Infective endocarditis (IE) is characterized by the difficulty of diagnosis, treatment and risk assessment of an unfavorable prognosis. Currently there are no approved scales and calculators for the risk of complications and death that help the practitioner make decisions, especially in patients with isolated right-sided IE. For right-sided IE, the timing of successful surgical treatment remains uncertain. Previously developed risk calculators (Italian Rizzi calculator and French Hubert) are poorly validated in a wide population of patients with IE, especially for right-sided IE. One of the required parameters of calculators is the determination of etiological affiliation. However, with negative results of microbiological studies reaching 56-83 %, this parameter becomes uninformative. Moreover, existing risk assessment tools do not take into account the activity of the disease (including laboratory activity), which intuitively is an important guideline for every doctor in decision-making. At the moment, there is a great need for the introduction of molecular biological methods to improve the quality of etiological diagnosis and in-depth study of possible biomarkers from simple (neutrophil/lymphocytic, platelet/lymphocytic and systemic immuno-inflammatory index) to more complex (neutrophil extracellular traps, cytokine profile). We present a clinical case of a young patient with acute tricuspid valve IE with giant vegetation (28 mm), complicated by severe valvular insufficiency without signs of heart failure, recurrent embolic syndrome in the pulmonary artery system with the formation of pulmonary hypertension, determining indications for cardiac surgical treatment. The etiological affiliation of IE to Staphylococcus aureus was established only by PCR. The urgent timing of intervention was determined based on an increase in new markers — neutrophil/lymphocytic index ≥20.0, systemic immuno-inflammatory index ≥2314.0 and neutrophil extracellular traps ≥14.2, indicating an extremely high risk of death. A fundamental pathohistological study of the tissue material revealed a low content of intact CD86+ proinflammatory macrophages, probably associated with their excessive destruction and uncontrolled release of copious amounts of proinflammatory cytokines, which led to rapid and severe damage to the tricuspid valve. Thus, modern management of patients with IE should be multiplex using current methods of etiological and imaging diagnostics, and aimed at early detection of patients at adverse risk for a timely differentiated approach to conservative or cardiac surgical treatment tactics.

Relevance. Effective responses are required due to the high incidence of cervical cancer (Cc) throughout the World. RT-PCRbased HPV-testing is becoming more prominent in secondary prevention worldwide, replacing cytology. Russian practice still relies on cytology as the primary method mainly because there is a lack of comparative evaluation of the diagnostic characteristics of cytology and HPV-tests. Aim. Evaluation of diagnostic characteristics of laboratory methods and the relevance of extended HPV genotyping for secondary prevention of cervical cancer. Materials & methods. The study included data (liquid cytology, histology, HPV-test results) from a survey of 653 women (M = 33.55 years old, ME = 32.0 years old, IQR: 26-38 years old) infected with 14 HPV types (16, 18, 31, 33, 35, 39, 45, 45, 51, 52, 56, 58, 59, 66, 68), with presence or absence of intraepithelial neoplasia of varying severity. The study analyzed the correlation of cervical cytology - histology, clinical sensitivity for high-grade squamous intraepithelial lesions (HSIL+), the incidence and the role of 14 oncogenic HPV types in the development of cervical intraepithelial pathology, positive predictive value (PPV) and the diagnostic accuracy of the HPV-test. Results. The agreement between cytology and histology is 67.20%. Clinical sensitivity of cytology is 83.78% for HSIL+ and 94.34% for any other than NILM result. The structure of the HPV population varies depending on the degree of neoplasia, with a constant predominance of HPV16. The clinical sensitivity of the laboratory component rises to 99.5% by conducting HPV-test for at least 12 types of virus. HSIL is more commonly associated with viruses of alpha-9 phylogenetic group, than with alpha-7 and alpha-5/6. The positive predictive value for HSIL+ is reduced depending on the HPV type: 16>33>58>35>45>31>18>52>39>59>58>56>68>66. Conclusions. Clinical sensitivity of the HPV-test exceeds that of cytology, so that secondary prevention of cervical cancer can be effectively achieved through HPV testing. The introduction of an extended genotyping provides more complete information about the risk of having HSIL+. The data obtained will form the basis for the development of directions for improving the epidemiological surveillance information subsystem of HPVassociated cervical diseases

