Human Herpesvirus Type Research Articles

Diffuse B-cell lymphoma in a child with HIV infection

Objective. To describe the case of diffuse B-cell lymphoma in a child with HIV infection.Results. A 16-year-old child with HIV infection and generalized lymphadenopathy was diagnosed with diffuse large B-cell lymphoma, stage III, negative central nervous system. The patient was diagnosed on the basis of the results of immunohistochemical study of biopaths of the tissue of the lymph nodes of the submandibular and right axillary region. The study in order to identify markers of active infection caused by the Epstein-Barr virus, cytomegalovirus and human herpesvirus type 6, made it possible to exclude the active phase of diseases that are the main infectious causes of lymphoproliferative syndrome. At the time of hospitalization, the patient was treated with antiretroviral therapy of the combined drug Eviplera. There was no HIV RNA in the blood, the level of CD4 lymphocytes was 0.4·109/l. The BFM chemotherapy regimen was used, which was accompanied by positive dynamics in the form of normalization of body temperature, reduction in the size of lymph nodes.Conclusion. This case shows that immunohistochemical examination of tissue biopsies of enlarged lymph nodes is of decisive importance in the diagnosis of lymphoma, the main non-infectious cause of lymphoproliferative syndrome in patients with HIV infection.

Клініка і діагностика скроневого медіанного склерозу, асоційованого з герпесвірусною інфекцією

У статті детально розглянуто клінічні й нейровізуалізаційні прояви особливої форми нейродегенеративного процесу, що отримав назву скроневого медіанного склерозу, асоційованого з герпесвірусною інфекцією. Розглянуто стадії розвитку нейродегенерації при ураженні структур лімбічної системи центральної нервової системи герпесвірусами людини 6-го і 7-го типів. Обговорено гетерогенність основних клінічних синдромів хвороби — нейропсихіатричних розладів, когнітивного зниження особистості й вегетативної дисфункції. Скронева медіанна епілепсія й скронева форма деменції є кінцевими наслідками розвитку нейродегенеративного процесу в пацієнтів із вірус-індукованим скроневим медіанним склерозом. Показано, що гіперінтенсивність сигналу від гіпокампів, острівців, парагіпокампальних звивин і мигдалеподібних тіл є типовою магнітно-резонансною ознакою скроневого медіанного склерозу. Обговорено проблеми диференціальної діагностики, зокрема з проявами автоімунних і паранеопластичних лімбічних енцефалітів, зумовлених продукцією антинейрональних автоантитіл, включаючи автоантитіла до молекули GAD65. Даний огляд є ще одним щаблем на шляху до впровадження в клінічну практику неврологів і психіатрів дієвого алгоритму з раннього виявлення скроневого медіанного склерозу, асоційованого з герпесвірусною інфекцією, і своєчасного призначення адекватного противірусного лікування й адресної імунотерапії.

Potential of an Eco-Sustainable Probiotic-Cleaning Formulation in Reducing Infectivity of Enveloped Viruses.

The COVID-19 pandemic has deeply influenced sanitization procedures, and high-level disinfection has been massively used to prevent SARS-CoV-2 spread, with potential negative impact on the environment and on the threat of antimicrobial resistance (AMR). Aiming to overcome these concerns, yet preserving the effectiveness of sanitization against enveloped viruses, we assessed the antiviral properties of the Probiotic Cleaning Hygiene System (PCHS), an eco-sustainable probiotic-based detergent previously proven to stably abate pathogen contamination and AMR. PCHS (diluted 1:10, 1:50 and 1:100) was tested in comparison to common disinfectants (70% ethanol and 0.5% sodium hypochlorite), in suspension and carrier tests, according with the European UNI EN 14476:2019 and UNI EN 16777:2019 standards. Human alpha- and beta-coronaviruses hCoV-229E and SARS-CoV-2, human herpesvirus type 1, human and animal influenza viruses, and vaccinia virus were included in the study. The results showed that PCHS was able to inactivate 99.99% of all tested viruses within 1–2 h of contact, both in suspension and on surface. Notably, while control disinfectants became inactive within 2 h after application, the PCHS antiviral action persisted up to 24 h post-application, suggesting that its use may effectively allow a continuous prevention of virus spread via contaminated environment, without worsening environmental pollution and AMR concern.

