National Institute of Allergy and Infectious Diseases



Infectious mononucleosis--known popularly as "mono" or "the kissing disease"--has been recognized for more than a century. Medical scientists have determined that 90 percent of mononucleosis cases are caused by the Epstein-Barr virus (EBV), a member of the herpesvirus group. Most of the remaining cases are caused by cytomegalovirus, another herpesvirus. This backgrounder focuses on mononucleosis caused by EBV.

Almost anyone at any ate can get mononucleosis. Although it has been diagnosed in infants and in the elderly, 70 to 80 percent of all documented cases involve persons between the ages of 15 and 30. No sex difference has been scientifically established, but studies suggest that the disease occurs slightly more often in men than in women. It is estimated that each year 50 out of every 100,000 Americans have mononucleosis symptoms. In college students, the rate is several times higher.

There appears to be no particular "season" for mononucleosis, although authorities in colleges and schools, where the disease has been well studied, report that they see most patients in the fall and early spring. Epidemics do not occur, but clustering of cases has been reported.


The virus that causes most cases of mononucleosis, EBV, infects two types of cells in the body--certain salivary gland cells, where it reproduces, and white blood cells called B cells or B lymphocytes. The virus can be found routinely in the saliva of most patients for at least 6 months after the acute infection has subsided. About 15 percent of people continue to have the virus in their saliva thereafter. Mono has thus earned the nickname "the kissing disease" because it is believed that adolescents and young adults may transmit the virus to each other through prolonged kissing. Sharing drinking glasses or beverage cans may also spread the virus.

Like all herpesviruses, after infection EBV remains in the body forever. People who have been infected with the virus are potentially contagious at various times throughout their lives; that is, they may serve as a "reservoir" of virus that spreads to others in the community. Therefore, person-to-person transmission is extremely difficult to trace and in most situations virtually impossible. Just how long a mononucleosis patient is infectious is unknown. However, the period of communicability seems to begin some time before symptoms appear and the disease is not highly contagious when symptoms do appear. It may take between 2 and 7 weeks after exposure for a susceptible person to develop symptoms. Patients do not need to be isolated, and household members or college roommates are at only slight risk of being infected. Mononucleosis is hard to catch; it is only transmitted through direct contact with virus-infected saliva.


The symptoms of mononucleosis can last a few days or as long as several months, but in most cases they disappear in 1 to 3 weeks. In fact, symptoms are non-existent or are so mild in most individuals that they are not even aware of their illness.

In adolescents and young adults, the illness usually develops slowly and early symptoms are vague. They may include a general complaint of "not feeling well," headache, fatigue, chilliness, puffy eyelids, and loss of appetite. Later, the familiar triad of symptoms appears: fever, sore throat, and swollen lymph glands, especially at the side and back of the neck, but also under the arm and in the groin. A fever of 101 F to 105 F lasts for approximately 5 days and sometimes continues intermittently for 1 to 3 weeks. (High fever late in the illness is likely due to bacterial complications.) The swollen lymph glands, varying in size from a bean to a small egg, are tender and firm. Swelling gradually disappears over a few days or weeks. The spleen is enlarged in 50 percent of mononucleosis patients, and the liver is enlarged in 20 percent. Tonsillitis, difficulty in swallowing, and bleeding gums may accompany these symptoms. Rarely, jaundice or a rash that lasts 1 or 2 days is seen.

In children, EBV infection can produce a different picture. A child may have a mild sore throat or tonsillitis or no symptoms at all, and the illness often goes unrecognized by the parent or teacher.

As mononucleosis symptoms appear, the body reacts to the virus in certain distinctive ways that can be detected through laboratory tests. White blood cells known as lymphocytes increase in number (a process known as lymphocytosis), and atypical-looking (activated) lymphocytes involved in fighting the virus infection are commonly seen in blood samples. The body produces antibodies, or specific proteins, that protect against EBV.

In EBV infection, there is also a characteristic increase in the production of substances called heterophil antibodies. These antibodies reflect EBV infection in the body but are not directed against the virus and do not serve a protective function. Of the three types of heterophil antibodies most often found in the blood of patients with mononucleosis, only one type (Paul-Bunnell) is closely related to the infection. Blood tests that measure lymphocytes and antibodies aid in the diagnosis of mononucleosis.


Symptoms play an important role in the diagnosis of mononucleosis, but because this disease is a masquerader, symptoms can be misleading. They may resemble, for instance, the sore throat of a "strep" infection, the painful stiff neck of meningitis, the abdominal pains of acute appendicitis, the cough and throat lesions of diphtheria, the rash of rubella or measles, or the swollen lymph glands seen in certain forms of cancer.

