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Epstein-Barr virus (EBV), the viral agent responsible for IM, is a ubiquitous herpes-virus first described by Epstein, Achong, and Barr in continuous cell lines derived from African Burkitt lymphoma tissues. The Henles first observed development of antibodies to EBV in a patient who had acute IM. Subsequent serologic surveys in 1967 confirmed EBV as the major cause of mononucleosis, mononuclosis, mono


EBV preferentially infects B lymphocytes and is transmitted primarily in saliva or, less commonly, by blood transfusion. It is not likely to be transmitted by aerosol or fomites. After an incubation period of 2 to 7 weeks following exposure, as many as 20% of the circulating B lymphocytes of adolescents or

The age of initial infection varies in different cultural and socioeconomic settings. In some poor urban settings or in developing countries, 80% to 100% of children are seropositive by 3 to 6 years of age. The majority of primary infections in such groups are subclinical or only mildly symptomatic. In

Given the widespread rate of infection in the general population, it may be assumed that EBV spreads relatively efficiently. However, in one family study, only 35% of nonimmune siblings developed EBV

Clinical Aspects

Primary EBV infection in young children usually is asymptomatic or presents with such mild, nonspecific symptoms as upper respiratory tract infection, tonsillopharyngitis, or prolonged febrile illness with or without lymphadenopathy. Older children are more likely to develop the typical signs and symptoms of IM. After an incubation period of 2 to 7 weeks, prodromal symptoms of malaise,

Mononucleosis due to cytomegalovirus (CMV) is the illness confused most frequently with EBV-induced IM. Patients who have CMV mononucleosis are, on average, older than those who have EBV-induced disease and exhibit fever and malaise as the major manifestations; pharyngitis and lymphadenopathy are less common than with EBV-induced IM.

Pharyngitis may be caused by a variety of other viral or bacterial organisms. Group A beta-hemolytic streptococci can be isolated from the throats of up to 30% of patients who have symptomatic IM and

EBV initially was believed to be the etiologic agent of chronic fatigue syndrome, an illness characterized by recurrent malaise, difficulty with concentration, headache, weakness, myalgias, arthralgias, pharyngitis, lymphadenitis, and low-grade fever. However, subsequent studies have not supported such an association. Although fewer than 5% of patients experience malaise and fever for as long as 3 to 4 months, some patients have been reported in whom signs and symptoms persisting for more than 6 months are associated with evidence of ongoing EBV replication. Some have labeled this disorder "chronic mono," but this is an extremely rare condition, and the etiology of the ongoing viral replication is uncertain.

Laboratory Evaluation

Although the classic tube heterophil titer is still performed in some laboratories, the "monospot" slide test is sensitive, specific, easily performed, and used more commonly. The sensitivity and specificity are 85% and 97%, respectively, in children older than 4 years of age. Symptomatic children younger


Treatment of IM is supportive. Adequate rest is advocated, but there is no evidence that bed rest hastens recovery. Fluids and a soft diet along with acetaminophen or ibuprofen will help ease the


The majority of individuals who have IM experience an uneventful course and recover without residual problems, although complications do occur infrequently and may be dramatic. Hematologic complications include a self-limiting anti-i-mediated autoimmune hemolytic anemia, which