Background. The prevalence of cervical cancer (Cca) in Russian women makes it crucial to study modern epidemiological characteristics and adjust control measures accordingly.The aim. To analyze trends in the incidence of cervical cancer in the Russian Federation.Materials and methods. A retrospective epidemiological study was conducted on cervical cancer incidence in Russian Federation from 2008 to 2021. The materials of annual statistical data “Malignant neoplasms in Russia (morbidity and mortality)” and “Status of oncological assistance to the population of Russia” (2008–2022), data of the federal statistical reporting form No. 5 “Information about preventive vaccinations” (2021), data on the number of studies conducted (cytological study and HPV-test based on RT-PCR) in the clinical diagnostic laboratory of Central Research Institute of Epidemiology of Rospotrebnadzor (2013–2021) were used.Results and discussion. The trends of Cca incidence varied depending on the women’s age. Starting in 2016, there was a stabilization of the level of morbidity in women aged 30–49 with the subsequent decrease from 2019 due to the strengthening of secondary prevention measures, including the active introduction of HPV-test into the diagnostic schemes conducted in the Russian Federation. Increased control of cervical cancer caused a rise in the proportion of cases diagnosed at an early stage (carcinomas in situ and I–II stages Cca), the increase of detection rate of in situ carcinomas per 100 cases of Cca, the growth of the proportion of carcinomas in situ to I–II stages Cca, rise of the percentage of the cases detected actively, decrease of the number of Cca cases detected at later stages and one-year mortality index.Conclusion. The epidemiological analysis of cervical cancer incidence shows that preventive measures are effective and that there is a need to intensify and increase their coverage.

Background: roseoloviruses, including human herpesvirus (HHV) 6A/B and HHV-7, are implicated in several diseases but remain underexplored among clinically healthy individuals. Aim: this study aims to assess the role of HHV-6A, HHV-6B, and HHV-7 in the onset of infectious and inflammatory diseases affecting the upper respiratory tract in children. Materials and Methods: during the initial phase, 139 children aged 1 to 16 years (median age 6 years) were evaluated, comprising 79 boys. The subjects were divided into two groups: the main group (children presenting with symptoms of acute respiratory viral infection (ARVI), n=75) and a comparison group (apparently healthy children, n=64). Blood samples and oral mucosal swabs were collected. In the second phase, the additional 41 children were assessed, including 31 boys aged 1 to 14 years (median age 7 years). These children were categorized into a group with grade 3 adenoid hypertrophy (n=27) and a comparison group (n=14, clinically healthy children). Tissue samples obtained during adenoidectomy or swabs from the pharyngeal tonsils were collected. Samples were analyzed for the presence of HHV DNA using PCR. Results: in the first phase, HHV DNA was identified in 124 (89%) children, with detection rates of 92% in the comparison group and 87% in the main group. The most prevalent viruses were HHV-6A/B (64%) and HHV-7 (65%). HHV-6A/B was more frequently detected in girls at 75% compared to 56% in boys, and in children under 4 years of age (82%). In the second phase, HHV DNA was found in 38 (93%) children, with a higher prevalence in the main group — 100% versus 79% in the comparison group. HHV-6B DNA was more frequently detected in the main group (96% vs. 36%). Conclusions: the findings underscore the significant role of HHV-6B in chronic inflammatory conditions and highlight the necessity for antiviral therapy, as opposed to HHV-7, which was equally prevalent in both healthy and symptomatic children. KEYWORDS: human herpesvirus 7, human herpesvirus 6A/B, adenoid hypertrophy, children. FOR CITATION: Vlasov P.V., Sabinina T.S., Musyka A.D., Soldatova E.Yu., Domonova E.A., Silveistrova O.Yu., Melekhina E.V. Roseolovirus role in the development of infectious and inflammatory diseases affecting the upper respiratory tract in children. Russian Medical Inquiry. 2024;8(11):624–630 (in Russ.). DOI: 10.32364/2587-6821-2024-8-11-4

