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Background: Infectious mononucleosis caused by Epstein-Barr Virus infection is a common acute infectious disease in children. About 40–80% of children with infectious mononucleosis have hepatic injury, and hepatic failure is one of the main causes of death in patients with fatal infectious mononucleosis. Identifying the demographics, presenting clinical characteristics and the risk factors of hepatic injury in infectious mononucleosis children are helpful to remind clinicians which patients are prone to have hepatic damage.Methods: A descriptive, cross-sectional study with a 31-month retrospective review was performed on all infectious mononucleosis children hospitalized in the pediatric department of Fuyang People's Hospital. Demographic data, presenting features, radiology imaging, clinical and laboratory parameters, and clinical outcomes of infectious mononucleosis children were collected.Results: Two-hundred twenty-one infectious mononucleosis inpatients were enrolled, and 43.9% (97/221) patients were considered to have a hepatic injury (defined as alanine amino transaminase > 40 U/L). Compared with patients without hepatic injury, hepatic injury patients were marked with a significantly higher percentage of hepatomegaly (31 vs. 49%), splenomegaly (58 vs. 81%) and palpebral edema (47 vs. 63%), higher age (3.05 ± 2.12 vs. 3.84 ± 2.44), hospitalization days (6.85 ± 2.64 vs. 8.08 ± 2.83), leukocyte (14.24 ± 5.32 vs. 18.53 ± 8.63), lymphocytes (9.48 ± 4.49 vs. 13.80 ± 7.47), the proportion of atypical lymphocytes (0.12 ± 0.07 vs. 0.15 ± 0.08) and aspartate aminotransferase (33.71 ± 10.94 vs. 107.82 ± 93.52). The results of correlation analysis and multiple linear regression analysis indicated that age (OR = 1.185; 95% CI = 1.035–1.357, p = 0.014), female (OR = 2.002, 95% CI: 0.261–0.955, p = 0.036) and splenomegaly (OR = 2.171, 95% CI: 1.018–4.628, p = 0.045) were independent risk factors of hepatic injury.Conclusions: In this study, the hepatic injury was associated with gender, age, and splenomegaly, which improved our understanding of risk factors about hepatic injury among infectious mononucleosis children.

Epstein–Barr virus (EBV) is an oncogenic virus infecting more than 95% of the world’s population. After primary infection—responsible for infectious mononucleosis in young adults—the virus persists lifelong in the infected host, especially in memory B cells. Viral persistence is usually without clinical consequences, although it can lead to EBV-associated cancers such as lymphoma or carcinoma. Recent reports also suggest a link between EBV infection and multiple sclerosis. In the absence of vaccines, research efforts have focused on virological markers applicable in clinical practice for the management of patients with EBV-associated diseases. Nasopharyngeal carcinoma is an EBV-associated malignancy for which serological and molecular markers are widely used in clinical practice. Measuring blood EBV DNA load is additionally, useful for preventing lymphoproliferative disorders in transplant patients, with this marker also being explored in various other EBV-associated lymphomas. New technologies based on next-generation sequencing offer the opportunity to explore other biomarkers such as the EBV DNA methylome, strain diversity, or viral miRNA. Here, we review the clinical utility of different virological markers in EBV-associated diseases. Indeed, evaluating existing or new markers in EBV-associated malignancies or immune-mediated inflammatory diseases triggered by EBV infection continues to be a challenge.

BackgroundEpstein-Barr virus (EBV) causes infectious mononucleosis (IM) that can lead to chronic fatigue syndrome. The CEBA-project (Chronic fatigue following acute EBV infection in Adolescents) has followed 200 patients with IM and here we present an immunological profiling of adolescents with IM related to clinical characteristics.MethodsPatients were sampled within 6 weeks of debut of symptoms and after 6 months. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated in vitro (n=68), and supernatants analyzed for cytokine release. Plasma was analyzed for inflammatory markers (n=200). The Chalder Fatigue Questionnaire diagnosed patients with and without chronic fatigue at 6 months (CF+ and CF- group, respectively) (n=32 and n=91, in vitro and plasma cohorts, respectively.ResultsBroad activation of PBMC at baseline, with high levels of RANTES (Regulated on activation, normal T-cell expressed and secreted) in the CF+ group, and broad inflammatory response in plasma with high levels of T-cell markers was obeserved. At 6 months, there was an increased β-agonist response and RANTES was still elevated in cultures from the CF+ group. Plasma showed decrease of inflammatory markers except for CRP which was consistently elevated in the CF+ group.ConclusionPatients developing chronic fatigue after IM have signs of T-cell activation and low-grade chronic inflammation at baseline and after 6 months.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT02335437.

Objective: To evaluate the effects of ganciclovir combined with recombinant human interferon on clinical efficacy and immune function of children with infectious mononucleosis(IM)., Methods: This was a retrospective study. Children (n=120) with IM hospitalized in Beijing Children's Hospital Affiliated to Capital Medical University Baoding Hospital from January 2020 to January 2022 were selected and randomly divided into study group and control group((n=60). Patients in the control group were treated with ganciclovir by intravenous infusion, and patients in the study group were given ganciclovir+recombinant human interferon-α1b. The time for eliminating clinical symptoms, the levels of inflammatory cytokines, immune function condition and T-lymphocyte subsets between the two groups were compared and analyzed., Results: After treatment, the time for body temperature returned to normal, time for recovery from cervical lymphadenopathy, time for recovery from hepatosplenomegaly and time for disappearance of angina and oral mucosal congestion in the study group were significantly shorter than those in the control group(p= 0.00); after treatment, the levels of TNF-a and IL-6 in the study group were significantly lower than those in the control group; the indexes of CD3 + and CD8 + in the study group were significantly lower than those in the control group; after treatment, the levels of CD4 + and CD4 + /CD8 + in the study group were significantly higher than those in the control group., Conclusion: Ranciclovir combined with recombinant human interferon-α1b, rapid improvements of clinical symptoms, significantly decreased inflammatory cytokines, improved T-lymphocyte function and no significant increase in adverse drug reactions were found in children with IM., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

