Infectious Mononucleosis: Epidemiology, Transmission, and Clinical Manifestations

Introduction

Infectious mononucleosis is an acute viral infection caused in approximately 90% of cases by Epstein–Barr virus (EBV), a member of the Herpesviridae family. The remaining cases may be caused by cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), human immunodeficiency virus (HIV), and adenoviruses (1). These viruses are widespread worldwide, with approximately 90–95% of the population infected (2). The term infectious mononucleosis was first introduced in 1920 following the investigation of a group of students presenting with pharyngitis, lymphocytosis, and atypical mononuclear cells. Humans are the only known reservoir of this infection (3).

EBV Transmission

The source of infection includes individuals with acute or chronic infectious mononucleosis as well as asymptomatic EBV carriers. Transmission is more likely to occur from asymptomatic carriers than from individuals with clinically apparent infectious mononucleosis. Healthy carriers may continue to shed the virus intermittently throughout life, and viral shedding may begin shortly after primary infection.

EBV is transmitted via respiratory droplets (during speaking, coughing, or sneezing) and through direct contact, such as kissing or sharing eating utensils. Less commonly, transmission occurs through blood transfusion. Because saliva is the primary route of transmission, infectious mononucleosis is often referred to as the "kissing disease" (4). Following infection, EBV-specific antibodies persist for life. The incubation period is approximately 6 weeks, with viral replication occurring initially in the oropharynx. Viremia can be detected approximately 2 weeks before the onset of clinical symptoms (5).

Infants younger than 1 year are protected by maternally derived antibodies acquired through breast milk, making EBV infection uncommon in this age group. Children younger than 5 years are frequently infected, although the infection usually presents with mild upper respiratory tract symptoms, making clinical diagnosis difficult. In adolescents and adults, 35–50% of primary infections result in infectious mononucleosis. Between 2006 and 2016, the incidence of infectious mononucleosis in Lithuania gradually declined but remained two to three times higher than the average incidence in the European Union (6). According to data from the Centre for Communicable Diseases and AIDS (ULAC), 24 cases of infectious mononucleosis were reported in January 2019: 18 cases in individuals aged 0–17 years, 4 cases in those aged 18–24 years, and 2 cases in the 25–34-year age group (7).

Clinical Manifestations

EBV infection typically presents with sore throat, enlarged lymph nodes—most commonly cervical, but also axillary and less frequently inguinal—together with generalized weakness, headache, and fever.

Most patients experience malaise, loss of appetite, and headache during the prodromal phase, followed by fever, which may occasionally reach 40°C and persist for up to 3 weeks. The pharynx and tonsils are usually erythematous, and approximately one-third of patients develop grayish or greenish tonsillar exudates. Pharyngitis occurs in approximately 80% of patients, splenomegaly in 8%, hepatomegaly in 7%, and palatal petechiae in approximately 25% (1, 8, 9).

Both anterior and posterior cervical lymphadenopathy may occur, unlike bacterial tonsillitis, which is typically associated with anterior cervical lymphadenopathy only. In addition to splenomegaly, hepatomegaly and elevated liver enzyme concentrations occur in approximately 80–90% of patients and usually normalize within about 20 days (1).

A rash is more common in patients treated with ampicillin or amoxicillin; however, this does not represent a true allergic reaction to these antibiotics (9). In untreated patients, rash occurs in approximately 4.2–13% of cases (10). Following antibiotic therapy during acute infectious mononucleosis, the incidence of rash increases to 27.8–69%, with some studies reporting rates as high as 90% after ampicillin administration (11–14).

Additional clinical features may include periorbital edema. Jaundice, central nervous system complications, and myocarditis are uncommon complications. As the fever subsides, pharyngitis gradually resolves, whereas lymphadenopathy may persist for 3–6 months. If symptoms continue for longer than 6 months, the condition is classified as chronic active Epstein–Barr virus infection.