Search

Copyright of Medicina Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Epstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design. Methods: Here we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses. Results: The MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine. Discussion: These results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation. [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]

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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pelvic inflammatory disease associated with cytomegalovirus infection in immunocompetent adults might be difficult to diagnose because of the rarity and relatively inconspicuous symptoms of infectious mononucleosis. Even if the main complaint is lower abdominal pain, careful search for symptoms latent outside the abdomen could lead to the diagnosis. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) reactivation in COVID-19 patients has been reported, but studies on its clinical significance are lacking. We herein report the occurrence of infectious mononucleosis (IM) due to EBV reactivation in a 60-year-old man with rheumatoid arthritis being treated with methotrexate and tocilizumab. The patient presented with a fever and tested positive for COVID-19. Laboratory findings revealed an increased atypical lymphocyte count, decreased platelet count, and elevated liver enzyme levels. Flow cytometry showed predominant expansion of reactive T cells. EBV reactivation was confirmed using real-time polymerase chain reaction. The patient was treated with remdesivir, and clinical improvement was observed after 10 days of treatment. Follow-up showed a gradual decrease in the EBV-DNA load with no recurrence of atypical lymphocytes. These findings suggest that COVID-19 in immunocompromised patients may lead to unexpected EBV reactivation and IM, even for patients outside the age at which IM is likely to occur. [ABSTRACT FROM AUTHOR]

Abstract Background Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). Methods We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). Results All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (r s = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. Conclusions All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.

Splenic rupture in haemodynamically unstable patients has traditionally been managed with splenectomy. This case report discusses the successful management of atraumatic splenic rupture, a rare but life-threatening complication of Epstein-Barr virus (EBV) infection, in a hemodynamically unstable patient. The patient, diagnosed with infectious mononucleosis (IM) secondary to EBV, presented with severe abdominal pain and a syncopal episode. Imaging revealed an American Association for the Surgery of Trauma (AAST) grade III splenic injury, which was subsequently upgraded to a grade IV injury on repeat imaging. The patient's condition deteriorated even with initial resuscitation, leading to splenic angioembolization. The procedure was successful and the patient was discharged after 5 days. This case highlights the efficacy of splenic artery embolization (SAE) in haemodynamically unstable patients with atraumatic splenic rupture, particularly in centers with interventional radiology resources, offering an alternative to splenectomy and its associated complications.

Spontaneous splenic rupture (SSR) is a relatively rare but potentially lethal complication of infectious mononucleosis (IM). While SSR is extremely rare in patients with proven IM, it is the most lethal complication of the infection (9% mortality rate) and can present completely asymptomatically or with abdominal pain and hemodynamic instability. As adolescents and young adults are the most affected population group, with this case report, we intend to raise the vigilance of any doctor treating those patients in the emergency department. We present the case of a 16-year-old patient with an atraumatic splenic rupture and hemoperitoneum secondary to an Epstein–Barr virus (EBV) infection. The patient underwent an exploratory laparotomy, and a splenectomy was performed. This case demonstrates that, even if SSR in patients with IM is extremely rare, it should always be considered in a patient with a relevant clinical presentation. [ABSTRACT FROM AUTHOR]

Background: Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). Methods: We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). Results: All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (rs = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. Conclusions: All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity. [ABSTRACT FROM AUTHOR]

