Наукові праці. Кафедра інфекційних хвороб
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Item Symptom‐based case definitions for COVID‐19: Time and geographical variations for detection at hospital admission among 260,000 patients(2022-08-07) Gavrylov, Anatoliy; Tieroshyn, VadymIntroduction: Case definitions are used to guide clinical practice, surveillance and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the Centers for Disease Control (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO) and UK Health Security Agency (UKHSA) case definitions by age, region and time. Case fatality ratios (CFRs) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test result were excluded. Results: A total of 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC) and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients who met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions, risking delayed medical care. Whileepidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.Item ISARIC-COVID-19 dataset: a prospective, standardized, global dataset of patients hospitalized with COVID-19(2022) Gavrylov, Anatoliy; Tieroshyn, VadymThe International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.Item Immunodiagnostics of cerebral toxoplasmosis depending on permeability of blood-brain barrier(2020) Bondarenko, A.; Katsapov, Dmytro; Gavrylov, Anatoliy; Didova, T.; Nahornyi, I.Objective: The aim of the work was to detect a diagnostic value of CNSToxoIndex - index of correlation between albumin concentration and anti-toxoplasma antibodies, which reflects local production of anti-toxoplasma IgG in CNS compared with their level in blood. Patients and methods: Materials and methods: 30 HIV-infected persons with the IV clinical stage (16 man and 14 women) aged from 25 to 49 years with clinical and instrumental signs of cerebral toxoplasmosis were selected from the general array of the patients treated in the Regional Clinical Infectious Hospital. A retrospective parallel detection of IgG T. gondii was performed in serum and CSF in patients, whose results of ELISA or PCR on T. gondii were positive. Blood serum and CSF were obtained from patients at the same time. All samples for analysis were stored at -20 °C and then tested on the RT-2100C Rayto Life and Analytical Sciences Co., Ltd (China) immunoassay analyser for quantitative detection of the level of specific anti-Toxicoplasma IgG. Detection of albumin concentration in serum and CSF was performed on the Chemray-120 Automated Biochemical Analyzer Rayto Life and Analytical Sciences Co., Ltd (China) using the Liquick Cor-ALBUMIN Diagnostic Kit. Results: Results: Specific IgG to T. gondii in blood plasma was found in 27 patients (90%) while in CSF only in 7 (23 %). The results of the research in this group of patients were represented by the following parameters: patient 1 (blood antiToxo IgG - 200 IU/ml, blood albumin - 36 g/l, CSF antiToxo IgG - 10 IU/ml, CSF albumin - 0.8 g/l, CNSToxolndex - 2.3); patient 2 (150 / 40 / 90 / 0.7 / 34.3, respectively); patient 3 (90 / 35 / 64 / 0.25 / 99.6); patient 4 (140 / 39/ 10/ 0.19/ 14.7); patient 5 (88 / 52 / 48 / 0.21 / 135.1); patient 6 (160 / 48 / 50 /0.15 / 100.0); patient 7 (122 / 42 / 15 / 0.17 / 30.4). Consequently, taking into consideration the diagnostic marker CNSToxolndex more than 10.0, cerebral toxoplasmosis was diagnosed only in six patients from seven, in whom anti-toxoplasma antibodies in CSF were detected. Patient 1, despite clinical symptoms similar to cerebral toxoplasmosis, and substitute signs of cerebral toxoplasmosis detected with the help of neuroimaging methods (volumetric formation of the right frontal lobe with a ring-shaped enhancement), availability of specific anti-toxoplasma antibodies in blood serum and CSF, diagnosis of cerebral toxoplasmosis has not been confirmed. M. tuberculosis DNA was found in CSF by PCR. Conclusion: Conclusions: CNSToxoIndex allows evaluating the local production of anti-toxoplasmic IgG in CNS and their diffusion from blood as a result of the blood-brain barrier damageand it is a powerful method of cerebral toxoplasmosis diagnostics in HIV-positive people as well.Item The role of polymorphism ASP299GLY of the gene TLR 4 in patients co-infected with HIV/HCV(Tbilisi State Medical University, 2018-07) Yurko, K.; Kozko, Volodymyr; Solomennik, A.; Bondar, O.; Sokhan, A.; Gavrylov, AnatoliyFor the first time it was conducted complex research of metabolic