Chronic Epstein-Barr Virus Infection Research Articles

Role of IL-27 in Epstein-Barr virus infection revealed by IL-27RA deficiency.

Epstein-Barr virus (EBV) infection can engender severe B cell lymphoproliferative diseases1,2. The primary infection is often asymptomatic or causes infectious mononucleosis (IM), a self-limiting lymphoproliferative disorder3. Selective vulnerability to EBV has been reported in association with inherited mutations impairing T cell immunity to EBV4. Here we report biallelic loss-of-function variants in IL27RA that underlie an acute and severe primary EBV infection with a nevertheless favourable outcome requiring a minimal treatment. One mutant allele (rs201107107) was enriched in the Finnish population (minor allele frequency = 0.0068) and carried a high risk of severe infectious mononucleosis when homozygous. IL27RA encodes the IL-27 receptor alpha subunit5,6. In the absence of IL-27RA, phosphorylation of STAT1 and STAT3 by IL-27 is abolished in T cells. In in vitro studies, IL-27 exerts a synergistic effect on T-cell-receptor-dependent T cell proliferation7 that is deficient in cells from the patients, leading to impaired expansion of potent anti-EBV effector cytotoxic CD8+ T cells. IL-27 is produced by EBV-infected B lymphocytes and an IL-27RA-IL-27 autocrine loop is required for the maintenance of EBV-transformed B cells. This potentially explains the eventual favourable outcome of the EBV-induced viral disease in patients with IL-27RA deficiency. Furthermore, we identified neutralizing anti-IL-27 autoantibodies in most individuals who developed sporadic infectious mononucleosis and chronic EBV infection. These results demonstrate the critical role of IL-27RA-IL-27 in immunity to EBV, but also the hijacking of this defence by EBV to promote the expansion of infectedtransformed B cells.

Sequential activation of DNA viruses by the RNA virus SARS-CoV-2 in patients with long COVID syndrome

Abstract Background Reactivation of Epstein-Barr virus (EBV) has been suggested to play role in long lasting multiorgan symptoms several months after the initial COVID-19 illness. Purpose The aim of our prospective study was to 1) to evaluate the reactivation of DNA viruses of EBV, Cytomegalovirus, Herpes simplex, Varicella zoster and Parvovirus-B19 by SARS-CoV-2 in patients with the diagnosis of long-COVID syndrome, 2) to investigate the effect of supposed virus reactivation on clinical conditions and long COVID syndromes. Methods Patients with long COVID syndrome were prospectively included into the Vienna PostCoV Registry between March 15th 2021 and September 30th 2021. - The time between COVID-19 infection and first clinical visit was 219±98 days (7±3 months). Clinical symptoms were documented and patients were divided into symptoms-oriented subgroups with dominantly respiratory, cardiovascular or neuropsychologic complaints. Qualitative and quantitative viral IgG and IgM titer of the selected DNA viruses of n=105 patients were compared with age and sex-matched healthy (non-infected, non-vaccinated, n=105) controls, who had neither spike- nor nucleocapsid antibodies, nor clinical history of COVID-19 disease. Results Long Covid patients had significantly higher cumulative number of IgM positivity of the DNA viruses (18.1% vs 6.7%, p=0.02), and significantly elevated quantitative EBV IgG (420±296 vs 339±282 mg/dL, p=0.033) and Parvo-B19 IgM (0.28±0.29 vs 0.03±0.12 mg/dL, p<0.001) titer as compared to healthy controls. Significantly more patients with long COVID symptoms had an EBV IgG titer above the detection limit as compared with healthy controls (40% vs 28%, p=0.018), suggesting EBV virus reactivation and chronic EBV infection. EBV IgG titer was significantly higher in patients with dominant respiratory symptoms, while elevated Parvo-B19 IgM titer was observed in patients with dominant cardiovascular complaints. In patients with long-COVID syndrome the quantitative EBV IgG titer increased with the time between infection and blood sampling (logarithmic correlation, p=0.011), suggesting the subclinical continuous EBV activation by the SARS-CoV2 RNA virus, while the quantitative Parvo-B19 IgM titer decreased linearly during the observation period. Conclusions In this study of patients with long-COVID syndrome, SARS-CoV-2 infection apparently activated certain types of DNA viruses (EBV, and Parvo-B19), as demonstrated by the significantly higher incidence of cumulative IgM positivity, and elevated EBV IgG and parvovirus-B19 IgM titers, in long-COVID patients compared to healthy controls.

