Description

• Epstein-Barr virus (EBV) is a member of the gamma herpes virus family; human herpes virus 4.
  • Two subtypes: ST1 predominates in Western Hemisphere, Southeast Asia; ST1 and ST2 equally prevalent in Africa
• Primary infection typically occurs in childhood. The majority of individuals seroconvert by 2 years of age with little clinical manifestation of illness. A second peak occurs in adolescence and young adulthood—this group commonly manifests infection as infectious mononucleosis (IM) (1).
• WHO classified EBV as “tumor virus” (group I carcinogen) due to cancer association.

Epidemiology

Incidence

• Military recruits, college students, and others living in cloistered and crowded populations have highest symptomatic infection rate. Overall rate in the United States is 500/100,000.
• Predominant age of symptomatic primary infection is 15 to 24 years; 200 to 800/100,000 affected
• Incidence increases during the summer months.

Prevalence

• Worldwide, 95% of population has been infected by adulthood. By age 5, 50% of children have been infected; the vast majority of those without manifesting symptoms.
• Seroconversion occurs later in childhood in developed countries; there is suggestion of race/ethnicity disparity in the United States with higher seroprevalence in non-Hispanic black, Asian, and Hispanic populations; also, higher prevalence in larger households and lower levels of parental education (2)

Etiology and Pathophysiology

• After inoculation, the virus replicates in the nasopharyngeal epithelium with resulting cell lysis, virion spread, and viremia. EBV exhibits dual tropism for B-cells and epithelial cells. The reticuloendothelial system is affected, resulting in a host response and the appearance of atypical lymphocytes in the peripheral blood. Viral genome can be detected in the oral cavity 1 week prior to symptoms.
• A polyclonal B-cell proliferative response follows. Relatively few (<0.1%) of circulating lymphocytes are infected by EBV in the acute illness.
• A persistent (asymptomatic) state ensues with the EBV genome invisible to the immune system. The maintenance of the invisible state (to host immunity) is thought to be due to EBV particles, wrapping themselves in host cell-derived membranes and a low rate of viral reproduction (1).
• Either through B-cell stimulation or diminished EBV-specific immune modulation, the previously latent EBV-infected B cells replicate and enter a “lytic” phase, allowing clinical expression of the EBV genome. Risk of this occurrence may be linked to host genetic factors, smoking, increased BMI, and low vitamin D/sunlight exposure. The proteins produced may either modify host response or contribute directly to malignancy (2).
• Immunosuppression (organ transplant/acquired immune deficiency) can result in transformation and lymphoproliferative disorders.

Risk Factors

• Age (highest incidence of symptomatic infection in adolescents and young adults)
• Sociohygienic level “crowded conditions”
• Geographic location
• Close, intimate contact; especially “deep kissing” in adolescents and young adults
• Immunosuppression
• Possibly some risk of transmission by fomites (e.g., shared toys)

General Prevention

• Avoid close physical contact with symptomatic EBV/IM patients.
• Meticulous hand washing and hygiene
• General precautions with potential blood exposure (EBV can be transmitted via blood contamination as well as hematopoietic cell and solid organ transplant.)
• EBV vaccines under investigation (Lack of intimate knowledge of mechanism of immune response has impaired the ability to develop an effective vaccine)

Commonly Associated Conditions

• IM: Symptomatic primary EBV infection is common in otherwise healthy adolescents and young adults.
  • Clinical features vary in severity and duration: In children age <10 years, generally mild; in adolescents and adults, symptoms can be more severe and protracted (are dependent on intensity of T-cell response).
  • Incubation period is 30 to 50 days (extremely long for a viral infection).
• X-linked lymphoproliferative syndrome (XLP—rare, inherited extreme vulnerability to EBV infection)
• Lymphoproliferative syndromes due to EBV infections in transplant recipients
• Lymphomas (B-cell lymphoblastic, T cell)
• Lymphocytic interstitial pneumonitis
• Hairy leukoplakia of the tongue, leiomyosarcoma, and CNS lymphomas in patients with AIDS
• Burkitt lymphoma (most common childhood tumor in Africa and Papua New Guinea where malaria is also endemic and may be a cofactor); much higher prevalence than other areas of the world
• Nasopharyngeal carcinoma (seen worldwide but highest prevalence in Africa and Asia)
• Parotid carcinoma
• Hodgkin lymphoma (most common EBV-associated malignancy in the United States, European Union)
• Postulated to be associated with multiple sclerosis (2 to 3 times incidence in EBV-positive individuals)
• Chronic active EBV (CAEBV) due to loss of host control of viral replication