Background: The goal was to study the difference of virological, immunologic, and inflammatory indicators between Epstein-Barr associated infectious mononucleosis (EBV-IM) and EBV associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to explore the evaluation indicators for monitoring the therapeutic efficacy of EBVHLH. Methods: Twenty children with EBV-IM (IM group) and 10 children with EBV-HLH (HLH group) were selected. Virology indicators were detected; the absolute count of lymphocyte, and lymphocyte subsets were detected; the levels of immunoglobulin and ferritin were assayed. Results: Compared to the IM group, the HLH group showed a decrease in EBV-specific VCA-IgM antibody levels (U = 29.0, p = 0.006) and an increase in EBV-specific NA-IgG antibody levels (U = 17.0, p = 0.001), while there was no significant difference in EB-DNA loads (t = 0.417, p = 0.680). The counts of lymphocytes, and various lymphocyte subsets in the HLH group were lower than those in the IM group. Inflammatory markers in the HLH group were significantly higher than those in IM group. Dynamic monitoring of virological, immunological, and inflammatory indicators in HLH patients during treatment showed that EBV DNA gradually decreased in patients with good prognosis. Inflammatory indicators significantly decreased and returned to normal, lymphocyte count significantly increased and returned to normal during treatment. However, patients with poor prognosis showed rebound increase in EBV DNA and inflammatory indicators in the later stage of treatment, while lymphocyte count further decreased with the recurrence of the disease. Conclusions: Exhausted and damaged immune function in host by persistent stimulation of EB viral antigen is one of the main pathogeneses of EB-HLH. Lymphocyte count and serum ferritin level are effective indicators to monitor the therapeutic efficacy during the treatment to HLH. [ABSTRACT FROM AUTHOR]

IntroductionEpstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design.MethodsHere we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses.ResultsThe MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine.DiscussionThese results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation.

Key Clinical Message Pelvic inflammatory disease associated with cytomegalovirus infection in immunocompetent adults might be difficult to diagnose because of the rarity and relatively inconspicuous symptoms of infectious mononucleosis. Even if the main complaint is lower abdominal pain, careful search for symptoms latent outside the abdomen could lead to the diagnosis.

Abstract In this study, Raman spectroscopy is applied to trace lymphocytes activation following contact with the Epstein–Barr virus (EBV) of the herpesvirus family. The biomarker of cell activation is found to be the 520 cm−1 band, indicating formation of immunoglobulins. The blood samples are obtained from patients diagnosed with infectious mononucleosis and treated at the University Hospital in Kraków. The lymphocytes’ Raman spectra are collected using a mapping technique, exciting samples with a 514.5 nm line of Ar + laser. Measurements are performed on the 1st, 4th, 6th, 12th and 30th day of hospitalization, until the patient has recovered. The highest intensity of the immunoglobulin marker is observed on the 4th day of hospitalization, while the results of the blood count of patients show the greatest increase in the number of lymphocytes at the beginning of hospitalization. No activated lymphocytes were observed in the blood of healthy volunteers. Some information is provided by the evaluation of B-cell activation by estimating the activated areas in the cells, which are determined by the presence of the Ig marker. The 900 cm−1 band and band around 1450 cm−1 are also analyzed as markers of the presence of the latent membrane protein, LMP2A (and 2B), of the EBV viral protein. The anomalous degree of depolarization observed in B-cells in the course of EBV infection appears to be due to the influence of a virus protein, disrupting BCR signal transduction.

Background: Epstein–Barr virus (EBV) is thought to be a necessary causative agent in the development of multiple sclerosis (MS). Infectious mononucleosis (IM), which occurs up to 70% of adolescents and young adults with primary EBV infection, appears to be a further risk factor but few studies have been highly powered enough to explore this association by time since IM diagnosis. Objective: The objective was to quantify the risk of MS in individuals with IM compared with the general population, with particular focus on time since IM diagnosis. Methods: In this retrospective cohort study using English national Hospital Episode Statistics from 2003 to 2023, patients with a hospital diagnosis of IM were compared with the general population for MS incidence. Results: MS incidence in patients with IM was nearly three times higher than the general population after multivariable adjustment (adjusted hazard ratio = 2.8, 95% confidence interval (CI = 2.3–3.4), driven by strong associations at long time intervals (>5 years) between IM diagnosis and subsequent MS diagnosis. Conclusion: While EBV infection may be a prerequisite for MS, the disease process of IM (i.e. the body's defective immune response to primary EBV infection) seems to be, in addition, implicated over the long term. [ABSTRACT FROM AUTHOR]