VEGETATIVE REACTIVITY OF CHILDREN WITH STREPTOCOCCAL TONSILITIS ON THE BACKGROUND OF HERPES VIRAL INFECTION

Streptococcal infection in children, its complications and adverse long-term consequences remain an urgent problem in pediatrics. Scientists continue to search for factors that shape the course of the disease. One of them is the timely and adequate response of the autonomic nervous system, which provides both short-term and long-term strategic adaptation of the organism. Violations of this adaptation can lead to the presence of comorbid conditions, which are increasingly common. The share of children is growing. infected with the herpes virus group, including human herpes virus type 6 (HHV-6).
 
 The aim of the work was to study the state of vegetative reactivity (VR) of children with streptococcal tonsillitis on the background of HHV-6 infection. In 68 children aged 4 - 15 years with tonsillitis of streptococcal etiology of moderate severity, vegetative reactivity was determined by cardiointervalography (CIG) followed by analysis of heart rate variability (CP) depending on the presence or absence of concomitant HHV-6 type of infection. The studies were performed in the acute period of the disease and in the period of early convalescence. The control group consisted of 20 healthy children, similar in age and sex. Static processing of the obtained results was performed using Excel and Statistica 6.0 using parametric and non-parametric research methods.
 
 Results.
 In the acute period of streptococcal tonsillitis in children of both groups there was a decrease in the humoral component in the regulation of the system and the level of activity of the parasympathetic ANS, as evidenced by a decrease in Mo and ΔX, independent of background, p> 0.05. There was an activation of the influence of the sympathetic link of the VNS, increased the degree of centralization of heart rate control in all patients, and this was confirmed by an increase in AMO and IN. Prior to the convalescence period, CIG parameters were restored only in patients without concomitant VGL-6 infection, and the interrelationships of the sympathetic and parasympathetic links of the VNS were restructured with increasing role of the latter. In patients with concomitant VGL-6 infection, the values ​​of ΔX and IN differed significantly from the control group, p˂0.05. Thus, in children with streptococcal tonsillitis on the background of HHV-6 infection, there was a decrease in the level of functioning of the sympathetic VNS, but complete recovery did not occur, indicating instability of adaptation processes, depletion of the parasympathetic VNS, which hides the possibility of failure of adaptation, recurrence of the disease and / or chronicity, the development of secondary disorders of the cardiovascular system.
 Conclusions.
 The acute period of streptococcal tonsillitis is accompanied by stress of the sympathetic VNS, the severity of which does not depend on the presence of concomitant herpes virus infection. In the period of convalescence of streptococcal tonsillitis in the presence of children with HHV-6 infection there is no complete recovery of autonomic reactivity, among which the most informative are ΔX and IN.

Features of the course of acute decompensated ischemic heart failure and/or ongoing adverse left ventricular remodeling in patients with identified human herpes virus type 6

