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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.

Purpose: Infectious mononucleosis (IM) is an acute and self-limiting lymphoproliferative disease, and according to literature data in 90% of cases is associated with primary Epstein-Barr (EBV) viral infection. However, the mononucleosis-like syndrome is also caused by a number of other pathogens such as HHV-6, CMV, HIV, adenoviruses, etc., which makes the laboratory diagnosis necessary to identify the etiology of the disease. We compared clinical with serological IM data and defined serological profiles requiring further laboratory investigation. Materials/ Methods: We investigated 746 patients with clinical symptoms for IM who had been tested in a virological laboratory at the „St.Marina“ University Hospital in the period 2010-2016, 57.6% (95% CI: 54.0% -61.2%, n = 430) were men. The average age of the subjects was 9.56 years (SD ± 8.26), lower in the boys. We used an indirect ELISA to detect anti-VCA IgM/IgG (Euroimmun, Germany). Conclusion: The serological markers used in our laboratories (anti-VCA IgM/IgG) in combination with symptoms and other laboratory results are in most cases sufficient to confirm primary EBV infection, but there are cases where additional studies are needed to accurately determine the stage of the infection. Serological profiles requiring ongoing studies are the isolated anti-VCA IgM and anti-VCA IgG models.

Infectious mononucleosis (MI) is caused by the Herpes viridae family of viruses. Currently, most researchers assign a leading role to the Epstein-Barr virus. In present time there are no unified clinical classification of infection mononucleosis, but many authors recognize the visceral form which involves cardiovascular system, adrenal glands, lungs, central neural system and others organs. The article describes a clinical case of MI in the 28-year-old patient. She applied for medical help with complaints of fever up to 39 °C, weakness in the legs and arms, weight loss and received symptomatic treatment on an outpatient department. After 2 months on the background of deterioration, she was hospitalized in an infectious diseases hospital with severe symptoms of intoxication, lymphoproliferative syndrome, myocarditis, pericarditis, hepatitis, polyneuropathy with quadriparesis, hypochromic anemia, thrombocytopenia. She was consulted by an oncologist and diagnosed with cervical cancer. Laboratory confirmation was obtained – Epstein-Barr virus was detected in the blood. Against the background of antiviral therapy, a regression of clinical symptoms was achieved in a week. The patient was transferred to a oncological hospital. It is recommended to examine patients with high fever of unknown etiology on myocardial infarction for the timely appointed etiotropic therapy.

Background: To better understand the epidemiology of primary Epstein-Barr virus (EBV) infection and to identify EBV-naïve candidates eligible to receive a prophylactic EBV vaccine, we screened freshmen from the University of Minnesota Class of 2025 for circulating EBV antibody, which is indicative of previous infection. This permitted us to compare their EBV antibody prevalence with that of 4 other freshman classes (Classes of 2010, 2011, 2016, 2021) that have been previously published. Methods: Freshman students were recruited during screening sessions in the residence halls. Venous blood was collected and the serum fraction tested for IgG antibody against EBV viral capsid antigen (VCA IgG) using commercial enzyme immunoassays. Results: All classes combined, 1196 participants were tested (female, 677; male, 513; did not identify gender, 6) who were 18–23 years old (median, 18; mean, 18.37). The EBV VCA IgG antibody prevalence was 58% (689/1196) and was higher in women than men. The EBV antibody prevalence of 64% (170/267) in the 2010 freshman class versus 52% (78/150) in the Class of 2025 was statistically significantly different (p = 0.0223, Fisher exact test).” Conclusions: Sufficient participants are available for a prophylactic vaccine trial. Antibody prevalence decreased over 15 years from 64% to 52%. If this trend continues, the number of EBV-naïve adolescents and young adults who are in the age group most susceptible to infectious mononucleosis will increase, strengthening the rationale to develop an effective prophylactic EBV vaccine.