Distinct association between chronic Epstein-Barr virus infection and T cell compartments from pediatric heart, kidney, and liver transplant recipients

Chronic Epstein-Barr virus (EBV) infection after pediatric organ transplantation (Tx) accounts for significant morbidity and mortality. The risk of complications, such as posttransplant lymphoproliferative disorders, in high viral load (HVL) carriers is the highest in heart Tx recipients. However, the immunologic signatures of such a risk have been insufficiently defined. Here, we assessed the phenotypic, functional, and transcriptomic profiles of peripheral blood CD8+/CD4+ T cells, including EBV-specific T cells, in 77 pediatric heart, kidney, and liver Tx recipients and established the relationship between memory differentiation and progression toward exhaustion. Unlike kidney and liver HVL carriers, heart HVL carriers displayed distinct CD8+ T cells with (1) up-regulation of interleukin-21R, (2) decreased naive phenotype and altered memory differentiation, (3) accumulation of terminally exhausted (TEX PD-1+T-bet−Eomes+) and decrease of functional precursors of exhausted (TPEX PD-1intT-bet+) effector subsets, and (4) transcriptomic signatures supporting the phenotypic changes. In addition, CD4+ T cells from heart HVL carriers displayed similar changes in naive and memory subsets, elevated Th1 follicular helper cells, and plasma interleukin-21, suggesting an alternative inflammatory mechanism that governs T cell responses in heart Tx recipients. These results may explain the different incidences of EBV complications and may help improve the risk stratification and clinical management of different types of Tx recipients.

Texture analysis of pharynx in chronic phase Epstein-Barr virus infection

Texture analysis of pharynx in chronic phase Epstein-Barr virus infection

Modification of the course of post-COVID syndrome associated with reactivation of chronic persistent Epstein−Barr virus infection and chronic nasopharyngotonsillitis of mixed etiology

A wide range of symptoms that occur in patients with post-COVID syndrome can include both manifestations of the clinical consequences of COVID-19 and symptoms of an exacerbation of a chronic pathology that they had before the development of coronavirus infection. Correct assessment of clinical data can help determine the origin of the existing manifestations of the disease and build a plan for adequate diagnostic and therapeutic measures.
 In the article, on the example of a clinical case, a variant of the modified (exacerbation of chronic pathology) course of the post-COVID syndrome was analyzed. An example of modern laboratory diagnostics of reactivation of chronic persistent EpsteinBarr virus infection and exacerbation of chronic nasopharyngotonsillitis of mixed viral-bacterial-mycotic etiology, developed against the background of post-COVID syndrome, is given. The principles of therapy for this comorbid condition are presented and explained.

The innate and T-cell mediated immune response during acute and chronic gammaherpesvirus infection.

Immediately after entry into host cells, viruses are sensed by the innate immune system, leading to the activation of innate antiviral effector mechanisms including the type I interferon (IFN) response and natural killer (NK) cells. This innate immune response helps to shape an effective adaptive T cell immune response mediated by cytotoxic T cells and CD4+ T helper cells and is also critical for the maintenance of protective T cells during chronic infection. The human gammaherpesvirus Epstein-Barr virus (EBV) is a highly prevalent lymphotropic oncovirus that establishes chronic lifelong infections in the vast majority of the adult population. Although acute EBV infection is controlled in an immunocompetent host, chronic EBV infection can lead to severe complications in immunosuppressed patients. Given that EBV is strictly host-specific, its murine homolog murid herpesvirus 4 or MHV68 is a widely used model to obtain in vivo insights into the interaction between gammaherpesviruses and their host. Despite the fact that EBV and MHV68 have developed strategies to evade the innate and adaptive immune response, innate antiviral effector mechanisms still play a vital role in not only controlling the acute infection but also shaping an efficient long-lasting adaptive immune response. Here, we summarize the current knowledge about the innate immune response mediated by the type I IFN system and NK cells, and the adaptive T cell-mediated response during EBV and MHV68 infection. Investigating the fine-tuned interplay between the innate immune and T cell response will provide valuable insights which may be exploited to design better therapeutic strategies to vanquish chronic herpesviral infection.