The study explored Epstein Barr Virus (EBV) exposure in 244 children using EBV-specific serology. Seroprevalence of EBV was 75-80%. Past infection and primary infection were observed in 52.04% & 8.6% respectively, whereas 23.36% showed no serological evidence of exposure to EBV. Age-stratification suggested maternal antibodies may have protected infants till 6 months of age, while the 1-3 year age group showed maximum primary infection and the 6 months to 1 year group showed the maximum susceptible group to EBV primary infection. There is a paucity of literature about EBV in India and further research is required for a better understanding of EBV pathogenesis and its clinical implications in Indian children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Infectious mononucleosis (IM) is a viral illness caused by the Epstein-Barr virus that typically manifests with pharyngitis, lymphadenopathy, and fatigue. In rare cases, IM can cause acute appendicitis. We present the case of an 18-year-old female who arrived at the emergency department with worsening abdominal pain and an ongoing cough. Initial imaging showed a questionably dilated appendix, and a follow-up examination revealed cervical lymphadenopathy. She later returned to the ED with severe abdominal pain, clinical signs of acute appendicitis, and a positive monospot test, which led to an appendectomy. This case illustrates the need for complete history taking and thorough physical examination in patients with acute appendicitis, as their condition may be due to an atypical underlying cause., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Buchmiller et al.)

Background: This study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM). Methods: Twenty-eight pediatric patients with IM aged 3–8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected. Results: The percentages and absolute numbers of CD3+ and CD8+ T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4+ and CD8+ T cells were decreased but with increased percentages of memory CD4+ and CD8+ T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αβ, and inhibitory receptors PD-1, TIGIT in CD8+ T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4+ and CD8+ T cells after stimulation with PMA/ionomycin in vitro. Multivariate analysis revealed that the percentage of HLA-DR+ CD8+ T cells was an independent prognostic marker for IM. The percentage of HLA-DR+ CD8+ T cells was significantly correlated with high viral load and abnormal liver function results. Conclusion: Robust expansion and upregulation of HLA-DR in CD8+ T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+ CD8+ T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM. [ABSTRACT FROM AUTHOR]

Ocular toxoplasmosis can present with an atypical, rare, bilateral involvement, and associated with acute retinal necrosis. It occurs in immunosuppressed patients, resulting in severe visual loss, if not quickly solved. We report an atypical case of ocular toxoplasmosis in a diabetic patient, who already showed a systemic aspect in a previous hospitalization, which was elucidated by the ophthalmologic examination and history. In addition, the routine of the uveitis sector requesting serology in a directed and careful way was essential for the diagnosis of systemic toxoplasmosis associated with atypical bilateral ocular lesion, mimicking acute retinal necrosis with good outcome. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the effectiveness of ribonucleic acid in the correction of immune disorders in patients with infectious mononucleosis (IM) caused by EBV. Materials and methods. We examined 110 patients with a mean age of 23.3 ± 4.2 years with IM, among whom women accounted for 52.7 % (n = 58). The material for the study was the serum of patients obtained during the disease course. The set of tests of patients with IM included clinical and biochemical methods, enzyme-linked immunosorbent assay, polymerase chain reaction method, immunogram. Statistical processing of the obtained data was performed with «Statsoft Statistica v. 10.0 for Windows» using the methods of variation and correlation statistics. Results. The obtained results analysis revealed changes in the system of cellular and humoral parts of the immune system and the diversity of the immune response in patients with IM. The progressive nature of changes in immune parameters indicated the formation of secondary cellular immune imbalance, activation of the humoral link, a change in the balance of immunoregulatory mediators towards Th2 cells. Significant changes in the cellular immune system were observed in the acute period and were characterized by the increase in the number of cells with killer activity, namely mature T-lymphocytes (CD3+), cytotoxic T-suppressor cells (CD8+), cells expressing the activation marker CD25+ (IL-2 receptor), and by the Th1/Th2 ratio increase. The appointment of combination therapy including ribonucleic acid was accompanied by immunomodulatory and antiviral effects, that was reflected in a more pronounced positive dynamics of immunological parameters, namely in strengthening the proliferative response, compared with the group of patients receiving only basic therapy. Conclusion. The expediency of the combination therapy application: the drug Nuclex (ribonucleic acid) (250 mg) 2 capsules 3 times a day for 14 days and valacyclovir (500 mg) at a dose of 1000 mg (2 tablets) 3 times a day for 14 days, is justified for the correction of immune disorders in patients with IM caused by EBV. [ABSTRACT FROM AUTHOR]

Infectious Mononucleosis (IM) is commonly caused by Epstein-Barr Virus (EBV) or Cytomegalovirus (CMV). Both virus groups are part of the Herpesviridae family with EBV causing most IM infections. Children with EBV infections are usually asymptomatic but when clinical signs manifest, they are often indistinguishable from other viral infections. EBV infections associated with erythema multiforme (EM) cases are rare in clinical report. This case study highlights the clinical course and management of a 14-year-old child presenting to the Emergency Department at Children's Medical Center with atypical oral lesions and acute gingival pain. [ABSTRACT FROM AUTHOR]

Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein‐Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology. Background: Infectious mononucleosis secondary to Epstein-Barr Virus is a common infection in young adults. Infection usually involves a self-limiting course of fevers, sore throat, malaise, and myalgias. Transaminitis is a relatively common complication; clinical jaundice, however, is rare. This case report highlights an uncommon complication of Epstein-Barr Virus infection in which hepatocellular injury led to clinical jaundice as well as radiologic evidence of gallbladder pathology mimicking acute calculous cholecystitis. Case Report: A 17-year-old girl with no prior medical history presented to our Emergency Department 1 week after being diagnosed with infectious mononucleosis. She was hemodynamically stable and her physical exam was notable for scleral icterus with right upper quadrant tenderness and positive Murphy's sign. Multiple imaging modalities performed showed gallbladder wall thickening without common bile duct dilatation. A hepatobiliary iminodiacetic acid (HIDA) scan showed evidence of hepatocyte dysfunction with normal gallbladder filling. The imaging results obtained in conjunction with her laboratory testing and active infectious mononucleosis infection confirmed the patient's presentation was a result of her Epstein-Barr virus infection and did not require surgical intervention for cholecystectomy. Conclusions: This case report highlights a rare complication of Epstein-Barr Virus infection and demonstrates the utility of interpreting hepatic function testing in conjunction with relevant imaging modalities in cases of clinical jaundice. By doing so, we were able to conclude the patient's gallbladder pathology was related to acute acalculous cholecystitis (AAC) and did not warrant surgical intervention. The patient was given supportive care measures and made a full recovery. [ABSTRACT FROM AUTHOR]

The DRSA method (dominance-based rough set approach) was used to create decisionmaking rules based on the results of physical examination and additional laboratory tests in the differential diagnosis of Kawasaki disease (KD), infectious mononucleosis and S. pyogenes pharyngitis in children. The study was conducted retrospectively. The search was based on the ICD-10 (International Classification of Diseases) codes of final diagnosis. Demographic and laboratory data from one Polish hospital (Poznan) were collected. Traditional statistical methods and the DRSA method were applied in data analysis. The algorithm formed 45 decision rules recognizing KD. The rules with the highest sensitivity (number of false negatives equals zero) were based on the presence of conjunctivitis and CRP (C-reactive Protein) ≥ 40.1 mg/L, thrombocytosis and ESR (Erythrocyte Sedimentation Rate) ≥ 77 mm/h; fair general condition and fever ≥ 5 days and rash; fair general condition and fever ≥ 5 days and conjunctivitis; fever ≥ 5 days and rash and CRP ≥ 7.05 mg/L. The DRSA analysis may be helpful in diagnosing KD at an early stage of the disease. It can be used even with a small amount of clinical or laboratory data. [ABSTRACT FROM AUTHOR]

Primary Epstein-Barr virus (EBV) infection is the main cause of infectious mononucleosis (IM), which typically presents with a triad of fever, lymphadenopathy, and tonsillar pharyngitis in young adults. In contrast, neurological manifestations of IM are rare. We report on a 23-year-old man with subacute oculomotor nerve palsy followed by symptoms of IM 6 days later. Primary EBV infection was confirmed by PCR detection of EBV DNA in blood as well as by subsequent serology. High-resolution magnetic resonance imaging revealed an edematous change at the root exit zone and gadolinium enhancement of the right oculomotor nerve as well as pial enhancement adjacent to the right ventral mesencephalon. A review of the literature identified 5 further patients with isolated oculomotor nerve palsy as the presenting symptom of unfolding primary EBV infection. MRIs performed in 3 of those 5 patients revealed a pattern of contrast enhancement similar to that of the present case. This case report and literature review highlight that, although rare, IM should be considered in the differential diagnosis of oculomotor nerve palsy in young adults. [ABSTRACT FROM AUTHOR]

Diseases of the tonsils and adenoids are extremely common in children and make up a significant part of the paediatric ENT surgeon's practice, as well as presenting frequently to paediatric and primary care teams. The majority of adenotonsillar pathology in children is either infective or obstructive in nature. This article discusses the anatomy and pathophysiology of acute and chronic adenotonsillar disease and discusses how to evaluate a child with suspected adenotonsillar pathology clinically, in both the outpatient and emergency scenario. Surgical management and the adenoidectomy and tonsillectomy techniques are described. The current multidisciplinary working group guidelines regarding surgery for obstructive sleep apnoea in children are also highlighted. [ABSTRACT FROM AUTHOR]