Purpose: The EA (early antigen) is expressed during the lytic phase of the EBV life cycle, together with VCA (viral capsid antigen) and MA (membrane antigen). Antibodies to EA (D) IgG occur in the course of primary infection, but not in all patients. The titers increase in the first 3-4 weeks and usually last about 3-4 months. Their presence is also associated with reactivation of the infection due to impaired immune control of the viral replication. The aim of this study was to compare the primary immune response against the major antigens (VCA) and EA (D) in patients with clinically proven primary infection and to define the antibody response to the EA (D) antigen as a marker for reactivation in patients at risk. Materials/Methods: We examined 86 persons with lymphomas, incl. Hodgkin's lymphoma and non-Hodgkin's lymphoma, immunosuppressed patients, mainly with AML (acute myeloid leukemia) and primary infection (infectious mononucleosis, IM) patients. We used an indirect ELISA for anti-EA (D) IgM/IgG and anti-VCA IgM/IgG (Euroimmun, Germany). Results: Patients with аnti-EA(D) IgM were 29.1% (95% CI:19.8% - 39.9%, n=25) while patients with аnti-EA(D) IgG were 23.3% (95% CI:14.8%-33.6%, n=20) (p>0.05). As expected, younger individuals with IM diagnosis predominated among the positive patients. We found isolated аnti-EA(D) IgM in four persons (with lymphoma and immunosuppression) and isolated аnti-EA(D) IgG in five patients. Conclusion: The routine diagnostic tests used to detect antibodies to VCA have a much better diagnostic value in defining a primary infection. Use of antibodies against EA (D) in case of isolated anti-VCA IgM and anti-VCA IgG needs further evaluation. Use of anti-EA (D) IgG as a reactivation marker should be compared with Real-time PCR results.

Our aim was to study the effect of cycloferon on in vitro susceptibility of peripheral blood leukocytes to interferon-α2 in children with infectious mononucleosis in acute phase caused by Epstein-Barr virus (EBV). Materials and methods were as follows: the study included 23 children 4 to 6 years of age admitted in acute period of infectious mononucleosis. The control group consisted of 15 healthy children of the same age group. In vitro susceptibility of peripheral blood leukocytes to interferon-α2 was determined by the method of L.M. Kurtasova (2007).Four types of in vitro response of peripheral blood leukocytes to interferon-α2 upon induction by cycloferon have been revealed in both healthy children and patients with EBV-positive infectious mononucleosis. Differences in occurrence rates of these 4 types of reactions have been found among patients with EBVinfection, in comparison with the group of healthy children. There was no regular dose-dependent changes in susceptibility of peripheral blood leukocytes to interferon-α2 in vitro after cycloferon induction in the group of children with EBV-infection. depending on the dose, which have been revealed in healthy children.

Atypical mononuclear cells (AM) appear in significant numbers in peripheral blood of patients with Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). We investigated the number and lineage-specific clusters of differentiation (CD) expression of atypical mononuclear cells in 110 children with IM using the anti-CD antibody microarray for panning leukocytes by their surface markers prior to morphology examination. The AM population consisted primarily of CD8+ T cells with a small fraction (0%-2% of all lymphocytes) of CD19+ B lymphocytes. AM amount in children with mononucleosis caused by primary EBV infection was significantly higher than for IM caused by EBV reactivation or other viruses and constituted 1%-53% of all peripheral blood mononuclear cells compared to 0%-11% and 0%-8%, respectively. Children failing to recover from classic IM associated with primary EBV infection within 6 months had significantly lower percentage of CD8+ AM compared to patients with normal recovery rate. [ABSTRACT FROM AUTHOR]

Objective To explore the neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) and lymphocyte (LYM) counts in children The diagnostic value of infectious mononucleosis (IM). Methods A total of 134 hospitalized IM children from September 2017 to March 2020 were collected. According to laboratory data, a total of 60 children with healthy physical examination during the same period were selected as the normal control group. Calculate NLR, MLR, LYM based on the results of the peripheral blood test, and use ROC curve analysis of the diagnostic and predictive value of NLR, MLR and LYM in children with IM. Results The MLR and LYM values of children with IM were higher than those of the normal control group. The difference was statistically significant (P<0.01), and the difference in NLR values between the two groups was not statistically significant (P>0.05). ROC shows that the area under the ROC curve of NLR (AUC) is 0.397, the AUC of MLR is 0.648, and the AUC of LYM is 0.680. The AUC of MLR+LYM is 0.878, and the best cutoff value is 0.59, The sensitivity was 82.09% and the specificity was 85.00%. Conclusion MLR and LYM are used as an independent test index to predict children with IM. Early diagnosis of IM children has important clinical value. [ABSTRACT FROM AUTHOR]