Objective. To determine serum levels of immunoglobulin M (IgM) and G (IgG) antibodies to human herpes virus type 6 (HHV-6) (anti-HHV-6) and features of clinical and morphological portrait in patients with acute decompensated heart failure (ADHF) of ischemic genesis and/or adverse left ventricular (LV) remodeling.Material and Methods. This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials. gov (#NCT02649517) and comprised 25 patients (84% men) with ADHF and LV ejection fraction (EF) ≤ 40%. All patients underwent endomyocardial biopsy (EMB) with immunohistochemistry (IHC) analysis for the presence of HHV-6, compliment C1q, major histocompatibility complex of class II (MHC II), and B-lymphocyte antigen (CD19) as the markers of autoimmune reaction as well as the serum levels of anti-HHV-6 IgM and IgG. Serum levels of IgM and IgG were measured using enzymelinked immunosorbent assay (ELISA) with the calculation of positivity coefficient (PC) according to manufacturer instructions. The test results were interpreted as positive when PC value was greater than 0.8.Results. The endomyocardial biopsy study detected HHV-6 antigen expression in 15 (60%) out of 25 enrolled patients including 10 cases with diagnosed HHV-6-positive myocarditis and five patients with carriage of viruses. According to IHC, the autoimmune HHV-6 myocarditis was confirmed in three cases (30%). The data of ELISA (n = 18) detected anti-HHV-6 IgM in 5 patients (28%) and anti-HHV-6 IgG in 11 cases (61%). The simultaneous presence of both anti-HHV-6 IgM and IgG was detected in two patients (11%). In addition, anti-HHV-6 IgM and IgG were absent in two (11%) cases. Eight patients (44%) with HHV-6-positive myocarditis included three patients (17%) tested positive for serum anti-HHV-6 IgM, three patients (17%) tested positive for serum anti-HHV-6 IgG, and two patients (11%) who had nether anti-HHV-6 IgM nor anti-HHV-6 IgG in blood serum. Among virus carriers, one patient (20%) was tested positive for anti-HHV-6 IgM and four patients (80%) were tested positive for anti-HHV-6 IgG. The patients without HHV-6 antigen expression (n = 5, 28%) included one patient (5.6%) tested positive for anti-HHV-6 IgM and two patients (11%) tested positive for anti-HHV-6 IgG. The entire sample of patients was divided into two groups depending on the serum level of anti-HHV-6 IgM: group 1 comprised patients tested positive for anti-HHV-6 IgM (n = 5); group 2 comprised patients (n = 13) tested negative for anti-HHV-6 IgM. Clinical and instrumental parameters differed only in the duration of CHF history, which was greater in group 1 than in group 2 (11.0 [8.0; 12.0] vs. 22.5 [14.5; 75.5] months, respectively (p = 0.045). The groups did not significantly differ in the studied markers in myocardial tissue according to the results of IHC analysis. No associations were found between the severity of HHV-6 antigen expression and serum levels of anti-HHV-6 IgM and IgG.Conclusion. Patients with ADHF and/or adverse LV remodeling after complete myocardial revascularization had higher percentage of HHV-6 antigen expression whose severity was not associated with the serum levels of anti-HHV-6 IgM and IgG.

Цитомегаловирусная и смешанные вирусные инфекции у пациентов с воспалительными заболеваниями кишечника

Актуальность. Вопрос распространенности оппортунистических инфекций у лиц с воспалительными заболеваниями кишечника (ВЗК) остается актуальным. Особое внимание среди оппортунистических инфекций уделяется цитомегаловирусной (ЦМВ) инфекции. Клиническая активность ЦМВ-ассоциированного ВЗК, его длительность и степень тяжести, а также использование стероидов и анти-ФНО-α-агентов были идентифицированы как факторы риска неблагоприятных исходов. В диагностике ЦМВ важно не просто выявить наличие вируса в организме пациента, но и уточнить его этиологическую роль в развитии заболевания. В настоящее время рекомендуется проведение скрининга на ЦМВ у всех пациентов с ВЗК при гормональной резистентности, потере эффекта от поддерживающей терапии и при тяжелых эпизодах заболевания. Цель исследования: оценка частоты выявления изолированной цитомегаловирусной инфекции и смешанных (герпес и парвовирус В19) вирусных инфекций у пациентов с ВЗК и их влияние на активность заболевания. Материалы и методы. Обследовано 189 пациентов с ВЗК, 102 с язвенным колитом и 87 с болезнью Крона, среди них 98 женщин и 91 мужчина. Возраст пациентов составлял от 16 до 63 лет, в среднем (41,4 ± 4,8) года. Кроме стандартного клинико-эндоскопического обследования в соответствии с положениями Европейской организации по изучению болезни Крона и язвенного колита (ЕССО), активность заболевания оценивалась по показателям высокочувствительного С-реактивного белка, гомоцистеина, витамина D в сыворотке крови, альбумина в моче, кальпротектина и лактоферрина в кале. Всем пациентам проведено серологическое исследование крови методом иммуноферментного анализа на специфические антитела к герпесвирусам и IgG-/IgM-антитела к парвовирусу В19, а также определение ДНК вирусов простого герпеса 1, 2, 6-го типов, вируса Эпштейна — Барр, цитомегаловируса, герпеса зостер методом полимеразной цепной реакции. У всех пациентов также определяли уровни цитокинов в крови (фактор некроза опухоли α, интерлейкины 1β, -2, -4, -6, -8, -10, -18). Результаты. У пациентов с ВЗК частота выявления изолированной цитомегаловирусной инфекции составляет, по нашим данным, 19,5 %, а с учетом смешанных поражений — 29,6 %. Клинико-эндоскопическая картина (рефрактерность к базисной терапии, несоответствие между эндоскопической картиной и патоморфологическим заключением), а также данные лабораторных исследований указывают на более тяжелое течение заболевания при наличии цитомегаловирусной инфекции. Выводы. Полученные данные позволяют нам рекомендовать в дополнение к протоколам ЕССО определение наличия оппортунистических инфекций у пациентов с впервые выявленным ВЗК до начала базисной терапии, не дожидаясь развития рефрактерных к лечению форм заболевания.

