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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.
Transmission
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
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.
Diagnosis
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
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