• Infectious mononucleosis is often associated with prolonged fatigue. • The association with depression was unclear since large-scale studies were lacking. • This prospective cohort study included 12,510 individuals with the infection. • Infectious mononucleosis was associated with a 40% increased risk for depression. • The increased risk was significant to the period one year or later after the infection. Infectious mononucleosis is a clinical diagnosis characterized by fever, sore throat, lymph node enlargement and often prolonged fatigue, most commonly caused by Epstein-Barr virus infection. Previous studies have indicated that infectious mononucleosis can be followed by depression; however, large-scale studies are lacking. We used nationwide registry data to investigate the association between infectious mononucleosis and subsequent depression in this first large-scale study. Prospective cohort study using nationwide Danish registers covering all 1,440,590 singletons born (1977–2005) in Denmark by Danish born parents (21,830,542 person-years' follow-up until 2016); where 12,510 individuals had a hospital contact with infectious mononucleosis. The main outcome measures were a diagnosis of major depressive disorder (ICD-8: 296.09, 298.09, 300.4; ICD-10: F32) requiring hospital contact. Infectious mononucleosis was associated with a 40% increased hazard ratio (HR) for a subsequent depression diagnosis in the fully adjusted model (HR: 1.40, 95% CI: 1.26–1.56;n = 358), when compared to unexposed individuals. The increased risk of being diagnosed with depression was significant to the periods one to four years after the infectious mononucleosis diagnosis (HR: 1.40, 95% CI: 1.17–1.67;n = 121) and ≥ five years (HR: 1.40, 95% CI: 1.22–1.61;n = 207). We did not find any differences according to age (p = 0.61) nor sex (p = 0.30). In this largest study to date, infectious mononucleosis in childhood or adolescence was associated with an increased risk of a subsequent depression. Our findings have important clinical implications and identifies youth with infectious mononucleosis as a group at high risk of later depression in young adulthood. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) is estimated to infect more than 98% of adults worldwide and is one of the most common human viruses. Acute acalculous cholecystitis (AAC) of the gallbladder is an atypical complication of infectious mononucleosis caused by EBV. Conservative management has been described in the context of AAC caused by EBV. A surgical approach must be considered in the case of acute complications such as perforation or gallbladder gangrene. We present the case of a 10-year-old female patient with AAC due to infectious mononucleosis syndrome caused by primary EBV infection. [ABSTRACT FROM AUTHOR]

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The smudge cells are well studied as a prognostic factor for chronic lymphocytic leukemia, but it is also found in viral infections. We experienced a case of abnormal hyperleukocytosis (WBC 41,600/mm3) associated with infectious mononucleosis (IM). The smudge cells were observed in peripheral blood smears, and were counted by mistake for the normal lymphocytes by the automatic blood count meter.

Infectious mononucleosis is caused by Epstein.Barr virus (EBV) infection. Although typically self.limiting, complications such as splenic infarction and splenic rupture are described. A 17.year.old man presented in the emergency department due to a 3 days history of fever with chills, soreness, fatigue, and loose stool. Ultrasound examination showed a homoechogenic splenomegaly. Viral enteritis was diagnosed and the patient was dismissed. Six days later, he reassessed due to increasing left upper quadrant abdominal pain. Ultrasound showed inhomogeneous splenomegaly with irregular hypoechogenic subcapsular lesions. Contrast.enhanced ultrasound (CEUS) characterized the lesions as not perfused tissue until the late venous phase, compatible with spleen infarctions. Serologic studies were positive for EBV. In the literature, splenic infarction is considered under.recognized. Contrast.enhanced computed tomography (CECT) and magnetic resonance imaging are associated with costs and radiation (CECT). B.mode ultrasound examination is usually used as the first imaging modality, although showing a poor sensitivity in the question of splenic lesions/infarctions. CEUS has shown instead very good sensitivity and does not harm. Therefore, we recommend CEUS examination as the first imaging modality if suspicion of spleen infarction arises, especially when B.mode ultrasound is normal. [ABSTRACT FROM AUTHOR]

Background: Primary Epstein-Barr virus (EBV) infection presents typically with features of infectious mononucleosis (IM) but it may present with atypical symptoms. We aim to evaluate the epidemiological, clinical and laboratory characteristics of primary EBV infection in children in western Saudi Arabia.Methods: A retrospective analysis of the electronic data of all children who were admitted to the hospital and were tested for EBV-viral capsid antigen (VCA) IgM in the period from 1 January 2018 to 31 December 2019. All data of the children with positive EBV-VCA IgM were collected. Patients were divided into two groups; IM and the non-typical presentations groups.Results: Fort-two patients had positive EBV-VCA IgM; 71% had IM and 29% had non-typical presentations. IM was more common in early childhood (46.7%). The non-typical presentations were more in infants below 1 year (50%). Adolescents were less affected (6.7% and 16.7%, respectively). Time to diagnose EBV in the non-typical presentations group was longer than IM group; [3.4 (3.2-4.6) vs. 4.7 (4.1-5.5), p = 0.039]. The total leucocytes count was higher in the IM syndrome group compared to the non-typical presentation group [11 (10.3-17.7) vs. 5.5 (4.5-6.4), p < 0.0001].Conclusions: Primary EBV infection in healthy children in Saudi Arabia occurs more frequently in the younger age groups. IM syndrome occurs more frequently in early childhood. The non-typical presentation occurs more frequently in infants. While adolescents are less commonly affected by primary EBV. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects' clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV. [ABSTRACT FROM AUTHOR]

