Infectious mononucleosis

Abstract

Infectious mononucleosis is a clinical entity characterized by pharyngitis, cervical lymph node enlargement, fatigue and fever, which results most often from a primary Epstein-Barr virus (EBV) infection. EBV, a lymphocrytovirus and a member of the γ-herpesvirus family, infects at least 90% of the population worldwide, the majority of whom have no recognizable illness. The virus is spread by intimate oral contact among adolescents, but how preadolescents acquire the virus is not known. During the incubation period of approximately 6 weeks, viral replication first occurs in the oropharynx followed by viremia as early as 2 weeks before onset of illness. The acute illness is marked by high viral loads in both the oral cavity and blood accompanied by the production of immunoglobulin M antibodies against EBV viral capsid antigen and an extraordinary expansion of CD8(+) T lymphocytes directed against EBV-infected B cells. During convalescence, CD8(+) T cells return to normal levels and antibodies develop against EBV nuclear antigen-1. A typical clinical picture in an adolescent or young adult with a positive heterophile test is usually sufficient to make the diagnosis of infectious mononucleosis, but heterophile antibodies are not specific and do not develop in some patients especially young children. EBV-specific antibody profiles are the best choice for staging EBV infection. In addition to causing acute illness, long-term consequences are linked to infectious mononucleosis, especially Hodgkin lymphoma and multiple sclerosis. There is no licensed vaccine for prevention and no specific approved treatment. Future research goals are development of an EBV vaccine, understanding the risk factors for severity of the acute illness and likelihood of developing cancer or autoimmune diseases, and discovering anti-EBV drugs to treat infectious mononucleosis and other EBV-spurred diseases.

Figure 1

Pharyngitis demonstrating exudative tonsillitis and an enlarged uvula in a 19-year-old undergraduate university student 5 days after onset of infectious mononucleosis. In addition to pharyngitis, he felt febrile, had cervical lymphadenopathy, fatigue and loss of appetite. His sore throat lasted for 9 days and he was fatigued for 29 days.

Figure 2

Line immunoblots demonstrating IgG antibody responses to six EBV proteins at five timepoints from the day before onset of illness (day −1) to 172 days postonset. Band intensities equal to or greater than the cutoff control are considered to indicate a specific antibody response. The first antibodies to appear are directed against BZLF1 (immediate early), and p23 (VCA). Antibodies to p138 and p54 (EA) developed next, followed by p18 (VCA) antibodies. Antibodies against EBNA-1 were seen only on the serum sample collected 172 days after onset of illness.