Cases Of Infectious Mononucleosis Research Articles

Possible involvement in oncogenesis of a single base mutation in an internal ribosome entry site of Epstein-Barr nuclear antigen 1 mRNA.

It has been reported recently that the U leader exon located within the 5' untranslated region of Epstein-Barr nuclear antigen 1 (EBNA1) gene contains an internal ribosome entry site (IRES) element. Sequence analysis of the U leader exon was undertaken in samples from 19 patients with infectious mononucleosis and 19 patients with lethal lymphoproliferative diseases and in 15 spontaneously established lymphoblastoid cell lines. The sequence was conserved except for a single base substitution (T-C) at position 67,585. Although the mutation was detected in only one case of infectious mononucleosis, it was found in more than half of the lethal lymphoproliferative diseases and all lymphoblastoid cell lines. The results suggest that a mutation in the IRES element affects EBNA1 gene expression at the translational level and provides Epstein-Barr virus (EBV)-infected cells with a growth advantage, leading to immortalization of cells in vitro and to the development of lethal lymphoproliferative diseases in vivo.

Just another simple case of infectious mononucleosis?

Just another simple case of infectious mononucleosis?

Sexual history and Epstein-Barr virus infection.

To determine the role of sexual contact in transmission of Epstein-Barr virus (EBV) and occurrence of infectious mononucleosis (IM), a cross-sectional study was undertaken of EBV serologic testing and histories of IM and sexual behavior among 1006 new students at Edinburgh University. Prevalence of EBV seropositivity was significantly greater among women (79.2%) than among men (67.4%; P<.001) and among those who had ever been sexually active (82.7%) than among those who had not (63.7%; P<.001). Having a greater number of sex partners was a highly significant risk factor for EBV seropositivity. Two thirds of IM cases, but only a tenth of asymptomatic primary EBV infections, were statistically attributable to sexual intercourse. The findings suggest that EBV transmission occurs during sexual intercourse or closely associated behaviors. Transmission in this way appears to account for most cases of IM but for only a minority of cases of asymptomatic EBV infection, which mainly occur at younger ages.

The changing epidemiology of infectious mononucleosis?

Infectious mononucleosis is an acute and self-limited infection of the lymphatic system caused in over 90% of cases by a primary infection with Epstein-Barr virus (EBV), a member of the herpes virus group [1]. Infection during childhood is usually subclinical, whereas infection of adults results in infectious mononucleosis in 30± 75% of cases and can prove severe [2,3]. EBV infection in childhood is associated with low socioeconomic status, poor hygiene and crowding so that improved housing and decreasing family sizes may have resulted in a change in the epidemiology of EBV and therefore infectious mononucleosis [4,5]. To investigate this possibility we reviewed historical data of general practitioner (GP) consultations and hospitalisations in England and Wales over thirty years. Data on age-specific consultation rates for infectious mononucleosis in England and Wales were obtained from the Royal College of General Practitioners (RCGP) sentinel surveillance reports [6]. The surveillance programme is based on clinical diagnoses and uses a sample of practitioners throughout England and Wales which currently covers a population of over 600,000. Data for the calendar years 1989±1998 were extracted from the Hospitalisation Episode Statistics (HES, Department of Health) database that records every inpatient admission to National Health Service hospitals in England. Cases of infectious mononucleosis were identified using the International Classification Disease Codes 075* (ICD-9 up until 1995) and B27* (ICD-10 from 1996 onwards). The ICD-9 code 075* did not distinguish between different viral causes of infectious mononucleosis. For consistency, from 1996 onwards the ICD-10 code B27* was used which included infectious mononucleosis from EBV, cytomegalovirus (CMV), other viral causes and unspecified types. However, in practice

Lymphoid Tissues from Patients with Infectious Mononucleosis Lack Monoclonal B and T Cells