Aim. To study the features of macrophages in the tissues of resected valves in operated patients with infective endocarditis (IE), their significance and interaction with inflammatory markers to improve the effectiveness of IE diagnosis. Materials and methods. Prospectively the research included 25 adult patients with active IE (Duke criteria 2015) and 24 patients with heart defects without IE, hospitalized in a cardiosurgical hospital in Moscow (2021–2022). A standard laboratory and instrumental examination was carried out for the diagnosis of IE, including etiological diagnosis with microbiological and molecular biological methods, and echocardiographic examination of heart. Additionally, the neutrophil-to-lymphocyte ratio (NLR) was calculated. The study of macrophages was carried out in the tissues of resected valves with the determination of the expression of pro- and anti-inflammatory cytokine genes, macrophage markers (CD 68+) using real-time PCR. Results. Increased expression of proinflammatory cytokines IL-1β, TNF-α and IL-6 was revealed in the group of operated patients with IE with significant differences in IL-1β (CI [IQR] 0.00367 [0.00047–0.01553] vs 0.00018 [0.00012–0.00262]; p0.05) and IL-6 (CI [IQR] 0.00367 [0.00047–0.01553] vs 0.00018 [0.00012–0.00262]; p0.05) and IL-6 (CI [IQR] 0.00338 [0.00066–0.01674] vs 0.00054 [0.00044–0.00378]; p0.05). The expression of anti-inflammatory cytokines in valve tissues prevailed in the control group without significant differences from patients with IE. The macrophage marker CD 68+ was revealed in all examined patients with a significant quantitative predominance in the group of patients with IE. There were no differences in the expression of pro- and anti-inflammatory cytokines depending on the presence of embolic events, intracardiac complications, etiological affiliation to S. aureus, as well as hospital mortality and combined endpoint (death from all causes or recurrence of IE 6 months after surgery) in patients with IE with or without events. Cytokines IL-1β and IL-6 positively correlated with each other, with leukocytes and NLR. ROC analysis determined that IL-1β and NLR had the most favorable features for the diagnosis of IE [IL-1β AUC 0.816 (p=0.02), NLR AUC 0.807 (p=0.03)]. IL-6 did not show a diagnostic value in IE. The threshold value for IL-1β was 0.00029 (sensitivity 86.4%, specificity 60.0%, prognostic value of negative result 75.0% and positive 76.0%, AUC 0.761; p=0.008). Conclusion. The valve macrophages of patients with IE express elevated levels of proinflammatory cytokines IL-1β and IL-6, regardless of etiological affiliation or complicated course of IE. IL-1β has a high diagnostic value for determining the inflammatory activity in IE.

Objective. Determination of nucleic acids (NA) of significant viral and bacterial pathogens of respiratory infections in the tissue of a benign hypertrophied pharyngeal tonsil (HPT) in children. Materials and methods. 27 HPT tissue samples obtained during elective adenoidectomy from patients of two age groups were studied: from 2 to 6 years 11 months (G1), n = 13, boys (B) 10/77%, girls (G) 3/23%; from 7 to 13 years (G2), n = 14 B 8/57%, G 6/43%. NC of 8 human herpes viruses (HHV), 16 respiratory viruses and 4 bacterial pathogens were determined by NA amplification using reagent kits manufactured by the Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor. The statistical analysis was carried out by the StatTech program. Results. NA of infectious agents were detected in all the studied samples. The average number of pathogens detected in one sample was 7 ± 3 microorganisms: HHV DNA and bacterial DNA were found in 100% of children; NA of respiratory viruses – in 81% (11/85% in G1, 11/79% in G2). The most frequently detected NA are: human herpes virus 6B (HHV-6B) – 96%, Epstein–Barr virus (EBV) – 89%, human herpes virus 7 (HCV-7) – 81%. EBV was detected more often in boys 18/100% and 6/67%, p = 0.029. Among bacteria, DNA of Haemophilus influenzae (HI) was detected more often than others – 59%. Rhinovirus (hRv) was the most frequent respiratory virus – 56%, bokavirus ((hBov) – the second most common detection rate of 33%, more often in G1 – 7/54% than in G2 2/14%, p = 0.046. Prognostic models have been developed showing an increase in the probability of detection of Hemophilus influenza in the presence of rhinovirus (p = 0.031) and Staphylococcus aureus in the presence of bocavirus (p = 0.012). Conclusions. Up to 12 NC pathogens of infections were found in the tissues of HPT in one patient. The most common pathogens were HCV-6B, HCV-7, EBV, hRv, hBov, HI. Key words: human herpes virus 7, human herpes virus 6 A/B, Epstein–Barr virus, adenoid hypertrophy, children, respiratory viruses, topical bacterial lysates