Importance: The clinical characteristics of infectious mononucleosis (IM) in Chinese children have not been evaluated in multicenter studies, and the effectiveness of antiviral treatment are controversial. Objective: To investigate the clinical characteristics of Chinese children with IM and current status of antiviral therapy for affected patients. Methods: Hospitalized patients with IM were enrolled between 2018 and 2020 in five children's hospitals in China. The clinical characteristics were compared among four age groups: <3 years, 3–<6 years, 6–<10 years, and ≥10 years. The clinical characteristics of IM and effectiveness of antiviral therapy were compared among patients receiving acyclovir (ACV), ganciclovir (GCV), and no antiviral therapy (i.e., non‐antiviral group). Results: In total, 499 patients were analyzed; most patients were 3–<6 years of age. The most common symptoms and signs included fever (100%), lymphadenopathy (98.6%), pharyngitis (86.4%), eyelid edema (76.8%), and snoring (72.9%). There were significant differences in rash, hepatomegaly, and liver dysfunction among the four age groups. Patients aged < 3 years had a lower incidence of liver dysfunction and a higher incidence of rash. Among the 499 patients, 50.1% were treated with GCV, 26.3% were treated with ACV, and 23.6% received no antiviral therapy. Compared with the non‐antiviral group, patients in the ACV and GCV groups had longer durations of fever (P < 0.001). There were no significant differences in the incidences of complications among the three treatment groups. Interpretation: The incidence of IM in Chinese children peaked at 3–<6 years of age. Clinical features of IM varied according to age. Patients receiving antiviral therapy exhibited more serious clinical manifestations than did patients without antiviral therapy. The effectiveness of antiviral therapy for IM requires further analysis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the proportion of surface activation markers on natural killer (NK) cells in children with infectious mononucleosis (IM) and to explore its clinical relevance. A total of 17 children hospitalized with IM were included in this study as the experimental group. Meanwhile, healthy children matched for age and gender served as controls. First, we isolated peripheral blood mononuclear cells from children with IM and healthy children. Then, NK cell surface markers were stained with monoclonal antibodies and analyzed by flow cytometry. The results showed that the percentage of CD3−CD16+ NK cells was higher in peripheral blood lymphocytes from children with IM than that from healthy children (t = −4.52, P < 0.05). And the expression of the surface activation markers CD69 and CD25 on CD3−CD16+ NK cells was also higher in children with IM (t = −7.729, P < 0.05; t = −5.068, P < 0.05). There was a positive correlation between the percentage of CD3−CD16+ NK cells in peripheral blood and the duration of fever in children with IM (r = 0.530, P < 0.05). Therefore, the proportion of NK cell subsets in children's peripheral blood changes in the acute phase of IM, suggesting that NK cells enhance their cytotoxicity and play a role in the control of infection in children with IM. Higher levels of CD3−CD16+ NK cells and the association with disease progression suggest that these cells might be a useful index to help evaluate the disease course. [ABSTRACT FROM AUTHOR]

BackgroundThis study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM).MethodsTwenty-eight pediatric patients with IM aged 3–8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected.ResultsThe percentages and absolute numbers of CD3+ and CD8+ T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4+ and CD8+ T cells were decreased but with increased percentages of memory CD4+ and CD8+ T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αβ, and inhibitory receptors PD-1, TIGIT in CD8+ T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4+ and CD8+ T cells after stimulation with PMA/ionomycin in vitro. Multivariate analysis revealed that the percentage of HLA-DR+ CD8+ T cells was an independent prognostic marker for IM. The percentage of HLA-DR+ CD8+ T cells was significantly correlated with high viral load and abnormal liver function results.ConclusionRobust expansion and upregulation of HLA-DR in CD8+ T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+ CD8+ T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.

Currently, infectious mononucleosis (IM) is a clinically diagnosed condition. According to the American Family Physician criteria for IM, splenomegaly is the key factor that distinguishes IM from other causes of sore throat. Though heterophile antibody tests are often ordered to confirm diagnosis of IM, this test has a high false-negative rate early in the course of the disease. This case report provides an example of how the use of ultrasound to diagnose splenomegaly and subsequently mononucleosis increases diagnostic accuracy.

Strong epidemiologic evidence links Epstein–Barr virus (EBV) infection and its altered immune control to multiple sclerosis (MS) development. Clinical MS onset occurs years after primary EBV infection and the mechanisms linking them remain largely unclear. This review summarizes the epidemiological evidence for this association and how the EBV specific immune control is altered in MS patients. The two main possibilities of mechanisms for this association are further discussed. Firstly, immune responses that are induced during a symptomatic primary EBV infection, namely infectious mononucleosis, might be amplified during the following years to finally cause central nervous system (CNS) inflammation and demyelination. Secondly, genetic predisposition and environmental factors might not allow for an efficient immune control of the EBV-infected B cells that might drive autoimmune T cell stimulation or CNS inflammation. These two main hypotheses for explaining the association of the EBV with MS would implicate opposite therapeutic interventions, namely either dampening CNS inflammatory EBV-reactive immune responses or strengthening them to eliminate the autoimmunity stimulating EBV-infected B cell compartment. Nevertheless, recent findings suggest that EBV is an important puzzle piece in the pathogenesis of MS, and understanding its contribution could open new treatment possibilities for this autoimmune disease.

Epstein-Barr virus (EBV) is one of the most widespread viruses in the world; more than 90% of the planet’s adult population is infected. Symptomatic primary infection by this Herpesviridae corresponds to infectious mononucleosis (IM), which is generally a benign disease. While virus persistence is often asymptomatic, it is responsible for 1.5% of cancers worldwide, mainly B cell lymphomas and carcinomas. EBV may also be associated with autoimmune and/or inflammatory diseases. However, no effective treatment or anti-EBV vaccine is currently available. Knowledge of the proteins and mechanisms involved in the different steps of the viral cycle is essential to the development of effective vaccines. The present review describes the main actors in the entry of the virus into B cells and epithelial cells, which are targets of interest in the development of prophylactic vaccines aimed at preventing viral infection. This review also summarizes the first vaccinal approaches tested in humans, all of which are based on the gp350/220 glycoprotein; while they have reduced the risk of IM, they have yet to prevent EBV infection. The main proteins involved in the EBV latency cycle and some of the proteins involved in the lytic cycle have essential roles in the oncogenesis of EBV. For that reason, these proteins are of interest for the development of therapeutic vaccines of which the objective is the stimulation of T cell immunity against EBV-associated cancers. New strategies aimed at broadening the antigenic spectrum, are currently being studied and will contribute to the targeting of the essential steps of the viral cycle, the objective being to prevent or treat the diseases associated with EBV.