Rapid and inexpensive blood tests can detect heterophil antibodies (Paul-Bunnell antibodies) in about 80 percent of persons with a current or recent infection. These antibodies can appear in sufficient strength to give a positive diagnosis as early as the fourth day and generally by the twenty-first day of illness. Heterophil antibodies can persist for months, however, so their appearance does not prove current infection. Furthermore, the level of heterophil antibodies in the blood does not correlate with the severity of symptoms.

The slide agglutination mono "spot test," which is widely used to screen for heterophil antibodies, is inexpensive, requires less than 3 minutes and can be performed in a physician's office. Spot tests are generally accurate, but they can give falsely positive or falsely negative results. Sometimes, appearance of heterophil antibodies is delayed, and a repeat test may be necessary to establish a diagnosis. Moreover, young children, older adults, and individuals with EBV infections that do not resemble classic mononucleosis are less likely to develop heterophil antibodies.

If a patient with negative spot test results is seriously ill or has unusual symptoms, additional tests must be conducted to rule out other illnesses or infections (such as toxoplasmosis or rubella). An EBV serologic profile is a series of blood tests that will provide a definite diagnosis of mononucleosis that is caused by EBV. Appearance of the antibodies specific for EBV proteins correlates with the stages of infection. The profile is highly accurate, but it is expensive. An physicians have access to laboratories that can perform these tests if they are necessary.

Treatment and Recovery

Usually, mononucleosis is an acute, self-limited infection for which there is no specific therapy. For years, standard treatment was bed rest for 4 to 6 weeks, with limited activity for 3 months after all symptoms had disappeared. Today, doctors usually recommend avoiding strenuous exercise only. One real hazard of uncomplicated mononucleosis is the possibility of damaging one's enlarged spleen. Therefore, lifting, straining, and competitive sports should be avoided until recovery is complete. Other activity should be limited only by symptoms and how a person feels.

Treatment of the acute phase of the illness is symptomatic and nonspecific because there is no drug treatment for mononucleosis. Rest, plenty of fluids to guard against dehydration, and a well-balanced diet are recommended. Aspirin or acetaminophen is given for headache, muscle pains, and chills, and salt gargles are recommended for sore throats. Corticosteroid hormones such as prednisone can help lessen some of the symptoms of mononucleosis, but because of their potential toxicity these drugs are best reserved for treatment of severe complications.

Since antibiotics are ineffective, they should not be prescribed for mononucleosis itself. Some patients with mononucleosis develop streptococcal throat infections, which should be treated with penicillin or erythromycin. Ampicillin--a form of penicillin--should not be used. In mononucleosis patients given ampicillin, 70 to 80 percent develop a rash for unknown reasons. Although not a true allergic reaction, the rash may be diagnosed as such, and the patient may be instructed unnecessarily to avoid penicillins in the future.

More than 90 percent of mononucleosis infections are benign and uncomplicated, but fatigue and weakness that continue for a month or more are not uncommon. The illness may be more severe and long-lasting in adults over the age of 30. There are rare cases of death from the infection, following airway obstruction, rupture of the spleen, inflammation of the heart or tissues surrounding the heart, or central nervous system involvement. Steroid drugs are used to treat these complications. If the spleen should rupture, surgery to remove it, and transfusions and other therapy for shock, must be initiated immediately.

Although EBV remains in the body indefinitely following a bout of mononucleosis, the disease rarely recurs. Nearly all individuals who have repeated mono-like illnesses are either seriously immune impaired, such as transplant recipients, or are actually experiencing sequential infections with different viruses that can provoke similar symptoms. In addition, several scientific studies now have confirmed that EBV does not play a role in most cases of chronic fatigue syndrome.

Further Research

Scientists believe that increased knowledge of normal and abnormal immune responses will lead to an understanding of how EBV can cause a relatively benign illness, like mononucleosis, and also play a role in much more serious, sometimes fatal, diseases. Epstein and Barr, two British scientists after whom EBV is named, first found evidence of the virus in B lymphocytes of patients with a rare form of cancer of the lymph system. This cancer, known as Burkitt's lymphoma, occurs primarily in Africa.

Scientists have learned a lot about how EBV affects the body's cells in mononucleosis. EBV is known to increase the number of B lymphocytes, which have receptors for the virus on their surfaces. The normal response of the body to this increase in B cells is a corresponding increase in T lymphocytes, another component of the immune system, which change in appearance to become atypical cells. Some of these T cells apparently limit the spread of the virus from cell to cell; others suppress the proliferation of the B cells. This suppression is what seems to eliminate the infection. Normally, the T cell response subsides as the patient recovers from mononucleosis.

Prepared by:
Office of Communications
National Institute of Allergy and Infectious Diseases National Institutes of Health
Bethesda, MD 20892

Public Health Service
U.S. Department of Health and Human Services

April 1992