The Prevalence and Clinical Manifestations of Co-Infection in Pediatric Infectious Mononucleosis: A Single-Centered, Retrospective Study

Background: Recent studies indicate that the incidence of infectious mononucleosis (IM) has increased in China. Furthermore, it has been shown that children diagnosed with IM are prone to acquiring other pathogens. However, there is limited research on the prevalence of these co-infections in children with IM. Thus, we conducted this study to determine the prevalence of coinfections and common pathogens, as well as to compare clinical manifestations in children with and without coinfections. Methods: This retrospective observational study was conducted at the Department of Pediatrics Zhongnan Hospital of Wuhan University, Wuhan, China, with data from January 2018 to January 2023. Data, including demographics, symptoms, lab results, and complications, were collected from the hospital’s electronic database and analyzed. The statistical analysis included descriptive statistics, independent samples t-tests and Mann-Whitney tests to compare the means of continuous variables. Statistical significance was determined by p-values less than 0.05. Results: The study involved 216 participants diagnosed with IM, predominantly males (61.6%) aged 0 - 4 years (50.9%). Coinfection was detected in 39.8% of children, with multiple pathogens present in 33.72% of these cases. Among coinfection cases, 40% occurred in children under 5 years old, and females made up 54.2% of these cases. Mycoplasma pneumoniae (MP) was the most prevalent pathogen, accounting for 18.1% of cases. Influenza B (IFB) and Influenza A (IFA) viruses were found in 16.7% and 13.9% of participants, respectively, indicating a notable occurrence of respiratory pathogen coinfections. Male gender, fever, tonsillopharyngitis, lower HGB levels, higher ESR, CRP, and AST levels were correlated with coinfections. Conclusion: In summary, the study revealed a high prevalence of coinfections among children diagnosed with IM, particularly involving Mycoplasma pneumoniae and influenza viruses. These coinfections were notably common in children under 5 years old and were more frequent among females. Clinical manifestations such as fever and tonsillopharyngitis, along with specific laboratory findings including lower hemoglobin levels, elevated ESR, CRP and AST levels, were found to be correlated with coinfections.

Research Advances in Infectious Mononucleosis Caused by Epstein-Barr Virus

Infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV), manifests as the classic triad of fever, pharyngitis, and cervical lymphadenopathy. Severe cases may involve organ damage, most commonly affecting the liver. Diagnosis relies on a combination of clinical presentation and laboratory parameters, with commonly used indicators including EBV-specific antibodies, EBV-DNA load, and the ratio of atypical lymphocytes. Treatment primarily involves symptomatic supportive care, with a cautious approach to the routine use of antiviral medications. In recent years, significant research in traditional Chinese medicine has been conducted in China, showing promising advancements. This article provides a comprehensive review of EBV-induced infectious mononucleosis, offering insights for clinical diagnosis and treatment.

A Case of Infectious Mononucleosis Induced Jaundice Complicated by Possible Drug Induced Liver Injury (DILI)

In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior symptoms. Physical and Laboratory tests confirmed the primary diagnosis of infectious mononucleosis, however, prior history of treatment with multiple drugs led to a diagnosis of DILI as a complication. Appropriate treatment with I.V. antibiotics, hepatoprotective agents, steroids as well as discontinuation of all potential hepatotoxic agents showed significant improvement in patients’ symptoms and overall condition.

The Positivity Rate of Epstein-Barr Virus Anti-Viral Capsid Antigen IgG among Children with Infectious Mononucleosis in Diyala-Iraq

Background: Epstein-Barr virus (EBV) is a double-stranded linear DNA human herpesvirus that is transmitted primarily through saliva during childhood. Although the majority of primary EBV infections are clinically asymptomatic, clinical cases are presented as infectious mononucleosis (IMN) syndrome. Objectives: This study was conducted to explore the rate of EBV anti-VCA IgG among children who were clinically suspected as having IMNin Diyala province. Subjects and Methods: This is a cross sectional study that was carried out during 2018 in Diyala province-Iraq. A total of 370 blood samples were collected from 190 children under 15 years of age who were clinically suspected as having IMN, and 180 apparently healthy children as controls. The anti EBV VCA IgG antibodies were detected in serum using the VCA IgG ELISA kit (from Dia.Pro Diagnostic Bioprobessrl-Italy). Statistical analysis was carried out using the SPSS-version 25. A statistical significance was considered whenever the P value was ≤ 0.05. Results: The results showed that the IgG positivity rate among suspected IMN patients was insignificantly higher in the age group 10 - 14 years old children (80.8%, P = 0.364). In control subjects the highest positivity rate was in the age group of 1 - 4 years with a statistically significant difference (79.5%, P = 0.002). In suspected IMN patients, the age group of 10 - 14 years had the highest mean concentration ± SD of anti-VCA IgG 44.018 ± 38.644 arbitrary units per milliliter (arbU/ml), while in controls, the highest value 38.018 ± 34.908 (arbU/ml) was in the age group of 1 - 4 years, with insignificant difference in either group (P = 0.257 and 0.072, respectively). The results also showed that in both suspected IMN patients and control subjects, females showed higher IgG positivity rate (70.6%, and 75.5%) compared to males (64.8%, and 65.1%) with insignificant difference in both groups (P = 0.392 and 0.126) respectively. Similarly, the IgG mean concentration ± SD was insignificantly higher in females in both suspected IMN patients and control subjects (P = 0.447 and 0.256) respectively. 21 (87.5%) of IgM positive suspected IMN patients were also IgG positive with a statistically significant association (P = 0.028). Conclusion: The positivity rate of anti-EBV VCA IgG among apparently healthy subjects in Diyala province was 70.6%, which increases by age with slight association with clinical suspicion of infectious mononucleosis.

Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase

In order to explore the value of combined detection of atypical lymphocytes （ATL） and transaminase （alanine aminotransferase, ALT＇ asparate aminotransferase, AST） in the diagnosis of infectious mononucleosis （IM）, The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis （AH） patients, 44 upper respiratory infection （URI） patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously （ALT〉40 IU/L, AST〉45 IU/L） in 57.4% （31/54） IM patients. There was significant difference （P〈0.01） between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

SISTER CHROMATID EXCHANGES FREQUENCY IN PATIENTS WITH MONONUCLEOSIS

Biomonitoring with cytogenetic methods consistto compare a known or suspected exposed groups with acontrol group with different endpoints.Generallyfactors which may influence the baseline levels ofsister chromatid exchanges frequency fall in 2 cate-gories:technical and biological factors.In additionto age,sex,drug use,smoking habits,health statusmight also be relevant.During a long term survey ofpeople professionally exposed to ethylene oxide

Recurrence of infectious mononucleosis in adults after remission for 3 years:A case report

BACKGROUND Infectious mononucleosis(IM)is a disease caused by Epstein–Barr virus(EBV).EBV infection is common in children;however,it can cause IM in adults.Studies on recurrence of IM in adults after remission are limited.CASE SUMMARY We report a 28-year-old man who presented with IM-like symptoms with mild liver damage after initial remission of IM for 3 years.He was first diagnosed with IM and treated in 2015.Follow-up tests in 2016 and 2017 did not show any abnormalities.In November 2018,he presented with swelling of the tonsils.He was misdiagnosed with acute suppurative tonsillitis and treated for 5 d.No signs of improvement were observed.He was readmitted with recurrent fever,pharyngalgia,fatigue,and systemic muscle pain.Examinations revealed enlargement of the tonsils and cervical lymph nodes.Blood tests revealed elevated transaminase levels.Anti-EBV test was positive,indicating virus reactivation.IM recurrence was confirmed on the basis of laboratory tests and clinical manifestations.He was treated with antiviral,anti-infective,and hepatoprotective drugs and vitamin supplements.His condition improved and no abnormalities were observed during follow-up.CONCLUSION Recurrence of IM after remission is possible in adults;therefore,long-term followup and monitoring are essential.

Expression and clinical significance of miRNA-146a and IRF-3 in children with infectious mononucleosis

Objective:To investigate the expression levels of interferon regulatory factor 3(IRF-3)and miRNA146a in peripheral blood of children with infectious mononucleosis and the effect of miRNA146a on IRF-3 expression.Methods:In an in vivo experiment,the expression levels of IRF-3 and miRNA146a in peripheral blood of 45 children with infectious mononucleosis and 34 healthy controls were detected by real-time PCR.The in vitro experiment was performed to examine the effect of miRNA146a on IRF-3 expression levels by transfecting miRNA146a mimics and their inhibitors.Results:There was significant difference in IRF-3 gene expression in peripheral blood between healthy controls and children with infectious mononucleosis(t=30.340,P<0.001)while miRNA146a expression was significantly increased compared with healthy controls(t=34.659,P<0.001),and there was a negative correlation between the two groups(r=-0.960,P<0.05).In HeLa cells,transfection with miRNA146a mimics significantly decreased the expression of IRF-3 mRNA(t=8.270,P<0.001)and protein(t=46.170,P<0.001),while miRNA146a inhibitor significantly up-regulated the expression of IRF-3 mRNA(t=8.582,P<0.001)and protein(t=25.891,P<0.001).Conclusion:miRNA146a may be involved in the down-regulation of IRF-3 gene expression by Epstein-Barr virus in children with infectious mononucleosis and then involved in the pathogenesis of infectious mononucleosis.