In typical cases of infectious mononucleosis (IM), lymphoid tissue is rarely submitted for pathological examination. When lymphoid tissues from IM cases are examined, the histological appearance of IM may be difficult to distinguish from malignant lymphoma. The purpose of this study was to address the utility of clinical molecular assays for T and B cell clonality in distinguishing IM from lymphoid malignancy. DNA was recovered from paraffin-embedded archival lymphoid tissues of 18 cases of IM and 13 control cases representing other reactive lymphoid hyperplasias. T cell receptor gamma (TCR-gamma) and immunoglobulin heavy chain (IgH) gene rearrangements were assayed using our standard clinical polymerase chain reaction procedures targeting each of the four functional variable (V) families and the three joining (J) families of the TCR-gamma gene, and framework III of the IgH gene, respectively. In 17 of 18 cases of IM, no monoclonal T or B cell populations were detectable. One case, the only spleen specimen in the study, had an oligoclonal pattern of TCR-gamma rearrangements. The control cases representing other reactive hyperplasias also lacked monoclonality. The assays used were sensitive to clonal populations as small as 5% of cells. In this case series, no monoclonal lymphoid populations were identified in any case of IM. This finding suggests that molecular studies are useful in distinguishing IM from lymphoid neoplasms.

Diagnosis of atypical cases of infectious mononucleosis.

The variable manifestations of infectious mononucleosis rarely cause clinicians to suspect primary Epstein-Barr virus or cytomegalovirus infection; consequently, costly diagnostic tests and unnecessary treatments are undertaken. Seventeen cases of clinically atypical and 11 cases of clinically typical infectious mononucleosis were diagnosed through screening for atypical and apoptotic lymphocytes in the peripheral blood samples by means of an automated hematologic analyzer. Atypical and typical cases did not differ significantly with respect to peripheral white blood cell counts; percentages of lymphocytes, atypical lymphocytes, CD4(+) lymphocytes, human leukocyte antigen--DR positivity in CD3 lymphocytes, or apoptotic cells in blood smear after incubation; or levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Only the percentage of CD8(+) lymphocytes was significantly higher in patients with typical infectious mononucleosis than it was in patients with atypical infectious mononucleosis. Because certain atypical cases of infectious mononucleosis display laboratory abnormalities that are characteristic of typical infectious mononucleosis, enhanced awareness can help in the diagnosis.

Parotid mass: Epstein–Barr virus and facial paralysis

Infectious mononucleosis is a common diagnosis in the pediatric and young adult population. Symptoms include low grade fever, malaise, odynophagia, and cervical lymphadenopathy. Neurological manifestations are uncommon, but include cranial nerve neuropathies. We describe a case of infectious mononucleosis in a pediatric patient who presented with a parotid mass and facial nerve palsy. Diagnosis was confirmed with a monospot test and Epstein–Barr virus antibody panel. The patient was managed conservatively with near total recovery of facial nerve function. This case demonstrates the need to consider infectious etiology prior to surgical intervention of a pediatric patient with facial nerve paresis and a parotid mass.

A Case of Infectious Mononucleosis

A Case of Infectious Mononucleosis

Accumulation of p53 in infectious mononucleosis tissues

Epstein-Barr virus (EBV) infects lymphocytes, where it persists indefinitely for the life of the host; whether the virus interacts with p53 to maintain itself in these cells is unknown. Lymphoid biopsy samples from 10 patients with infectious mononucleosis (IM) were examined for expression of p53 by immunohistochemistry. Accumulation of p53 was detected in all 10 cases, primarily in large lymphocytes of the expanded paracortex. The presence of EBV was confirmed in all 10 cases by EBER1 (EBV-encoded RNA) in situ hybridization, whereas 11 non-IM control samples lacked significant EBER1 and did not express p53 in paracortical lymphocytes. Interestingly, EBV infection alone does not cause accumulation of intracellular p53, because many more cells expressed EBER1 than p53 in the IM tissues. To determine whether p53 was confined to the subset of infected cells in which viral replication was occurring, BZLF1 immunostains were performed. Viral BZLF1 was detected in 8 of 10 IM tissues; however, the paucity and small size of the BZLF1-expressing lymphocytes suggests that they are not the same cells overexpressing p53. To further examine the relationship between p53 and EBV gene expression, the tissues were studied for latent membrane protein 1 (LMP1) expression by immunohistochemistry. Viral LMP1 was observed in the large paracortical lymphocytes of all 10 cases of IM, indicating co-localization of p53 and LMP1 in these cells. Our findings confirm that p53 overexpression is not specific for nodal malignancy and that p53 accumulation is characteristic of IM. Because p53 was not coexpressed in the same cells as BZLF1, it appears that BZLF1 is not directly responsible for p53 accumulation. Nevertheless, co-localization of p53 and LMP1 in activated-appearing lymphocytes suggests that EBV infection is responsible for p53 accumulation. HUM PATHOL 31:1397-1403.