The Epstein Barr virus (EBV) is a ubiquitous pathogen that has infected and remains in more than 90% of the adult population, in infectious particles in tissue cells, the virus establishes a latent infection for life, it is one of the most common viruses common in humans, it has also been linked to a large number of diseases, among which certain tumors and cancers of different types stand out. The objective of the research was to analyze the prevalence and scientific bases of the immunopathogenesis of Epstein Barr virus infection. A documentary research was carried out, through the bibliographic search of articles published in the last 5 years in English and Spanish, in databases and scientific search engines such as PubMed, Elsevier, Scielo, Redalyc, Google Academic and DOAJ. EBV infection infects 90% of the population, is transmitted mainly through saliva, affects children and adolescents, predominantly males. The history of EBV infection has been associated with oncogenic capacity and given its cosmopolitan extension, the need to investigate it is evident, especially when there is still no specific treatment or vaccine for its prophylaxis. [ABSTRACT FROM AUTHOR]

We followed college students before, during, and after infectious mononucleosis (IM) for the development of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We used network analysis to study relationships between pre-illness cytokine data amongst three groups of participants: those 30 who went on to develop ME/CFS following IM (and met one case definition), those 18 who went on to develop severe ME/CFS (S-ME-CFS) following IM (and met greater than one case definition), and those 58 who recovered following IM (controls). We recruited 4501 college students; approximately 5% developed IM during their enrollment at university. Those who developed IM were evaluated at a 6-month follow-up to determine whether they recovered or met criteria for ME/CFS; those who met >1 set of criteria for ME/CFS were termed S-ME/CFS. Patterns of pre-illness cytokine networks were then classified according to the following characteristics: membership, modularity, Eigen centrality, Total centrality, and mean degree. Network statistics were compared across groups using a one-way analysis of variance (ANOVA). Those with S-ME/CFS had a more interconnected network of cytokines, whereas recovered controls had more differentiated networks and more subgroupings of cytokine connections. Those with ME/CFS had a network that was denser than the controls, but less dense than those with severe ME/CFS. The distinct network differences between these three groups implies that there may be biological differences between our three groups of study participants at baseline. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the diagnostic value of Epstein-Barr virus (EBV) DNA load in blood samples of patients with EBV-associated diseases, and proposed a strategy for the interpretation of positive EBV DNA results.Methods: Derivation and validation cohorts were established to evaluate the clinical significance of EBV DNA loads in the peripheral blood mononuclear cells (PBMCs) and plasma from EBV-infected patients. EBV DNA loads were compared and receiver operating characteristic curves were employed to assess the optimal cutoff values of EBV DNA for identification of EBV-associated diseases.Results: The derivation and validation cohorts comprised 135 and 71 subjects, respectively. EBV DNA loads in the PBMCs of the EBV-associated diseases group was significantly higher than that of the EBV non-associated diseases group (5.8 × 104 vs 7.8 × 103 copies/106 cells, P<0.0001). The diagnostic cut-off value of viral load in PBMCs for EBV-associated diseases was determined to be 1.6 × 104 copies/106 cells. The combined EBV DNA load cutoff in PBMCs and positive EBV DNA qualitative detection in plasma (>500 copies/mL) allowed for the differentiation of EBV-associated and non-associated diseases; the sensitivity and specificity were 80.6 and 96.8%, respectively.Conclusions: The strategy of combining EBV DNA loads in PBMCs and plasma will potentially help identify EBV-associated diseases. [ABSTRACT FROM AUTHOR]

Two atypical cases of infectious mononucleosis in two teenagers with initially negative serology and non-evocative blood examinations are reported. The first patient had recently traveled to Africa, and Epstein-Barr virus negative serology led us to make many extensive investigations. The second patient complained of asthenia for a month, and PET/CT was performed to suspicion of lymphoma. PET scan revealed hypermetabolic lymph nodes in the supradiaphragmatic and subdiaphragmatic stations, along with 18 F-FDG uptake in the spleen and pharynx, raising more suspicion of lymphoma. Fortunately, Epstein-Barr virus DNA testing was performed and turned positive in both cases, and Epstein-Barr virus serology subsequently became positive. Diagnosing EBV infection can be challenging in rare cases, as EBV-specific serology may be negative in the early stages and confounding factors may be present. Therefore, Epstein-Barr virus DNA testing should be considered early in the diagnostic algorithm to prevent unnecessary investigations in similar cases., Competing Interests: 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., (© 2024 The Authors.)