Objective: To analyze clinical and laboratory features to predict the outcome of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients. Materials and methods: Retrospective analysis of medical histories of HIV-infected patients with CNS lesions in 2015–2017, and dynamic monitoring of HIV patients with CNS lesions in 2018–2019, who were intensive care unit (ICU) in Infectious Clinical Hospital No. 2 of the Department of Health of Moscow. Results and discussion: A total 196 patients with encephalitis/meningoencephalitis: 124 (63%) patients with detected JCPyV in the cerebrospinal fluid (CSF) — study group (JCPyV+), 72 patients with undetectable JCPyV in CSF — comparison group (JCPyV–). Late terms of hospitalization were noted, mainly in the JCPyV+ group (mean — 58±6 days). The majority of patients had severe immunodeficiency, in the JCPyV+ group the number of patients with CD4<200 cells/μl was significantly higher than in the JCPyV– group (87.8% and 75.8%, p<0.05). Only 22% of patients received antiretroviral therapy (ART) prior to hospitalization. The main clinical manifestations of PML in the study were: paralysis and paresis of the limbs, speech impairment, cognitive disorders in combination with cerebral symptoms in the absence of meningeal signs. In 87.8% patients with positive JCPyV DNA no other pathogens were detected in the CSF; in the patients without PML the detection of infectious agents in the CSF was also rare (14.3%). The disease led to the death for 78% patients in the JCPyV+ group and 72% JCPyV– group, p>0.05. The chance of survival was 2.5 times higher for patients admitted to hospital less than 14 days after deterioration (OR=2.468 [95% CI: 1.244–4.898]). Patients with CD4<200 cells/μL were 5.5 times more chance to die than patients with higher CD4 rates (OR=5.449 [95% CI: 2.388–12.431]). There was no relationship between the concentration of JCPyV DNA and HIV RNA in the CSF and their impact for the disease outcome. Conclusion: Survival prognosis for PML during treatment in ICU was worser for patients hospitalized after 14 days from the onset of symptoms and with CD4<200 cells/μL. Early ART initiation for all HIV-positive individuals significantly reduces the number of opportunistic infections and improve life expectancy.

Background. If infective endocarditis (IE) is suspected, the determination of the etiology is of fundamental importance for the verification of the disease and the appointment of effective therapy. Microbiological diagnostic features are important, but they often need to be supplemented by culture-independent studies of pathological agents. Aim. To investigate of the diagnostic advantage and value of quantitative analysis of molecular biological methods (polymerase chain reaction - PCR, sequencing) in addition to microbiological examination of whole venous blood in IE. Materials and methods. We examined 124 patients with suspected or significant IE (DUKE 2015) hospitalized in the Vinogradov City Clinical Hospital (2015-2021). All patients underwent parallel microbiological (cultural) and molecular biological (PCR or PCR followed by sequencing) examination of venous whole blood samples. Results. The introduction of an early parallel PCR study into the algorithm for the etiological diagnosis of IE made it possible to obtain an additional advantage in 43/124 (34.7%) patients, which made it possible to exclude unreliable results in the determination of CoNS skin commensals and pathogens atypical for IE or contamination and identify the true pathogens, and also for the first time to isolate the etiopathogenetic pathogen with a negative microbiological study. It was shown that in IE associated with CoNS, the association with the disease was confirmed by PCR in 21.4% (3/14) and refuted in 71.4% (10/14). The coincidence of the results of microbiological and PCR studies of blood samples was obtained only in 35/95 (36.8%). Positive results of PCR analysis of blood of biological material with negative results of culture were obtained in 22/51 (43.1%), of which 2/22 (9.0%) were able to confirm the presence of Bartonella spp DNA. The presented complex algorithm made it possible to significantly increase the possibility of intravital identification of the pathogen in the blood from 58.9 to 76.6%. IE with unknown etiology was present in 29/124 (23.4%) patients. A parallel PCR study allowed timely correction of antibiotic therapy in 43/124 (34.7%) patients. Conclusion. Expansion of indications for the use of PCR studies, primarily whole venous blood samples, is justified, not only in IE with negative results of microbiological examination, but also as a control method for the reliability of the results of traditional (cultural) diagnostic methods.