Cholestatic hepatitis is a rare complication of acute Epstein-Barr virus (EBV) infection. Here, we presented a case of acute cholestatic hepatitis secondary to acute infectious mononucleosis, who presented with complaints of abdominal pain, yellowing of the eyes and body, itching, widespread body pain, fever, nausea and vomiting. It was emphasized that EBV infection should also be considered in the differential diagnosis of cholestatic hepatitis etiology. [ABSTRACT FROM AUTHOR]

In this study, Raman spectroscopy is applied to trace lymphocytes activation following contact with the Epstein–Barr virus (EBV) of the herpesvirus family. The biomarker of cell activation is found to be the 520 cm−1 band, indicating formation of immunoglobulins. The blood samples are obtained from patients diagnosed with infectious mononucleosis and treated at the University Hospital in Kraków. The lymphocytes’ Raman spectra are collected using a mapping technique, exciting samples with a 514.5 nm line of Ar + laser. Measurements are performed on the 1st, 4th, 6th, 12th and 30th day of hospitalization, until the patient has recovered. The highest intensity of the immunoglobulin marker is observed on the 4th day of hospitalization, while the results of the blood count of patients show the greatest increase in the number of lymphocytes at the beginning of hospitalization. No activated lymphocytes were observed in the blood of healthy volunteers. Some information is provided by the evaluation of B-cell activation by estimating the activated areas in the cells, which are determined by the presence of the Ig marker. The 900 cm−1 band and band around 1450 cm−1 are also analyzed as markers of the presence of the latent membrane protein, LMP2A (and 2B), of the EBV viral protein. The anomalous degree of depolarization observed in B-cells in the course of EBV infection appears to be due to the influence of a virus protein, disrupting BCR signal transduction. [ABSTRACT FROM AUTHOR]

Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively. [ABSTRACT FROM AUTHOR]

Primary Epstein‐Barr virus (EBV) infection occasionally causes EBV‐infectious mononucleosis (EBV‐IM) and EBV‐hemophagocytic lymphohistiocytosis (EBV‐HLH). Although EBV‐IM is mostly mild and self‐limiting, EBV‐HLH is a life‐threatening disease characterized by excessive immune activation. However, the pathogenesis of EBV‐HLH is yet to be fully elucidated. A diagnostic biomarker for EBV‐HLH is desirable because early diagnosis and treatment are critical for the effective management of patients. In this study, the proteomic profiling of plasma was performed using liquid chromatography‐mass spectrometry to identify proteins specific to EBV‐IM and EBV‐HLH. Furthermore, pathway analysis was performed for the proteins upregulated in patients with EBV‐IM and EBV‐HLH. Compared to healthy controls, 63 and 18 proteins were upregulated in patients with EBV‐IM and EBV‐HLH, respectively. Pathway and process enrichment analyses revealed that the complement system was the most enriched category of upregulated proteins in EBV‐IM, whereas proteins related to immune effector processes were the most enriched in EBV‐HLH. Among the 18 proteins upregulated in EBV‐HLH, seven were exclusive to EBV‐HLH. These specific proteins were associated with three pathways, and apolipoprotein E was commonly found in all the pathways. Proteomic analysis may provide new insights into the host response to EBV infection and the pathogenesis of EBV‐related diseases. [ABSTRACT FROM AUTHOR]

This study examined the distinctions between multisystem inflammatory syndrome associated with coronavirus disease 2019, Kawasaki disease, and infectious mononucleosis. These three inflammatory disorders have commonalities according to clinical and laboratory results, particularly in relation to eosinophil levels. In this retrospective, single-center study, we documented the examination records (acute phase reactants and complete blood count) and clinical and cardiological findings of 130 patients diagnosed with multisystem inflammatory syndrome, Kawasaki disease, and infectious mononucleosis. These patients were treated and received follow-up care in our hospital from March 12, 2020, to September 13, 2022, as per the hospital records. Statistical analyses were performed using NCSS 2007, version 1 software. Eosinopenia was more prevalent in children with multisystem inflammatory syndrome than in those with Kawasaki disease, who showed normal or elevated eosinophil counts. The eosinophil counts in patients with infectious mononucleosis typically fell within the normal range. Our study found no correlation between the eosinophil counts and cardiac involvement in pediatric patients with either condition. These findings indicate a higher prevalence of eosinopenia in patients with multisystem inflammatory syndrome, irrespective of cardiac involvement, than in those with Kawasaki disease. Despite similarities in clinical findings, Kawasaki disease and multisystem inflammatory syndrome in children necessitate further studies for distinct characteristic elucidation. [ABSTRACT FROM AUTHOR]