disorders in patients co-infected with HIV/HCV and was shown that they are characterized by disturbances of mineral, lipid and carbohydrate metabolism types. It was established significantly higher values of indicators of mineral, lipid and carbohydrate metabolism types in patients co-infected with HIV/HCV compared with patients with chronic hepatitis C and HIV-infected persons. In patients co-infected HIV/HCV appears significantly more frequent the polymorphism Asp299Gly of the gene TLR4 (χ2 = 4,5; p<0,05) when compared with healthy donors, which plays a significant role in the development of metabolic disorders, such correlation is confirmed by those relationships: a strong direct relationship between the polymorphism Asp299Gly of TLR4 gene and the content of insulin (r = 0,66; p<0,001), insulin resistance (r=0,66; p<0,001), the absolute number of CD45+ of T-lymphocytes (r=0 45; p<0,001); a moderate direct relationship with the content of TNF-α (r=0,32; p<0,05), CRP (r=0,34; p<0,05), the absolute number of CD3+ of T-lymphocytes (r=0,34; p<0,05), the content of triglyceride (r=0,39; p<0,02), moderate inverse relationship with the zinc content (r = -0,34; p<0,05 ), the relative number of CD4 +,% (r = -0,32; p<0,05). The system of monitoring of metabolic disorders in patients co-infected with HIV/HCV based on the definition of polymorphism Asp299Gly gene TLR4, the presence of which indicates a high risk of metabolic disturbances (OR=23,3; p<0,05) and requires further investigation, namely the definition of an index of insulin resistance, insulin levels, TNF-α, C-reactive protein, zinc and triglyceride levels in dynamics at intervals of 6 months that allow for timely diagnosis and correction of metabolic disorders.Item Factors affecting the fatal outcome in HIV-infected patients with encephalitis(Tbilisi State Medical University, 2018-08) Hvozdetska, M.; Kozko, Volodymyr; Yurko, K.; Gavrylov, Anatoliy; Solomennyk, A.Despite the successful use of ART up to 40-70% of HIV(+) individuals have neurologic complications caused both by the HIV itself and by the reactivation of OIs on the background of severe immunodeficiency. Nowadays, there are no universally recognized criteria that allow predicting the outcome of encephalitis caused by OIs in this category of patients. The aim of our study was to assess factors affecting the fatal outcome in HIV(+) patients with CNS involvement. Retrospectively we selected 53 HIV(+) patients with confirmed encephalitis due to OIs. Depending on the outcome of the disease, patients were divided into groups: non-survivors (n=22) and survivors (n=31), after compared their clinical manifestation, history of the disease and life, CSF results in the first days of admission. It has been established that the factors affecting the fatal outcome in HIV(+) patients with encephalitis are: the severity of the patient’s condition upon admission, acuteness of the onset of the disease, the severity of neurologic symptoms, the degree of co-morbidity, the level of immunosuppression and viral load, absence of ART.Item Biochemical parameters of cerebrospinal fluid in patients with acute viralmeningitis and meningoencephalitis(2018) Kozko, Volodymyr; Sokhan, A.; Burma, Ya.; Kuznetsova, Anastasiia; Gavrylov, AnatoliyThe aim. Determination of the diagnostic value of lactate, lactate dehydrogenase, cholinesterase, acid phosphatase and cholinesterase in CSF for early diagnosis and prognosis of acute viral meningitis and meningoencephalitis. Materials and methods. 92 patients with a confirmed viral etiology of the disease were examined. Among them – 20 patients with HSV 1,2 neuroinfection, 19 patients with EBV, 15 with VZV, 14 with HHV-6 and 24 patients with enterovirus neuroinfection. Patients were divided into groups depending on the etiology and severity of the disease. In addition to analyzing the clinical course of the disease, we conducted a CSF study to determine the level of lactate, lactate dehydrogenase, creatinine kinase, cholinesterase and acid phosphatase on admission to hospital and after 10-12 days of treatment. Results of the study. The highest mean age was observed in patients with VZV meningitis – 38.27±18.24 years, the youngest were patients with enterovirus infection – 24.05±5.72 (р˂0.001). The number of women and men was the same in almost all groups, but among patients with HSV 1, 2 neuroinfection women were significantly prevalent – 16 (80 %) out of 20 cases. The most severe