Cases Of Infectious Mononucleosis Research Articles

B-100 Utilization and Performance of Monospot and Epstein-Barr Virus Antibody Profile Testing for Diagnosis of Infectious Mononucleosis in Adolescents and Adults

Abstract Background Epstein-Barr virus (EBV) antibody profile, which includes IgM and IgG antibodies against EBV viral capsid antigen (VCA), IgG antibodies against early antigen (EA) and nuclear antigen (EBNA), is recommended by the CDC for diagnosing infectious mononucleosis (IM) and differentiating acute versus past infection. Conversely, the monospot test, which detects reactive heterophile antibodies, is not recommended by the CDC due to its low sensitivity in young children and non-specific nature. However, monospot tests remain widely used, especially as point-of-care testing at emergency department visits, likely related to their technical ease, rapid turnaround, and low cost. In this study, we compared the utilization and performance of the monospot test and EBV profile for the diagnosis of primary IM in adolescent and adult patients. Methods A retrospective review was conducted on consecutive monospot tests (Acceava Mono Cassette, Abbott) and EBV profiles (multiplex assay on Bioplex analyzer, Bio-Rad) performed between August 16, 2020, and August 15, 2021 in our hospital system. Cases with concurrent monospot and EBV profile testing were evaluated for qualitative agreement between the two methods. A chart review was conducted for cases with discrepant results between monospot and EBV antibody profile tests to assess the performance of these two methods. The final EBV infection status for each case was determined by clinical manifestation, relevant lab findings, and EBV profile results. Results A total of 1,524 monospot tests were performed, with an overall positive rate of 12.4%. The majority of tests were from the emergency departments (ED, 47.5%) and outpatient settings (48.7%), with inpatient tests comprising 3.8%. Notably, the positive rate was highest among outpatients (13.4%), followed by ED patients (12.3%), and lowest among inpatients (1.5%). In contrast, 3,769 EBV profile tests were performed, yielding an overall VCA IgM positive rate of 11.8% and 2.9% equivocal cases. Outpatient settings accounted for the majority of EBV profile tests (81.5%), followed by inpatients (16.2%) and ED patients (2.3%). Inpatients also exhibited a lower positive rate (7.5%) than ED (13.1%) or outpatients (13.1%). Among 364 cases concurrently tested by both the mono spot and the EBV profile, the negative agreement between the two tests was 97.7%, while the positive agreement was 52.8%. Discrepancies included 8 monospot-positive but VCA IgM-negative cases and 58 VCA IgM-positive but monospot-negative cases. Chart review revealed that monospot and EBV profiles missed 4 and 40 cases of primary IM, respectively. Additionally, 7 cases of past EBV infection exhibited prolonged VCA IgM positivity, and 2 cases of VCA IgM were falsely positive, likely due to cross-reaction with cytomegalovirus or B. burgdorferi IgM. Sensitivity/specificity for EBV profile and monospot were 96.4%/97.4% and 64.0%/100.0%, respectively. Conclusions The EBV profile demonstrates high sensitivity and specificity and is suitable as the primary test for diagnosing IM. While the monospot test exhibits good specificity, its lower sensitivity necessitates further testing with the EBV profile, particularly for patients with a high suspicion of IM, to avoid missed diagnoses.

Metabolomic differences between exanthematous drug eruption and infectious mononucleosis.

