Систематический обзор. Современные представления об инфекции, вызываемой Betapolyomavirus hominis

Reactivation of Betapolyomavirus hominis (BKPyV) in kidney and hematopoietic stem cell recipients can lead to serious complications such as BKPyV-associated nephropathy followed by transplant rejection and BKPyV-associated hemorrhagic cystitis. Early diagnosis of the disease is hampering by the possible combination of infection of BKPyV with other post-transplant pathologies and the absence of specific symptoms. Replication of BKPyV is currently the only reliable prognostic sign of the development of long-term consequences, so patient management is basseting on monitoring the concentration of viral DNA. However, consistency between the results of determining the viral load and the development of post-transplant complications associated with BKPyV reactivation cannot be achieving without effective means of standardizing laboratory testing. This review covers the current understanding of the epidemiology; pathogenesis and the clinical features of the disease associated with BKPyV, and also considers in detail the current methods of laboratory diagnosis infection of BKPyV.Реактивация Betapolyomavirus hominis (BKPyV) у реципиентов почки и гемопоэтических стволовых клеток может приводить к серьезным осложнениям в виде BKPyV-ассоциированной нефропатии с последующим отторжением трансплантата и BKPyV-ассоциированного геморрагического цистита. Раннюю диагностику заболевания затрудняет возможное сочетание BKPyV-инфекции с другими патологиями посттрансплантационного периода и отсутствие специфической симптоматики. Репликация BKPyV на данный момент является единственным достоверным маркером развития отдаленных последствий, поэтому ведение пациентов основано на мониторинге концентрации вирусной ДНК. Однако согласованность между результатами определения вирусной нагрузки и развития осложнений посттрасплантационного периода, связанных с реактивацией BKPyV, не может быть достигнута без эффективных средств стандартизации лабораторного исследования.Данный обзор охватывает текущее понимание эпидемиологии вируса, патогенеза и клинических особенностей заболеваний, ассоциированных с BKPyV, а также подробно рассматривает современные методы лабораторной диагностики BKPyV-инфекции

ПРОГРЕССИРУЮЩАЯ МНОГООЧАГОВАЯ ЛЕЙКОЭНЦЕФАЛОПАТИЯ У ВИЧ-ИНФИЦИРОВАННЫХ ПАЦИЕНТОВ: ОСОБЕННОСТИ КЛИНИЧЕСКОЙ КАРТИНЫ И ДИАГНОСТИКИ (ОБЗОР ЛИТЕРАТУРЫ)

Progressive multifocal leukoencephalopathy (PML) is one of the most severe opportunistic diseases of the central nervous system, which leads to multiple demyelination of brain structures, neurological symptoms and frequent death or disability of the patient. The etiological factor of this disease is Human polyomavirus 2 (JCPyV).This pathogen is widespread – antibodies are found in 80% of the world›s population. However, the clinical symptoms of this infection appear only in people with a pronounced decline in cellular immunity. Until 1980 progressive multifocal leukoencephalopathy was extremely rarely diagnosed. Now days the main cause of the clinical symptoms of PML is immunodeficiency caused by HIV infection. Clinical manifestations of PML are characterized by various non-specific neurological symptoms, similar to other lesions of the central nervous system, the symptoms progress slowly over several months, and usually lead to death. Diagnosis of PML is based on laboratory and instrumental methods, such as DNA JCPyV detection in the cerebrospinal fluid, brain biopsy, and radiation diagnostic methods. There is no effective prevention and etiotropic therapy for PML. Improved parameters of cellular immunity and antiretroviral treatment in HIV positive patients significantly increase the life expectancy of patients with PML. Despite the ability of drugs to prevent the progression of the disease, pathological changes in the brain are irreversible and lead to persistent disability of patients, therefore, it is necessary to diagnose PML in the early stages of the disease.Прогрессирующая многоочаговая лейкоэнцефалопатия (ПМЛ) – тяжелое оппортунистическое заболевание центральной нервной системы (ЦНС), приводящее к множественной демиелинизации структур головного мозга с частым летальным исходом или инвалидизацией пациента. Этиологическим фактором возникновения этого заболевания является Human polyomavirus 2 (JCPyV). Данный возбудитель широко распространен – антитела к нему обнаруживаются у 80% населения земного шара. Однако клинические симптомы этой инфекции проявляются лишь у людей с выраженным снижением клеточного иммунитета. До 1980 г. ПМЛ диагностировалась крайне редко. С увеличением числа ВИЧ-инфицированных в мире распространённость ПМЛ значительно возросла. Клиническая картина ПМЛ характеризуется различной неспецифической неврологической симптоматикой, сходной с другими поражениями ЦНС, симптомы прогрессируют обычно медленно, в течение нескольких месяцев, и, как правило, приводят к летальному исходу. Решающее диагностическое значение при постановке диагноза ПМЛ отводится лабораторным и инструментальным методам исследования, таким как обнаружение ДНК JCPyV в ликворе, определение характерных изменений при использовании лучевых методов диагностики и биопсия мозга, которая малодоступна в рутинной клинической практике. На сегодняшний день не существует эффективной этиотропной терапии ПМЛ. Доказано лишь увеличение продолжительности жизни пациентов при улучшении параметров клеточного иммунитета и на фоне антиретровирусной терапии при лечении ВИЧ-инфекции. Несмотря на способность лекарственных препаратов предотвратить прогрессирование заболевания, патологические изменения, возникшие в веществе головного мозга, необратимы и приводят к стойкой инвалидизации пациентов, поэтому в первую очередь необходима диагностика ПМЛ на ранних этапах болезни