The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma

Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs. EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV 94.6%, HHV-6 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%). Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Effects of Alloferon versus Valaciclovir for Treating Chronic Epstein-Barr Virus Infection

Background and objectivesThis study aimed to analyze the influence of alloferon on the Epstein-Barr virus (EBV) DNA copy number in saliva samples and the changes of natural killer (NK) cell content, cytotoxic activity of killer cells, and production of interferon alpha and gamma in patients suffering chronic EBV infection (CEBVI) at 6 weeks after therapy completion.

Можливості лікування хворих на неконтрольовану бронхіальну астму з реактивацією епштейн-барр вірусної інфекції у постковідному періоді

Abstract. Both before the beginning of the pandemic of the coronavirus disease (COVID-19), and now, the problems of uncontrolled bronchial asthma (BA) are extremely relevant. The COVID-19 negatively affects the control of BA. Often, loss of asthma control after acute COVID-19 occurs due to secondary infectious complications, including reactivation of chronic Epstein-Barr virus (EBV) infection. The aim: to develop a treatment scheme for patients with uncontrolled asthma with reactivation of EBV infection in the post-COVID period and determine its effectiveness. Materials and methods. Clinical and functional indicators, laboratory results and data of chest computed tomography (CT) in dynamics in 114 patients (aged 18 to 85 years) with post-COVID syndrome who were being treated in clinical departments of National institute of phthisiology and pulmonology, National Academy of Medical Sciences of Ukraine (NIFP NAMNU) were analyzed. Among them, the diagnosis of BA was found in 17 patients. The presence of EBV infection was determined by PCR of saliva and nasopharyngeal samples. Patients with reactivation of EBV infection were treated additionally to the basic BA therapy with acyclovir, tablets, 400 mg 4 times a day for 20 days; 15 drops of proteflazid for 15-30 minutes before meals 2 times a day for 2 months and local healing therapy. Asthma control before and after treatment was determined by the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ-7) according to the GINA-2022 guidelines. All patients underwent a study of the pulmonary function before and after treatment according to spirometry data. Results. In 12 out of 17 (70.6 %) patients with BA with post-COVID syndrome, reactivation of chronic EBV infection was detected and treated. After 20 days of treatment, the patients had an improvement in the control of asthma symptoms: ACT increased from (11.4 ± 0.7) points to (20.8 ± 0.7) points, ACQ-7 decreased from (2.6 ± 0.2) points to (0.9 ± 0.1) points, p < 0.05. Improvement of the condition was observed in all patients, and the clinical effectiveness of treatment in terms of symptom control (minimum clinically important difference for the AKT index — 3 points, and for ACQ-7 — 0.5 points) was achieved in 10 (83.3 %) of 12 patients. After treatment, all parameters of spirometry improved, and peak expiratory flow, forced expiratory volume in 1 second, and parameters of large-, medium-, and small- airway patency increased with reliably significant differences. The functional efficiency of the studied treatment regimen was 75.0 %. Conclusions. For patients with uncontrolled BA with reactivation of EBV infection in the post-COVID period, in whom control of the symptoms of the disease cannot be achieved by standard methods, in addition to the basic treatment, the appointment of acyclovir, proteflazid and local healing therapy is indicated. The clinical effectiveness of the proposed treatment is 88.3 %, and the functional effectiveness is 75.0 %. Key words: bronchial asthma, asthma control, COVID-19, post-COVID-19 period, Epstein-Barr virus.