Exanthematous drug eruption and infectious mononucleosis (IM) are both exanthematous diseases. Current research on exanthematous drug eruption and IM mainly targets identifying these disorders, the resulting differences at the metabolism level have not yet been systematically analyzed. A total of 30 cases of exanthematous drug eruption and IM, 10 patients without exanthema and 10 healthy volunteers were enrolled, 3mL of fasting venous blood was collected, the serum metabolite content was detected by gas chromatography-mass spectrometry metabolomics. A total of 165 metabolites were identified, exhibiting significant differences in plasma metabolic trends between exanthematous drug eruption and IM, and pinpointed 28 potential biomarkers. Notable changes were seen in the metabolic activities of the pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA-cycle), and galactose metabolism, characterized by increased levels of gluconate, gluconolactone, glucose, galactaric acid, and mannose, along with decreased amounts of pyruvic acid, succinic acid, malic acid, and glycerol, indicating an impairment in the exanthematous drug eruption group's capacity to endure oxidative stress and regulate energy metabolism. In contrast to its medication without rash counterpart, the exanthematous drug eruption group's plasma displayed distinct metabolic routes, predominantly in the processing of arginine and proline, along with the TCA. This resulted in a marked reduction in urea levels and a rise in pyruvate, citrate, and ornithine, indicating hypoxic stress as the primary cause of these rashes. In contrast to the healthy control group, the IM group showed 26 potential biomarkers, marked by increased levels of ketoglutaric acid, malic acid, pyruvic acid, and oxoglutaric acid, and reduced amounts of glutamine, galacturonic acid, arachidonic acid, trimethylphosphonic acid ester, gluconolactone, and indole acetic acid. Mainly, the metabolic pathways included the TCA, breaking down alanine, aspartate and glutamate metabolism, and the processing of D-glutamine and D-glutamate metabolism, underscoring the body's crucial role in generating energy and inflammatory agents through the citric acid cycle. The comparison of serum metabolomic features of exanthematous drug eruptions and IM outlines a unique pattern closely related to the differences in the pathogenesis of these two exanthematous diseases.

Clinical case of infectious mononucleosis with facial neuropathy

Clinical case of infectious mononucleosis with facial neuropathy

Comparative Clinical Characteristics of Cytomegalovirus and Epstein-Barr Virus Mononucleosis in Immunocompetent Hosts: Experience from a Tropical Setting.

Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV) are herpesviruses that cause different clinical syndromes depending on the host's immune status. EBV is known for causing infectious mononucleosis (IMN), which presents with fever, pharyngitis, cervical lymphadenopathy, and atypical lymphocytes. CMV can also cause a mononucleosis syndrome with similar symptoms but is less frequently reported. Comparative studies on IMN and CMV mononucleosis from India are rare. This study aimed to elucidate the clinical characteristics of IMN and CMV mononucleosis in a South Indian tertiary care center, emphasizing the differences in their presentations. A retrospective analysis using Electronic Medical Records (EMR) from a tertiary care hospital at Thiruvananthapuram, Kerala, was conducted, including patients diagnosed with IMN or CMV mononucleosis based on clinical and serological tests during 2017 to 2023. Immunocompromised patients were excluded. The study compared demographic, clinical, and laboratory characteristics between the two groups. Out of 136 IMN cases and 17 CMV mononucleosis cases, the CMV group had a significantly higher median age (34.0 years) compared to the IMN group (20.0 years). The CMV group experienced a longer duration of fever (median 14.0 days) compared to the IMN group (5.0 days). Sore throat, cervical lymphadenopathy, and tonsil enlargement were significantly less common in CMV cases. The study concludes that CMV mononucleosis is more likely in older adults with prolonged fever and an absence of sore throat, tonsillitis, or cervical lymphadenopathy.

A case of infectious mononucleosis caused by Epstein-Barr virus complicated by autoimmune hemolytic anemia

We represent a rare clinical case of infectious mononucleosis with hepatitis, caused by Epstein-Barr virus, complicated by rare secondary autoimmune hemolytic anemia associated with warm agglutinins in a 16-year-old patient. The disease was long-lasting, with a two-wave course of febrile fever. Signs of hepatitis with the development of anemia of moderate severity appeared during the second wave of febrile fever. The etiology of the disease was confirmed by the detection of Epstein-Barr virus DNA in blood and the detection of anti-VCA IgM antibodies to Epstein-Barr virus in the absence of anti-EBNA IgG antibodies. Hemolytic anemia was verified using markers of hemolysis (increased lactate dehydrogenase activity, decreased haptoglobin concentration), and positive results of a direct Coombs test. After successful initiation of prednisone therapy and clinical improvement, the patient was discharged from the hospital on the 24th day of disease to continue treatment on an outpatient basis (prednisone was replaced by methylprednisolone).This case demonstrates the development of a rare autoimmune complication in infectious mononucleosis caused by the Epstein-Barr virus.