Herpes Infections in Suspected Cases of Yellow Fever in the Democratic Republic of the Congo.

In the battle to quickly identify potential yellow fever arbovirus outbreaks in the Democratic Republic of the Congo, active syndromic surveillance of acute febrile jaundice patients across the country is a powerful tool. However, patients who test negative for yellow fever virus infection are too often left without a diagnosis. By retroactively screening samples for other potential viral infections, we can both try to find sources of patient disease and gain information on how commonly they may occur and co-occur. Several human arboviruses have previously been identified, but there remain many other viral families that could be responsible for acute febrile jaundice. Here, we assessed the prevalence of human herpes viruses (HHVs) in these acute febrile jaundice disease samples. Total viral DNA was extracted from serum of 451 patients with acute febrile jaundice. We used real-time quantitative PCR to test all specimens for cytomegalovirus (CMV), herpes simplex virus (HSV), human herpes virus type 6 (HHV-6) and varicella-zoster virus (VZV). We found 21.3% had active HHV replication (13.1%, 2.4%, 6.2% and 2.4% were positive for CMV, HSV, HHV-6 and VZV, respectively), and that nearly half (45.8%) of these infections were characterized by co-infection either among HHVs or between HHVs and other viral infection, sometimes associated with acute febrile jaundice previously identified. Our results show that the role of HHV primary infection or reactivation in contributing to acute febrile jaundice disease identified through the yellow fever surveillance program should be routinely considered in diagnosing these patients.

XƏRÇƏNG XƏSTƏLİKLƏRİNİN YARANMASINDA VİRUS VƏ BAKTERİYALARIN ROLU

Recently, there have been some scientific studies proving the role of viruses and bacteria in the development of cancer. Among them are eighteen types of pathogens (Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium, human papillomavirus (HPV), Barr (EBV) virus, Ephthia virus-human cell 1 (HTLV-1), human herpes virus type 8 (HHV-8) and human immunodeficiency virus type 1 (HIV-1), belong to group 1 carcinogens. Further study of the role of viruses and bacteria in the development of cancer is of great importance for the early prevention of cancer. Key words: cancer, viruses, bacteria

Retrospective Analysis of the Management of Kaposi’s Sarcoma: Single-Center Experience

Introduction: Kaposi’s sarcoma (MK) is most likely caused by human herpes virus type 8 (HHV-8) which develops particularly in individuals infected with HIV. This disease causes purplish or brownish tumors on the skin. Other organs can be affected, such as the mucous membranes, and the viscera. The goal of our study is to describe the epidemiological, clinical and therapeutic profile of this disease. Chemotherapy has big interest in Kaposi sarcoma.

Presence of human herpesvirus type 6, polyoma BK virus and parvovirus B19V in non-transplanted patients with hematological malignancies and neutropenic fever

BackgroundFebrile neutropenia is a common complication in adult patients undergoing chemotherapy for hematological malignancies. A potential causative agent is identified in approximately one third of the fever episodes. ObjectivesWe here investigated whether reactivated infection with human herpes virus 6 (HHV-6), polyoma BK virus (BKV) and parvovirus B19 (B19V) is associated with this condition. Study DesignIn a cross-sectional study, blood samples were collected at hospitalization of adult patients who developed neutropenic fever during chemotherapy for non-transplanted hematological malignancies. Detection of HHV-6A, HHV-6B, BKV and B19V DNA was performed by quantitative PCR. Clinical and laboratory data were extracted from medical records. ResultsA total of 23 of 148 (16%) samples, representing 14 of 79 (18%) patients, were PCR positive for DNA representing at least one of the three viruses; HHV-6 (n = 7 samples), BKV (n = 16 samples) and B19V (n = 6 samples). None of the samples were positive for HHV-6A DNA and all B19V DNA positive samples had viral loads below 500 copies/mL. All fever episodes, with the exception of two episodes for one BKV DNA positive patient, presented alternative presumed causative agents of the fever as detected by routine clinical diagnostics. Levels of hemoglobin, leukocyte counts, neutrophil counts, electrolytes, and creatinine were comparable for fever episodes with and without detectable viral DNA. ConclusionAlthough HHV-6B, BKV and B19V DNA could be detected in blood during a few neutropenic febrile episodes in non-transplanted hematological patients, the presence was not clearly associated to the fever.

