Patient Test Information

Mononucleosis (Mono) Test

Also known as:

Mononucleosis Spot Test; Mononuclear Heterophile Test; Heterophile Antibody Test; Monospot

Formal name:

Heterophile Antibody Titer

Related tests:

Epstein-Barr Virus (EBV) Antibody Tests; Complete Blood Count; Strep Throat Test; TORCH; CMV Tests; CSF Analysis; Blood Smear

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Why Get Tested?

To detect and help diagnose infectious mononucleosis (mono)

When to Get Tested?

When a person, especially an adolescent, has symptoms of mononucleosis, including fever, sore throat, swollen glands, and fatigue

Sample Required?

A blood sample drawn from pricking of your fingertip or from a vein in your arm

Test Preparation Needed?

None

How is it used?

The mononucleosis test is used to help determine whether a person with symptoms has infectious mononucleosis (mono). The test is used to detect proteins in the blood called heterophile antibodies that are produced by the immune system in response to an Epstein-Barr virus (EBV) infection, the most common cause of mono. (For more on mono, see the "What is being tested?" section.)

A mono test is frequently ordered along with a complete blood count (CBC). The CBC is used to determine whether the number of white blood cells (WBCs) is elevated and whether a significant number of reactive lymphocytes are present. Mono is characterized by the presence of atypical white blood cells.

If the mono test is initially negative but the healthcare practitioner still suspects mono, a repeat test done a week or so later may be used to determine whether heterophile antibodies have developed. If the mono test is persistently negative, a test specific for EBV antibodies may be used to help confirm or rule out the presence of an EBV infection. A strep test may also be ordered along with a mono test to determine whether a person's sore throat is due to strep throat (group A streptococcal infection) instead of or in addition to mononucleosis.

When is it ordered?

The mono test is primarily ordered when a person, especially a teen or young adult, has symptoms that a healthcare practitioner suspects are due to infectious mononucleosis. Symptoms can sometimes be confused with those of a cold or the flu. Some of the more common signs and symptoms of mono include:

  • Fever
  • Headache
  • Sore throat
  • Swollen glands in the neck and/or armpits
  • Extreme weakness or fatigue

Some people may experience additional signs and symptoms such as:

  • Stomach pain
  • Enlarged liver and/or spleen
  • Rash

The test may be repeated when it is initially negative but suspicion of mono remains high.

What does the test result mean?

A positive mono test with an increased number of white blood cells and reactive lymphocytes on a blood smear in the presence of symptoms associated with mono indicates a likely diagnosis of infectious mononucleosis.

A negative mono test requires careful interpretation.

  • If symptoms and reactive lymphocytes are present but the mono test is negative, then it may be too early to detect the heterophile antibodies or the affected person may be one of a small percentage of people who do not make heterophile antibodies. The mono test may be repeated at a later time and/or tests specific for EBV antibodies may be performed to help confirm or rule out the mononucleosis diagnosis.
  • Most infants and young children will not make heterophile antibodies, so they will have negative mono tests even when infected with EBV. This population is rarely tested, however, because they do not usually have symptoms of infectious mononucleosis.
  • People with negative mono tests and few or no reactive lymphocytes may be infected by another microorganism that is causing symptoms, such as a cytomegalovirus (CMV) or toxoplasmosis. If the infection occurs during pregnancy, it can be important to determine the cause since some of these other infections have been associated with pregnancy complications and injury to the fetus. It is also important to identify strep throat when present because it requires prompt treatment with antibiotics. (Since EBV is a virus, it cannot be treated with antibiotics.)

Is there anything else I should know?

The mono test is rapid and easy to perform, but it is specific for heterophile antibodies, not EBV. It can also be positive in people with lymphoma, lupus, and some gastrointestinal cancers, although it is not used as a diagnostic or screening tool for these conditions.

When the mono test is negative and/or a healthcare practitioner wants to obtain more information about the presence and status of an EBV infection, the healthcare practitioner may order one or more of a combination of EBV antibodies. These tests can indicate whether a person is susceptible to EBV, has had a recent infection, has had EBV infection in the past, or has a reactivated EBV infection.

