Infectious mononucleosis, commonly known as mono, is a contagious illness typically caused by the Epstein-Barr virus (EBV). This virus is a member of the herpes family and is transmitted primarily through saliva, earning mono the nickname “the kissing disease.” The infection often presents with a triad of symptoms, including profound fatigue, persistent fever, and swollen lymph nodes in the neck. While a doctor can suspect mono based on a physical examination and symptoms, confirming the diagnosis requires laboratory evidence.
The Rapid Monospot Test
One of the most common initial laboratory tests for suspected mononucleosis is the Monospot test, a type of heterophile antibody test. This rapid screening method detects antibodies produced by the immune system in response to the infection. Unlike tests that look for the virus itself, the Monospot test detects non-specific antibodies that react with cells from other species, such as sheep or horse red blood cells.
The primary advantage of this test is its speed and convenience, often providing results within an hour during a single office visit. A positive Monospot result, when combined with the typical clinical signs of fever and swollen glands, is generally considered sufficient to confirm a diagnosis. However, this test has a significant limitation related to the timing of the infection.
Heterophile antibodies may not be detectable early in the disease course, often leading to a false-negative result, especially during the first week of symptoms. The test is notably unreliable in young children, where the sensitivity can be quite low. In adults, the Monospot test can have a false-negative rate of up to 25% during the first seven days of illness. A negative Monospot result does not definitively rule out mononucleosis, and a doctor may order more specific testing if symptoms persist.
Identifying Specific EBV Antibodies
When the initial Monospot test is negative or if the diagnosis needs to be definitively confirmed, a doctor will often order an Epstein-Barr Virus (EBV) antibody panel. This blood test is more precise because it looks for antibodies specifically directed against EBV proteins, offering a detailed picture of the infection’s timing. The panel assesses the presence of different classes of antibodies, which helps distinguish between a current, recent, or past infection.
The panel focuses on three markers: Viral Capsid Antigen (VCA) IgM, VCA IgG, and Epstein-Barr Nuclear Antigen (EBNA) IgG. The VCA IgM antibody is one of the first markers to appear following exposure to the virus, and a positive result generally indicates an acute or very recent infection. These IgM antibodies typically become undetectable within a few months after the illness resolves.
The VCA IgG antibody also appears early in the infection but, unlike IgM, it persists for the remainder of a person’s life. The presence of VCA IgG alone signifies past exposure and immunity to the virus. Finally, the EBNA IgG antibody develops much later, usually appearing six to eight weeks after the initial infection has begun.
The interpretation of the three markers together allows for accurate staging of the disease. For example, a positive VCA IgM combined with a negative EBNA IgG confirms an acute primary EBV infection. Conversely, a positive VCA IgG and a positive EBNA IgG, with a negative VCA IgM, indicates a past infection and lifelong immunity.
General Changes Seen in Blood Counts
Beyond the specific antibody tests, a routine Complete Blood Count (CBC) can reveal supplementary findings that support a diagnosis of mononucleosis. A hallmark sign of the infection is the presence of atypical lymphocytes, which are unusually shaped white blood cells that appear on a peripheral blood smear. These cells are activated T-lymphocytes, and their count often exceeds 10% of the total white blood cell differential in acute mono cases.
The total white blood cell count typically shows a moderate increase, a condition known as leukocytosis, with a proportional rise in lymphocytes. Infectious mononucleosis often affects liver function. Blood work commonly shows a mild to moderate elevation of liver enzyme levels, specifically aspartate aminotransferase (AST) and alanine aminotransferase (ALT).