Evaluation of Cytomegalo Virus Seropositivity in Haemodialysis Patients and its Relation to Metabolic Syndrome

Background: Chronic haemodialysis patients are at high risk for infection because the process of haemodialysis (HM) requires vascular access for prolonged periods. The humanCytomegalo Virus (CMV) is a DNA virus belonging to the Herpesviridae family, Betaherpsvirnae subfamily and Cytomegalo virus gender, known as Human Herpes Virus Type 5, one of the main causes of morbidity. Acute CMV infection is characterized by system-wide viremia after which latency and lifelong persistence is established in selected cells such as CD34+ monocytes and hematopoietic progenitor cells in humans. Objective: The work was designed for early detection of CMV infection and metabolic syndrome (MetS) in patients on HD. Patients and Methods: In this cross-sectional study, 80 patients under regular HD due to end-stage renal disease (ESRD) had participated in the study from HD Unite of Nasr City Health Insurance Hospital in Cairo in the period from June 2019 to December 2019. Results: In the present study, patients were divided into three groups, first group 78 patients were positive for CMV IgG (97.5%), second group 11 patients were positive for CMV IgM (13.8%) and third group 10 patients were positive for both IgG and IgM (12.3%). In our studythe females have more CMV antibodies. In the present study, patients with metabolic syndrome were 68 (85%). Patients who had MetS and CMV IgG were 68 (100%). The relationship between MetS and CMV IgG is statistically proved. Conclusion: the importance of early investigation for metabolic syndrome components especially in patients who are immunocompromised like HD patients because of the high prevalence of both chronic CMV infection and reactivation.

Chicken pox and pregnancy: risks to mother and fetus. Ways to solve the problem

Chickenpox is a common disease leading to a large number of clinical manifestations, ranging from mild spontaneously resolving forms to severe complicated cases requiring hospitalization and parenteral therapy. Despite the fact that this infection is benign in the majority of cases, it can lead to disseminated life-threatening processes in pregnant women and unimmunized newborns infected during the perinatal period, as well as it can cause intrauterine death and fetal abnormalities.Currently, there are no unified therapeutic approaches in the management of pregnant women with chickenpox. The nature and severity of infection in children depends on the moment of infection (before or after birth, intrapartum), the immune status of the mother against the human herpesvirus type 3 (HHV-3), the gestational age of the fetus and the presence of concomitant conditions.

Частота развития и особенности клинического течения герпесвирусных менингитов у детей и взрослых по данным областной инфекционной клинической больницы города Тюмени

Aim. The objective is to explore the incidence rate and the specifics of the clinical course of herpesviral meningitis in children and adults. Materials and methods. The post-hoc analysis of 23 patients’ records has been carried out. The patients were admitted to State Budgetary Healthcare Institution of the Tyumen Region, Clinical Hospital for Infectious Diseases, City of Tyumen, during the period of 2018-2019 diagnosed with meningitis of herpesviral etiology. When analysing the data the following aspects were taken into account: age, sex, etiological agent, complaints at admission, results of clinical examination and laboratory findings. Results. Twenty-three (23) cases of herpesviral meningitis were registered during the period of two (2) years; mixed infection was detected in every fifth patient. Epstein Barr viral meningitis was diagnosed in most cases and was detected 3.5 times oftener in adults than in children. Herpes Simplex Virus meningitis was the second one in terms of detection rate and it affected only adults. Varicella Zoster Virus meningitis was detected two times rarer than Herpes Simplex Virus and only in adults. The herpesviral meningitis caused by human herpes virus type 6 was detected with the same rate as Varicella Zoster meningitis but was registered among children only. Cytomegaloviral meningitis was detected in one adult who was affected by severe immune deficiency. Conclusion. The detected specifics of the incidence of the herpesviral meningitis with respect to a patient’s age will enable a practitioner to suggest the possible meningitis etiology and to prescribe appropriate treatment thus improving the prognosis for the disease.

A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson's Disease.

The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.