Introduction:Cervical cancer (CC) is a prevalent malignancy affecting women globally. The primary causative factor of CC is the high-risk oncogenic human papillomavirus (HR-HPV). However, it is noteworthy that not all women infected with HR-HPV develop cancer, indicating the potential involvement of genetic predisposition in the development of CC. This study aims to identify genetic risks and their distribution in groups of women with different epidemiological features of HR-HPV.Materials and methods:A comparison was conducted among four groups of women, comprising 218 HPV-negative women, 120 HPV-positive women, 191 women diagnosed with cervical intraepithelial neoplasia (CIN) grade 2 or 3, and 124 women diagnosed with CC. The analysis focused on four single nucleotide polymorphisms (SNPs): rs55986091 in HLA-DQB1, rs138446575 in TTC34, rs1048943 in CYP1A1, and rs2910164 in miRNA-146a.Results:The rs55986091-A allele exhibited a protective effect within the "CC" group when compared to the "HPV-Negative" group (OR = 0.4, 95% CI= 0.25-0.65) using a log-additive model. Additionally, similar protective effects were observed in the "CIN 2/3" group compared to the "HPV-Negative" group (OR = 0.47, 95% CI = 0.28-0.79).Conclusion:The data obtained emphasize the importance of developing PCR-based diagnostic kits for the identification of SNP alleles, particularly for rs55986091, among HR-HPV-positive women within the Russian population.

Relevance. The global strategy for cervical cancer elimination includes the active implementation of primary, secondary and tertiary prevention programs. In the Russian Federation, screening for the detection of malignant neoplasms of the cervix is carried out while women contact specialists, as well as an organized procedure during preventive medical examinations of the certain groups of adults. The study of the population structure of circulating human papillоmavirus (HPV) types, and evaluation of the effectiveness of the recommended diagnostic models will improve the direction of the fight against cervical cancer and introduce optimal preventive solutions. Aim. Retrospective analysis of screening effectiveness for the detection of malignant neoplasms of the cervix, carried out during the medical examination in one institution of Moscow. Materials and methods. The study examined 1068 women aged 20 to 81 years (M = 37.82, Me = 35, IQR 27–47 years) from one institution in Moscow over a 5-year follow-up period (2017–2021). The screening was based on the co-testing model: liquid-based cytology with Papanicolaou staining and classification according to the Bethesda system and quantitative Real Time HPV-test with determination of the 14 HPV DNA types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Results. The prevalence of the 14 HPV oncogenic types was 14.87% (95% CI: 12.86–17.13%), the most common were 16 (16.98%), 31 (14.47%), 52 (13.21%). The study determined HPV types with the highest relative risk of persistence: 33, 58, 45, and 52 (p < 0.005). The frequency of HPV detection depended on the age of the examined women and was the highest in the age group of 20–29 years (25.58%). The baseline prevalence was 11.82% (95% CI: 9.98–13.94%). 6 HSIL cases associated with HPV types 16 and 31 were identified. 4/6 were in women under 30 years. The probability of intraepithelial lesions of the cervix increased with an increase of HPV DNA concentration: 23.65% and 66.67% with a viral load of 4.0–6.0 lg copies per 105 human cells and > 6.0 lg copies per 105 human cells, respectively. Conclusions. The study confirmed the great value of HPV- test in screening for the detection of malignant neoplasms of the cervix during the medical examination of the certain groups of adult population, taking into account the advantages of typing and quantitative determination of HPV DNA, as well as the need to consider lowering of the recommended age for the start of HPV-testing.

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.