Competing Interests: Conflicts of interest None.

Teaching point: Atraumatic splenic rupture is a rare but life-threatening complication of infectious mononucleosis., Competing Interests: The author has no competing interests to declare., (Copyright: © 2024 The Author(s).)

Objective: This study aimed to investigate specific clinical diagnostic methods for children with infectious mononucleosis (IM) complicated by acute acalculous cholecystitis (AAC)., Methods: We conducted a retrospective analysis of 171 cases of IM diagnosed in the infectious disease ward of Children's Hospital of Nanjing Medical University between January 2020 and December 2020. All IM patients underwent abdominal ultrasound examinations to assess the liver, gallbladder, and spleen. Fourteen patients with symptoms of AAC underwent a follow-up assessment one week later., Results: The estimated incidence of AAC in hospitalized IM children was 8.2%. Both groups of patients presented with fever, abdominal pain, and eyelid edema upon admission. Characteristic radiological findings of AAC were observed, including gallbladder (GB) distention, increased GB wall thickness and increased common bile duct diameter. Analysis of laboratory results revealed no statistically significant differences in leukocyte, absolute lymphocyte count, CD3+, CD3 + CD4+, CD3+ CD8+, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or Gamma-Glutamyl Transferase (GGT) levels between the AAC(+) and AAC(-) groups on admission. However, these parameters were not significant risk factors for AAC. After discharge, relevant indicators in non-AAC patients gradually decreased to normal levels, while those in AAC(+) patients did not show a significant decrease., Conclusion: While cases of IM complicated by AAC are relatively uncommon, the utilization of abdominal ultrasound offers a reliable tool for confirming this diagnosis. Routine abdominal ultrasound examinations are recommended for IM patients to improve early detection and treatment of associated conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Gao, Cao and Mei.)

Timely and reliable laboratory diagnostics is a necessity for patient safety and good patient management. Success in external quality assessment (EQA) reflects on the everyday work in a clinical laboratory. This study evaluated the reliability of serological point-of-care (POC) testing for the Epstein-Barr virus (EBV) that causes infectious mononucleosis (IM). Data from the results of 95 external quality control (EQC) samples, altogether 18 885 results during an eight-year period (2010-2017) were collected from 273 Finnish testing sites. Diagnosing acute infectious mononucleosis (EBV IM) is based on clinical, haematological and serological findings. Heterophile antibody tests are used for this purpose because they can be carried out at POC and are cheap and robust to perform. In this study, the data showed that the testing sites used 3 test methods and 17 different test kits; of the kits, 4 were used during the whole study period. The most commonly used test methods were immunochromatographic assays (12 test kits, 17 959 EQC results). Latex agglutination (4 test kits, 504 results) and immunofiltration test methods (one kit, 422 results) were also used. The overall success rate was 99.3% (for positive samples 99.6%, for negative samples 99.1%). The success rates of the different test methods varied from 94.3% for the immunofiltration method to 99.6% for the latex agglutination method. The lowest success rates were found for negative samples: 82.0% (QuickVue, Quidel [immunochromatographic method]), 91.3% (RDT EBV IgM Assay, Bio-Rad [immunofiltration method]). The results of the negative samples that represented old EBV immunity were the most difficult to interpret with a success rate of 98.9% compared to success rates of clearly positive (99.6%) and negative (99.5%) samples (P <.001). Especially the immunofiltration method (RDT EBV IgM Assay) produced 13.7% false positive results for samples of old immunity. The data showed that 42 of the studied 95 EBV IM EQA rounds were reported as expected (true positive or true negative) by all testing sites. [ABSTRACT FROM AUTHOR]

Infectious mononucleosis (IM) with histopathologic characteristics of T-cell lymphoma is uncommon. IM, caused by Epstein-Barr virus, is a self-limiting, benign lymphoproliferative disorder. Transferred through saliva, blood, and semen, it presents clinically in adolescents with fever, pharyngitis, and lymphadenopathy. While literature has reported cases of IM mimicking Hodgkin's lymphoma, the histopathologic resemblance of IM to T-cell lymphomas is uncommon. In this report, we present a patient who clinically presented with symptoms of IM, which was confirmed through the monospot test. The novelty of this case was that tonsillar hyperplasia initially was interpreted as T-cell lymphoma in a patient with IM. [ABSTRACT FROM AUTHOR]

A 53-year-old woman presented during the SARS-CoV-2 pandemic with an 18-day history of pyrexia, myalgia, progressive dyspnoea and loss of taste and smell after a close contact had tested positive for SARS-CoV-2. In this period two swabs had been negative for SARS-CoV-2. Clinical examination was normal. During this admission a third SARS-CoV-2 swab was negative, and investigations showed mildly elevated inflammatory markers, mildly deranged liver function, atypical lymphocytes on a blood film and a normal chest x-ray. Her Epstein–Barr virus serology was positive and thus the diagnosis was infectious mononucleosis.