An Investigation into the Significance of HHV-6 in Catatonia and Mental Health Disorders

In this paper, the effects of all types of Human Herpes Virus (HHV-6) is reviewed in relation to encephalopathy, catatonia and mental health disorders due to recent research indicating that HHV-6 does a lot more than just causing Roseola, encephalitis and encephalopathy and that it could be the key to the recent rise in mental health disorders.
 The review suggests that the hypothesis that HHV-6 can lead to encephalopathy, catatonia and mental health disorders is true. The links between HHV-6, catatonia and mental health disorders are clear, and it seems necessary to do more research into the topic. It is possible HHV-6 plays a big role in causing catatonia among patients due to it causing encephalopathy and possibly causing and/or assisting the onset of mental health disorders, both of which are known to cause catatonia. HHV-6 is a relatively unknown pathogen to the wider population, but research is now indicating its prevalence and its effects could be behind the recent rise in mental health disorders.

A simple and rapid approach for human herpesvirus type 8 subtype characterization using single base extension.

Sequence analysis of the ORFK1 of human herpesvirus type 8 (HHV-8) allows the identification of six major subtypes (A-F), which are related to human migrations and the clinical progression of Kaposi's sarcoma. Sequencing and subsequent phylogenetic analysis of ORFK1 is considered to be the most reliable method for HHV-8 genotyping. However, it exhibits challenges and limitations. Herein, we designed and validated a single base extension (SBE) protocol for characterization of HHV-8 ORFK1 subtypes. A nested polymerase chain reaction (PCR) protocol was carried out to amplify a small 294-bp PCR product encompassing four single nucleotide polymorphisms at positions 360, 406, 465 and 527 of the HHV-8 genome. Finally, a multiplex SBE technique was developed and validated in 20 samples previously genotyped by phylogenetic analysis. The patterns obtained in this reaction could successfully discriminate between ORFK1 subtypes. The typing results obtained completely matched with those of the 'gold standard' method in all analysed samples. This method can reliably identify HHV-8 subtypes A, B and C, which are the most prevalent ones worldwide, and the remaining subtypes (D, E and F). SBE can be useful as an efficient, rapid and low-cost screening method for viral genotyping in a single tube, particularly samples with low-quality DNA, and with easy data interpretation.

Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer's disease

Alzheimer's disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI. 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein-Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity. The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD. The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

Seroprevalence of Herpes Simplex Virus Type 2 and Human Herpesvirus Type 8 among Prostate Cancer Patients Compared to Cancer-Free Men

Background: As one of the most prevalent cancers in men, prostate cancer is a condition with multiple causes. Viral infections have been identified as one of the major sources of elevated incidence of prostate cancer. Objectives: The purpose of this research was to assess the association of the risk of prostate cancer and its aggressiveness with seropositivity of herpes simplex virus 2 (HSV-2) and/or human herpesvirus 8 (HHV-8). Methods: Totally, 103 men with prostate cancer as cases and 81 healthy individuals as controls were included in this case-control analysis and provided a serum sample. The specific IgG antibodies against HSV-2 and HHV-8 were screened by enzyme-linked immunosorbent assay (ELISA). To determine the association between HSV-2, HHV-8, prostate-specific antigen (PSA) level, and demographic variables with incidence of prostate cancer, univariate and multivariate logistic regression models were applied. Results: The results of the univariate logistic regression model showed a statistically significant association between HSV-2 and HHV-8 seropositivity, PSA level, age, and smoking with prostate cancer incidence (P ≤ 0.20). The multivariate logistic regression model results after adjusting for the potential confounding variables showed a significant statistical association between the mean of PSA level [adjusted odds ratio (OR): 3.44; 95% CI: 2.15 - 5.51; P < 0.001) and incidence of prostate cancer. Moreover, the results of univariate and multivariate logistic regression model showed a significant statistical association between age [adjusted OR: 0.88; 95% confidence interval (CI): 0.81 - 0.95; P = 0.001] and HSV-2 and also significant statistical association was found between PSA (adjusted OR: 1.02; 95% CI: 1.005 - 1.03; P = 0.006) and HHV-8. Conclusions: Although the seroprevalence of HSV-2 and HHV-8 was higher in patients with prostate cancer than in the control group, it cannot be concluded that there is a significant association between the seropositivity of these viruses and prostate cancer incidence. However, the findings showed a significant statistical association between age and seropositivity of HSV-2 and also a significant statistical association between PSA levels and seropositivity of HHV-8.