Key Clinical Message In patients with symptoms of viral infection and marked thickening of the gallbladder wall, it is important to suspect acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis. Abstract A 35‐year‐old Japanese man presented with fever, abdominal right upper quadrant pain, and liver dysfunction. Positive immunoglobulin M and ‐G antibodies and negative nuclear antigen for Epstein–Barr virus were observed. Abdominal ultrasonography revealed a markedly thickened gallbladder wall. Acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis was diagnosed.

Infectious mononucleosis is an acute anthroponotic disease that develops as a result of human infection with viruses of the Herpesviridae family: Epstein – Barr virus (EBV), cytomegalovirus (CMV), herpes viruses of the 6th (HHV-6) and 7th types.The aim of our work was to study the clinical features and laboratory parameters of the course of infectious mononucleosis in patients of three age groups.Material and methods. A retrospective analysis of 156 medical records of patients who were on outpatient treatment by an infectious disease specialist at Clinical Medicine Center MedMix was carried out. Patients were divided into three categories according to the age criterion: the first group from 0 to 5 years consisted of 58 (37.2 %) children, the second group was represented by persons from 5 to 18 years old – 58 (37.2 %), the third group was formed by patients from 18 to 53 years old – 40 (25.6 %) people.Results and its discussion. Among children aged 0 to 5 years, boys (67.2 %) more frequently fell sick, and in the group from 18 to 53 years, females (70 %) were more likely to have the disease. Clinical symptoms such as generalized lymphadenopathy (82.7 %), nasopharyngeal lesions (79.3 %) and changes in the general blood test (86.2 %) were most frequently detected in children aged up to 5 years, while fever (81 %) and oropharyngeal lesions (74.1 %) were most frequently detected in patients aged from 5 to 18 years. Liver damage with the development of acute induced viral hepatitis was recorded in all age groups (24.1, 27.6 and 30 %). EBV infection was most frequently diagnosed among children aged from 5 to 18 years and persons aged from 18 to 53 years (in 62.1 and 70 % of cases, respectively, p < 0.05). Mixed infection with the combination of VEB + CMV + HHV-6 was significantly more frequent in children under 5 years of age (34.5 %; p < 0.05).Conclusions. In childhood, the clinical manifestations of infectious mononucleosis were more pronounced. Such intense course of the disease caused frequent visits to an infectious disease specialist and diagnostics with the establishment of an etiological agent. The dominance of EBV infection in the development of infectious mononucleosis in all groups was established. However, at the age up to 5 years, the most common mixed infections were the following combinations: EBV + CMV, EBV + HHV-6, EBV + CMV + HHV-6 and CMV + HHV-6.

Key Clinical Message: In patients with symptoms of viral infection and marked thickening of the gallbladder wall, it is important to suspect acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis. A 35‐year‐old Japanese man presented with fever, abdominal right upper quadrant pain, and liver dysfunction. Positive immunoglobulin M and ‐G antibodies and negative nuclear antigen for Epstein–Barr virus were observed. Abdominal ultrasonography revealed a markedly thickened gallbladder wall. Acalculous cholecystitis due to Epstein–Barr virus‐induced infectious mononucleosis was diagnosed. [ABSTRACT FROM AUTHOR]

