How Mononucleosis Is Diagnosed

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The diagnosis of infectious mononucleosis (mono) is usually made based on the symptoms, findings in a physical examination, and blood tests. Mono is usually caused by the Epstein-Barr virus (EBV) or similar viruses, but strep throat and some other conditions may need to be ruled out. While the Centers for Disease Control (CDC) no longer recommends the ​monospot test, many guidelines still encourage using this test to help identify the cause of mono.

mononucleosis diagnosis
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You probably won't immediately suspect you or your child has mono because the early symptoms are like those of a cold, the flu, or strep throat. The symptoms most likely to send you to the doctor are swollen lymph nodes in the neck, extreme fatigue, sore throat, fever, and body aches that have lasted for longer than 10 days.

Most colds and other viral infections get better after seven days, so the 10-day point is a good indicator that you're dealing with something beyond these self-resolving illnesses.

The symptoms can be mild in babies and younger children.

It is important not to rely on self-diagnosis for mono as the symptoms could be those of illnesses that need a different course of treatment. You should note the timeline of the symptoms, including when you or your child first started feeling sick, which symptoms developed, and how long they have lasted. This can help your doctor make a diagnosis if the symptoms don't go away on their own by day 10.

You should see your doctor immediately with any of the serious symptoms of mono. These include a high fever (101.5 degrees or more), pain in the abdomen, severely swollen throat or tonsils, difficulty breathing or swallowing, limb weakness, or a severe headache. These could be due to mono, but could also be owed to other conditions and complications.

Labs and Tests

Your doctor will look at your symptoms and your age (since people infected with EBV are more likely to develop mono if they are a teenager or young adult). She will perform a physical evaluation where she will look in the back of your throat for the typical spots (petechiae), feel your neck and other areas where you may have swollen lymph nodes, and listen to your lungs.

Your doctor will usually order a complete blood count (CBC) and an antibody test. If you have a sore throat, it is likely that a rapid strep test will be performed. In pregnant women, more extensive antibody testing may be done to rule out causes other than EBV that have more potential to affect the pregnancy.


If you have mono, your CBC will typically show an elevated white blood count (WBC) with more lymphocytes than usual, which is known as lymphocytosis. These lymphocytes will also have an atypical appearance when the medical technologist examines the blood under the microscope. Lymphocytes are a part of your body's immune system and it is natural for them to be elevated during certain types of infections. You will also have fewer of the other predominant type of white cells, neutrophils, and you may have a lower than usual platelet count.

Antibody Testing

Your blood may be analyzed in a laboratory for antibodies, although this test isn't strictly needed for a diagnosis of infectious mononucleosis. Antibodies are produced by your immune system to fight infection by a virus or other organisms your system considers to be a threat.

The monospot (heterophile antibody test) is an older test that is commonly used to make the mono diagnosis. A positive monospot test accompanied by the symptoms of mono helps confirm a diagnosis of infectious mononucleosis. However, the CDC says the monospot test is no longer recommended because it produces too many inaccurate results.

Monospot tests can be false-negative about 10 percent to 15 percent of the time, particularly in the early stages of the illness. You stand an approximately 25 percent chance of getting a false-negative test result if you are tested within the first week of symptom onset. This may also happen if you waited too long to see a doctor because the heterophile antibodies rapidly decrease after you've been infected for about four weeks. Furthermore, if you have mono from a different virus than EBV, such as CMV, the monospot won't detect it.

If your monospot test is negative but you have all the symptoms of mono, your doctor will likely repeat the test before doing more extensive antibody tests. These tests may be done if the illness symptoms aren't typical for mononucleosis or you have been ill for more than four weeks. You may be tested for cytomegalovirus or Toxoplasma antibodies. More specific tests for EBV include:

  • Viral capsid antigen (VCA)
  • Early antigen (EA)
  • EBV nuclear antigen (EBNA) tests

Mononucleosis Doctor Discussion Guide

Get our printable guide for your next doctor's appointment to help you ask the right questions.

Doctor Discussion Guide Woman

Differential Diagnosis

A sore throat, fever, and swollen glands seen in mono can appear much like the symptoms of strep throat. A rapid strep test or throat culture can help distinguish these. Strep throat usually responds quickly to antibiotics, while they have no effect on mono.

Influenza can also mimic some of the symptoms of mono but usually doesn't produce swollen neck glands. Influenza will usually get better in less than two weeks.

Mono-like symptoms can be seen in infections other than Epstein-Barr virus. Other agents that can produce these symptoms include cytomegalovirus (CMV), adenovirus, human immunodeficiency virus (HIV), rubella, hepatitis A, human herpesvirus-6, and the parasite Toxoplasma gondii.

Illness with some of these agents, especially CMV and Toxoplasma gondii, may be designated as infectious mononucleosis or called a mono-like illness. As with EBV mono, only supportive treatment is recommended. However, these illnesses can complicate pregnancy, so further tests to identify the cause of the illness are recommended for moms-to-be.

If a doctor uses a monospot test, it can be falsely positive when the patient has conditions that include hepatitis, leukemia, lymphoma, rubella, systemic lupus erythematosus, and toxoplasmosis. The doctor must use the patient's symptoms and other tests to distinguish between these conditions.

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Article Sources
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  1. Centers for Disease Control and Prevention. About Infectious Mononucleosis

  2. Centers for Disease Control and Prevention. Epstein-Barr Virus and Infectious Mononucleosis. Laboratory Testing

  3. Ishii T, Sasaki Y, Maeda T, Komatsu F, Suzuki T, Urita Y. Clinical differentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan. J Infect Chemother. 2019;25(6):431-436. doi:10.1016/j.jiac.2019.01.012

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