High abundance of human herpesvirus 8 in wastewater from a large urban area.

This study assesses the diversity and abundance of Human Herpesviruses (HHVs) in the influent of an urban wastewater treatment plant using shotgun sequencing, metagenomic analysis and qPCR. Influent wastewater samples were collected from the three interceptors that serve the City of Detroit and Wayne, Macomb and Oakland counties between November 2017 to February 2018. The samples were subjected to a series of processes to concentrate viruses which were further sequenced and amplified using qPCR. All nine types of HHV were detected in wastewater. Human Herpesvirus 8 (HHV-8), known as Kaposi's sarcoma herpesvirus, which is only prevalent in 5-10% of USA population, was found to be the most abundant followed by HHV-3 or Varicella-zoster virus. The high abundance of HHV-8 in the Detroit metropolitan area may be attributed to the HIV-AIDS outbreak that was ongoing in Detroit during the sampling period. The approach described in this paper can be used to establish a baseline of viruses secreted by the community as a whole. Sudden changes in the baseline would identify changes in community health and immunity.

Cellular composition of macrophage infiltration in patients with acute decompensation of ischemic HFrEF depending on the diagnosed human herpes virus type 6

Abstract Funding Acknowledgements Type of funding sources: None. Objective To determine the cellular composition of macrophage infiltration in patients with acute decompensation of ischemic heart failure (ADHF) depending on the diagnosed human herpes virus type 6 (HHV6) antigen expressions in myocardial tissue. Methods This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials.gov (#NCT02649517) and included 25 patients (84% men, LVEF of 29.17 ± 9.4%) with ADHF. Inclusion criteria were ADHF, not earlier than 6 months after optimal surgery (PCI or/and CABG) and optimal drug treatment for HF according to ESC guidelines. Invasive coronary angiography was performed in all patients to exclude the progression of coronary atherosclerosis. All patients underwent endomyocardial biopsy with immunohistochemically analysis (IHC) for presence of HHV6. Immunohistochemical criteria of myocarditis were at least 14 leukocytes per sq. mm in the myocardium including up to 4 monocytes and 7 or more CD3+ T lymphocytes per sq. mm. Macrophage infiltration in the heart was assessed by double immunofluorescence. CD68 was a marker for the cells of the macrophage lineage, CD80 was considered as M1-like macrophage and CD163, CD206, stabilin-1 were as M2-like macrophage biomarkers. Each area was evaluated in 5 random fields. The 1 patient who did not have IHC was excluded from the analysis. Results After IHC, HHV6 antigen expression were detected in 63% (n = 15). There were HHV6-positive myocarditis in 42% (n = 10) and HHV6-positive patients without myocarditis - 21% (n = 5). HHV6-negative myocarditis was identified in 25% (n = 6) cases. HHV6-negative patients without myocarditis were founded in 12% (n = 3). Group with HHV6-positive myocarditis had a greater number of CD 45 (19.5 [14.0;31.0] & 14.0 [12.0;21.0], p = 0.446) and CD 68 (18.0 [14.0;30.0] & 12.0 [9.0;15.0], p = 0.075) cells than group with HHV6-negative myocarditis. The number of CD 68 (18.0 [14.0;30.0] & 12.0 [8.0; 14.0], p = 0.049) and CD 45 (19.5 [14.0;31.0] & 8.0 [7.0;8.0], p = 0.003) significantly were differed between groups with HHV6-positive myocarditis and with HHV6-positive patients without myocarditis. The analysis of macrophage infiltrate in the groups showed differences between groups with HHV6-positive myocarditis and HHV6-negative myocarditis only in the number of CD68-/CD80+ macrophages (57.0 [33.0;68.0] & 85.0 [75.5;110.0], p = 0.009). Cellular composition of macrophage infiltration is presented in pic. 1. Conclusions The incidence of myocardial HHV6 antigen expression was 63% in patients with ADHF. There were HHV6-positive myocarditis in 42% and carriage of HHV6 in 21% in this study. HHV6-positive myocarditis has been associated with a lot of number of CD 45 and CD 68 in myocardial tissue. The predominance of M2-like macrophages was observed in patients with HHV6-positive myocarditis and carriage of HHV6. There were the largest number of CD 68-/CD 80+ macrophages (M1) were detected in patients with HHV6-negative myocarditis. Abstract Figure.