Introduction: 3D‐DIFF scattergram of the Mindray BC‐6800 haematological analyser shows morphological abnormalities and lymphocyte cluster splitting related to the presence of reactive lymphocytes. This study aims to assess whether these cytographic changes are useful in detecting both activated and apoptotic lymphocytes, leading to an improvement in the laboratory diagnostic process of infectious mononucleosis. Methods: Two hundred three samples with modified shape and doubled lymphocyte cluster of DIFF scattergram (study group) were divided into two different subgroups: with and, respectively, without serological evidence of ongoing IM. Activated and apoptotic cells in peripheral blood were counted by light microscopy or gating in the instrumental dot plots. Values of apoptotic cells counted by microscopy were compared with those resulting from gating. Results: Samples with both shape change and doubled lymphocyte cluster had serological profiles according to the diagnosis of ongoing infectious mononucleosis. Blood smears review was positive for reactive lymphocytes in all 112 samples (100%). An underestimation of apoptotic cell count by light microscopy compared with the gating in the instrumental scatterplot was also observed (96 out of 112, 85.7%). Conclusion: The additional lymphocyte cluster was significantly associated with activated and apoptotic lymphocytes in samples with serology suggesting ongoing infectious mononucleosis. Considering the significance of clue for infectious mononucleosis assigned to the apoptotic lymphocytes, a specific flag such as "apoptotic cells?" could be associate with the related cluster. Such a flag could be used for dedicated rules for smears review, thus increasing infectious mononucleosis detection in laboratories that do not usually practise instrumental cytograms observation. [ABSTRACT FROM AUTHOR]

In cases of skin eruptions over the course of antibiotic therapy and concomitant viral infection, differential diagnosis is often challenging. Confirming or ruling out drug hypersensitivity is not always a clear-cut question. Drug reaction with eosinophilia and systemic symptoms (DRESS) cases, for example, is classified as severe cutaneous adverse reactions due to drugs, but frequently the clinical manifestations do not completely fit into the diagnosis of DRESS. The aim of the present paper is to highlight similarities and differences among DRESS syndrome and DRESS-like rashes during viral infections and amoxicillin intake in children, in order to highlight those aspects that can help clinicians in early detection. We describe the dermatological, clinical, and laboratory characteristics of five patients hospitalized for DRESS-like skin rashes appearing roughly 1 week since the start of an amoxicillina course for upper respiratory tract infection (URTI) symptoms. The data are compared with those of 3 patients with early-onset DRESS syndrome. The absence of eosinophilia might be an initial marker to help identifying DRESS-like rashes; a quick clinical improvement and the confirmation of a viral infection able to explain the symptoms can help to finally rule out DRESS syndrome. Conclusion: A rapid, correct diagnosis of such DRESS-like rashes during viral infections allows more appropriate management and avoids unnecessary, life-long exclusion of useful and effective antibiotics because of a falsely "amoxicillin-allergy" labelling. What is Known: • Viral infections are common causes of skin rashes in children during antibiotic intake and may require differential diagnosis with drug reactions. • Early-onset DRESS syndrome is usually induced by antibiotics and appears ≤15 days after drug intake. What is New: • Prominent midface edema, maculopapular rash, and mild-to-moderate systemic symptoms may appear in children during viral illnesses treated with amoxicillin few days after drug intake, and may require differential diagnosis with early-onset DRESS. • In such cases, absence of eosinophilia, low (2-3) RegiSCAR score, confirmation of viral etiology, and a rapid resolution of the rash (2-5 days) might help to rule out DRESS; conversely, at an early stage, the presence of eosinophilia should suggest a diagnosis of DRESS. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is one of the most widespread viruses in the world; more than 90% of the planet's adult population is infected. Symptomatic primary infection by this Herpesviridae corresponds to infectious mononucleosis (IM), which is generally a benign disease. While virus persistence is often asymptomatic, it is responsible for 1.5% of cancers worldwide, mainly B cell lymphomas and carcinomas. EBV may also be associated with autoimmune and/or inflammatory diseases. However, no effective treatment or anti-EBV vaccine is currently available. Knowledge of the proteins and mechanisms involved in the different steps of the viral cycle is essential to the development of effective vaccines. The present review describes the main actors in the entry of the virus into B cells and epithelial cells, which are targets of interest in the development of prophylactic vaccines aimed at preventing viral infection. This review also summarizes the first vaccinal approaches tested in humans, all of which are based on the gp350/220 glycoprotein; while they have reduced the risk of IM, they have yet to prevent EBV infection. The main proteins involved in the EBV latency cycle and some of the proteins involved in the lytic cycle have essential roles in the oncogenesis of EBV. For that reason, these proteins are of interest for the development of therapeutic vaccines of which the objective is the stimulation of T cell immunity against EBV-associated cancers. New strategies aimed at broadening the antigenic spectrum, are currently being studied and will contribute to the targeting of the essential steps of the viral cycle, the objective being to prevent or treat the diseases associated with EBV. [ABSTRACT FROM AUTHOR]

