When should one screen for infectious mononucleosis (Mono)

From the Guidelines

Screening for mononucleosis should be considered when patients present with symptoms including persistent sore throat, fatigue, fever, swollen lymph nodes, and enlarged spleen or liver, particularly in adolescents and young adults (15-24 years old) with these symptoms. The diagnosis of mononucleosis can be challenging due to its nonspecific symptoms, which can also be seen in other conditions such as streptococcal pharyngitis 1. The most common initial test is the heterophile antibody test (monospot), which can be performed as a rapid point-of-care test with results available within minutes. This test detects heterophile antibodies produced in response to Epstein-Barr virus (EBV), the causative agent in about 90% of mononucleosis cases.

• Key symptoms that warrant testing include: + Persistent sore throat + Fatigue + Fever + Swollen lymph nodes (particularly in the neck) + Enlarged spleen or liver
• The heterophile antibody test is the first line of testing, but it may be falsely negative, particularly early in the illness or in children under 10 years 1.
• For patients with negative monospot results but strong clinical suspicion, EBV-specific antibody tests, such as those for IgG and IgM to viral capsid antigen (VCA) and Epstein-Barr nuclear antigen (EBNA), may be necessary to confirm the diagnosis 1.
• The presence of VCA IgM (with or without VCA IgG) antibodies in the absence of antibodies to EBNA indicates recent primary infection with EBV, while the presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample and therefore not likely implicating EBV as a cause 1.
• Testing is important because mononucleosis symptoms can mimic other conditions, and proper diagnosis helps avoid unnecessary antibiotic use and allows appropriate management of complications such as splenic rupture.

From the Research

Screening for Mononucleosis

• The decision to screen for mononucleosis should be based on the presence of symptoms such as sore throat, fever, tonsillar enlargement, fatigue, lymphadenopathy, pharyngeal inflammation, and palatal petechiae 2.
• A heterophile antibody test is the best initial test for diagnosis of EBV infection, with 71% to 90% accuracy for diagnosing IM, but it has a 25% false-negative rate in the first week of illness 2.
• The presence of EBV-specific immunoglobulin M antibodies confirms infection, but the test is more costly and results take longer than the heterophile antibody test 2.
• Tests for antibodies to Epstein-Barr viral capsid antigen or Epstein-Barr nuclear antigen are the most sensitive and highly specific, but are also the most expensive for diagnosing infectious mononucleosis 3.
• The polymerase chain reaction assay for Epstein-Barr virus DNA is more sensitive than the heterophile antibody test in children, is highly specific, but is also expensive 3.

Timing of Screening

• Screening for mononucleosis is typically considered in patients presenting with symptoms, particularly in adolescents and young adults aged 15 to 24 years 4, 2.
• The risk of complications, such as splenic rupture, is higher in the first three weeks of illness, and athletic participation is not recommended during this time 2.
• Early, accurate and informed laboratory test results are vital for diagnosis, appropriate treatment, and management of infectious mononucleosis 5.

High-Risk Groups

• Children are at the highest risk of airway obstruction, which is the most common cause of hospitalization from IM 2.
• Patients with immunosuppression are more likely to have fulminant EBV infection 2.
• Individuals with certain genetic mutations may be at risk of long-term consequences, such as certain cancers and autoimmune diseases, as a result of EBV infection 6.