Accumulation of p53 in infectious mononucleosis tissues

Epstein-Barr virus (EBV) infects lymphocytes, where it persists indefinitely for the life of the host; whether the virus interacts with p53 to maintain itself in these cells is unknown. Lymphoid biopsy samples from 10 patients with infectious mononucleosis (IM) were examined for expression of p53 by immunobistochemistry. Accumulation of p53 was detected in all 10 cases, primarily in large lymphocytes of the expanded paracortex. The presence of EBV was confirmed in all 10 cases by EBER1 (EBV-encoded RNA) in situ hybridization, whereas 11 non-IM control samples lacked significant EBER1 and did not express p53 in paracortical lymphocytes. Interestingly, EBV infection alone does not cause accumulation of intracellular p53, because many more cells expressed EBER1 than p53 in the IM tissues. To determine whether p53 was confined to the subset of infected cells in which viral replication was occurring, BZLF1 immunostains were performed. Viral BZLF1 was detected in 8 of 10 IM tissues; however, the paucity and small size of the BZLFI-expressing lymphocytes suggests that they are not the same cells overexpressing p53. To further examine the relationship between p53 and EBV gene expression, the tissues were studied for latent membrane protein 1 (LMP1) expression by immunohistochemistry. Viral LMP1 was observed in the large paracortical lymphocytes of all 10 cases of IM, indicating co4ocalization of p53 and LMP1 in these cells. Our findings confirm that p53 overexpression is not specific for nodal malignancy and that p53 accumulation is characteristic of IM. Because p53 was not coexpressed in the same cells as BZLFI, it appears that BZLF1 is not directly responsible for p53 accumulation. Never-theless, co-localization of p53 and LMPI in activated-appearing lymphocytes suggests that EBV infection is responsible for p53 accumulation.

Genital Ulceration as a Presenting Manifestation of Infectious Mononucleosis

This article describes a case of infectious mononucleosis (IM) in a 16-year-old fenlale adolescent who presented with fever, sore throat, cervical lymphadenopathy and genital ulcerations. Initially, this patient was thought to have herpes simplex viral infection secondary to the characteristic multiple genital ulcers. Seven cases (including this case) have reported an association between Epstein-Barr virus (EBV) infection and genital ulcerations. IM as a cause of genital ulcerations should be included in the differential diagnosis.

A Case of Infectious Mononucleosis with Fever and Cervical Lymphadenopathy

A Case of Infectious Mononucleosis with Fever and Cervical Lymphadenopathy

Epstein-Barr virus infection, Hodgkin's disease, non-Hodgkin's lymphoma, and reactive follicular hyperplasia in Japanese children: evaluation of paraffin-embedded specimens using polymerase chain reaction and immunohistochemistry.

