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Mononucleosis spot test
Mononuclear heterophile test
Heterophile antibody test
Nome formal
Heterophile antibody titer
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Este artigo foi modificado pela última vez em 10 de Julho de 2017.
At a Glance
Why Get Tested?
To detect and help diagnose infectious mononucleosis
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 a vein in your arm
Test Preparation Needed?
What is being tested?
Mononucleosis, or mono, refers to an infection caused by the Epstein-Barr virus (EBV). The infection 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 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.

EBV is very common. According to Centers for Disease Control and Prevention (CDC), up to 95% of people in the United States will have been infected by EBV by the time they are 40 years old. It is spread from person to person through saliva during close contact. Most of the time, the EBV infection occurs in childhood and causes few or no symptoms, but if first exposure to the virus occurs in adolescence, it can cause symptoms associated with infectious mononucleosis (mono) in about half of those infected. Mono can affect anyone at any age, but its prevalence is highest in populations of young people, such as are found at high schools, colleges, or in the military.

The mono test detects heterophile antibodies, which are made by the body in response to an infection by EBV. About 70% to 80% of those with mono produce heterophile antibodies. These proteins are not specific for EBV but, when found in adolescents in conjunction with mono symptoms, they help diagnose infectious mononucleosis. Mono is also characterized by the presence of atypical white blood cells (usually reported as reactive lymphocytes) as seen on a blood smear and by the presence of EBV antibodies in an infected person.

How is the sample collected for testing?

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

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

No test preparation is needed.
Accordion Title
Common Questions
  • How is it used?
    The mono test is used to help determine whether a person with symptoms of mon has infectious mononucleosis. It is frequently ordered along with a CBC (complete blood count). 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. A strep test may also be ordered with the mono test to determine whether a person’s sore throat is due to strep throat, a streptococcal infection instead of or in addition to mononucleosis.

    If the mono test is initially negative but the doctor still suspects mono, he may order a repeat test in a week or so to see if Heterophile antibodies have developed and/or order one or more EBV antibodies to help confirm or rule out the presence of a current EBV infection.

  • When is it ordered?
    The mono test is primarily ordered when an adolescent has symptoms that the doctor suspects are due to infectious mononucleosis. These can sometimes be confused with symptoms of a cold or the flu. Some of the more common symptoms of mono include:
    • fever
    • headache
    • sore throat
    • swollen glands in your neck and/or armpits
    • ongoing weakness or fatigue

    Some people may experience additional 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?
    If someone has a positive mono test, an increased number of white blood cells, reactive lymphocytes, and symptoms of mono, then that person will be diagnosed with infectious mononucleosis.

    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. Tests for other EBV antibodies and/or a repeat mono test 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 mono-like symptoms, such as a cytomegalovirus (CMV) or toxoplasmosis. If the infection occurs during pregnancy, it can be important to determine the cause, as some of the mono-like infections, but not EBV infection, have been associated with pregnancy complications and injury to the fetus. It is also important to identify strep throat, whenever present, because it requires prompt treatment 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, systemic lupus erythematosus (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 the doctor wants to obtain more information about the presence and status of an EBV infection, he 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 fourth week of illness, and the mono test will become negative as the infection resolves.

  •  How serious is a case of infectious mononucleosis?
    The symptoms of the disease usually resolve without treatment 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.
  • Is mononucleosis really a “kissing disease”?
    The spread of EBV requires intimate contact with the saliva of an infected person. Kissing does not have to occur for infection to arise, however. 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 may be able to 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 mono, by the time that they are 40 years old.

  • Does the Epstein-Barr virus cause chronic fatigue syndrome?
    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 site.
  • 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.
  • 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 rare, and cases of Burkitt’s lymphoma and nasopharyngeal carcinoma occur predominantly outside of the United States.
View Sources
Sources Used in Current Review

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 662-663.

Cunha, B. (Updated 2008 October 17). Infectious Mononucleosis. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/222040-overview through http://emedicine.medscape.com. Accessed May 2009.

Omori, M. (Updated 2009 April 02). Mononucleosis. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/784513-overview through http://emedicine.medscape.com. Accessed May 2009.

Smith, D. S. (Updated 2008 September 3). Mononucleosis. MedlinePlus Medical Encyclopedia eMedicine [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/000591.htm. Accessed May 2009.

Smith, D. S. (Updated 2008 September 3). Mononucleosis spot test. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003454.htm. Accessed May 2009.

Sources Used in Previous Reviews

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp 594-595.

Corbett, JV. Laboratory Tests & Diagnostic Procedures with Nursing Diagnoses, 4th ed. Stamford, Conn.: Appleton & Lang, 1996. Pp. 373-374.

Ebell, M. (2004 October 1). Epstein-Barr Virus Infectious Mononucleosis. American Family Physician [On-line journal]. Available online at http://www.aafp.org/afp/20041001/1279.html through http://www.aafp.org.

Schmid, S., Leader Herpesvirus Group (2005 September 13, Updated). Epstein-Barr Virus and Infectious Mononucleosis. CDC, National Center for Infectious Diseases [On-line information]. Available online at http://www.cdc.gov/ncidod/diseases/ebv.htm through http://www.cdc.gov.

National Center for Infectious Diseases. Epstein-Barr Virus and Infectious Mononucleosis. Available online at http://www.cdc.gov/ncidod/diseases/ebv.htm through http://www.cdc.gov.

Nebraska Health and Human Services System. Infectious Mononucleosis (Mono) Disease Fact Sheet. Available online at http://www.hhs.state.ne.us/epi/epimono.htm through http://www.hhs.state.ne.us.