Livedo Reticularis in a Patient with EBV Mononucleosis

A 23-year-old woman with serologically confirmed EBV mononucleosis presented with fever, exudative pharyngitis, periorbital and lid edema, cervical lymphadenopathy, and splenomegaly. Two weeks after the onset of symptoms she developed a generalized symmetrical reticular eruption of unbroken hexagons characteristic of livedo reticularis that resolved over several weeks as her condition improved. To our knowledge, this is the first reported case of livedo reticularis to occur in a patient with EBV mononucleosis.

A Case of Infectious Mononucleosis Complicated by Severe Thrombocytopenia and Hyperuricemia

Infectious mononucleosis (IM) by Epstein-Barr virus is usually a benign, self-limiting disease. Mild to moderate immune thrombocytopenia in the setting of IM is very common and appears in approximately half of these patients, however it rarely presents in severe form and troublesome haemorrhage is even rarer. Rapid spontaneous resolution is possible, with the role of steroids being controversial. Furthermore, elevation of the levels of uric acid because of immune thrombocytopenia is observed in high frequency;however this finding is usually not mentioned. It is attributed to a transient increase in purine turnover, it appears more often in men (with its peak within the first 2 weeks of IM) and it is treated with intravenous fluids and bicarbonates. The present case report describes the case of a young female patient who develops severe thrombocytopenia and intense hyperuricemia following an Epstein-Barr infection. No severe bleeding appeared, levels of uric acid normalised within the first two weeks of treatment and platelet levels rise back to normal within a month under corticosteroid therapy.

EBNA2免疫组化在EB病毒阳性淋巴组织疾病中的表达意义

目的观察EBNA2免疫组化在不同EB病毒阳性淋巴组织疾病中的表达差异、分析其在病理诊断与鉴别诊断中的价值。方法收集344例EB病毒阳性的淋巴组织疾病,总结EBNA2免疫组化在病变中的表达特点。结果不同的EBV阳性淋巴组织病变,EBNA2的阳性表达不同:IM中阳性39例(39/46),EBV阳性的弥漫大B细胞淋巴瘤3例(3/30),淋巴瘤样肉芽肿1例(1/5),纤维素相关弥漫大B细胞淋巴瘤2例(2/2),浆母细胞淋巴瘤1例(1/14),免疫相关淋巴组织增殖性疾病32例(32/58)(包括移植后淋巴组织增殖性疾病21例,HIV相关Burkitt淋巴瘤1例,HIV相关弥漫大B细胞淋巴瘤2例,原发免疫缺陷疾病相关淋巴组织疾病6例,医源性免疫相关淋巴组织增殖性疾病2例)。其余均显示EBNA2阴性。②不同病变中的EBNA2阳性细胞表达明显不同:传染性单核细胞增多症中的EBNA2阳性细胞相对较少,并且多呈散在分布,几乎很少见到簇状聚集的情况。EBNA2阳性细胞多表现为≤10个/HPF,少见11~50个/HPF,仅有个别病例显示大于50个/HPF。免疫相关淋巴组织增殖性疾病中,出现大量EBNA2阳性细胞,阳性细胞较弥漫分布,大部分为强阳性,并且阳性细胞多显示大于50个/HPF。结论EBNA2阳性在疾病的诊断及鉴别诊断提供了新的依据,具有一定的价值;当病变表达EBNA2时,提示患者可能存在免疫缺陷或处于免疫失调状态,对临床诊断及治疗具有一定的指导意义。

Epidemiological characteristics and disease burden of infectious mononucleosis in hospitalized children in China:A nationwide retrospective study

Epstein-Barr virus(EBV)is very common,with the infection rate in adults over 90%worldwide.Infectious mononucleosis(IM)is caused by primary infection with EBV.Most IM patients are generally considered to have a favorable prognosis,but a few patients will also develop complications.Children with severe symptoms will require hospitalization.However,the disease burden of children hospitalized with IM in China has been rarely described.In this study,we included the Face sheets of discharge medical records from 27 member children's hospitals of Futang Research Center of Pediatric Development from Jan 1st,2016 to Dec 31st,2020,and medical information such as gender,age,region,time of admission,length of stay and expenditure were extracted.There were 24,120 IM cases,which accounted for 0.42%(24,120/5,693,262)of all hospitalized cases during this period.The ratio of male to female was 1.48:1.Hospitalization for IM in the 4-6 years age group was the highest among inpatients of all age groups.Case numbers increased year by year between 2016 and 2020,and the monthly hospitalization was generally high from Jul to Sep but reduced from Jan to Feb per year.Bronchitis/pneumonia and hepatic dysfunction were two common complications in hospitalized IM patients.The median length of stay was 8 days,and the median cost of hospitalization was 970.59 US dollars.This study will help understand the epidemiological characteristics and disease burden of hospitalized children with IM in China.