Oсобливості загострень бронхіальної астми в постковідному періоді

Abstract. COVID-19 proceeds in waves and is unpredictable, the disease can take a severe course after a temporary improvement, so the period of recovery of patients after COVID-19 is of particular importance. Some patients with bronchial asthma (BA) have worsening of symptoms and exacerbation of asthma after COVID-19. The aim: to investigate the features and frequency of the exacerbations of asthma during post-COVID-19 period among hospitalized to pulmonology department patients with post-COVID-19 syndrome. Materials and methods. Clinical and functional parameters, laboratory results, the data of the chest computed tomography (CT) and fibrobronchoscopy in the dynamics in 114 patients with post-COVID syndrome who were treated in the clinical departments of the Yanovskyi National institute of phthisiology and pulmonology NAMS of Ukraine were analyzed. Patients underwent microbiological examination of sputum or bronchoalveolar lavage for the presence of bacterial and fungal infection. The presence of Epstein-Barr virus (EBV) infection was determined by polymerase chain reaction (PCR) of saliva and nasopharyngeal samples. Results. Among 114 patients (aged 18 to 85 years) with post-COVID syndrome who were in hospital treatment, 17 (14.9 %) patients had exacerbation of BA. All examined asthma patients in the post-COVID period had an uncontrolled course of asthma. In 4 (23.5 %) of 17 patients BA was combined with chronic obstructive pulmonary disease, and 3 (17.6 %) patients had bronchiectasis, 8 (47.1 %) patients were observed for cardiovascular diseases, 2 (11.8 %) — due to diseases of the digestive and endocrine systems. Seasonal allergic rhinitis was diagnosed in 4 (23.5 %) patients, annual allergic rhinosinusitis in 6 (35.3 %), and polypous ethmoiditis in 1 (5.9 %) patient. 7 (41.2 %) patients had chronic tonsillitis. According to the spirometry data, more than half of the patients had fixed bronchial obstruction and small airways obstruction. A positive test for EBV was determined in 12 (70.6 %) of 17 patients using the PCR test of saliva and nasopharyngeal material. Conclusions. The features of the exacerbations of BA in the post-COVID period are the lack of effect from the step up of the maintenance therapy, the use of systemic steroid therapy and antibacterial therapy, the absence of the development of additional emphysematous changes in the lungs according to the chest CT data, reactivation of chronic EBV infection.

A chronic EBV infection causing persistent facial erythema multiforme and a retrospective literature review: A case report

Epstein-Barr virus (EBV) infection is associated with a variety of diseases and can involve multiple organs and systems, with complex and nonspecific clinical manifestations that are easily misdiagnosed. Chronic EBV infection with persistent erythema multiforme (EM) on the cheek as the main manifestation is very rare and has been reported rarely. This article reports a case of an adolescent female with chronic EBV infection who presented with chronic symmetrical erythema lesions on the face for 4 years, exacerbated with photophobia, lacrimation, Henoch-Schonlein purpura (HSP)-like rash, decline in granulocyte and erythrocyte lineages, hematuria, and proteinuria for 1 week. The disease was initially misdiagnosed as systemic lupus erythematosus (SLE) and later confirmed as chronic EBV infection by skin biopsy. In the case, EBV infection not only caused chronic facial EM, but also induced acute HSP and purpura nephritis (hematuria and proteinuria type). The child was treated with 1 week of glucocorticosteroids in adequate doses combined with acyclovir antiviral therapy and 3 sessions of hemoperfusion. After discharge, she took prednisone acetate (15 mg twice a day) orally for 1 month and then discontinued. She was discharged with her rash relieved and normal blood routine test and urine routine test. After 13 months of long-term follow-up, her facial erythema and hyperpigmentation became lighter, and there was no new rash on the whole body, and no abnormality in continuous monitoring of complete blood count and urine test. This case suggests the need to be alert for chronic EBV infection in adolescent females with chronic facial EM rash and multiple organs and systems injury, in addition to connective tissue diseases such as SLE.

Low Level of Advanced Glycation End Products in Serum of Patients with Allergic Rhinitis and Chronic Epstein-Barr Virus Infection at Different Stages of Virus Persistence.

Advanced glycation end products (AGEs) are formed in a nonenzymatic reaction of the reducing sugars with amino groups of proteins, lipids, and nucleic acids of different tissues and body fluids. A relatively small number of studies have been conducted on the role of AGEs in allergic inflammation. In this study, patients with allergic rhinitis (AR) were examined for the presence of Epstein-Barr virus and the content of fluorescent and nonfluorescent AGEs. We have also determined the level of a unique epitope (AGE10) which was recently identified in human serum using monoclonal antibodies against synthetic melibiose-derived AGE (MAGE). The levels of AGE10 determined with an immunoenzymatic method revealed no significant difference in the patients' blood with intermittent AR and chronic EBV persistence in the active and latent phases. It has been shown that there is a statistically significantly smaller amount of AGEs and pentosidine in groups of patients, both with and without viremia, than in healthy subjects. In turn, higher levels of immune complexes than of AGE10 were detected in the groups of patients, in contrast to the control group, which had lower levels of complexes than AGE10 concentration. In patients with active infection, there is even more complexes than of noncomplexed AGE10 antigen. The lower level of AGE in allergic rhinitis patient sera may also be due, besides complexes, to allergic inflammation continuously activating the cells, which effectively remove glycation products from the body.