The three primary differential diagnoses for a patient with systemic and hematological involvements (fever, lymphadenopathy, and hepatosplenomegaly), skin rashes, and sore pharynx are infections, connective tissue diseases, and malignancies. In this case report, we discuss possible illusory similarities between these categories that can aid in the diagnostic workup of primary care physicians. Practical Implications. The clinical course of (Infections mononncleosis, MI) patients with and their histopathological data rarely differ; Therefore, early testing for IM caused by EBV is recommended. This article will help physicians face similar cases

Introduction. Epstein–Barr virus (EBV) is one of the most common herpesviruses and has a pronounced genetic polymorphism. The study of the phylodynamic characteristics of the virus is an important aspect of the study of evolutionary changes in the LMP-1 gene and their consequences. The aim of the work was a philodynamic analysis of EBV isolates from Nizhny Novgorod region based on the C-terminal fragment of the LMP-1 gene. Materials and methods. The study included 158 EBV isolates obtained from blood leukocytes and saliva of children aged 1–17 years with a diagnosis of infectious mononucleosis caused by EBV (n = 68) and apparently healthy children of comparable sex and age (n = 29). LMP-1 genovariants were obtained using the Sanger sequencing method. Comparative analysis of amino acid sequences was performed using the MEGA X program. Philodynamic analysis of the obtained nucleotide sequences and isolates deposited in GenBank was carried out using the BEAST v. 1.10.4 software package. Recombination analysis was performed using the Simplot program. Results. 158 nucleotide sequences of the C-terminal fragment of the LMP-1 gene from Nizhny Novgorod region EBV isolates were obtained and deposited in the GenBank database. The circulation time of the nearest common ancestor for the modified B95-8 genovariants with G212S + E328Q + S366T and NC mutations with the D250N substitution has been established dating back to 1994 and 1923. The rate of evolution of these genovariants was the highest and amounted to 1.298 × 10–4 and 7.868 × 10–4 nucleotide substitutions/site/year. Recombinations were detected in the Nizhny Novgorod region sequences Med-, B95-8, China 1 with mutations G212S, G212S, E214Q, respectively. Conclusion. For the first time, a phylodynamic characterization of Nizhny Novgorod region isolates and LMP-1 EBV genovariants isolated in various regions of the world is given. The data obtained expand the existing understanding of the circulation of EBV LMP-1 genovariants in the territory of the European part of Russia.

Background: Epstein-Barr virus (EBV) is a DNA virus that infects almost all adults. It is usually asymptomatic or causes a self-limiting illness but rarely can present serious complications. Case Description: We hereby report the case of a 28-year-old female who presented to us with a history of fever with malaise and an episode of Malena. She was hemodynamically stable. She had thrombocytopenia, elevated transaminases, and polyserositis on workup. She was evaluated for the same and found to be EBV positive with remaining infective and autoimmune workup within normal limits. Her symptoms persisted for a total duration of approximately 3 weeks before she became asymptomatic and was discharged. Conclusion: This case highlights that EBV should be considered as a differential diagnosis in such cases with atypical presentations especially in young adults. [ABSTRACT FROM AUTHOR]

Introduction: Infectious mononucleosis (IM) is a common infectious disease in children mainly caused by Epstein–Barr virus (EBV) infection, followed by abnormal immune response, and resulting in serious complications. However, there are few clinical analyses of immune responses in children with IM at different stages. Methods: This study combined EBV serological test and EBV DNA test to diagnose the infection status of children with IM, and the infection status was divided into primary acute IM infection (AIM), primary late IM infection (LIM) and reactivation IM infection (RIM). Results: The results revealed that the absolute numbers of leukocytes and CD8+ T lymphocytes in primary IM infection were significantly higher than those in reactivation infection, while the frequencies of CD4+ T lymphocytes and B cells were significantly lower than those in reactivation infection. In addition, the activities of ALT, AST, α‐HBDH and LDH in liver function indicators in primary infection were significantly increased compared with reactivation infection. Similarly, the EBV DNA levels of the primary infection were significantly higher than that of the reactivation infection. Conclusion: There are differences in immune response at different stages of infection, which can provide guidance for effective treatment in children with IM infection. [ABSTRACT FROM AUTHOR]

