From the Guidelines
The best test for acute infectious mononucleosis (mono) is the heterophile antibody test, commonly known as the Monospot test. This rapid screening test detects heterophile antibodies produced during EBV infection and provides results within minutes. For patients with suspected mono who present with symptoms like fever, sore throat, fatigue, and lymphadenopathy, the Monospot test offers good sensitivity (85-90%) and specificity (95-100%) after the first week of illness 1. If clinical suspicion remains high despite a negative Monospot, specific EBV serologic testing should be performed, particularly looking for the presence of VCA-IgM antibodies which indicate acute infection. The Monospot test is preferred initially due to its rapid turnaround time, lower cost, and reasonable accuracy, though it may yield false negatives in children under 12 and during the very early stage of infection (first week) 1.
Some key points to consider when interpreting the results of the Monospot test include:
- False-negative results are obtained in approximately 10% of patients, and are especially common in children younger than 10 years 1
- The presence of VCA-IgM antibodies indicates recent primary infection with EBV, while the presence of EBNA antibodies indicates infection more than 6 weeks from the time of the sample 1
- Complete blood count findings that support the diagnosis include lymphocytosis with atypical lymphocytes (>10%), though these are not specific to mono 1
It's also important to note that other tests, such as EBV serologic testing, may be necessary to confirm the diagnosis in certain cases, particularly if the Monospot test is negative but clinical suspicion remains high 1. However, the Monospot test remains the preferred initial test due to its rapid turnaround time and reasonable accuracy.
In terms of the evidence, the most recent and highest quality study supports the use of the Monospot test as the initial diagnostic test for acute infectious mononucleosis 1. This study, published in 2013, provides guidance on the utilization of the microbiology laboratory for diagnosis of infectious diseases, including EBV infection. The study recommends the use of the Monospot test as the first line laboratory diagnostic test for EBV infection, and provides guidance on the interpretation of results and the use of additional tests, such as EBV serologic testing, in certain cases.
From the Research
Diagnostic Tests for Acute Infectious Mononucleosis
The diagnosis of acute infectious mononucleosis (mono) can be made using various tests, including:
- Heterophile antibody test (Monospot) 2, 3, 4, 5
- Epstein-Barr virus (EBV) specific antibody tests, such as:
- Other tests, such as immunoblotting and molecular biology methods, may also be used to interpret serological findings and define the status of the infection 4
Interpretation of Test Results
The interpretation of test results can be complex, and the diagnosis of infectious mononucleosis must be made with caution, considering possible sources of error 6. The presence of IgM antibodies to VCA and VCA IgG without EBNA-1 IgG indicates acute infection, whereas the presence of VCA IgG and EBNA-1 IgG without VCA IgM is typical of past infection 4. However, serological findings may sometimes be difficult to interpret, and additional tests may be necessary to solve any problems that may arise in routine laboratory practice 4.
Clinical Diagnosis
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 5. However, heterophile antibodies are not specific and do not develop in some patients, especially young children 5. EBV-specific antibody profiles are the best choice for staging EBV infection 5.