Infectious mononucleosis is a common in the pediatric population. Its clinical presentation is rather stereotyped in older children and adolescents, with symptoms made of moderate to high fever, sore throat, fatigue, and lymphadenopathy. Biologically, lymphocytosis, and a mild rise in liver function tests are usual. We report a case of acute acalculous cholecystitis as the initial presentation of infectious mononucleosis in a 12-year-old girl whose main presenting complaints were upper abdominal pain and fever. The diagnosis was confirmed by positive Epstein-Barr virus serology and the typical gallbladder appearance on the abdominal ultrasound. Clinicians are reminded of the existence of this association that, we believe, is likely more frequent than thought earlier. Patients' outcome is spontaneously favorable under supportive therapy alone. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV)‐based serologic antibody and viral nucleic acid assays have been found to be feasible means to diagnose infectious mononucleosis (IM) caused by EBV in children. In this study, we will further explore their diagnostic value for IM by EBV in different age stages and over the course of the disease. A collection of 616 children from clinically suspected IM cases was studied. Indirect immunofluorescence (IIF) for EBV‐specific antibody (Euroimmun) combined with plasma EB viral nucleic acid assay (real‐time fluorescence quantitative polymerase chain reaction reverse‐transcription polymerase chain reaction) were used as reference methods. The diagnostic efficiency of the peripheral blood routine test, serologic antibody test, and plasma EB viral nucleic acid assay for the diagnosis of IM was evaluated, respectively. The sensitivity, specificity, Youden' index and the area under curve (AUC) were 93.08%, 87.77%, 0.81 and 0.904 (95% confidence interval [CI]: 0.878–0.931) for the peripheral lymphocyte test (lymphocytosis > 5 × 109/L), 98.27%, 91.13%, 0.89 and 0.947 (95% CI: 0.927–0.967) for the plasma EBV‐DNA test, and 84.08%, 96.33%, 0.80 and 0.902 (95% CI: 0.874–0.930) for the EBV viral capsid antigen (VCA)‐IgG avidity test. The plasma EBV‐DNA test has a higher diagnostic value than the VCA‐IgG avidity test in children aged <6 years, especially aged <3 years; the peripheral lymphocyte test and plasma EBV‐DNA test are suitable for the early stage of the disease, while the VCA‐IgG avidity test for after 7 days of the disease. EBV antibody detection (IIF) should be combined with EBV nucleic acid detection in children age <6 years and the early stage of the disease. [ABSTRACT FROM AUTHOR]

Since the 1980s it is known that immune responses to the Epstein-Barr virus (EBV) are elevated in multiple sclerosis (MS) patients. Recent seroepidemiologial data have shown that this alteration after primary EBV infection identifies individuals with a more than 30-fold increased risk to develop MS. The mechanisms by which EBV infection might erode tolerance for the central nervous system (CNS) in these individuals, years prior to clinical MS onset, remain unclear. In this review I will discuss altered frequencies of EBV life cycle stages and their tissue distribution, EBV with CNS autoantigen cross-reactive immune responses and loss of immune control for autoreactive B and T cells as possible mechanisms. This discussion is intended to stimulate future studies into these mechanisms with the aim to identify candidates for interventions that might correct EBV specific immune control and/or resulting cross-reactivities with CNS autoantigens in MS patients and thereby ameliorate disease activity. • Recent seroepidemiological evidence suggests that EBV infection initiates prodromal MS disease in susceptible individuals. • Frequency of EBV life cycle stages and their tissue distribution might be altered in MS patients. • Cross-reactive antibody and T cell responses between EBV antigens and myelin autoantigens have been observed in MS patients. • Immune control of autoreactive B and T cell responses might be compromised by EBV infection and improved by HCMV infection. • Alterations of EBV infection and immune control in MS patients could be targeted for disease modification. [ABSTRACT FROM AUTHOR]

We report the case of a 44-year-old woman presenting with edema of the upper eyelids and enlarged salivary glands. Slit lamp examination found features of bilateral dacryoadenitis with no abnormalities in the anterior and posterior segments. Based on the clinical manifestations and additional test results, the diagnosis of infectious mononucleosis was confirmed. [ABSTRACT FROM AUTHOR]

Spontaneous spleen rupture (SSR) is a fatal and rare pathology causing acute abdomen. SSR secondary to infectious mononucleosis (IM) is quite rare (0.06-0.5%), and it is the most common cause of IM associated death. A 43 years old male patient, who had no previous severe disease history, chronic drug use, or previous operation applied to our emergency outpatient clinic of general surgery. The patient had complaints of severe abdominal pain, nausea, vomiting, and diarrhea. In abdominal computerized tomography, diffuse free fluid with respectively increased in density (hemorrhage?) was observed. Emergency operation was decided, because patient developed acute peritonitis signs. During exploration in the operation, it was observed that spleen was ruptured at multiple sites, and bleeding was ongoing, and splenectomy was performed. Serology was consistent with the previous EBV infection. It was mentioned in the pathology report that there was no neoplastic infiltration, and infectious causes should be investigated. No problem has been encountered during approximately two years' follow-up. SSR secondary to EMN is a rare, fatal, and very severe pathology. Diagnosis is delayed, or it is not even diagnosed because there is no trauma. Correct diagnosis on time, and decision of emergency surgical intervention can be life-saving. [ABSTRACT FROM AUTHOR]