Copyright of Farmacie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The three primary differential diagnoses for a patient with systemic and hematological involvements (fever, lymphadenopathy, and hepatosplenomegaly), skin rashes, and sore pharynx are infections, connective tissue diseases, and malignancies. In this case report, we discuss possible illusory similarities between these categories that can aid in the diagnostic workup of primary care physicians. Practical Implications. The clinical course of (Infections mononncleosis, MI) patients with and their histopathological data rarely differ; Therefore, early testing for IM caused by EBV is recommended. This article will help physicians face similar cases. [ABSTRACT FROM AUTHOR]

We present the case of a 70-year-old woman presenting with nausea, diarrhoea and a generalised rash. Initial blood tests revealed obstructive deranged liver function tests and low haemoglobin. A haemolysis screen revealed raised reticulocytes, low haptoglobin and a positive direct antiglobulin test. 6 days into her admission, she developed lower limb weakness and loss of sensation. MRI spine showed no significant findings. Cerebrospinal fluid showed raised white blood cell count and raised protein. Nerve conduction studies were normal. The clinical picture was in keeping with transverse myelitis. Autoimmune and viral screens were negative except for a single result which provided the unifying diagnosis: Epstein--Barr virus (EBV). She responded to high dose intravenous corticosteroids and her rehabilitation is ongoing. EBV should be considered even in the older population. [ABSTRACT FROM AUTHOR]

Key Clinical Message When seeing patients who present with atypical lymphocytes and abdominal pain without accompanying symptoms of pharyngitis or lymphadenopathy, acalculous cholecystitis caused by CMV infection should be considered as a differential diagnosis. Abstract A teenage man presented with a fever and epigastric pain. The patient tested positive for cytomegalovirus IgG and IgM. Abdominal ultrasonography and contrast‐enhanced CT revealed hepatosplenomegaly and gallbladder wall thickening. MRI did not identify gallstones or tumorous lesions. He was diagnosed with infectious mononucleosis and acalculous cholecystitis caused by cytomegalovirus.

ObjectiveThis study aimed to investigate specific clinical diagnostic methods for children with infectious mononucleosis (IM) complicated by acute acalculous cholecystitis (AAC).MethodsWe 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.ResultsThe 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.ConclusionWhile 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.

Abstract Background and aim Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. Methods We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. Results Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. Conclusions IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.

Key Clinical Message: When seeing patients who present with atypical lymphocytes and abdominal pain without accompanying symptoms of pharyngitis or lymphadenopathy, acalculous cholecystitis caused by CMV infection should be considered as a differential diagnosis. A teenage man presented with a fever and epigastric pain. The patient tested positive for cytomegalovirus IgG and IgM. Abdominal ultrasonography and contrast‐enhanced CT revealed hepatosplenomegaly and gallbladder wall thickening. MRI did not identify gallstones or tumorous lesions. He was diagnosed with infectious mononucleosis and acalculous cholecystitis caused by cytomegalovirus. [ABSTRACT FROM AUTHOR]

Spontaneous splenic rupture (SSR) is a relatively rare but potentially lethal complication of infectious mononucleosis (IM). While SSR is extremely rare in patients with proven IM, it is the most lethal complication of the infection (9% mortality rate) and can present completely asymptomatically or with abdominal pain and hemodynamic instability. As adolescents and young adults are the most affected population group, with this case report, we intend to raise the vigilance of any doctor treating those patients in the emergency department. We present the case of a 16-year-old patient with an atraumatic splenic rupture and hemoperitoneum secondary to an Epstein–Barr virus (EBV) infection. The patient underwent an exploratory laparotomy, and a splenectomy was performed. This case demonstrates that, even if SSR in patients with IM is extremely rare, it should always be considered in a patient with a relevant clinical presentation.

