Behavioral, Virologic, and Immunologic Factors Associated With Acquisition and Severity of Primary Epstein-Barr Virus Infection in University Students

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455.
The Journal of Infectious Diseases (Impact Factor: 6). 10/2012; 207(1). DOI: 10.1093/infdis/jis646
Source: PubMed


University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity.

EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay.

Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were 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 numbers of NK cells and CD8(+) T-cells but not in numbers of CD4(+) T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8(+) lymphocytosis (P = .0003).

Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8(+) lymphocytosis correlated with disease severity.

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    • "Viremia is an interesting topic of virus infection and many researchers have taken great efforts to establish correlation between the clinical manifestation and the duration or the magnitude of viremia in several viral diseases. In some viral infections, such as the Epstein–Bar virus and cytomegalovirus disease [33–35], the presence or the magnitude of viremia may be able to predict clinical severity, while in other cases, such as dengue virus, norovirus and hantavirus, the presence of viremia usually only indicated the active stage of disease, but did not absolutely predict the clinical severity [36–39]. The observation in our study suggested that EV71 might be more similar to the later ones. "
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    ABSTRACT: Background Enterovirus 71 (EV71) is a great disease burden across the whole world, particularly in Southeast Asia. However, in recent decades, the pathogenesis of severe EV71 infection was not well understood. This study was aimed to investigate the correlation between the presence of viremia and the clinical severity of EV71 infection. Methods We organized a prospective cohort study and enrolled laboratory-confirmed EV71 cases in six tertiary care hospitals in Taiwan during the EV71 epidemic from 2011 to 2012. Blood samples were collected once in the acute stage, on the first day of admission. We used real-time RT-PCR to detect EV71 viremia. Demographical and clinical data were collected and the clinical severity was categorized into four grades. Data analysis was performed to identify the risk factors of viremia and the correlation between viremia and clinical severity of EV71 infection. Results Of the total 224 enrolled patients, 59 (26%) patients were confirmed to have viremia. Two-thirds (68%) of viremic cases were detected within the first three days of infection. Viremia occurred more frequently in children under the age of one year old (odds ratios [OR] 4.82, p < 0.001) but the association between the presence of viremia and complicated EV71 infection was not found (OR 1.02, p = 0.96). In the viremia group, patients had significantly more severe complications if viremia was detected after the third day of disease onset (26% vs. 5%, p = 0.03). Conclusions Viremia occurred more frequently in children under the age of one year and viremia detected beyond three days after the onset of disease correlated with more severe disease in EV71 patients.
    BMC Infectious Diseases 07/2014; 14(1):417. DOI:10.1186/1471-2334-14-417 · 2.61 Impact Factor
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    • "Indeed, both the total number of CD8 T cells/ml blood or the ratio of CD8 to CD4 T cells in the blood provided the best predictor of disease severity in a large prospective study. [38] Thus, using data from the qPCR superarray approach described above, we examined the correlation between gene expression and CD8 lymphocytosis. We found that expression of type I IRGs individually, or as a group, did not correlate strongly (Figure 7). "
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    ABSTRACT: Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.
    PLoS ONE 01/2014; 9(1):e85422. DOI:10.1371/journal.pone.0085422 · 3.23 Impact Factor

  • The Journal of Infectious Diseases 10/2012; 207(1). DOI:10.1093/infdis/jis647 · 6.00 Impact Factor
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