Behavioral, Virologic, and Immunologic Factors Associated with Acquisition and Severity of Primary Epstein-Barr Virus Infection in University Students.
ABSTRACT Background. University students were studied prospectively to determine the incidence and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity.Methods. EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by PCR. Lymphocyte and NK cell numbers and activation were measured by flow cytometry, and plasma cytokines by Luminex.Results. Of 546 students screened, 202 (37%) were antibody-negative and 143 of them enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (P < .01). Viremia was transient but median oral shedding was 175 days. Increases were observed in NK and CD8 but not CD4 T cell numbers during acute infection. Severity of illness correlated positively with both blood EBV load (P=0.015) and CD8 lymphocytosis (P=0.0003).Conclusions. Kissing was a significant risk for primary EBV infection; 89% of infections were symptomatic; blood viral load and CD8 lymphocytosis correlated with disease severity.
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ABSTRACT: Epstein-Barr virus (EBV) causes a variety of clinical manifestations from asymptomatic infection to acute infectious mononucleosis in human. Moreover, the EBV infection is associated with malignancies. The large-scale EBV seroepidemiology across all age groups has been lacking in Taiwan. A total of 1411 serum samples were tested to examine the seroprevalence of EBV in 2007. The samples were collected during an island-wide seroepidemiological survey of vaccine preventable diseases in Taiwan. The enzyme-linked immunosorbent assay was performed to detect anti-EBV viral capsid IgG in sera. Demographic and personal health data were obtained by questionnaires. The overall weighted seropositive rate of EBV was 88.5% (95% CI, 86.7%-90.1%). The seropositive rate of EBV reached 52.8% (95% CI, 44.0%-61.6%) in children aged 2 years, rapidly rose to 88.7% (95% CI, 79.0%-95.1%) in those aged 5-7 years and 93.0% (95%CI, 83.0%-98.1%) for those aged 14-16 years. Age and higher educational level were associated with the increased EBV seropositive rate. In Taiwan, people had the EBV infection early in life. Children under 7 years should be the primary target popution of public health measures in the future.PLoS ONE 01/2015; 10(1):e0115836. DOI:10.1371/journal.pone.0115836 · 3.53 Impact Factor
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ABSTRACT: 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.PLoS Pathogens 03/2015; 11(3):e1004746. DOI:10.1371/journal.ppat.1004746 · 8.06 Impact Factor
Article: Infectious mononucleosis[Show abstract] [Hide abstract]
ABSTRACT: 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.02/2015; 4(2):e33. DOI:10.1038/cti.2015.1