Infections and immune dysregulation in ataxia-telangiectasia children with hyper-IgM and non-hyper-IgM phenotypes: A single-center experience

Ataxia-telangiectasia (A-T) is a severe syndromic neurodegenerative inborn error of immunity characterized by DNA reparation defect, chromosomal instability, and hypersensitivity to ionizing radiation, thereby predisposing affected individuals to malignant transformation. While the leading disease symptomatology is associated with progressively debilitating cerebellar ataxia accompanied by central and peripheral nervous system dysfunctions, A-T is a multisystemic disorder manifesting with the heterogeneity of phenotypic features. These include airway and interstitial lung disease, chronic liver disease, endocrine abnormalities, and cutaneous and deep-organ granulomatosis. The impaired thymic T cell production, defective B cell development and antibody production, as well as bone marrow failure, contribute to a combined immunodeficiency predisposing to infectious complications, immune dysregulation, and organ-specific immunopathology, with the A-T hyper-IgM (HIGM) phenotype determining the more severe disease course. This study aimed to clarify the immunodeficiency and associated immune dysregulation as well as organ-specific immunopathology in children with A-T. We also sought to determine whether the hyper-IgM and non-hyper-IgM phenotypes play a discriminatory role and have prognostic significance in anticipating the clinical course and outcome of the disease. We retrospectively reviewed the medical records of twelve A-T patients, aged from two to eighteen years. The patients' infectious history, organ-specific symptomatology, and immunological workup including serum alpha-fetoprotein, immunoglobulin isotypes, IgG subclasses, and lymphocyte compartments were examined. For further comparative analysis, all the subjects were divided into two groups, HIGM A-T and non-HIGM A-T. The clinical evaluation of the study group showed that recurrent respiratory tract infections due to viral and bacterial pathogens and a chronic obstructive airway disease along with impaired humoral immunity, in particular complete IgA deficiency, were noted in all the A-T patients, with both HIGM and non-HIGM phenotypes. The most important features with the discriminatory role between groups, were autoimmune disorders, observable four times more frequently in HIGM than in non-HIGM A-T. Two patients with the HIGM A-T phenotype were deceased due to liver failure and chronic Epstein-Barr virus (EBV) infection. It may therefore be assumed that the HIGM form of A-T is associated with more profound T cell dysfunction, defective immunoglobulin class switching, chronic EBV expansion, and poorer prognosis.

New drugs for multiple sclerosis: new treatment algorithms.

To discuss recent changes in the multiple sclerosis (MS) treatment algorithm and to present therapies currently in MS clinical trials. High efficacy disease modifying therapies are optimally beneficial when used in the early, inflammatory phase of MS. Bruton's tyrosine kinase has emerged as an important therapeutic target for both relapsing and progressive forms of MS. Multiple therapies targeting remyelination failed to provide conclusive evidence of broad therapeutic benefit; however, more targeted approaches offer hope that myelin repair might be achieved resulting in specific clinical improvements. Strategies targeting chronic Epstein-Barr virus infection and dysbiosis of the gut microbiome are the first to link microbial risk factors for MS and therapeutic interventions. A striking number of diverse treatments under investigation bodes well for development of better and more effective therapies in MS.

Case Report: Predominant brain superficial location of Epstein-Barr virus-related primary central nervous system diffuse large B cell lymphoma in a young woman with primary Sjögren’s syndrome

Epstein-Barr virus (EBV)- related primary central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) is very rare in young patients without immunodeficiency. The predominant brain superficial location of EBV-related primary CNS DLBCL, and its’ concurrence with EBV-related lumbar-sacral radiculitis are special and have not been described previously. A young female patient presented with multiple cranial neuropathies, radiculopathy of lower limbs, and urinary retention. Her series brain magnetic resonance imaging (MRI) revealed dynamic changes, starting from lesions mainly in cranial nerves to mammillary body, pineal body, meninges, and finally in the bilateral cerebellum and cerebral lobes. Lumber spinal MRI showed enhancement in meninges and cauda equine roots. 18-fluorodeoxyglucose PET-CT revealed remarkably increased glucose metabolism in the lesions shown on the aforementioned brain MRI and lumbar spinal MRI, as well as right axillary lymph nodes. The biopsy of a whole axillary node on right side indicated EBV-related lymphoproliferation. Lumbar meninges and cauda nerves biopsy revealed chronic inflammation. By cerebral spinal fluid cytology and in situ hybridization, EBV-encoded small RNA (EBER) positive large B cell lymphoma was identified. The patient also had primary Sjögren’s syndrome (PSS). The patient died two weeks after treatment with rituximab, lenalidomide and methylprednisolone. She had survived for four and a half months since symptom onset. The patient presented with several stages of EBV-related complications in the nervous system, chronic EBV infection of lumbar-sacral radiculitis, and primary CNS DLBCL, indicating the process from chronic EBV infection to DLBCL in nervous system. Intracranial acute bacterium infection probably exacerbated the progression of CNS DLBCL. The concomitant sufferings of PSS reflected immune-dysfunction might have increased the risk of EBV-related CNS DLBCL in this young patient.