Flow Cytometry as the Tool to Define Peripheral Blood Leukocyte Signatures in Acute EBV Infection.

Primary Epstein-Barr virus (EBV) infection which can manifest as infectious mononucleosis (IM) is commonly acquired during childhood. EBV primarily invades B cells leading to a lytic reaction; the control of the infection is handled by natural killer and T cells in immunocompetent individuals. The infection has a wide spectrum of clinical findings and can lead to serious complications in patients with certain underlying immunological dysfunctions. We retrospectively investigated peripheral white blood cell populations' surface marker characteristics in IM using a comprehensive flow cytometry marker panel. Twenty-one cases of IM and seventeen EBV-seropositive cases without IM serving as controls were included. We observed novel alterations in lymphocyte, neutrophil, and monocyte populations. In addition to increased activated cytotoxic T cells and low B cells, we demonstrated high T-large granular lymphocyte (T-LGL) populations in IM cases. Furthermore, despite T cells' increased HLA-DR expression, another activation marker, CD11b, was lower in T-LGL populations. Monocytes showed increased CD16 expression; CD64 was higher in neutrophils. Our findings point to monocyte and neutrophil activation which may account for acute clinical features and may contribute to the understanding of IM immunobiology. Furthermore, they may serve as a useful tool in investigating inherited and post-transplant conditions characterized by deficiencies in controlling EBV infection.

Clinical analysis of infectious mononucleosis complicated with acute acalculous cholecystitis.

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

The Economic Burden of Epstein–Barr Virus Infection in the Russian Federation

Introduction: Epstein–Barr virus-related diseases are of great medical and social importance, which requires assessment of economic losses due to costs of medical care and sickness absenteeism. Objective: To propose a methodology for assessing economic damage and to use it for quantification of total damages caused by Epstein–Barr virus (EBV) infections in the Russian Federation in 2022. Materials and methods: The economic damage from EBV infections was determined using official statistics on cases of infectious mononucleosis (2022), upper respiratory tract infections, cardiac arrhythmias, atopic dermatitis, dorsopathy, chronic tonsillitis in the acute phase, cerebrovascular disease, psoriasis, and multisystem inflammatory syndrome associated with COVID-19. Results: Based on the methodology for assessing economic damages described in the article, we found that the total financial losses from EBV-associated diseases in the Russian Federation in 2022 amounted to 1,203.0 billion or 1.2 trillion rubles, which is significantly higher than similar values for all other registered infectious diseases with the exception of COVID-19. COVID-19-related multisystem inflammatory syndrome, upper respiratory tract infections, and cerebrovascular disease account for more than 90 % of all losses. The structure of total costs is dominated by indirect economic losses (1,096.75 billion rubles or 91.2 %) due to sickness absence from work. Conclusion: The findings allow us to outline directions of developing measures to reduce the economic damage from EBV-associated diseases.

An overlooked cause of hepatitis and thrombocytopenia with clinico-biochemical discrepancy: A case of infectious mononucleosis

A 22-year-old male was admitted to the outpatient clinic with fatigue, fever, and a sore throat. High transaminase levels, moderate thrombocytopenia, and elevated acute phase reactants were detected ten times. Ultrasound imaging revealed hepatosplenomegaly and a peripheral blood smear showed Downey cells. Epstein-Barr virus (EBV) infection was considered the definite diagnosis, and EBV serology was performed. His mild clinic improved to normal within days, but the patient's clinical progression and laboratory findings were incompatible. Laboratory results were on the extreme side, while the clinic was mildly deteriorating. EBV viral capsid antigen IgM was high, supporting the initial diagnosis. Biochemical normalization followed clinical improvement many days later. Clinicians should know that EBV infection may be mild, while laboratory results illustrate extreme findings.