Abstract Background Epstein-Barr virus (EBV) is an important human pathogen which causes lifelong infection of > 90% people globally and is linked to infectious mononucleosis (arising from infection in the later teenage years) and several types of cancer. Vaccines against EBV are in development. In order to determine the most cost-effective public health strategy for vaccine deployment, setting-specific data on the age at EBV acquisition and risk factors for early infection are required. Such data are also important to inform mathematical models of EBV transmission that can determine the required target product profile of vaccine characteristics. We thus aimed to examine risk factors for EBV infection in young people in England, in order to improve our understanding of EBV epidemiology and guide future vaccination strategies. Methods The Health Survey for England (HSE) is an annual, cross-sectional representative survey of households in England during which data are collected via questionnaires and blood samples. We randomly selected individuals who participated in the HSE 2002, aiming for 25 participants of each sex in each single year age group from 11 to 24 years. Stored samples were tested for EBV and cytomegalovirus (CMV) antibodies. We undertook descriptive and regression analyses of EBV seroprevalence and risk factors for infection. Results Demographic data and serostatus were available for 732 individuals. EBV seroprevalence was strongly associated with age, increasing from 60.4% in 11–14 year olds throughout adolescence (68.6% in 15–18 year olds) and stabilising by early adulthood (93.0% in those aged 22–24 years). In univariable and multivariable logistic regression models, ethnicity was associated with serostatus (adjusted odds ratio for seropositivity among individuals of other ethnicity versus white individuals 2.33 [95% confidence interval 1.13–4.78]). Smoking was less strongly associated with EBV seropositivity. Conclusions By the age of 11 years, EBV infection is present in over half the population, although age is not the only factor associated with serostatus. Knowledge of the distribution of infection in the UK population is critical for determining future vaccination policies, e.g. comparing general versus selectively targeted vaccination strategies.

Objective. The article is devoted to the study of the content of the main immune parameters in patients with infectious mononucleosis (IM) in the dynamics of the disease. Materials and methods. A clinical examination of IM patients (n = 60) and patients of the control group (n = 20) included the study of complaints, epidemiological history, history of disease and life, objective examination, standard instrumental and laboratory studies in dynamics, detection of EBV DNA in saliva and blood serum, and a comprehensive analysis of immune parameters. The main subpopulations of peripheral blood lymphocytes (CD3 +; CD4 +; CD8 +; CD16 +; CD8 + CD28 +; CD8 + CD28-; CD20 +; CD25 +) were determined by flow laser cytometry on a FACS-Calibur apparatus (USA) using monoclonal antibodies. For identification of INF-γ (Th1-cells), IL-4 (Th2-cells) in the cytoplasm of T-lymphocytes, monoclonal antibodies INF-γ-PC-5, IL-4-PE (eBioscience, Beckman Caulter, R & D System) were used. Results. A comprehensive study of the state of the subpopulations of reacting immune cells revealed significant violations of cellular parts of the immune response compared to the control group. It was established that the immune response in patients with IM during the height of the disease is characterized by an imbalance in the cell link (as evidenced by an increase in the content of CD3+, CD4+, and a simultaneous increase in the content of CD16+, CD25+). In the period of convalescence, violations have been identified that will persist without reaching the levels of the control group in a larger number of IM patients. Conclusion. The results obtained indicate significant changes in the structural characteristics of the cellular immunity system and the multidirectional immune response in IM. The progressive character of changes in immune parameters in IM indicates the formation of a secondary cellular immune imbalance, a change in the balance of immunoregulatory mediators towards the Th2 link during the formation of protracted and chronic forms of EBV-infection.

Objectives. The article presents the results of research on the definition of criteria for predicting the adverse course of infectious mononucleosis (IM) in children on the basis of the structural organization of lymphocytes of blood. Materials and methods. There were 68 children aged three to fifteen years suffering from IM under supervision. The diagnosis of IM was verified by PCR (detection of EBV DNA in the blood) and ELISA (anti-EBV Ig M and Ig G). The biophysical organization of the cytoplasmic membrane of lymphocytes was determined by the method of electron paramagnetic resonance (EPR) of spin probes using the method of additional broadening at microwave parameters 9.39 gHz, amplitude of high-frequency modulation 1 gauge, magnetic field scan time 200 sec, time constants 0.1 milliseconds (ms). Microviscosity of the intracellular environment of lymphocytes was determined by the mobility parameter of a water-soluble probe (nickel ferricyanide), which easily penetrates into the cytoplasm and in combination with extracellular paramagnetic ions, allows to evaluate the microviscosity of intracellular contents in relative units (r.u.). Results. According to the results of observations, it is established that at the stages of manifestation of the disease there are pronounced violations of the biophysical organization of the structure of lymphocytes in the form of a decrease of viscosity and elastic properties of intracellular content and cytoplasmic membrane of lymphocytes. It was characterized by the fact that the average values of the penetration rate of the electron paramagnetic resonance of the spin probe (PR EPR s.p) in patients of both groups were significantly higher than the normative ones. In the group with smooth course, they exceeded the norm by 1.5 times, and in patients with prolonged course by 1.8 times, and the values of the microviscosity of intracellular contents (MIC) were significantly reduced compared to the control - by 22.1% in patients with a smooth course of the disease and 25.1% - with a prolonged course of IM. Conclusions. In patients with prolonged course of IM these disorders were more pronounced than in the smooth course of the disease. In the period of convalescence, the indicators of the biophysical organization of the structure of lymphocytes of patients with a smooth course of IM did not differ from the norm, and in patients with a prolonged course of the disease, their reliable deviation was revealed.