Clinical and laboratory differences between primary acute and reactivation of chronic Epstein-Barr viral infection in children (systematic review and meta-analysis)

At the moment, the clinical differences between primary acute and reactivation of chronic infection caused by Epstein-Barr virus (EBV) have not been fully studied.The aim is to identify clinical and laboratory differences between primary acute and reactivation of chronic EBV infection in children aged 0—17 years.Materials and methods. A systematic review and meta-analysis of publications was carried out, which were searched through the bibliographic databases PubMed, Cyberleninka, eLibrary, as well as using the Researchgate scientific network. The total number of keyword search results was 1,830 publications, of which 26 were included in the study according to the results of the selection. 1318 cases of active EB infection were subjected to meta-analysis, including 917 cases of acute primary and 401 cases of reactivation.Results. Distinctive signs of primary acute EBV infection are fever, generalized lymphadenopathy, enlargement of cervical lymph nodes, acute tonsillitis, exanthema, excess of ALT reference values, leukocytosis, the presence of atypical mononuclears. With the reactivation of chronic EBV infection, the clinical manifestations are less pronounced, but in 24% of cases the disease is accompanied by the development of interstitial pneumonia. Characteristic signs are hypertrophy of the lymphoepithelial pharyngeal ring and thymomegaly, not described in primary acute infection.Conclusion. The revealed clinical and laboratory differences between primary acute and reactivation of chronic EBV infection in children aged 0—17 years can be used for differential diagnosis of these conditions.

Epidemiological characteristics of Epstein–Barr virus infection

Introduction. The Epstein–Barr virus (EBV) is one of the most common pathogens — it infects 90% of the world’s population. However, specific characteristics of the EBV infection epidemic process remain unidentified. The previous studies focusing on assessment of incidence rates for infectious mononucleosis (IM) tend to ignore the serological status of the population.The aim of the study was to identify epidemiological characteristics and assess the prevalence of serological markers for EBV infection for further epidemic control measures development.Materials and methods. In Moscow, the thorough analysis was performed using the data on IM incidence (Form 2 "Data on Infectious and Parasitic Diseases") and test results for 138,232 people checked for presence of VCA IgG, EBNA IgG, VCA IgM, EA IgG, and EBV DNA in their blood and saliva in 2011–2020.Results. The periodic pattern of IM incidence was discovered, demonstrating the repetitive peaks every 9 to 11 years and a strong direct correlative relationship with detection rates for active EBV infection markers. The intra-annual dynamics of IM incidence is characterized by a seasonal upswing during cold seasons of the year, reaching its peaks in October, November, or February and associated with a marked decrease in the VCA IgG and EBNA IgG seroprevalence. Children within the 1 to 17-year age range are groups at risk for acquiring primary infection, demonstrating significantly lower detection rates for chronic EBV infection (VCA IgG and EBNA IgG) markers and higher rates for VCA IgM and EBV DNA markers in blood compared to adults. The contribution of adult population to the epidemic process is formed through reactivation of chronic infection, which is observed primarily among women.Conclusion. The identified characteristics are essential for comprehensive understanding of the EBV infection epidemic process and can be used for developing preventive and anti-epidemic measures.