Emperipolesis, Apoptosis and Hemophagocytosis during Acute Epstein-Barr Virus (EBV) infection: A Case Report

An eight-year-old patient had intermittent high grade fever and pharyngitis since one week. Later, he developed left-sided cervical lymphadenitis. Subsequently, he also developed palatal petechiae. Absolute lymphocyte count (ALC) was raised (ALC 20,262 cells/mm³). Hepatosplenomegaly was also detected. Clinically, the current case was diagnosed as a case of infectious mononucleosis. Possibility of infection by Epstein-Barr virus was considered. FNAC was done. Blood-mixed aspirate showed monocytoid cells with mild pleomorphic nuclei, and clumped chromatin. Inconspicuous nucleoli and abundant eosinophilic cytoplasm were seen. Foci of apoptosis were also seen. Frequent mitoses were seen. Findings were suggestive of acute reactive lymphocytic hyperplasia with hemophagocytosis and apoptosis. EBV DNA was detected by RT PCR with linear reporting range of 3.3×104 IU/ml. Herewith, we describe a case of infectious mononucleosis with emperipolesis and hemophagocytosis. Keywords: Epstein-Barr virus associated hemophagocytosis syndrome (EBVAHS).

Expression and Clinical Significance of Peripheral Blood IL-17A, IL-22, Tim-3, and gal-9 in Children with Infectious Mononucleosis.

To investigate the expression and clinical significance of peripheral blood interleukin (IL)-17A, IL-22, T cell immunoglobulin molecule-3 (Tim-3), and galectin-9 (gal-9) in children with infectious mononucleosis (IM) caused by the Epstein-Barr virus (EBV). Peripheral blood of 54 children with IM (case group) was collected and divided into a liver damage group and a non-liver damage group. During the same period, 20 healthy children were in the control group. IL-17A and IL-22 were measured by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction was used to measure the mRNA expression of Tim-3 and gal-9. Their correlation with clinical indicators was then analyzed. The IL-17A expression level was higher in the case group than in the control group, while Tim-3, gal-9, and IL-22 were lower than those in the control group. Tim-3 was positively correlated with gal-9, but negatively correlated with IL-17A. Tim-3 and gal-9 were positively correlated with CD4+/CD8+ cells. Conversely, they were negatively correlated with CD3+, CD3+CD8+, white blood cell, lymphocyte (L), alanine transaminase (ALT), aspartate transaminase (AST), glutamyl transpeptidase (GGT), and lactate dehydrogenase (LDH). In the case group, IL-17A was positively correlated with L, GGT, and LDH, but negatively correlated with the natural killer (NK) cell count. IL-17A and IL-22 were positively correlated with CD3+, CD3+CD8+, ALT, and AST, but they were negatively correlated with the ratio of CD4+/CD8+. In the liver damage group, IL-17A, IL-22, CD3+, CD3+CD8+, immunoglobulin A (IgA), IgG, IgM, L, ALT, AST, GGT, LDH, and α-hydroxybutyrate levels were higher than those in the non-liver damage group. However, Tim-3, gal-9, the ratio of CD4+/CD8+, and NK were lower than those in the non-liver damage group. IL-17A, IL-22, Tim-3, and gal-9 are involved in the immune pathogenesis of IM caused by EBV infection in children, which may be related to immune liver injury.

Clinical case: observation of a child with Chediak-Higashi syndrome

Chediak-Higashi syndrome is a rare immunodeficiency condition with generalized cellular dysfunction, with an autosomal recessive type of inheritance. Mostly young children suffer, death caused by infections or malignant neoplasms often occurs before they reach the age of 10 years. We describe a case of infectious mononucleosis caused by Epstein-Barr virus in a 3-year—old boy against the background of a rare hereditary Chediak-Higashi syndrome with the development of hemophagocytic syndrome.

Association of SH2 domain-containing protein 1A, immunoglobulins and T lymphocyte subsets with Epstein- Barr virus infections.

