Chapter 311

The Epstein-Barr virus (EBV) is recognized as the major cause of heterophil-positive and heterophil-negative infectious mononucleosis. Manifestations of EBV infection are varied and range from asymptomatic infection to fulminant lymphoproliferative disease. The virus is associated with a number of malignancies, including African Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease, and a spectrum of posttransplant lymphoproliferative diseases. The specific role of EBV in each tumor is now defined, in a number of circumstances, to the level of specific cell type and receptors, intracellular pathways, gene expression, and cytokine production.

### Epidemiology

It is important to recognize that acute primary Epstein-Barr virus (EBV) infection is not synonymous with infectious mononucleosis. Most EBV infections acquired at any age, but particularly during childhood, are asymptomatic. Seroepidemiologic studies demonstrate that from 20% to 100% of children worldwide have antibodies to EBV by 6 years of age.9 In contrast, in the United States, only 40% to 50% of adolescents are seropositive,9-11 with higher socioeconomic groups being less likely to have evidence of prior infection. Seropositivity increases with age in all populations, so that almost all adults have serologic evidence of past EBV infection. Seroconversion is particularly high in college, where 10% to 15% of susceptible persons become infected each year. This group of EBV-naive adolescents in industrialized countries is susceptible to develop EBV-associated IM, much more common in the United States and Western Europe than in unindustrialized countries.

EBV is excreted in oropharyngeal secretions (low titer of virus even during acute illness) and is transmitted by contact with saliva via kissing or other mucosal contact with contaminated objects.12 Healthy seropositive individuals intermittently shed EBV into their oropharynx. Blood products or transplanted tissues can transmit EBV and are particularly problematic for seronegative immunocompromised transplant recipients. There is no evidence of urinary or fecal excretion. Transplacental transmission appears to be rare. Shedding of virus appears to be more frequent in immunosuppressed individuals, 60% of whom may excrete EBV at any one time. Because virus shedding is of a low titer in even immunocompromised patients, standard precautions are adequate for isolation of patients with acute or past EBV infections.12

The epidemiology of infectious mononucleosis is closely related to the age of primary EBV infection. In the United States, the incidence of infectious mononucleosis is approximately 50 per 100,000 persons per year, but in individuals 15 to 25 years old, the incidence doubles.13 Those areas where children are infected at an early age have the lowest incidence of the disease. Among susceptible adolescents and young adults, studies measuring both apparent and inapparent EBV infections indicate a clinical-to-subclinical ratio of 1:2 to 1:3. Although the ratio of clinical-to-subclinical infections in young children is not well defined, the incidence of the typical infectious mononucleosis syndrome is low.

### Pathophysiology

Epstein-Barr virus (EBV) is a member of the family Herpesviridae (gamma herpesvirus), which contains linear double-stranded DNA surrounded ...

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