course was observed in groups of EBV and HHV-6 neuroinfections. Neuroinfections of enterovirus etiology had the most favorable course. The obtained data indicate the dependence of the levels of indicators, which were determined primarily from the severity of the disease. So the level of creatinine kinase and acid phosphatase in patients with moderate severity was significantly higher in comparison with severe patients (p<0.05). The lactate level was higher in patients with severe neuroinfection (p<0.05). The highest levels of lactate were detected in patients with HHV-6 meningoencephalitis (p<0.05). The level of cholinesterase was significantly lower in severe patients. Conclusions. The obtained data confirm the presence of deep metabolic disturbances in the brain tissues in all patients with acute viral neuroinfections both at the onset of the disease and in the dynamics of treatment. Determination of levels of creatinine kinase, acid phosphatase, lactate and cholinesterase in CSF of patients with acute viral neuroinfection has a high diagnostic value, but cannot be used to predict an unfavorable course of the diseaseItem Pathomorphological peculiarities of tuberculous meningoencephalitis associated with HIV infection(2017) Kozko, Volodymyr; Bondarenko, A.; Gavrylov, Anatoliy; Shevchenko, O.; Gargin, VitaliyBackground and aims: One of the most severe manifestation displays of tuberculosis (TB) generalization is meningitis/meningoencephalitis. The purpose of this work was to improve the diagnostic efficiency of TB central nervous system (CNS) affection in human immunodeficiency virus (HIV)-infected persons. Materials and methods: Meninges and cerebral tissues, taken from died patients, who were HIV-infected and dead from TB of CNS affection, were investigated histologically. Results and discussion: Our examination showed that clinical course of the pathologic process loses the peculiarity of TB-undulating character, and changes in tissues have monomorphism that appears in the presence of the same type of granulomas with a few Pirogov–Langhans cells. Alterative reactions with formation of the large fields of caseous necrosis, necrotic focuses, areas of infiltration with polymorphic cellular elements went out on the first plan in the disorder of cerebrum in patients with the terminal stage of HIV infection. The tendency to decrease in inflammatory–proliferative processes was observed, which is confirmed by the presence of the poorly expressed cellular reaction on the peripheries of focuses of caseous necrosis. Conclusion: Morphologic features of tuberculous meningoencephalitis in HIV-infected patients are the presence of edema, gliosis, trombovasculitis, small focal hemorrhage, tuberculous granuloma formation with a small number of Pirogov–Langhans cells, and the prevalence of alterative–exudative reactions.Item Cerebrospinal fluid levels ofneurospecific markers in adult patients with bacterial meningitis(Тбилисский государственный медицинский университет, 2017) Sokhan, A.; Zots, Y.; Gavrylov, Anatoliy; Iurko, Kateryna; Solomennik, A.; Kuznetsova, AnastasiiaAt present, the great attention is given to the neurospecific markers as their elevated level in the cerebrospinal fluid corresponds to the degree of destruction of relevant CNS cells. Therefore, actual direction of the studies of the pathogenesis and diagnosis of CNS diseases is to determine levels of neurospecific markers in the cerebrospinal fluid (CSF). The purpose of the study was to evaluate the diagnostic and prognostic role of NSE, S-100 protein, GFAP and MBP levels in CSF of patients with acute bacterial meningitis. S-100 protein, NSE, GFAP and MBP levels in CSF of patients with acute pneumococcal and meningococcal meningitis were determined during admission and after 10-12 days of treatment. Patients were divided into groups depending on the etiology and severity of the disease. 60 cases of acute bacterial meningitis, as a study group, and 12 cases with acute respiratory infection and meningism, as a control group, were analyzed. It is shown that CSF levels of NSE, S-100 protein, GFAP and MBP on the first day of admission were significantly increased (P<0,05), depending on the severity of the disease. The highest levels of neurospecific markers have been identified in non-survivors (P<0,001). The concentration changes of CSF neurospecific markers are found to be helpful as a diagnostic and prognostic marker in acute bacterial meningitis.