Наукові праці. Кафедра інфекційних хвороб
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Item Myelin basic protein and its diagnostic value in hiv-infected individuals with 4th clinical stage and neuroinfections(2021) Kozko, Volodymyr; Hvozdetska-Shaar, Maryna; Sokhan, Anton; Yurko, Kateryna; Solomennyk, GannaIt was shown that in HIV-infected patients, pathomorphological changes in the white matter in the form of demyelinization are already observed in the early stages of the disease. The most studied marker of this process is myelin basic protein that can be detected in cerebrospinal fluid or serum immediately after acute myelin breakdown. The aim. To assess the diagnostic value of myelin basic protein content in serum and cerebrospinal fluid of HIVinfected individuals with 4th clinical stage and central nervous system opportunistic infections. Materials and methods. Using ELISA with diagnostic kit “MBP ELISA” (Ansh Labs, USA), we studied the myelin basic protein content in serum and cerebrospinal fluid of 53 HIV-infected patients with 4th clinical stage and central nervous system opportunistic infections depending on its etiology, the outcome of the diseases and according to Glasgow coma scale score. As well correlation analysis with some laboratory and clinical indicators was performed. Results. We found significantly increased myelin basic protein content in both cerebrospinal fluid and serum of HIVinfected patients 4th clinical stage with central nervous system opportunistic infections compared to control (p˂0.01), which indicate the presence of active demyelinization in central nervous system. The highest cerebrospinal fluid myelin basic protein was registered in patients with an unfavourable outcome of the disease, as death or residual neurologic deficit, and patients with cerebral toxoplasmosis. The cerebrospinal fluid myelin basic protein had an association with the size of white matter lesions on magnetic resonance imaging and serum myelin basic protein content. Conclusions. Myelin basic protein detection in cerebrospinal fluid as well as in serum can serve as an additional quantitative marker of myelin disruption, which can be used along with magnetic resonance imaging for the diagnosis improvement and prognosis of central nervous system opportunistic infections in HIV-infected individuals with 4th clinical stageItem 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 Global, regional, and national incidence, prevalence and mortality of HIV, 1980-2017, and projections to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2017 Study(2019-08-19) Tahvi, D Frank; Sokhan, ABackground Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce agesex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections.Item Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study – 2012 – 2015(2019-08-13) Raben, D.; Sullivan, A.; Kutsyna, G.; Hadzˇiosmanović, V.; Vassilenko, A.; Mitsura, Viktar; Pedersen, C.; Anderson, J.; Begovac, J.; Dragsted, U.; Bertisch, B.; Grzeszczuk, A.; Minton, J.; Necsoi, V.; Kitchen, M.; Ajana, F.; Sokhan, A.; Comi, L.; Farazmand, P.; Pesut, D.; De Wit, S.; Gatell, J.; Gazzard, B.; Monforte, A.; Rockstroh, J.; Yazdanpanah, Y.; Champenois, K.; Jakobsen, M.; Lundgren, J.Background It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. Methods Individuals aged 18–65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015.Results Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5–3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. Conclusion The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.Item Effectiveness of Intravenous Isoniazid and Ethambutol(2019-08-31) Butov, Dmytro; Feshchenko, Yurii; Kuzhko, Mykhailo; Gumeniuk, Mykola; Yurko, Kateryna; Grygorova, Alina; Tkachenko, Anton; Nekrasova, Natalia; Tlustova, Tetiana; Kikinchuk, Vasyl; Peshenko, Alexandr; Butova, TetianaBackground: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. Methods: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. Results: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). Conclusion: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.Item Diagnostic value of neurospecific markers NSE, S-100, GFAP, MBP and BDNF in cerebrospinal fluid in patients with viral meningitis(2018) Kozko, Volodymyr; Sokhan, A.; Burma, Ya.The aim of the work - to determine the diagnostic value of the levels of neurospecific markers NSE, GFAP, S-100, MBP, and BDNF in the CSF of adult patients with viral meningitis. Patients and Methods. 50 cases of acute viral meningitis were analyzed. There were 21 patients with HSV 1,2 infection, 19 patients with EBV infection, 10 patients with enteroviral meningitis. The CSF level of neuro-specific markers was determined in the first and 10-12 days of treatment using the ELISA method. Results. The most significant changes were identified in patients with severe illness. On the first day o f treatment, the levels of NSE, S-100, GFAP, MBP, and BDNF in patients with moderate severity of the disease were lower in patients with enteroviral meningitis (P<0.001). In severe cases NSE, GFAP and BDNF were higher (P<0.05) in patients with HSV neuroinfection. The neuro-specific markers NSE, S-100, GFAP and MBP on the first day of treatment were in direct strong correlation with the severity of neurological symptoms. The strongest (r=0.712) direct correlation is observed between the severity of neurological symptoms and the level of NSE and GFAP. At the same time, we found a strong reverse correlation (r=-0.727) between the level of BDNF and the duration of neurological symptoms. Conclusions. Increased levels of NSE, S-100, GFAP and MBP indicate presents damages of neurons astroglia and myelin nerves in all cases of viral meningitis. Major changes are observed in patients with severe neuroinfection. In patients with severe herpes viral meningitis/meningoencephalitis, the activity of regenerative processes in the tissues of the central nervous system decreases due to a decrease of CSF BDNF level (P<0.05).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 Diagnostic Value of Neurospecific Markers NSE, S-100, GFAP, MBP and BDNF in Cerebrospinal Fluid in Patients with Viral Meningitis(Тернопільський державний медичний університет, 2018) Kozko, V.; Sokhan, A.; Burma, Ya.The aim of the work – to determine the diagnostic value of the levels of neurospecific markers NSE, GFAP, S-100, MBP, and BDNF in the CSF of adult patients with viral meningitis. Patients and Methods. 50 cases of acute viral meningitis were analyzed. There were 21 patients with HSV 1,2 infection, 19 patients with EBV infection, 10 patients with enteroviral meningitis. The CSF level of neuro-specific markers was determined in the first and 10–12 days of treatment using the ELISA method. Results. The most significant changes were identified in patients with severe illness. On the first day of treatment, the levels of NSE, S-100, GFAP, MBP, and BDNF in patients with moderate severity of the disease were lower in patients with enteroviral meningitis (P˂0.001). In severe cases NSE, GFAP and BDNF were higher (P˂0.05) in patients with HSV neuroinfection. The neuro-specific markers NSE, S-100, GFAP and MBP on the first day of treatment were in direct strong correlation with the severity of neurological symptoms. The strongest (r=0.712) direct correlation is observed between the severity of neurological symptoms and the level of NSE and GFAP. At the same time, we found a strong reverse correlation (r=-0.727) between the level of BDNF and the duration of neurological symptoms. Conclusions. Increased levels of NSE, S-100, GFAP and MBP indicate presents damages of neurons astroglia and myelin nerves in all cases of viral meningitis. Major changes are observed in patients with severe neuroinfection. In patients with severe herpes viral meningitis/meningoencephalitis, the activity of regenerative processes in the tissues of the central nervous system decreases due to a decrease of CSF BDNF level (P<0.05)Item 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 Оцінка прихильності до антиретровірусної терапії у хворих на ко-інфекцію HIV/HBV(2015) Бондаренко, Андрій Володимирович; Козько, Володимир Миколайович; Гвоздецька, Марина Геннадіївна; Юрко, Катерина Володимирівна; Черкасов, О.П.