Abstract Background Multiple immunopathological responses to viruses are observed in infectious mononucleosis (IM), a manifestation of primary infection with Epstein-Barr virus (EBV). Protective effects of the negative immunoregulatory molecule interleukin-37 (IL-37) have been observed in various bacterial and viral infections. However, the function of IL-37 in IM remains unknown. Methods Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of IL-37 in the peripheral blood of patients diagnosed with IM, and the variation of lymphocyte subsets. Furthermore, the associations between IL-37 expression and the percentage of lymphocyte subgroups were analyzed. Results Patients with IM had severe immune dysfunction. The control group had a lower expression of IL-37 than the patients with IM. There were significant associations between IL-37 expression and both the proportion of CD3+T cells and the ratio of CD3+CD4+ to CD3+CD8+T cells. Patients with higher levels of IL-37 expression had lower levels of the liver inflammation indicators, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Conclusions IL-37 may affect the immune pathogenesis of patients with IM infected with EBV, and may have immunotherapeutic benefit for EBV-associated illnesses.

Oluf Andersen,1 Ingemar Ernberg,2 Anna Karin Hedström3 1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Microbiology, Tumor and Cell Biology, Biomedicum Q8C, Karolinska Institutet, Stockholm, 171 77, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenCorrespondence: Anna Karin Hedström, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, 171 76, Sweden, Tel +46762736426, Email anna.hedstrom@ki.seAbstract: Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBV-related CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.Keywords: Epstein-Barr virus, infectious mononucleosis, central nervous system disease, multiple sclerosis, treatment, vaccination

Abstract Background The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics. Materials and methods In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher’s exact and Welch’s tests were used to perform univariable statistical analyses. Results The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p

Ever since its discovery as the first human oncogenic virus, Epstein-Barr virus (EBV) has been the focus of many researchers and is one of the best-studied pathogens. EBV is a major causative agent of Burkitt lymphoma, Hodgkin lymphoma, post-transplantation lymphoproliferative disorder, NK/T cell lymphoma, chronic active EBV disease, nasopharyngeal carcinoma, gastric carcinoma, and infectious mononucleosis. Although a truly comprehensive understanding of the virus and the associated disorders remains elusive, major breakthroughs in molecular cloning and omics analyses are shedding new light on this important virus. For example, EBV is now implicated in autoimmune diseases and neurodegenerative disorders. This review provides an overview of the molecular biology of EBV, the research history, the associated disorders, and the epidemiology.

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 with18F-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.

BackgroundInfectious mononucleosis after primary infection with Epstein-Barr virus (EBV-IM) has been linked to the development of myalgic encephalomyelitis/chronic fatigue-syndrome (ME/CFS) in children, adolescents, and young adults. Here, we present clinical phenotypes and follow-up data from a first German cohort of young people with ME/CFS following EBV-IM.Methods12 adolescents and 13 young adults were diagnosed with IM-triggered ME/CFS at our specialized tertiary outpatient service by clinical criteria requiring post-exertional malaise (PEM) and a history of confirmed EBV primary infection as triggering event. Demographic information, laboratory findings, frequency and severity of symptoms, physical functioning, and health-related quality of life (HRQoL) were assessed and re-evaluated 6 and 12 months later.ResultsYoung adults displayed more severe symptoms as well as worsening of fatigue, physical and mental functioning, and HRQoL throughout the study, compared to adolescents. After one year, 6/12 (54%) adolescents no longer met the diagnostic criteria for ME/CFS while all young adults continued to fulfill the Canadian consensus criteria. Improvement in adolescents was evident in physical functioning, symptom frequency and severity, and HRQoL, while young adults showed little improvement. EBV serology and EBV DNA load did not correlate with distinct clinical features of ME/CFS, and clinical chemistry showed no evidence of inflammation. Remarkably, the median time from symptom onset to ME/CFS diagnosis was 13.8 (IQR: 9.1–34.9) months.ConclusionsME/CFS following EBV-IM is a severely debilitating disease often diagnosed late and with limited responses to conventional medical care, especially in adults. Although adolescents may have a better prognosis, their condition can fluctuate and significantly impact their HRQoL. Our data emphasize that biomarkers and effective therapeutic options are also urgently needed to improve medical care and pave the way to recovery.