The mono test is used to help determine whether a patient 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 is present. A strep test may be ordered with the mono test to determine whether a person’s sore throat is due to 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 EBV antibodies to help confirm or rule out the presence of a current EBV infection.

The mono test is primarily ordered when an adolescent patient has symptoms such as fever, headache, swollen glands, and fatigue that the doctor suspects are due to infectious mononucleosis. The test may be repeated when it is initially negative but suspicion of mono remains high.

If a patient has a positive mono test, an increased number of white blood cells, reactive lymphocytes, and symptoms of mononucleosis, then they 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 patient may be in the small number of people who do not make heterophile antibodies. 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.

Patients 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 damage to the fetus. It is also important to identify strep throat, whenever present, because it should be treated promptly with antibiotics.

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

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.