Effect of Compound Glycyrrhizin Injection on Liver Function and Cellular Immunity of Children with Infectious Mononucleosis Complicated Liver Impairment

Objective： To investigate the effects of Compound Glycyrrhizin Injection （CGI） on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment （IM-LI） and to explore its clinical therapeutic effect. Methods： Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group. All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase （ALT）, aspartate aminotransferase （AST） and total bilirubin （TBil） were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. Results： Baseline of the percentage of CD3^＋ , CD8^＋ lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD 4^＋ lymphocyte and the CD4^＋/CD8^＋ ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children （ P〈0.01 ）. These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group （P〈0.01）. Conclusion： Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

Clinical characteristics and effectiveness of antiviral agents in hospitalized children with infectious mononucleosis in China:A multicenter retrospective study

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

Clinically Controlled Study on Children's Infectious Mononucleosis Treated by Chinese Medicine

Objective： To evaluate the clinical efficacy and safety of Chinese drugs for the treatment of children＇s infectious mononucleosis （CIM）. Methods： Sixty CIM patients were assigned into the treated group and the control group, patients in the treated group were administered with Chinese herbal decoction, and those in the control group were treated with intravenous dripping of ganciclovir 10 mg/kg per day, for a treatment course of 14 days. Results： The total effective rate was 96.0% in the treated group and 97.1% in the control group, showing insignificant difference between groups. The efficacy in the treated group was superior to that in the control group on the fever clearance time （3.0 ± 1.5 days vs 4.9 ± 3.9 days ） and the disappearance time of cervical lymph node swelling （0.8 ± 1.0 score vs 1.5 ± 1.2 score）, showing statistical significance （all P〈0.05）. T-cell subsets were markedly improved in both groups after treatment. Adverse reaction occurred in four cases of the control group. Conclusion： Using Chinese herbs for clearing heat, removing toxin, activating blood circulation, and dissolving stasis is effective and safe for the treatment of CIM. It can effectively improve the clinical symptoms and shows a certain effect on immune regulation.

Dapsone-induced infectious mononucleosis-like syndrome in a patient with pemphigus vulgaris

Dapsone syndrome is characterized by high fever, skin rash, methemoglobinemia, liver toxicity, and generalized lymphadenopathy.The incidence of me dapsone syndrome is increasing with the extensive application of dapsone. However it is rarely reported in pemphigus. We present a case of ＂infectious mononucleosis-like＂ dapsone syndrome in a patient with pemphigus vulgaris. The syndrome appeared when he was being treated methylprednisolone, which was commonly used as a treatment for dapsone syndrome.

The sero-epidemiology of infectious mononucleosis in Neyshabur,Northeast Iran during 2010-2014

Objective:To detect infectious mononucleosis(IM)prevalence in Neyshabur,Northeast Iran during 2010-2014.Methods:This cross-sectional descriptive epidemiological survey was performed to reveal the prevalence of IM in Neyshabur between 2010 and 2014.A total of 114 individuals were studied.Briefly,individuals with positive test for specific immunoglobulin G and immunoglobulin M in the agglutination test were determined as positive cases.Results:The overall prevalence of IM was 14%.Mean±SD of age for IM test was 18.96±15.79.The age groups of 0-10 and 21-30 were the most positive cases in this period.In addition,31-40 and over 50 years were not positive cases.Male individuals were significantly more positive and likewise,it was observed that there were significantly higher positive cases of IM in spring and summer.Conclusions:Among the five years of this study,it was a decreasing status from 2010(23.1%)to 2014(9.1%),though a slight fluctuation had occurred.The prevalence of IM was low in Neyshabur City.Moreover,children and male individuals had relatively higher prevalence of the disease.Furthermore,it was observed a higher rate of IM in spring and summer.

传染性单核细胞增多症患儿多个临床检测指标的临床意义

传染性单核细胞增多症（infectious mononucleosis,IM）是一种由EB病毒（epstein-barr virus,EBV）引起的急性或亚急性全身性疾病。它在人群中的感染十分常见,该病多见于学龄前与学龄儿童。感染后多无明显症状,也可涉及全身各个系统,临床表现多种多样,常易被误诊[1],给临床诊断带来困难。

The role of Epstein-Barr virus in multiple sclerosis:from molecular pathophysiology to in vivo imaging

Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus(EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.

Epstein-Barr virus:Silent companion or causative agent of chronic liver disease?

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.