulations (TNK cells (p<0.001), T-helper lymphocytes (<0.001), cytotoxic T-lymphocytes (p<0.001), NK cells (<0.001) and T-lymphocytes (<0.001)). At the same time, the level of activated T-lymphocytes was statistically significantly higher (p<0.001) than the same indicator in the control group. When analyzing immunological parameters after 12.7±1.12 days, an increase in the total number of lymphocytes (p<0.001), T-lymphocytes (p=0.003), T-helper cells (p=0.015) was found; an increased content of activated T-lymphocytes (p<0.001) and a low level of TNK cells (p<0.001). The indicators of the phagocytic link in patients with COVID-19 in the first days of the disease were within the reference range (similar indicators in the control group). Repeated examination of patients (sample 2) showed an increase in the phagocytic activity of leukocytes and monocytes (p<0.003 and p<0.09, respectively). At the beginning of the disease, already on the 4th-5th day of the disease, specific IgM and IgG antibodies to SARS-CoV-2 were detected in the blood serum of patients, by the second week of the disease their level was significantly higher than in the first study (p<0.009).
Conclusion. At the onset of the disease, insufficiency of the cellular link of immunity was noted, which is probably as sociated with a violation of immunoregulatory mechanisms. At the same time, an increase in the level of activated T-lymphocytes indicates an overactivation of immune reactions, i.e. it can be said that there is an imbalance in the immune response in COVID-19.
The aim of the study was to identify the predictors of length of hospital stay in patients with acute COVID-19, based on the pathophysiological particularities of SARS.
Materials and methods: The study was conducted from December 2020 to May 2021 on 103 randomized patients (59 men, mean age 62±13 years, body mass index 30.3±5.5 kg/m2 ) with moderate to severe acute COVID-19 infection who were hospitalized for emergency non-invasive oxygen therapy. Log-regression models were used to assess the suitability of some functional spirometric variables and/or SpO2/FiO2 surrogate oxygenation index to predict the duration of inpatient treatment from the day of the examination (≤ 7 vs. > 7 days).
Results: The analysis of the receiver operating characteristic curves showed that the relative indicator of the “ventilatory reserve” (the ratio of maximum voluntary ventilation to minute ventilation at rest, VR= MVV / MV) has sufficient sensitivity (82%), specificity (69%) and the area under the curve (AUC=0.7), although the SpO2/FiO2 ratio has a better predictive capacity (78%, 84% and 0.8 accordingly). The model combining these two integral indicators of gas exchange and the respiratory muscles reserve showed the best sensitivity (89%), specificity (84%) and area under the curve (0.9).
Conclusion: The proposed model for determining of the hypoxia vector by assessing the severity of ventilation-perfusion dissociation with indicators of oxygenation and ventilation showed that the MVV/MV ratio and SpO2/FiO2 ratio can be used alone and especially in combination, as effective outcome predictors of the acute phase of the infectious process caused by SARS-CoV-2.
Objective: to assess anti-pertussis immunity in schoolchildren aged 7–17 who complained of a prolonged cough during the 11-year follow-up period.
Materials and methods. The study included 1046 patients aged 7 to 17 years who applied to the Consultative and Diagnostic Center of the G.N. Gabrichevsky Research Institute of Epidemiology and Microbiology with complaints of prolonged cough in the period from 2010 to 2020. Blood serums were examined in ELISA with the determination of IgM, IgG, IgA antibodies using RIDASCREEN test system (Germany).
Results. An active infection with the detection of IgM and/ or IgA, IgG antibodies above threshold levels was detected in 51,3% of children with prolonged cough, while annually in a fairly high percentage throughout the follow-up period. Active pertussis infection, established based on the detection of IgM, IgG, IgA antibodies above thresholds in blood serum samples, prevailed in children 12–15 years old, accounting for more than 60% in children with prolonged cough. Antipertussis immunity as a result of childhood vaccination or previous disease was detected in 16.1-20.2% of people in the period 2010–2014 and in 12,8-20,9% in 2015–2020.
Conclusion. The results obtained by us on the study of anti-pertussis immunity in schoolchildren confirm the presence of active latent circulation of the pathogen whooping cough among children of this age cohort and, therefore, the presence of unaccounted for cases of the disease. This confirms the importance of timely diagnosis of pertussis, isolation of children for the period of active infection and justifies the need for the widespread introduction of a second revaccination against pertussis.
Objective: to determine the cytokine profile in blood serum in patients with severe hemorrhagic fever complicated by acute renal failure.
Materials and methods. The examined persons were divided into a control group – 46 people (healthy), a group of patients with an average course of the disease – 35 people, and a group of patients with severe severity, complicated by acute renal failure – 38 people. Blood was taken from the subjects for the study of cytokines. The determination of cytokines was carried out by enzyme immunoassay using test kits in accordance with the manufacturer’s instructions.
Results. In patients with hemorrhagic fever, both with moderate and severe, there was an increase in interleukins IL-1β, IL-6, IL-10 compared with the control group. However, the values of these interleukins were significantly higher in patients with severe hemorrhagic fever complicated by acute renal failure compared with the group of patients with moderate severity. The values of IL-8, IFN-γ and SDF-1α changed only in patients with severe course. At the same time, there was an increase in the expression of IL-8 and a decrease in IFN-γ compared with the control group. IL-8 and IFN-γ did not change statistically in patients who had just been admitted to the hospital, as well as in patients with an average degree of the disease. A change in the SDF-1α chemokine also turned out to be specific for patients with a severe course of the disease: its values increased in comparison with the control group. No significant changes in SDF-1α were detected in patients who had just been admitted to the hospital, as well as in the group of patients with moderate severity of the disease.