Results obtained in previous studies on the relationship between exposure to organic solvents and risk of multiple sclerosis are not entirely consistent. The aim of this study was to investigate the relationship between exposure to organic solvents and risk of multiple sclerosis and possible interactions between exposure to solvents and smoking; exposure to solvents and infectious mononucleosis; exposure to solvents and D-vitamin. The case-control study on Evironmental Factors In Multiple Sclerosis (EnvIMS) was used. We examined two samples, the first one made up of 1.197 MS patients, and the second one, 2.361 healthy controls from Sweden and Norway; both group were matching in terms of their sex and age. We examined their exposure to organic solvents prior to the study; we also examined whether they had suffered from infectious mononucleosis, their outdoor activity (D-vitamin) and smoking status. The relationships between exposure to solvents and other risk factors were estimated as odds ratios (ORs) with 95 % confidence interval (95 % CI) using logistic regression. Exposure to organic solvents was found to be associated with an increased MS risk, OR 1.51 (95 % confidence interval (CI): 1.19–1.90; p = 0.001), adjusted OR was 1.36 (95 % CI: 1.05–1.75; p = 0.020). Adjusted ORs for different combinations including exposure to solvents and other risk factors such as smoking, infectious mononucleosis and D-vitamin showed an increased risk of MS. Among those who reported infectious mononucleosis there was no increased risk associated with exposure to solvents, OR 1.03 (95 % CI: 0.48–2.19). The increased risk seems to be present only in individuals with unfavorable smoking status and low D-vitamin status.

Resumen: Introducción: El objetivo de este estudio es conocer las características epidemiológicas, clínicas y analíticas de la primoinfección por el virus de Epstein-Barr (VEB) en niños sin diagnóstico previo de ninguna enfermedad inmune y su relación con la forma de presentación clínica. Pacientes y métodos: Estudio retrospectivo de pacientes entre 0 y 15 años con IgM sérica frente a la cápside viral del VEB positiva o indeterminada, durante un período de 22 meses. Se analizaron datos epidemiológicos, clínicos y de laboratorio y se compararon según tuvieran una clínica típica (síndrome mononucleósico) o no típica. Resultados: Se incluyeron 103 niños. La mediana de la edad fue de 7 años (3-12,5 años). El 63% de los pacientes presentaron clínica típica o síndrome mononucleósico y el 37% una clínica no típica. La edad fue significativamente menor en el grupo de clínica no típica (p = 0,03) y recibieron menos tratamiento antibiótico (p = 0,015). En los parámetros analíticos no hubo diferencias estadísticamente significativas excepto en la PCR, discretamente más elevada en el grupo de clínica típica (p = 0,04). El 33% de los pacientes tuvieron anticuerpos heterófilos positivos. El 20% tuvieron una IgM frente a la cápside viral indeterminada, la mayoría con clínica oligosintomática o atípica. El 21% tuvieron IgM positivas para otros virus y 3 de ellos fueron posibles falsos positivos para el VEB. Conclusiones: En nuestra población, la primoinfección por VEB es frecuente en niños de menor edad, y en ellos predominan las formas oligosintomáticas. El porcentaje de anticuerpos heterófilos positivos ha sido muy bajo en nuestra muestra. Los casos con IgM frente a la cápside viral indeterminada son más frecuentes en el grupo de clínica no típica. Es común detectar coinfección con otros virus. Abstract: Introduction: The aim of this study is to assess epidemiological, clinical and laboratory characteristics of primary infection by Epstein-Barr virus (EBV) in children without previous diagnosis of any immune disease and its relationship with clinical presentation. Patients and methods: A retrospective study was conducted on all children from 0 to 15 years with IgM against viral capsid of EBV positive or indeterminate during a 22 month period. Epidemiological, clinical and laboratory data were analysed and compared between typical (mononucleosis syndrome) and non-typical clinical symptoms. Results: The study included a total of 103 children, with a median age of 7 years (3-12.5 years). Almost two-thirds (63%) of patients had typical clinical signs, with a mononucleosis syndrome, and 37% had a non-typical presentation. The non-typical clinical group had a lower age (P = .03) and took less antibiotic than the typical clinical group (P = .015). From laboratory studies, there were no differences between the groups, except in RCP, which was higher in typical clinical group (P = .04). Heterophile antibodies were positive in 33% of patients. An indeterminate IgM against viral capsid was present in 20% of the patients, and most of them had an oligosymptomatic or atypical presentation. An IgM positive for other viruses was found in 21%, and 3 of them were suspicious of false positive for EBV. Conclusions: In the studied population, a primary infection due to EBV is common in younger ages, and they have usually an oligosymptomatic clinical presentation. A very low percentage of positive heterophile antibodies were found. Cases with indeterminate IgM against viral capsid are more frequent in the non-typical clinical group. Co-infection with other viruses is common.

Introduction: Epstein–Barr virus (EBV) infects more than 95% of the world’s population and is associated with infectious mononucleosis as well as a number of cancers in various geographical locations. Despite its significant health burden, no licenced prophylactic or therapeutic vaccines are available. Areas covered: Over the last two decades, our understanding of the role of EBV infection in the pathogenesis and immune regulation of EBV-associated diseases has provided new lines of research to conceptualize various novel prophylactic and therapeutic approaches to control EBV-associated disease. In this review, we evaluate the prophylactic and therapeutic vaccine approaches against EBV and various immunotherapeutic strategies against a number of EBV-associated malignancies. This review also describes the existing and future prospects of improved EBV-targeted therapeutic strategies. Expert opinion: It is anticipated that these emerging strategies will provide answers for the major challenges in EBV vaccine development and help improve the efficacy of novel therapeutic strategies.