Epstein-Barr virus (EBV) infections are common in Japanese children, with infectious by EBV type 1. The relationships between EBV infection and lymphadenopathies in Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL), reactive follicular hyperplasia (RFH), and infectious mononucleosis (IM) in 37 Japanese children were evaluated. Formalin-fixed, paraffin-embedded lymph node specimens that were obtained at surgical resection or biopsy were evaluated for the presence of EBV DNA and the latent membrane protein-1 (LMP-1) using polymerase chain reaction (PCR) and immunohistochemical staining. The PCR detected EBV DNA in nine of 13 (69.2%) patients with RFH, including a case of IM, all three (100%) patients with HD, and one of 21 (4.8%) patients with NHL. All EBV-positive samples contained EBV type 1. Reed-Sternberg's cells in HD were immunohistochemically positive for LMP-1, whereas all cases of RFH and NHL were negative for LMP-1. Results suggest that EBV infection may be related to HD. Although no proof exists that EBV infection contributes to the transformation of cells, thus causing RFH or NHL, the present authors suggest that the EBV-positive cases in Japanese children demonstrate a relationship between the clinical and histopathological features of the lymphadenopathy and EBV-type 1 infection.

Expression of epstein-barr virus encoded nuclear antigen 1 in benign and malignant tissues harbouring EBV.

To determine levels of expression of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) in benign and malignant tissues harbouring EBV in relation to EBNA1 promoter usage. Expression of EBNA1 was investigated by means of immunohistochemistry using a mixture of two EBNA1 specific monoclonal antibodies, 1H4-1 and 2B4-1. The presence of EBV was detected by EBER1/2 RNA in situ hybridisation. Detection of promoter specific EBNA1 transcripts was by RT-PCR analysis. EBNA1 positive cells were detected in all 20 EBV associated B cell lymphomas, 18 of which had arisen in immunocompromised patients; in eight of nine EBV associated T cell lymphomas; in 11 of 27 EBV positive cases of Hodgkin's disease; and in reactive lymphoid tissue harbouring EBV, including four cases of infectious mononucleosis. A diffuse EBNA1 staining pattern was observed in most of the EBV associated B cell lymphomas and was comparable with the EBER1/2 staining pattern. In the T cell lymphomas the number of EBNA1 positive cells was usually considerably less than the number of EBER1/2 positive ones. RT-PCR analysis revealed that in tumours with restricted EBNA1 expression-that is, T cell lymphomas and Hodgkin's disease lesions, EBNA1 transcripts were usually generated only by the F/Q promoter, whereas in B cell lymphomas EBNA1 transcripts were usually generated by both the C/W and F/Q promoters. EBNA1 is expressed in all types of tissue harbouring EBV, but the level of expression varies greatly. This may be the result of differential promoter usage.

Otolaryngologic clinical patterns in pediatric infectious mononucleosis

Purpose: Classic infectious mononucleosis (IM) is uncommon in children; therefore, the incidence of severe pharyngotonsillitis complicating the infection is not well established. This study was undertaken to better define the management of complications with special emphasis on the use of parenteral steroids and the role and timing of surgical management. Materials and Methods: A retrospective review of all cases of IM encountered between January 1989 through December 1993 was undertaken. Results: There were 109 patients admitted with IM. Sixty patients (55%) were admitted for severe pharyngotonsillitis. Twenty-nine patients in this subgroup were felt to have symptoms of severe upper airway obstruction and were treated with parenteral steroids. Surgical intervention was required in three patients. Conclusion: The study shows a higher incidence of admissions for severe pharyngotonsillitis complicating IM than reported in the adult literature. It suggests that routine use of parenteral steroids is indicated in cases of severe upper airway obstruction and may decrease the need for suraical intervention.

Evaluation of a New Epstein-Barr Virus Combi Test for Rapid Serologic Diagnosis of Infectious Mononucleosis

We evaluated the EBV Combi Test (Virion) in serum samples from 574 children with a clinical presentation suggestive of infectious mononucleosis (IM) and compared its performance with several other EBV serological tests. Out of 574 sera 66 gave an acute IM pattern, 406 gave a past infection pattern and 102 were found negative in the EBV Combi Test. Positive VCA IgM and VCA IgG IFA results, in the absence of EBNA antibodies, were found in 62 cases in which the EBV Combi Test gave an acute IM pattern. In addition, 4 to the 574 tested sera gave an acute positive result in the EBV Combi Test (two of them were VCA IgM positive and the other two VCA IgM negative but also EBNA negative). None of these four sera were CMV IgM or Toxoplasma gondii IgM positive. The heterophile antibody test was positive in only 28, and VCA IgM EIA positive in 44 of the 62 IM cases. These data confirm the necessity for an EBV serological diagnosis in children where the clinical diagnosis of EBV infectious mononucleosis must be confirmed or ruled our.