Conclusion. The results obtained indicate the diagnostic value of cytokine determination in severe hemorrhagic fever complicated by acute renal failure. Changes in the parameters of some cytokines, detected only in the profile of patients with severe severity, require further research to clarify their role in the pathogenesis of hemorrhagic fever, and also open up opportunities for considering them as biomarkers.
Epidemiology
The results of the analysis of the system of epidemiological surveillance of infectious diseases in the Socialist Republic of Vietnam and the assessment of the possibilities of its improvement are presented. The levels of organization of epidemiological surveillance in Vietnam, their compliance with the administrative division of the country (state, provincial, district and commune levels) are shown. It is noted that epidemiological surveillance has a passive nature and is based on the online reporting system of the Department of Preventive Medicine, which has been the official notification channel for 42 infectious diseases since 2016. For the purposes of epidemiological surveillance, all registered infectious diseases are divided into 3 groups according to the potential for epidemic spread (A, B and C), on which strategies for carrying out sanitary and anti-epidemic (preventive) measures depend. It has been established that modern computer technologies, including geoinformation systems, in Vietnam have found their application in certain areas of epidemiological surveillance of current infectious diseases, but further improvement of the methods of their use for these purposes is required.
Clinical Case
The paper describes a rare case of pneumocystosis of the small intestine, diagnosed in the surgical material of a 39-year-old man with HIV infection using histological and immunohistochemical methods. After the treatment, the patient was discharged.
Brucellosis is the most common and severe infectious disease in the group of zoonotic infections. This disease is characterized by a multisysitemic lesion. The difficulties in diagnosing this disease are associated with the pathogenetic features of the development of brucellosis, namely prolonged bacteremia, which causes the development of secondary foci of infection in various organs and tissues, manifested by a variety of clinical manifestations, the erasure of symptoms of the disease, as well as the appearance of rare clinical forms of brucellosis.
One of the rare clinical manifestations of chronic brucellosis is the defeat of the cardiovascular system and the defeat of the nervous system. According to the latest literature data, cardiovascular complications of brucellosis in humans account for only 3%, but are the main cause of death in 80%. Damage to the nervous system is rare, with a registered frequency of 3% to 13%.
Clinical manifestations of neurobrucellosis are diverse and can mimic many other neurological diseases. The most common manifestations of brucellosis may be meningitis, meningoencephalitis. Despite the rare occurrence, these forms of the disease are severe, lead to disability and mortality with late diagnosis. The article presents clinical cases of brucellosis with lesions of the heart and central nervous system.
The article describes a clinical case of atypical severe course of parvovirus B19 infection, similar in its manifestations to meningococcal infection, with combined infection with Meningococcus, Hemophilus bacillus, influenza A virus.
A patient hospitalized with acute respiratory disease and toxicoderma had new symptoms within 24 hours: headache, hemorrhagic rash, decrease in blood pressure to 80/50 mm Hg, fever up to 39.8 0C. Based on the symptoms, a preliminary clinical diagnosis was made: “Meningococcal infection, generalized form – meningococcemia, severe course. Infectious-toxic shock of the 2nd degree.”
During laboratory examination of clinical samples of the patient by bacteriological, serological and molecular genetic methods, there was no growth of bacterial microflora in liquor, blood and smears from the pharynx and nose. Genetic material (DNA and RNA) of Neisseria meningitides, Haemophilus influenza and influenza A/H3N2 was detected in a smear from the nasal cavity.
At the same time, parvovirus B19 DNA was isolated in the patient’s cerebrospinal fluid and blood in a high viral load (Ct 21.1 and Ct 4.9, respectively). The patient was found to have not only IgG, but also IgM antibodies to parvovirus B19, which is a confirmation of acute parvovirus B19 infection. A pronounced allergic reaction was confirmed by a high index of total IgE (1068 units/ml). Thus, we have described an atypical case of laboratoryconfirmed parvovirus B19 infection in the presence of bacterial-viral mixed infection and an allergic reaction in the patient.
The most common clinical form of tularemia in Europe is ulcerative bubonic, which has a summer-autumn seasonality. When infected with water and food, the development of oropharyngeal and abdominal forms is possible. The rarity of registration of such forms is associated not only with the low frequency of such cases of infection, but also with the complexity of diagnosing diseases with an atypical clinic. Important for the correct diagnosis are the results of specific laboratory diagnostics and a qualitatively collected epidemiological history. The results of zooparasitological monitoring allow assessing the risk of infection in certain territories. The article provides descriptions of two cases of severe abdominal tularemia, registered in autumn 2021 – winter 2022 in the Republic of Karelia, which has been one of the most disadvantaged regions of Russia in recent years. In the first case, in a 15-year-old boy, the disease began acutely, the main symptoms were high fever, abdominal pain, vomiting, loose stools, foci of skin hyperemia with clear uneven edges without infiltration in the left knee joint and right inguinal region, hepatomegaly, mesoadenitis. In indirect gemagglutination reaction with tularemia diagnosticum on the third day from the onset of the disease antibodies in titer 1:640. Infection probably occurred when eating food during a trip to the forest zone of the city, where infected rodents were previously detected. In the second case, a 17-year-old girl living in a village was diagnosed with a peritonsillar abscess 3 weeks before a sharp rise in temperature, abdominal pain, vomiting and loose stools. Later he developed renal and hepatic insufficiency, polyserositis. The antibodies titer was 1:320 after 3 weeks and 1:2650 after 5 weeks. Infection probably occurred through consumption of rodent-contaminated vegetables.