INFECTIOUS MONONUCLEOSIS

Infectious Mononucleosis

Infectious Mononucleosis

Introduction

Infectious mononucleosis is a clinical syndrome that is most commonly associated with primary Epstein-Barr virus (EBV) infection. EBV is a gamma herpesvirus with a double-stranded DNA genome of about 172 kb. Natural EBV infection occurs in humans only and results in a lifelong infection. Although the overwhelming majority of cases of infectious mononucleosis occur during primary EBV infection, infectious mononucleosis syndromes have also been reported in chronically infected persons after T-lymphocyte depletion with monoclonal antibodies against CD3.

Seroepidemiologic surveys indicate that over 95% of adults worldwide are infected with EBV. In industrialized countries and higher socioeconomic groups, half the population has primary EBV infection between 1 and 5 years of age, with another large percentage becoming infected in the second decade. Primary EBV infections are rare in the first year of life, presumably because of high maternal seroprevalence and the protective effect of passively transferred maternal antibodies. In developing countries and lower socioeconomic groups, most EBV infections occur in early childhood. Primary infections in young children are often manifested as nonspecific illnesses; typical symptoms of infectious mononucleosis are uncommon.

Background

Infectious mononucleosis most commonly affects those who have primary EBV infection during or after the second decade of life. Because economic and sanitary conditions have improved over past decades, EBV infection in early childhood has become less common, and more children are susceptible as they reach adolescence. For example, rates of seroprevalence among children 5 to 9 years of age in urban Japan dropped from over 80% in 1990 to 59% from 1995 to 1999. The overall incidence of infectious mononucleosis in the United States is about 500 cases per 100,000 persons per year, with the highest incidence in the age group of 15 to 24 years. A total of 30 to 75% of college freshmen are seronegative for EBV. Each year, approximately 10 to 20% of susceptible persons become infected; infectious mononucleosis develops in 30 to 50% of these persons. There are no obvious annual cycles or seasonal changes in incidence, and there is no apparent predisposition on the basis of sex.

Pathophysiology

EBV transmission occurs predominantly through exposure to infected saliva, often as a result of kissing and less commonly by means of sexual transmission. The incubation period, from the time of initial exposure to the onset of symptoms, is estimated at 30 to 50 days. Lytic infection of tonsillar crypt epithelial cells, B lymphocytes, or both results in viral reproduction and high levels of salivary shedding, which decrease over the first year of infection but persist for life. Latently infected memory B lymphocytes circulate systemically and serve as lifelong viral reservoirs; such lymphocytes transiently express only a highly restricted set of EBV genes and thus are largely inapparent to immune-surveillance cells. Vigorous responses to EBV by CD4+ and CD8+ T lymphocytes are expanded in patients with infectious mononucleosis. Evidence suggests that these cellular immune responses limit primary EBV infection and control chronic infection but may also contribute to the symptoms of infectious ...