Effect of Antibiotic Therapy on the Sensitivity of Etiological Diagnostic Methods in Patients with Infective Endocarditis after Surgery

Aim. Assessment of impact  of the duration  of preoperative  antimicrobial  therapy  (AMT) on the sensitivity  of microbiological examination and polymerase  chain reaction (PCR) of blood/tissues of resected valves in operated patients with infective endocarditis  (IE).Materials and methods. 52 operated patients with active IE were included prospectively (Duke criteria, 2015). All patients underwent microbiological examination of blood  before  admission  to the cardiac  surgery  hospital,  as well as parallel  simultaneous microbiological examination and  PCR  of blood/tissues of excised  valves,  followed  by Sanger  sequencing. The duration  of preoperative  treatment  was  calculated  from the first day of AMT according to IE diagnosis to the day of surgery.Results. The causative agent of IE was established in 84.6% (n=44) patients by means of complex etiological diagnosis. A significant  decrease in the sensitivity of microbiological examination of venous blood was revealed when performed  in the period before and after hospitalization to a surgical hospital (up 44.2% to 17.3%, p<0.05). When comparing microbiological examination of blood/tissues of resected valves and PCR of blood/tissues of resected valves, molecular biological  methods demonstrated the greatest sensitivity, with a great advantage when examining the tissues of resected valves (17.3% and 19.2% vs. 38.5% and 75.0%, respectively;  p<0.001). The microbiological examination of venous blood performed  at an early date before admission  to the cardiac  surgery  hospital was comparable in sensitivity to the PCR blood test performed  at a later date after prolonged AMT,  and significantly less sensitive in relation to the PCR of resected valve tissues [44.2% and 38.5% (p>0.05) vs. 75.0% (p<0.05)]. In course of AMT 1-28 days,  there were comparable results of microbiological examination with PCR blood examination and significantly better results of PCR of resected valve tissues [31.0% and 34.5% and 41.4% (p>0.05) vs 72.4% (p<0.001), respectively], and with AMT ≥ 29 days, microbiological examination of any biological  material was negative  in all patients,  and PCR of blood/tissues of resected valves retained high sensitivity (0% and 0% vs. 34.8% and 78.3%, respectively; p<0.01).Conclusion. Long-term preoperative AMT significantly reduced the sensitivity of microbiological examination of resected valve blood/tissue in operated patients with IE, whereas PCR of resected valve blood/tissue was highly sensitive even with preoperative AMT for more than 29 days

A Case Report of Differential Diagnosis of Causes of Severe Valvular Heart Disease (Takayasu's Arteritis, Infective Endocarditis and Myxomatous Degeneration) with the Key Role of Histological and PCR Examination

Aortic valve lesion is a common and may have diverse causes, from degenerative, congenital and infectious diseases to autoimmune conditions. We present a rare case of Takayasu arteritis and severe heart lesion due to the myxomatous degeneration of the aortic and mitral valves associated with development of infective endocarditis (IE) complicated by abscess, fistula, valve perforation and recurrent acute decompensated heart failure in a young female patient. A combined use of histopathological and PCR analyses of valve tissues was critically important for differential diagnosis of the valve lesions, as it made it possible to identify the true cause of the disease. The presence of Takayasu arteritis has played an indirect role by creating conditions for the development of immunosuppression and determining the disease severity and its progression