Введение. Проблема тяжелых поражений ЦНС у больных ВИЧ-инфекцией актуальна. Цель исследования. Описание спектра поражений ЦНС, определение диагностического значения наличия и различных концентраций РНК ВИЧ и ДНК возбудителей вторичных заболеваний в СМЖ и крови для верификации природы энцефалита у больных ВИЧ-инфекцией. Материалы и методы. Обследованы 5485 больных ВИЧ-инфекцией, 1310 с поражением ЦНС. Исследованы образцы СМЖ (1667), сыворотки крови (743) и плазмы крови (3623) с определением ДНК патогенов и РНК ВИЧ. Применяли пакеты статистических программ Statistica v. 10.0 и SPSS v. 20, язык программирования R, таблицы сопряженности с критерием χ2 Пирсона, ROC-анализ. Результаты. Показаны спектр вторичных неврологических патологий у больных ВИЧ-инфекцией, частота выявления и количественные характеристики РНК ВИЧ, ДНК возбудителей нейроинфекций в СМЖ. Связь между количеством РНК ВИЧ в крови и СМЖ статистически значима, но в 7,5% случаях концентрация РНК ВИЧ в СМЖ превышала >10 раз показатель в плазме. Вследствие высокой диагностической чувствительности теста отсутствие ДНК возбудителей вторичных заболеваний и РНК ВИЧ СМЖ исключает их роль в развитии энцефалита. Диагностическая специфичность качественного определения ДНК T. gondii, M. tuberculosis, C. neoformans, JCPyV равна 100%. Необходимо количественное определение РНК ВИЧ, ДНК ЦМВ, ДНК ВЭБ, ДНК ВГЧ-6 А/В типа, грибов рода Сandida в СМЖ для подтверждения этиологии поражения ЦНС. Определение ДНК ЦМВ в СМЖ в концентрации >16 600 копий/мл, лейкоцитах крови >4,65 lg копий/105 клеток, плазме крови >62 700 копий/мл с 95% вероятностью подтверждает ЦМВ-этиологию энцефалита. Заключение. Качественное и количественное определение ДНК возбудителей вторичных заболеваний и РНК ВИЧ в СМЖ имеет решающее значение в своевременной расшифровке природы неврологической патологии у больных ВИЧ-инфекцией. Introduction. The problem of severe CNS lesions in patients with HIV infection is relevant. Objective of the study. Description of the spectrum of CNS lesions, determination of the diagnostic value of the presence and different concentrations of HIV RNA and DNA agents of secondary diseases in CSF and blood to verify the nature of encephalitis in patients with HIV infection. Materials and methods. 5485 patients with HIV infection were examined, 1310 with CNS damage. CSF (1667), blood serum (743) and blood plasma (3623) samples with the determination of pathogens DNA and HIV RNA were examined. Statistical software packages Statistica v. 10.0 and SPSS v. 20, programming language R, conjugacy tables with Pearson χ2 criterion, ROC analysis were used. Results. The spectrum of secondary neurological pathologies in patients with HIV infection, the frequency of detection and quantitative characteristics of HIV RNA, DNA of pathogens of neuroinfections in CSF are shown. The association between the amount of HIV RNA in the blood and CSF is statistically significant, but in 7.5% of cases, the concentration of HIV RNA in the CSF exceeded > 10 times the plasma value. Due to the high diagnostic sensitivity of the test, the absence of DNA of secondary disease pathogens and HIV RNA CSF excludes their role in the development of encephalitis. The diagnostic specificity of qualitative DNA determination of T. gondii, M. tuberculosis, C. neoformans, JCPyV is 100%. It is necessary to quantify HIV RNA, CMV DNA, EBV DNA, HHV-6 A/В DNA, Candida fungi in the CSF to confirm the etiology of the CNS lesion. Determination of CMV DNA in CSF at a concentration of > 16,600 copies/mL, blood leukocytes > 4.65 lg copies/105 cells, blood plasma > 62,700 copies/mL with 95% probability confirms CMV-etiology of encephalitis. Conclusion. Qualitative and quantitative determination of DNA of secondary disease agents and HIV RNA in CSF is crucial in timely decoding of the nature of neurological pathology in patients with HIV infection.

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 clinical observation of the treatment non-compliance consequences with clinical guidelines and principles of empirical therapy selection in a female patient with intravenous drug abuse, viral hepatitis C and HIV infection, with a history of a COVID-19 and the development of uncontrolled staphylococcal infective endocarditis (IE) of the tricuspid valve, complicated recurrence of early prosthetic IE is presented. Successful treatment was achieved only by a combination of tricuspid valve replacement and the appointment of etiotropic therapy for S. aureus (MSSA). The typical clinical scenario was not accompanied by the choice of adequate empirical antibiotic therapy, despite the high suspicion of association with MSSA, which determined the complicated course of IE. Only the polymerase chain reaction of the heart valve tissue played a key role in the etiological diagnosis. The use of valve tissue polymerase chain reaction in addition to traditional microbiological methods is a valuable diagnostic study.

Aortic valve lesion is a common cardiopathy, which may have very 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 valve cusps associated with the development of infectious 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 structural cardiopathy associated with myxomatous degeneration and a prior IE. The presence of Takayasu arteritis has played an indirect though apparently decisive role by creating conditions for the development of immunosuppression and determining the disease severity and progression rate.