Epstein-Barr virus (EBV) is a member of the herpes virus family and is characterized by fever, lymphadenopathy, and sore throat. In this report, we present a 20-year-old woman with a four-day history of fever, chills, nausea, vomiting, jaundice and abdominal pain, and a diagnosis of acalculous cholecystitis, acute hepatitis with hemolytic anemia due to infectious mononucleosis. After the confirmation of acute acalculous cholecystitis along with hemolytic anemia, prednisolone was initiated for the patient. Supportive measures resolved the symptoms of acalculous cholecystitis.

Post-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication, frequently associated with Epstein-Barr virus (EBV), which develops after solid organ or stem cell transplantation. Immunosuppression received by transplant recipients has a significant impact on the development of PTLD by suppressing the function of T cells. The preferential proliferation of NKG2A-positive natural killer (NK) cells during primary symptomatic EBV infection known as infectious mononucleosis (IM) and their reactivity toward EBV-infected B cells point to a role of NK cell in the immune control of EBV. However, NK cell-mediated immune response to EBV in immunosuppressed transplant recipients who develop PTLD remains unclear. In this study, we longitudinally analyzed the phenotype and function of different NK cell subsets in a cohort of pediatric liver transplant patients who develop PTLD and compared them to those of children with IM. We found persistently elevated plasma EBV DNA levels in the PTLD patients indicating suboptimal anti-viral immune control. PTLD patients had markedly decreased frequency of CD56dimNKG2A+Killer Immunoglobulin-like receptor (KIR)− NK cells from the time of diagnosis through remission compared to those of IM patients. Whilst the proliferation of CD56dimNKG2A+KIR− NK cells was diminished in PTLD patients, this NK cell subset maintained its ability to potently degranulate against EBV-infected B cells. Compared to cytomegalovirus (CMV)-seropositive and -negative IM patients, PTLD patients co-infected with CMV and EBV had significantly higher levels of a CMV-associated CD56dimNKG2ChiCD57+NKG2A−KIR+ NK cell subset accumulating at the expense of NKG2A+KIR− NK cells. Taken together, our data indicate that co-infection of CMV and EBV diminishes the frequency of CD56dimNKG2A+KIR− NK cells and contributes to suboptimal control of EBV in immunosuppressed children with PTLD.

Objective: Elevated levels of anti-EBNA-1 antibodies and infectious mononucleosis (IM) history have consistently been associated with multiple sclerosis (MS) risk. We aimed to study whether these aspects of Epstein–Barr virus (EBV) infection represent separate risk factors for MS and whether they both interact with MS-associated HLA genes in disease development.Methods: Two Swedish-population-based case–control studies were used, comprising 5,316 cases and 5,431 matched controls. Subjects with different HLA alleles, EBNA-1, and IM status were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Causal mediation analysis was used to assess to what extent the relationship between IM history and MS risk was mediated by high anti-EBNA-1 antibody levels and vice versa.Results: The causal mediation analysis revealed that both aspects of EBV infection mainly act directly on MS risk. The direct effect of elevated anti-EBNA-1 antibody levels on MS risk, expressed on the OR scale, was 2.8 (95% CI 2.5–3.1), and the direct effect of IM history on MS risk was 1.7 (95% CI 1.5–2.0). A significant interaction between the two aspects of EBV infection was observed (RERI 1.2, 95% CI 0.3–2.0), accounting for about 50% of the total effect. Further, both aspects of EBV infection interacted with DRB1*15:01 and absence of A*02:01.Interpretation: Elevated anti-EBNA-1 antibody levels and IM history are different risk factors for MS. The two aspects of EBV infection act synergistically to increase MS risk, indicating that they partly are involved in the same biological pathways.