The role of molecular methods in diagnosis of opportunistic diseases in HIV-infected patients

Objective: to assess the diagnostic significance ot opportunistic diseases pathogens detection in biological samples from HIV- infected patients. Methods: in 2007-2013,4133 adult hospital patients were examined (76% had AIDS; CD4 blood count < 200 cells/mcL - 75%). 6847 biological samples (blood samples, BAL, CSF, etc.) were examined for M. tuberculosis, Cytomegalovirus, C. albicans, C. glabrata, C. cruzei, C. neoformins, T. gondii, H. Simplex l-ll, HerpesVI, Epstein-Barr virus (EBV) and JC-virus DNAs, and HIV RNA presence and concentration (PCR-test in Federal Budget Institution of Science 'Central Research Institute of Epldemiol-ogy* was used). Results: The role of the main opportunistic diseases pathogens DNA presence and concentrations in biological fluids and tissues in diagnosis was established; the central role of molecular methods in prompt diagnosis of opportunistic diseases in HIV-infected people was proven.С целью определения диагностического значения выявления ДНК возбудителей вторичных заболеваний в биологических материалах у больных ВИЧ-инфекцией в 2007-2013 гг. обследовано 4133 стационарных взрослых пациентов (в стадии 4Б (СПИД) - 4В (СПИД) - 76%, количеством С04-лимфоцитов в крови <200 кл/мкл - 75%). Исследовано 6847 биоматериалов (образцов крови, БАЛЖ, СМЖ и др.) на наличие и количественное определение ДНК М. Tuberculosis, Cytomegal-ovirus, С. albicans, С. glabrata, С. cruzei, С. neoformins, Т. gondii, Н. Simplexl-ll, HerpesVI, ВЭБ, JC-вируса, РНК ВИЧ молекулярными методами (ПЦР-тест-системы ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора). Установлено диагностическое значение качественного и количественного содержания ДНК возбудителей основных оппортунистических заболеваний в биологических жидкостях и тканях; обоснована центральная роль молекулярных методов в своевременной постановке этиологического диагноза вторичных патологий у больных ВИЧ-инфекцией

Progressive multifocal leukoencephalopathy in HIV-infected patients: clinical features and diagnosis (literature review)

Progressive multifocal leukoencephalopathy (PML) is one of the most severe opportunistic diseases of the central nervous system, which leads to multiple demyelination of brain structures, neurological symptoms and frequent death or disability of the patient. The etiological factor of this disease is Human polyomavirus 2 (JCPyV).This pathogen is widespread – antibodies are found in 80% of the world›s population. However, the clinical symptoms of this infection appear only in people with a pronounced decline in cellular immunity. Until 1980 progressive multifocal leukoencephalopathy was extremely rarely diagnosed. Now days the main cause of the clinical symptoms of PML is immunodeficiency caused by HIV infection. Clinical manifestations of PML are characterized by various non-specific neurological symptoms, similar to other lesions of the central nervous system, the symptoms progress slowly over several months, and usually lead to death. Diagnosis of PML is based on laboratory and instrumental methods, such as DNA JCPyV detection in the cerebrospinal fluid, brain biopsy, and radiation diagnostic methods. There is no effective prevention and etiotropic therapy for PML. Improved parameters of cellular immunity and antiretroviral treatment in HIV positive patients significantly increase the life expectancy of patients with PML. Despite the ability of drugs to prevent the progression of the disease, pathological changes in the brain are irreversible and lead to persistent disability of patients, therefore, it is necessary to diagnose PML in the early stages of the disease

Modern trends in identification of causative agents in infective endocarditis

Advances in the diagnosis and treatment of patients with infectious endocarditis are limited by the high frequency of cases with an unknown etiology and imperfection of microbiological (cultural) methods. To overcome these problems new approaches to the identification of infectious endocarditis pathogens were introduced, which allowed achieving certain positive results. However, it should be noted that despite the wide variety of diagnostic tools currently used, there is no ideal method for etiological laboratory diagnosis of infectious endocarditis. The article discusses the features and place of immunochemical, molecular biological (MALDI-TOF MS, real-time PCR, sequencing, in situ fluorescence hybridization, metagenomic methods, etc.), immunohistochemical methods, and their advantages and limitations