We aimed to analyze the levels and associations of SH2 domain-containing protein 1A (SH2D1A), immunoglobulins and T lymphocyte (TL) subsets in children with Epstein-Barr virus (EBV) infections. Sixty children with EBV infections admitted from January 2019 to January 2022 were selected, including 29 cases of infectious mononucleosis (IM group) and 31 cases of chronic active EBV infections (CAEBV group). Another 42 healthy children undergoing physical examination in the same period were selected as a control group. Their changes in SH2D1A, immunoglobulins and TL subsets (CD3+, CD4+ and CD8+) were compared. The levels of CD3+, CD4+ and CD8+ in the IM group were higher than those of the control group (P < 0.05), while they were lower in the CAEBV group than those of the control and IM groups (P < 0.05). The levels of SH2D1A, signaling lymphocyte activation molecule (SLAM) and SLAM-associated protein (SAP) were significantly higher in the IM group than those in the control and CAEBV groups (P < 0.05). The CAEBV group had decreased protein expressions of SLAM and SAP compared with those of the IM group. SH2D1A was positively correlated with immunoglobulin A, immunoglobulin G and TL subsets (CD3+, CD4+ and CD8+) (P < 0.05). Detecting SH2D1A, immunoglobulins and TLs contributes to the diagnosis and differentiation of IM and CAEBV.

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

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

Polypharmacy in Infectious Mononucleosis Management: Case Series

Background. Infectious mononucleosis is acute viral disease that often forces pediatricians, especially in outpatient departments, to prescribe antibiotics. However, viral infections even with prolonged fever and marked intoxication symptoms do not require antibacterial therapy. Unreasonable antibiotics’ administration leads to increase in antibiotic resistance, increase of treatment cost, and development of incorrect therapy understanding in patients. Clinical case description. The authors presented 3 clinical cases of infectious mononucleosis with typical course in children. All patients were unreasonably administered antibacterial therapy with three or more drugs in absence of any clinical and laboratory signs of bacterial infection. Conclusion. Patients with infectious mononucleosis do not require antibacterial therapy due to viral origin of the disease, regardless disease course duration and severity, except the cases with confirmed comorbid bacterial infection.

Clinical and etiological aspects of human Betaherpesvirus infection 6: a review

The literature review is devoted to the modern concept of human betaherpesvirus 6 (human herpesvirus 6; HHV-6). The analysis of the literature mainly for the last five years was carried out. The article provides a brief background on the history of the discovery of viruses, highlights the taxonomy of HHV-6, new views on the etiological features of the HHV-6A and HHV-6B viruses, in particular, the possibility of their gene integration. Differences between HHV-6A and B are described. Modern views on the etiological relationship of various diseases of the central and peripheral nervous system, а heart, other organs and systems with HHV-6A and HHV-6B are presented. There have been cases of infectious mononucleosis associated with HHV-6, as well as exanthemа subitum that is mostly typical for children under 2 years old. Modern ideas about the possibilities and problems of HHV-6 infection laboratory diagnosis and treatment of children and adult are given. Obtained data points out necessary of a unified protocol creation for the examination and treatment of HHV-6.

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.

传染性单核细胞增多症5例中EBNA2表达研究

传染性单核细胞增多症5例中EBNA2表达研究

Kissing genetic MS risk loci to life.

Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system (CNS) [1]. Its debilitating effects on sensory, motor, autonomic, and neurocognitive functions affect primarily young adults, especially women (two to three times more frequent than in men), and is most frequent in northern countries, affecting more than 150 individuals of every 100,000 inhabitants e.g. in Canada and the Scandinavian countries. The development of this often initially relapsing/remitting and later progressive disease is associated with genetic and environmental risk factors [1, 3]. The major histocompatibility complex (MHC) class II gene locus is by far the most prominent genetic risk factor, and altered immune responses to the Epstein Barr virus (EBV), the causative infectious agent of most cases of infectious mononucleosis or “kissing disease”, have in recent years emerged as the most prominent environment induced risk factors for MS [1]. Interestingly, particularly infectious mononucleosis as symptomatic primary EBV infection, caused by a lymphocytosis of mainly lytic EBV antigen specific CD8+ T cells, and elevated antibody responses against EBV have been found to synergize with the MS associated MHC class II molecule HLA-DRB1*1501 to increase MS risk seven- to fifteen-fold, respectively [1]. Moreover, EBV infection seems to precede MS onset by several years in nearly all patients. Thus, EBV infection currently appears as a prerequisite for MS development that increases the risk for this autoimmune disease in genetically susceptible individuals.

EB病毒相关传染性单核细胞增多症81例临床分析

EB病毒相关传染性单核细胞增多症81例临床分析