Infectious Mononucleosis

Infectious mononucleosis -- known popularly as "mono" or  "the kissing disease" -- has been recognized for more  than a century. An estimated 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 certain other herpesviruses,  particularly cytomegalovirus. This fact sheet focuses on  mononucleosis caused by EBV.

EBV is a common virus that scientists estimate has  infected over 90 percent of people aged 40 or older  sometime during their lives. These infections can occur  with no symptoms of disease. Like all herpesviruses, EBV  remains in the body for life after infection, usually kept under control by a healthy immune system.

Almost anyone at any age can get mononucleosis. Seventy  to 80 percent of all documented cases, however, involve  persons between the ages of 15 and 30. Both men and  women are affected, but studies suggest that the disease  occurs slightly more often in men than in women. Doctors  estimate that each year 50 out of every 100,000  Americans have mononucleosis symptoms. Among college  students, the rate is several times higher.

Mononucleosis does not occur in any particular "season,"  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 doctors have reported clustering of cases.


EBV, the virus that causes most cases of  mononucleosis, infects and reproduces in the  salivary glands. It also infects white blood  cells called B cells. Direct contact with  virus-infected saliva, such as through  kissing, can transmit the virus and result in  mononucleosis. Someone with mononucleosis,  however, does not need to be isolated.  Household members or college roommates have  only a slight risk of being infected unless  they come into direct contact with the  patient's saliva.

A person is infectious several days before  symptoms appear and for some time after acute  infection. No one knows how long this period  of infectiousness lasts, although the virus  can be found routinely in the saliva of most  people with mononucleosis for at least six  months after the acute infection has subsided.  It can be detected in the saliva of about 15  percent of people for years after first  infection.


Symptoms may take between two and seven weeks  to develop after exposure to the virus and can  last a few days or as long as several months.  In most cases, however, they disappear in one  to three weeks. In fact, mononucleosis  symptoms may be nonexistent or so mild that  most people are not even aware of their  illness.

In adolescents and young adults, the illness  usually develops slowly and early symptoms are  vague. Symptoms 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 a few days and sometimes continues  intermittently for one to three weeks. (High  fever late in the illness suggests bacterial  complications.) The swollen lymph glands,  varying in size from that of 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 one or two days is  present.

In young children and older adults (more than  35 years old), mononucleosis may be difficult  to diagnose because the typical mononucleosis  symptoms are not present. A doctor may suspect  mononucleosis in older adults, however, if the  patient has had a high fever for at least a  week, has an enlarged liver, has abnormal  liver function studies, or has neurologic  symptoms. In children, EBV infection can  produce a different picture. A child may have  a mild sore throat or tonsillitis or have 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 called 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.  Blood tests that measure lymphocytes and  antibodies aid in the diagnosis of  mononucleosis.

In EBV infection, the body's immune system  also produces more of substances called  heterophil antibodies (Paul-Bunnell  antibodies). These antibodies indicate that an  EBV infection is present in the body, but they  are not directed against the virus itself and  do not serve a protective function. Because  other types of infections and immunologic  reactions also induce heterophil antibodies,  their presence suggests, but does not indicate  specifically, an EBV infection.

Symptoms play an important role in the  diagnosis of mononucleosis. But because this  disease can masquerade as other diseases,  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 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 21st  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  three minutes, and can be performed in a  physician's office. Spot tests are generally  accurate, but they can give false positive or  false 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, the  doctor should conduct additional tests to rule  out other illnesses or infections (such as HIV  infection, toxoplasmosis or rubella). An EBV  serologic profile is a series of blood tests  that, if done and interpreted correctly, 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. All physicians have access to  laboratories that can perform these tests if  they are necessary.

The single most meaningful test result to  confirm a recent EBV infection is the  demonstration of immunoglobulin M (IgM)  antibodies to an EBV protein called the viral  capsid antigen (VCA). This assay can be done  several ways, but unfortunately some of the  commercial test kits are overly sensitive and  give false positive results.

Another way to prove recent EBV infection is  to have blood collected at two separate time  points, preferably at the first sign of  symptoms and again three to four weeks later.  The doctor will send both blood samples  together to a lab for testing. A more than  four-fold increase in immunoglobulin G (IgG)  antibodies to several of the EBV-VCA proteins  indicates recent infection.

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 four to six weeks,  with limited activity for three months after  all symptoms had disappeared. Today, doctors  usually only recommend avoiding strenuous  exercise. One real hazard of uncomplicated  mononucleosis is the possibility of damaging  one's enlarged spleen. Therefore, the patient  should avoid lifting, straining, and  competitive sports until recovery is complete.  A person should limit other activity according  to symptoms and how he or she feels.

Treatment of the acute phase of the illness is  symptomatic and nonspecific because there is  no specific drug treatment for mononucleosis.  Rest, plenty of fluids to guard against  dehydration, and a well-balanced diet are  recommended. Doctors usually recommend  acetaminophen or ibuprofen for headache,  muscle pains, and chills, and salt gargles for  sore throats. (Children and adolescents with a  fever should not take aspirin because it can  increase the risk of Reye syndrome.) Oral  steroid drugs such as prednisone can help  lessen some of the symptoms of mononucleosis,  but because of their potential toxicity, these  drugs are best reserved for treating severe  complications.

Antibiotics are ineffective against viruses,  and they should not be prescribed for  mononucleosis itself. Some patients with  mononucleosis also develop streptococcal  (bacterial) throat infections, which should be  treated with penicillin or erythromycin.  Ampicillin (a form of penicillin) should not  be used. When mononucleosis patients take  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 last longer in adults over the  age of 30. Airway obstruction, rupture of the  spleen, inflammation of the heart or tissues  surrounding the heart, and severe bone marrow  or central nervous system involvement are  rare, life-threatening complications that are  treated with steroid drugs. If the spleen  should rupture, a doctor will immediately have  to remove it surgically and start transfusions  and other therapy for shock.

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 either have a  seriously impaired immune system, 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  cause 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 production 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.

NIAID, a component of the National Institutes of Health,  supports research on AIDS, tuberculosis, malaria and  other infectious diseases, as well as allergies and  immunology. NIH is an agency of the U.S. Department of  Health and Human Services.

Prepared by: Office of Communications and Public Liaison  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 July 1999