Human herpesvirus type 6 (HHV-6) is a lymphotropic virus that is an etiological agent of infectious mononucleosis (IM) in children. HHV-6- mediated infectious mononucleosis (HHV-6M) does not have clearly defined clinical features. Nowadays immunopathogenetic aspects of this disease have not been fully understood. The purpose of this work was to study the characteristics of the quantitative composition of populations of immunocompetent cells of peripheral blood in children with HHV-6M. The material for the study was samples of peripheral blood from children with “infectious mononucleosis” diagnosis and from virtually healthy children. Depending on the etiologic cause of the disease, children with IM were divided into three groups: HHV-6M, IM of other etiology and mixed infection (combination of HHV-6 and Epstein–Barr virus and/or Cytomegalovirus). Virtually healthy children formed the fourth group. In blood samples, the absolute content of the following populations of immunocompetent cells was determined by the method of flow cytometry: the total population of T-lymphocytes, T- helpers, cytotoxic T-lymphocytes, double positive T-lymphocytes (CD4+CD8+), NK cells and B-lymphocytes. Discriminant analysis was carried out: based on the obtained data on the population composition of blood cells we constructed a model of a child’s attribution to one of the four groups analyzed in pairs. We used the method of machine learning — the algorithm of gradient boosting over decision trees. It was determined whether it is possible to classify patients on the basis of the studied indicators and which combination of indicators is optimal for classification. As a result of the study it was possible to classify the following pairs of groups: healthy children — children with HHV- 6M, healthy children — children with IM of other etiology, children with HHV-6M — children with IM of other etiology. When solving the problem of classifying children from group with mixed infection and from any other group, it was not possible to find a model of satisfactory quality. In comparison with virtually healthy children, children with HHV-6M were characterized by an increased content of the total population of T-lymphocytes and cytotoxic T-cells, as well as by a reduced content of doub le-positive T-lymphocytes. Compared with children with IM of other etiology, children with HHV-6M were characterized by an increased content of cytotoxic T-lymphocytes, T- helpers, B-lymphocytes and a reduced number of double-positive T cells. Our results indicate that HHV-6-mediated infectious mononucleosis causes changes in the quantitative composition of certain populations of immunocompetent cells of peripheral blood, different from those of other etiology, in children.

Purpose: Anti-VCA IgM is a marker for establishing primary infection with Epstein-Barr Virus (EBV), it usually appears in combination with anti-VCA IgG. It has been shown that there is a risk of non-specific IgM reactivity due to cross-reactions, interference with rheumatoid factor or autoantibodies. These antibodies may also occur during reactivation. In these cases, Immunoblot based tests may be useful to confirm the ELISA result. We compared the results of anti-VCA IgM in ELISA and Immunoblot IgM in patients with evidence of primary EBV infection (infectious mononucleosis, IM) and/or reactivation/reinfection. Materials/Methods: We examined 32 serum samples with commercial immunoblot (Euroline Anti-EBV Profile 2 (IgM), Euroimmun, Germany). Samples were tested primarily for anti-VCA IgM/IgG in ELISA. Patients with IM were 11, and those with probable reactivation/reinfection - 21. Results: We found positive results at 31.3% (95% CI: 16.1% -50.0 %, n = 10) of all subjects. Patients with IM and isolated anti-VCA IgM in ELISA (81.8%) were negative in Immunoblot IgM. Positive in Immunoblot IgM was 38.1% (n = 8) of the patients with suspected reactivation. We confirmed a primary infection in three of them due to the low avidity of anti-VCA IgG and missing anti-EBNA1 IgG. In five of the patients, the presence of anti-VCA IgM may be interpreted as reactivation/reinfection. Conclusion: Patients with IM and isolated anti-VCA IgM models in ELISA were not confirmed in the Immunoblot test. Approximately 43% of patients of possible reactivation was also negative in the test.

Purpose: In Bulgaria, the diagnosis of Epstein-Barr virus (EBV) infection is performed via ELISA testing of IgM and IgG against viral capsid antigen (anti-VCA IgM and anti-VCA IgG). With the current study, we try to answer is there any benefit of determination of IgG against the nuclear antigen of EBV (anti-EBNA-1 IgG) in the laboratory practice. Material/Methods: The prospective study included 82 serum/plasma samples tested for anti-VCA IgМ, anti-VCA IgG, anti-EBNA1 IgG and anti-VCA IgG avidity in ELISA (Euroimmun, Luebeck, Germany). Quantitative variables were reported as mean, and standard deviation (mean±SD) and the qualitative variables were reported as a number and a relative proportion (%). Results: Anti-EBNA1 IgG positive patients were 74.4% (95% CI:63.6% - 83.4%) of all tested individuals. Their mean age was significantly higher (30.5;SD±20.5)of this of patients without anti-EBNA1 IgG (14.5; SD±14.1) (p < 0.05).The first group of patients (with infectious mononucleosis, anti-VCA Ig M negative) had the highest number of anti-EBNA1 IgG negative results. Negative for аnti-EBNA 1 IgG were 12% of patients with Hodgkin's lymphoma. Conclusion: Determination of anti-EBNA1 IgG together with anti-VCA should be considered in the initial serological testing in EBV diagnostics. As different immune responses against the EBNA1 antigen exist, clinicians should interpret the results carefully with regard to the clinical symptoms, the immune status and the laboratory markers. We found anti-EBNA1 IgG ELISA tests exceptionally useful to distinguish primary and past infections in anti-VCA IgM(+)/anti-VCA IgG (+) patients.