Epstein-Barr virus as a trigger for autoimmune hepatitis in susceptible individuals

During follow-up of healthy relatives of 13 patients with autoimmune hepatitis, seven cases of infectious mononucleosis due to Epstein-Barr virus (EBV) occurred. In two of these seven, before EBV infection, there was a defect in suppressor-inducer T lymphocytes specifically controlling immune responses to the asialoglycoprotein receptor, an antigen expressed on the hepatocyte surface. In these two, antibodies to this autoantigen persisted and increased after infectious mononucleosis, and autoimmune hepatitis developed within 4 months. In susceptible individuals, EBV is a trigger for autoimmune hepatitis.

A Case of Infectious Mononucleosis Complicated by Myopericarditis

A Case of Infectious Mononucleosis Complicated by Myopericarditis

Identification of Potential Hot Spots in the Carboxy-Terminal Part of the Epstein-Barr Virus (EBV) BNLF-1 Gene in Both Malignant and Benign EBV-Associated Diseases: High Frequency of a 30-bp Deletion in Malaysian and Danish Peripheral T-Cell Lymphomas

In this study, we have sequenced the C-terminal part of the Epstein-Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV-positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T-cell lymphomas (PTLs) and from tonsils of Danish infectious mononucleosis (IM). Our study showed that some of the 7 single-base mutations and the 30-bp deletion previously detected between codons of amino acid 322 and 366 in the BNLF-1 gene of the nasopharyngeal carcinoma cell line CAO were present in all Malaysian PTLs and in 60% of the Danish PTLs. In HD and the IM cases, the mutations were present in about 30%. The 30-bp deletion and the single base mutations occurred independently, and mutations were detectable in the majority of EBV type B-positive cases. These findings suggest that the 30-bp deletion and the 7 single-base mutations in the C-terminal part of the CAO-BNLF-1 gene do not characterize a new EBV type A substrain. Rather, some of the positions of single base mutations and the 30-bp deletion are hot spots that may have mutated independently through the evolution of EBV strains.

Patterns of Cytokine Gene Expression in Infectious Mononucleosis

Primary infection with Epstein-Barr virus (EBV) may arise as infectious mononucleosis (IM) in adolescents and young adults. Morphologically, IM-affected lymphoid tissue is characterized by expanded interfollicular areas with formation of atypical lymphoid blasts. It is assumed that morphology and clinical presentation of IM are related to characteristic patterns of cytokine production by EBV-infected and reactive cells. We studied IM tonsils of eight patients and six normal tonsils with a double in situ hybridization procedure using [35S]-labeled RNA probes specific for various cytokines and digoxigenin-labeled probes for the detection of the nuclear EBV encoded RNA transcripts, EBER 1 and 2. All of the IM cases displayed the same distinct cytokine gene expression pattern. When compared with interfollicular areas of normal tonsils, expression of lymphotoxin (LT), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, but not IL-8 or IL-1 alpha was strongly enhanced in interfollicular areas in IM tonsils. LT was expressed predominantly by EBV-infected cells. TNF-alpha transcripts were also present in EBV-infected cells, although in smaller proportions. IL-6 specific signals were only found in few EBV-infected cells. IL-1 alpha-, IL-1 beta-, and IL-8-specific signals were not observed in EBV-infected cells, but were present at high signal intensity in many cells within and around foci of EBV-infected cells (IL-1 beta), next to areas of necrosis (IL-8, IL-1 beta), or in epithelial cells (IL-1 alpha). These data suggest that EBV infection in form of IM results in induction of specific sets of cytokine genes in EBV-infected and in neighboring EBV-negative cells contributing to the characteristic morphology and cellular arrangement of the lesion as well as the clinical presentation.