Chronic Epstein-Barr viral infection in children: a clinical case

The urgency of Epstein-Barr virus infection is explained by wide circulation of Epstein-Barr virus among children and adults, its tropism to immunocompetent cells with lifelong persistence after primary infection and polymorphism of clinical manifestations from subclinical forms, infectious mononucleosis to formation of oncological, autoimmune hematological diseases.Persistence of Epstein - Barr virus Leads to suppression of cellular immunity, decreased production of interferons and nonspecific protection factors, which contributes to reactivation of persistent infection, most often without mononucleosis-like syndrome, and the appearance of atypical mononuclears in blood with the formation of lymphoproliferative, intoxication, astheno-vegetative syndrome, long-term subfebrile condition, which dictates the need for immunocorrective therapy. This article presents a clinical case describing and analyzing the course of a chronic Epstein-Barr virus infection in a preschool child (5 years 8 months) with a pre-morbid background. Episodes of reactivation of chronic persistent infection occurred under the mask of acute respiratory infection with lymphoproliferative syndrome, purulent tonsillitis, purulent adenoiditis. Therapy, including antibiotics, short-course antiviral agents, bacterial lysates, and physiotherapy, had a temporary and short-lived effect. meglumine acridonacetate. The described clinical case demonstrates the effectiveness of the inclusion of meglumine acridonacetate, which has antiviral, immunomodulatory and anti-inflammatory effects, in the complex treatment of Epstein-Barr virus infection, This allowed to obtain fairly rapid positive clinical dynamics of relieving intoxication and febrile and lymphoproliferative syndromes in the acute period, and subsequently - astheno-vegetative syndrome and achieve the transition of active chronic Epstein - Barr virus infection into a latent form.

The impact of chronic Epstein-Barr virus infection on the liver graft of pediatric liver transplant recipients: A retrospective observational study.

Chronic high Epstein-Barr virus loads (CHEBV) are commonly observed in pediatric liver transplant patients. However, it is unclear how CHEBV impacts the liver graft. The aim of this study was to clarify the clinical and pathological impacts of CHEBV on the liver graft. From 2012 to 2020, we retrospectively investigated 46 pediatric liver transplant patients (under 16 years) who survived ≥6 months. The patients were divided into two groups: CHEBV group (EBV DNA >10000 IU/ml of whole blood for ≥6 months) and nonchronic high EBV (NCHEBV) group (patients who did not meet CHEBV criteria). Tacrolimus was reduced to <3.0 ng/ml in patients with EBV DNA >5000IU/ml. Blood biochemistry data and pathological findings, obtained at the time of protocol and episodic biopsies, were compared between the two groups. Out of 46 patients, 28 CHEBV and 18 NCHEBV patients were enrolled. The blood biochemical examination did not show a significant difference between the two groups. In addition, no significant differences between the two groups were found in the pathological findings, including frequency of late acute rejection and the progression of fibrosis at the time of both protocol and episodic biopsies. Appropriate adjustment of immunosuppression for CHEBV management may have contributed to the prevention of the progression of fibrosis. CHEBV had little adverse effect on the liver graft. Graft fibrosis might have been avoided through optimal dose modification of tacrolimus. Further long-term monitoring is necessary because CHEBV may affect the pediatric liver graft in the long term.

Hemophagocytic Lymphohistiocytosis Triggered by Leishmaniasis: A Case Report and Literature Review

Patient: Female, 40-year-old Final Diagnosis: Hemophagocytic Lymphohistiocytosis Symptoms: Chills • fatigue • fever • myalgia • sweating Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background:Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome. It is a result of uncontrolled hyperactivation of the reticuloendothelial system with a release of a huge amount of proinflammatory cytokines in the bloodstream, causing a cytokine storm. It may be primary due to genetic defects and secondary, triggered by viruses, bacteria, parasites, lymphoproliferative, and autoimmune diseases. We present a rare case of HLH triggered by leishmaniasis. HLH accounts for only about 1% of all leishmaniasis cases.Case Report:The patient was a 40-year-old previously healthy woman, who has been diagnosed with secondary HLH caused by leishmaniasis. A chronic Epstein-Barr virus (EBV) infection was initially mistakenly interpreted as a trigger agent, because Leishmania amastigotes, present on the first bone marrow biopsy, were not recognized. The treatment with cyclosporin A and corticosteroids suppressed the cytokine storm and prevented the development of complications. Two months later, because of a reactivation of the disease, the patient was referred to a hematologist. A second bone marrow aspiration was performed, in which numerous Leishmania parasites were finally identified.Conclusions:The aim of this case report is to provide more information about the rare phenomenon of secondary HLH triggered by leishmaniasis. Early recognition of the syndrome and its triggering agents will improve disease outcomes and prevent unnecessary treatment with immunosuppressive drugs.