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Infectious Mononucleosis

(Epstein-Barr Virus (EBV) Infection)

By Craig R. Pringle, BSc, PhD, Professor Emeritus, School of Life Sciences, University of Warwick

Epstein-Barr virus causes a number of diseases, including infectious mononucleosis.

  • The infection is spread through kissing or other close contact with an infected person.

  • Symptoms vary, but the most common are extreme fatigue, fever, sore throat, and swollen lymph nodes.

  • A blood test is done to confirm the diagnosis.

  • Acetaminophen or nonsteroidal anti-inflammatory drugs can relieve fever and pain.

Infection with the Epstein-Barr virus (EBV) is very common. EBV is a type of herpesvirus called herpesvirus 4 (see Herpesvirus Infection Overview). In the United States, about 50% of all children 5 years of age and nearly 95% of adults have had an EBV infection.

Most of these infections cause symptoms similar to those of a cold or other mild viral infections. Sometimes adolescents and young adults develop different and more severe symptoms from EBV infection. This disease is called infectious mononucleosis. Infectious mononucleosis is named for the large numbers of white blood cells (mononuclear cells) in the bloodstream. Adolescents and young adults usually catch infectious mononucleosis by kissing or having other intimate contact with someone infected with EBV.

After the initial infection, EBV, like other herpesviruses, remains in the body, mainly in white blood cells, for life. Infected people shed the virus periodically in their saliva. They are most likely to infect others during shedding, which usually causes no symptoms.

Rarely, EBV contributes to the development of several uncommon types of cancer, such as Burkitt lymphoma and certain cancers of the nose and throat. It is thought that specific viral genes alter the growth cycle of infected cells and cause them to become cancerous. EBV does not cause chronic fatigue syndrome (see More Information), as was once suspected.

Symptoms and Complications

EBV can cause a number of different symptoms, depending on the strain of the virus and several other, poorly understood factors. In most children younger than 5, the infection causes no symptoms. In adolescents and adults, it may or may not cause symptoms.

The usual time between infection and the appearance of symptoms is thought to be 30 to 50 days. This interval is called the incubation period.

The four main symptoms of infectious mononucleosis are

  • Extreme fatigue

  • Fever

  • Sore throat

  • Swollen lymph nodes

Not everyone has all four symptoms. Usually, the infection begins with a general feeling of illness (malaise) and fatigue, which is usually most severe during the first 2 to 3 weeks but may last longer. These vague symptoms are followed by fever, sore throat, and swollen lymph nodes. The fever usually peaks at about 103° F (about 39.5° C) in the afternoon or early evening. The throat is often very sore, and puslike material may be present at the back of the throat. Most commonly, the lymph nodes of the neck are swollen, but any lymph node may be swollen. In some people, the only symptom is swollen lymph nodes.

The spleen is enlarged in about 50% of people with infectious mononucleosis. In most infected people, an enlarged spleen causes few if any symptoms, but it may rupture, particularly if injured. The liver may also enlarge slightly. Rarely, jaundice develops, and sometimes the area around the eyes is swollen.

Rashes develop infrequently. However, people with an EBV infection who take the antibiotic ampicillin usually develop a rash.

Other very rare complications include seizures, nerve damage, behavioral abnormalities, inflammation of the brain (encephalitis) or tissues covering the brain (meningitis), anemia, and blockage of airways by the swollen lymph nodes.

How long symptoms last varies. After about 2 weeks, symptoms subside, and most people can resume their usual activities. However, fatigue may persist for several more weeks and, occasionally, for months. Fewer than 1% of people die, usually because of complications such as encephalitis, rupture of the spleen, or blockage of the airways.


  • A blood test

The symptoms of infectious mononucleosis also occur in many other viral and bacterial infections. Therefore, infectious mononucleosis is often unrecognized. However, swollen glands, particularly in the neck, strongly suggests infectious mononucleosis.

Usually, a simple blood test known as a heterophil antibody or monospot test is done to confirm the diagnosis. Sometimes early in the infection or in young children, the monospot test is negative, and if doctors strongly suspect the infection, they repeat the test. If it is still negative, other specific antibody blood tests for EBV are done to confirm the diagnosis.

Often, a complete blood count is also done. Finding many characteristic mononuclear white blood cells (atypical lymphocytes) may be the first clue that the diagnosis is infectious mononucleosis.


  • Initially rest

  • Pain relievers

  • Sometimes corticosteroids

There is no specific treatment.

People with infectious mononucleosis are encouraged to rest during the first week or two, while symptoms are severe. After about 2 weeks, they may be as active as they want. However, because of the risk of rupturing the spleen, heavy lifting and contact sports should be avoided for 1 month, until doctors confirm by examination or sometimes ultrasonography that the spleen has returned to normal size.

Acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin or ibuprofen) can relieve fever and pain. However, aspirin should not be given to children because of the risk of Reye syndrome, which can be fatal (see Reye Syndrome).

Some complications, such as severe swelling of the airways, may be treated with corticosteroids.

Currently available antiviral drugs have little effect on the symptoms of infectious mononucleosis and should not be used.