Clinical and laboratory evaluation of infants and children with Epstein- Barr virus-induced infectious mononucleosis: report of 32 patients (aged 10-48 months)

Ca, Horwitz; Henle, W; Henle, G; Goldfarb, M; Kubic, P; Gehrz, RC; Balfour, HH Jr; Fleisher, GR; Krivit, W

doi:10.1182/blood.v57.5.933.bloodjournal575933

Cited by 15 publications

(18 citation statements)

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“…Furthermore, the IgM+IgG± donors were likely infected within the last 120 days and may be at a different stage of infection. Secondly, ensuring children are truly asymptomatic in this setting can be challenging as reliance on maternal perception may not be reliable and careful clinical studies of infants or children have described AIM like symptoms in some instances [ 45 ]. To combat this, the children all underwent a health screen by the study clinician, including baseline clinical observations such as weight, height, temperature and heart rate and where indicated a rapid malaria test.…”

Section: Discussionmentioning

confidence: 99%

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

et al. 2015

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Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms.

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Section: Discussionmentioning

confidence: 99%

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

et al. 2015

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“…If symptoms occur, the majority of them have clinical evidence suggestive of IM, such as significant cervical adenopathy and tonsillar pharyngitis following a viral prodrome of approximately five days [5]. Respiratory symptoms are frequently prominent, especially in young infants [6]. Supportive evidence is derived from the observation of lymphocytosis and increased circulating atypical lymphocytes, along with a positive heterophile antibody test [1].…”

Section: Discussionmentioning

confidence: 99%

Primary Epstein-Barr virus infection in a 40-day-old infant

Najafi

Tafreshi

Hasheminejad

2015

J Pediatr Infect Dis

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Most cases of primary Epstein-Barr virus (EBV) infection during infancy and early childhood are mild or subclinical; therefore, the diagnosis of an EBV infection is not performed easily in this age group. Infectious mononucleosis (IM) is rarely reported during infancy. We report a 40-day-old infant with cervical node enlargement, cough, and coryza symptoms who was finally identified as having a case of primary IM based on the patient's clinical features and serological tests. Â© 2013 - IOS Press and the authors. All rights reserved

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“…Thus, assays specific for EBV must be performed in these cases, lest the diagnosis of infectious mononucleosis be missed. 23 Infectious mononucleosis in preadolescents is not rare. As a pediatrician, one of us (HHB) has seen numerous cases in children younger than 12 years old.…”

Section: Clinical Manifestations Of the Acute Illnessmentioning

confidence: 99%

“…Approximately 40% of children 4 years of age or younger do not develop heterophile antibodies following a primary EBV infection. 23 If the heterophile is the only test ordered, the diagnosis will be missed. Second, heterophile antibodies by definition are not specific and may be present in infections caused by other pathogens, malignancies and autoimmune diseases.…”

Section: Diagnosis Of Infectious Mononucleosis Because Of Primary Ebvmentioning

confidence: 99%

Infectious mononucleosis

2004

Blood

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Infectious mononucleosis is a clinical entity characterized by pharyngitis, cervical lymph node enlargement, fatigue and fever, which results most often from a primary Epstein-Barr virus (EBV) infection. EBV, a lymphocrytovirus and a member of the γ-herpesvirus family, infects at least 90% of the population worldwide, the majority of whom have no recognizable illness. The virus is spread by intimate oral contact among adolescents, but how preadolescents acquire the virus is not known. During the incubation period of approximately 6 weeks, viral replication first occurs in the oropharynx followed by viremia as early as 2 weeks before onset of illness. The acute illness is marked by high viral loads in both the oral cavity and blood accompanied by the production of immunoglobulin M antibodies against EBV viral capsid antigen and an extraordinary expansion of CD8 + T lymphocytes directed against EBV-infected B cells. During convalescence, CD8 + T cells return to normal levels and antibodies develop against EBV nuclear antigen-1. A typical clinical picture in an adolescent or young adult with a positive heterophile test is usually sufficient to make the diagnosis of infectious mononucleosis, but heterophile antibodies are not specific and do not develop in some patients especially young children. EBV-specific antibody profiles are the best choice for staging EBV infection. In addition to causing acute illness, long-term consequences are linked to infectious mononucleosis, especially Hodgkin lymphoma and multiple sclerosis. There is no licensed vaccine for prevention and no specific approved treatment. Future research goals are development of an EBV vaccine, understanding the risk factors for severity of the acute illness and likelihood of developing cancer or autoimmune diseases, and discovering anti-EBV drugs to treat infectious mononucleosis and other EBV-spurred diseases.

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Clinical and laboratory evaluation of infants and children with Epstein- Barr virus-induced infectious mononucleosis: report of 32 patients (aged 10-48 months)

Cited by 15 publications

References 0 publications

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

Primary Epstein-Barr virus infection in a 40-day-old infant

Infectious mononucleosis

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