During the dynamic observation, clinical and laboratory results of 194 patients with infectious mononucleosis of Eрstein-Barr etiology of different age groups were summarized. In the comparative aspect, the identity of the symptoms is revealed. Along with this, the dependence of some clinical and laboratory parameters on the age of patients was found. Patients with preschool and school age often registered febrile fever, decreased appetite, raids on tonsils, the first appeared «snoring in a dream», hepatosplenomegaly. For teenagers and adults, icterus, a pronounced mononuclear response and cytolysis syndrome are more common.

Background. In Ukraine, as in the whole world, there is a tendency to increase in the number of diffuse liver diseases. Increased percentage of patients with liver disease among adults is mostly determined by the damages to hepatobiliary system in childhood. The purpose of the study was to evaluate the effectiveness of ursodeoxycholic acid (UDCA) in the therapy of liver damages due to Epstein-Barr virus (EBV). Materials and methods. Research design: prospective, open-label, controlled. Sixty children with EBV infectious mononucleosis (IM) aged 1 to 18 years old were screened. All patients were observed, examined during the acute period of the disease, and divided into 2 groups. The children of the main group (n = 35) received standard therapy for EBV IM in combination with UDCA, patients of the control group (n = 25) received standard treatment alone. Results. Received data showed that therapy improved by means of UDCA in EBV IM and liver damage promotes a faster regression of the main symptoms of infection, such as fever, appetite loss and jaundice, already on day 7 from the beginning of treatment and a more rapid norma­lization of indicators of the functional state of the liver (alanine aminotransferase, bilirubin, alkaline phosphatase, gamma glutamyltransferase, lactate dehydrogenase). The drug was well tolerated, no adverse reactions were observed. Conclusions. The inclusion of UDCA in the treatment scheme can improve the effectiveness of advanced therapy compared with standard one, promotes a more rapid regression of infection symptoms and a more rapid norma­lization of indicators of the functional state of the liver.

The article describes the features of the clinical course of infectious mononucleosis in a child caused by pathogens of the herpesvirus family (Epstein-Barr and herpes type 6).

ObjectivesFew studies of pediatric Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM) have been conducted in Korea. We evaluated the clinical features of children with IM to define differences according to age. MethodsWe conducted retrospective chart reviews of 68 children aged 0 to 15 years who were diagnosed by EBV-associated IM with EBV-Viral Capsid Antigen(VCA) IgM at laboratory test and were admitted between 2010 and 2014. The children were classified into four age groups: aged 0–3, 4–6, 7–9, and 10–15 years. ResultsThe age distribution of patients was as follows: 19 (27.9%) 0–3, 25 (36.8%) 4–6, 13 (19.1%) 7–9, and 11 (16.2%) 10–15. Fever was the most common presentation regardless of age. It was more common in the 0–3 group than the 4–6 group (P = 0.018). Pharyngitis was more common in the 7–9 group than the 0–3 group (P = 0.048), and myalgia was more common in the 10–15 group than the 0–3 group (P = 0.007). Pharyngitis was accompanied by lymphadenopathy, protracted fever, and rash. In the 0–3 age group, the prevalence of rash was higher while the percentage of atypical lymphocytes was lower, but there was no statistical support for this tendency. There were no differences in the frequency of hepatosplenomegaly or laboratory findings between age groups. ConclusionsIM is not uncommon in young children and its clinical presentation varies with age. Therefore, IM should be suspected in young febrile children with pharyngitis and rash despite low percentages of atypical lymphocytes.

A 19-year-old otherwise healthy male presented to the Emergency Department with left upper quadrant abdominal pain having felt a “pop” in his abdomen which was followed by nausea and lightheadedness. There was no evidence of trauma but 3 weeks earlier he began with symptoms of a sore throat and nasal congestion without cough. On subsequent investigation, given the patient’s acute abdominal pain, abnormal vitals and a non-diagnostic computed tomography scan, an emergent exploratory laparotomy was performed. There was 600 mL of blood evacuated from the abdomen. A 643-gram inflamed and ruptured spleen was identified and removed, and follow-up lab work was positive for heterophile antibody. This report describes spontaneous splenic rupture caused by infectious mononucleosis and compares characteristics of traumatic versus non-traumatic cases.