Overdiagnosis of congenital infections caused by Human Herpesvirus 6A/B (HHV-6A/B) in newborns with an inherited chromosomally integrated (ici) HHV-6A/B creates an unreasonable economic burden for the healthcare system and society. We assessed economic significance of detection and laboratory confirmation of iciHHV-6A/B in newborns with congenital infections during their inpatient treatment in Moscow in 2020. The introduction of a new method based on the quantitative detection of HHV-6A/B DNA in patient’s whole blood sample, nail plates and/or hair follicles by a real-time polymerase chain reaction will result in an economic effect with a minimum ratio of 1:68, will reduce healthcare costs in Moscow and optimize the epidemiological surveillance of vertically congenital infections in the region. The total estimated economic costs averted (including costs of pharmacotherapy, as well as clinical, laboratory, and instrumental examinations and other medical procedures in maternity and obstetric hospitals) will be approximately 6 million rubles per year for Moscow. Key words: economic significance, economic costs averted, Human Herpesvirus 6A/B, inherited chromosomally integrated Human Herpesvirus 6 A/B, newborns, congenital infections

Abstract Introduction Identification of a causative agent in patients with infective endocarditis (IE) is crucial for diagnostic and prescribing etiotropic therapy which defines positive outcome of a disease. High rate of a culture negative IE and inaccurate results of traditional microbiological methods raise a concern. So the methods of etiological diagnostics in IE are in need of development, particularly introduction of polymerase chain reaction (PCR) method might be helpful. Aim Modernisation of the algorithm of IE etiological diagnostic by introducing PCR Materials and methods The study included 85 cases of IE [first episode of IE (n=79), recurrence/relapse (n=6)] verified by DUKE criteria 2009, 2015, hospitalized in Moscow primary hospital from 2012 to 2017. All patient had venous blood investigated both with microbiological method and with broadrange and specific PCR. Following microorganisms' DNA were assessed by PCR: Staphylococcus spp. (MRCoNS, S. aureus and others), Streptococcus spp. (S. agalactiae, S. pyogenes and others), Enterococcus spp. (E. faecium, E. faecalis and others), Enterobacteriaceae, Klebsiella spp. (K. pneumoniae and others), E. coli, Proteus spp., A. baumanii, P. aeruginosa, Fungi (C. albicans, C. glabrata, Aspergillus spp. and others). Results Median age was 55.48 years (95% confidence interval (CI) 51.16–59.8), males 67.9%. History of cardiovascular diseases was in 54 (68.35%), diabetes mellitus in 18 (22.78%), hepatitis B and/or C in 31 (39.2%), intravenous drug dependency in 27 (34.18%), chronic kidney disease in 38 (48.1%), median Charlson comorbidity index was 5.44 (95% CI 4.52–6.37). Left-side IE was in 50 (63.29%), right-side IE – in 23 (29.12%), left-right-side IE in 6 (7.59%). Secondary IE was in 53 patients (62.3%). Embolic events were diagnosed in 27 cases (34.18%), in-hospital mortality – in 22 (27.8%). Microbiological method identified etiological agent in 55 of 85 cases (61.2%), featuring Staphylococcus aureus (n=23), Staphylococcus CoNS (n=6), Escherichia coli (n=1), Acinetobacter spp. (n=2), Streptococcus spp. (n=2), Enterococcus spp. (n=8), Klebsiella pneumoniae (n=2), Gemella haemolysans (n=2), several causative agents (n=6). Additional PCR testing identified etiology in 14 of 33 (42.2%) featuring Staphylococcus spp. (n=6), Enterococcus spp. (n=3), Streptococcus spp. (n=1), Aspergillus sp. (n=1) Pasteurella multocida (n=1), Enterococcus spp. + Staphylococcus spp. (n=1), Staphylococcus spp.+ A. baumanii + E. coli (n=1). PCR method identified 6 fals-positive results of microbilogical investigation [S. epidermidis (n=2), G. haemolysans, Acinetobacter spp., E. faecalis, K. pneumoniae], that are most probably due to preanalytical sample contamination Conclusions Introduction of PCR into the algorithm of IE etiological diagnostic increased validity of laboratory findings on 23.5%. True culture negative IE was present in 19 of 85 patients. Rate of mortality and complications in IE remains high. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Peoples' Friendship University of Russia (RUDN), Moscow, Russia