Heterophile antibodies decline after the sixth week of illness, and the mono test will become negative as the infection resolves.

What is being tested?

Infectious mononucleosis, commonly called mono, refers to an infection usually caused by the Epstein-Barr virus (EBV). The mono test detects proteins in the blood called heterophile antibodies that are produced by the immune system in response to an EBV infection.

Infectious mononucleosis is characterized by a particular set of symptoms that most often affects adolescents. People who have mono often have a fever, sore throat, swollen glands, and fatigue. Many will also have an enlarged spleen, and a few may have an enlarged liver. Symptoms of the infection usually arise about one month after the initial infection and may last for several weeks. The associated fatigue may last for several months. Mono is usually a self-limiting condition; the symptoms resolve without any specific treatment.

Epstein-Barr virus is very common and very contagious. According to the Centers for Disease Control and Prevention (CDC), most people in the United States are infected by EBV at some point in their lives. The virus is present in the saliva of an infected person and is easily spread from person to person through close contact such as kissing and through sharing utensils or cups.

Most of the time, EBV infection occurs in childhood and causes few or no symptoms. However, it can cause symptoms associated with infectious mononucleosis in about 25% of teens and young adults, according to the CDC. Mono can affect anyone at any age, but its prevalence is highest in populations of young people, such as students in high schools or colleges, or in the military.

The mono test is 71% to 90% accurate and may be used as an initial test for diagnosing infectious mononucleosis. However, the test does have a 25% false-negative rate due to the fact that some people infected with EBV do not produce the heterophile antibodies that the mono test is designed to detect. If a mono test is negative and suspicion it still high, then a test specific for EBV antibodies is usually performed.

A complete blood count (CBC) and blood smear are usually also performed, as mono is also characterized by a high white blood cell (WBC) count and the presence of atypical white blood cells (usually reported as reactive lymphocytes) as seen on a blood smear.

According to the CDC, examples of other causes of mono include:

How is the sample collected for testing?

A blood sample is drawn by needle from a vein in the arm or by pricking the finger.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

  1.  How serious is a case of infectious mononucleosis?

    The symptoms of the disease usually resolve with supportive treatment, such as plenty of rest and fluids, in one to four months. Sometimes, your spleen or liver may enlarge and you may have to limit your activity until these organs return to normal size. Heart problems or involvement of the central nervous system occur only rarely. Infectious mononucleosis may cause severe liver failure in males with a special XLP gene. In this rare case, mononucleosis can be fatal.

  2. Is mononucleosis really a "kissing disease"?

    The spread of Epstein-Barr virus (EBV) requires contact with the saliva of an infected person as occurs with kissing; however, kissing does not have to occur for infection to arise. Saliva on children's toys, water bottles, toothbrushes, drinking glasses, and hands can also transmit the virus. Transmission of this virus through the air or blood does not normally occur. The incubation period, or the time from infection to appearance of symptoms, ranges from 4 to 6 weeks.

    People who have infectious mononucleosis can spread the infection to others for a period of weeks. Many healthy people who have been previously infected can carry and spread the virus intermittently for life, and testing them for the virus is not practical. For these reasons, it is almost impossible to prevent spreading the virus and nearly everyone will have had an EBV infection, but not necessarily mono, by the time that they are 40 years old.

  3. Does the Epstein-Barr virus (EBV) cause chronic fatigue syndrome?

    To date, there is no laboratory evidence indicating that EBV infection causes chronic fatigue syndrome. For more information, visit the Centers for Disease Control and Prevention's web page on Chronic Fatigue Syndrome.

  4. Can I get infectious mononucleosis more than once?

    Although the symptoms of infectious mononucleosis usually go away in 1 or 2 months, EBV remains inactive in a few cells in the body for the rest of the person's life. Periodically, the virus can reactivate, and it is commonly found in the saliva of infected persons. This reactivation usually occurs without symptoms of illness.

  5. Can EBV cause other serious illnesses?

    EBV has been linked to certain cancers, such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and AIDS-related lymphoma, and continues to be studied for possible linkages to other cancers. The incidence of these diseases is low, and cases of Burkitt's lymphoma and nasopharyngeal carcinoma occur primarily outside of the United States.