EPSTEIN-BARR VIRUS (INFECTIOUS

MONONUCLEOSIS)

 Epstein-Barr virus (EBV) is a member of human

herpesvirus group consists of a linear DNA core
surrounded by a nucleocapsid and an envelope that
contains glycoproteins.
Infection with EBV is common, world-wide in
distribution and largely subclinical in early
childhood. EBV has been established as the
etiologic agent of heterophile-positive infectious
mononucleosis (IM), which occurs most frequently
in late adolescence or early adulthood.
EBV is also associated with several human tumors,
including nasopharyngeal carcinoma, Burkitt , s
lymphoma, Hodgkin, s disease, and B-cell
lymphoma.

EPIDEMIOLOGY

EBV infections occur worldwide.

The virus persists indefinitely in their B
Lymphocytes and is shed oral secretions.
Transmission of EBV occurs when susceptible
individuals come in close oral contact with
infectious saliva.
Casual contact is generally insufficient to
transmit infection, and spread of EBV among
susceptible, household contacts is infrequent.
Occasionally, the virus is transmitted by blood
products or donor tissues.

PATHOGENESIS
EBV is transmitted by salivary secretions.
The virus infects the epithelium of oropharynx
and the salivary glands and is shed from these
cells.
Although B cells may become infected after
contact with epithelial cells, studies suggest that
lymphocytes in the tonsillar cripts can be
infected directly.
The virus then spreads through the bloodstream.

 The proliferation and expansion of EBV infected B

cells along with reactive T cells during IM result in
enlargement of lymphoid tissue.
During the acute phase of IM, up to 1 in every 100 B
cells in the peripheral blood is infected by EBV;after
recovery ,1-50 in every 1 million B cells is infected.
During IM there is an inverted CD4+ /CD8+-cell
ratio. Data suggest that memory B cells, not
epithelial cells, are the reservoir for EBV in the
body.
Cellular immunity is more important than humoral
immunity in controlling EBV infection.

CLINICAL MANIFESTATIONS
EBV induces a broad spectrum of illness in
humans.
Classic or typical infectious mononucleosis is an
acute illness characterized clinically by sore
throat, fever, and lymphadenopathy; and
hepatomegaly and splenomegaly.
- serologically by the transient appearance of
heterophile antibodies;
- and hematologically by a mononuclear
leukocytosis that consists, in part. of atypical
lymphocytes.

 The age of the patient has a profound influence

on the clinical expression of EBV infection.
In children, primary EBV infection is often
asymptomatic. In patients of college age, the
ratio of clinically apparent to inapparent EBV
infection ranges from 1:3 to 3:1 .
Because of previously existing immunity, the
disease is less common in older patients.
Fever is present in over 90 percent of the
patients with infectious mononucleosis .
In most cases fever resolves over a 10-to 14 day
period.

 A rash, which may be macular, petechial,

scarlatinaform, urticarial or erythema
multiformelike, is present in about 5 percent of
patients.
Periorbital edema has been reported in up to
one-third of the cases in some series.
The pharynx is erythematous with an exudate in
about one-third of the cases .
Palatal petechiae may be seen in 25-60 percent
of the cases, but are not diagnostic of infectious
mononucleosis

 Cervical adenopathy, usually symmetric, is

present in 80-90 percent of the patients.
Posterior adenopathy is most common, but
submandibular and anterior adenopathy are
quite frequent as well, and axillary and inguinal
adenopathy also occur.
Abdominal
examination
may
detect
hepatomegaly in 10- 15 percent of the cases.
Splenomegaly is present in about one-half of the
cases, and is usually maximal at the beginning of
the second week of illness and regresses over the
next 7-10 days.

COMPLICATIONS
The vast majority of patients with
mononucleosis recover uneventfully.

infectious

Hematologic complications:
Autoimmune hemolytic anemia
Thrombocytopenia
Splenic rupture is a rare but dramatic compli-cation of
infectious mononucleosis.
The incidence of rupture is highest in the second or
third week of illness, but may be the first sign of
infectious mononucleosis.

Neurologic complications:
Aseptic meningitis
Encephalitis
Guillain-Barre syndrome
Bell s palsy
Transverse myelitis

Hepatic complications:
Consist largely of self-limited elevations of
hepatocellular enzymes.
Cardiac complications:
Clinically significant disease is very uncommon
ECG abnormalities-confined to S-T wave
abnormalities
Pericarditis
Myocarditis
Pulmonary complications:
Interstitial infiltrates in 3-5 percent of the cases

Clinical Course
The vast majority of cases of infectious
mononucleosis resolve spontaneously over a 2to 3 week period.
The sore throat is usually maximal for 3-5 days
and then gradually resolves over the course of a
week to 10 days.
Patients remain febrile for 10-14 days, but in the
last 5-7 days , the fever is usually low grade and
associated with little morbidity.

LABORATORY DIAGNOSIS
Hematologic Findings
The central hematologic manifestation of the
illness is the circulating lymphocytosis.
At presentation, a relative and absolute
mononuclear lymphocytosis is found in about 70
percent of the cases.
The lymphocytosis peaks during the second or
third week of illness, and monocytes and
lymphocytes account for 50-70 percent of total
white cell counts.

 Atypical lymphocytes are the hematologic

hallmark of infectious mononucleosis , and
account for about 30 percent of the differential
count at the height of the atypical lymphocytosis.

Syndromes in which Atypical lymphocytosis may be

found
Epstein-Barr virus-inducted infectious mononucleosis
Cytomegalovirus infections
Toxoplasmosis
Acute viral hepatitis
Rubella
Roseola
Mumps
Drug reactions

 A relative and absolute neutropenia is evident in

60-90 percent of the cases.
In most cases, the neutropenia is mild, with total
granulocyte counts of 2000-3000/mm3 .
Thrombocytopenia is also common , and 50
percent of the patients in one series manifested
platelet counts of 140 000/mm3.

 Heterophile Antibodies, originally described by

Paul and Bunnell as sheep erythrocyte
agglutinins, are present in about 90 percent of
the cases at some point during the illness.
Beef erythrocyte hemolysins and agglutinating
antibodies to horse, goat and camel erythrocytes
are
also
demonstrable
in
infectious
mononucleosis.
Heterophile antibodies may be demonstrable at
the onset of illness or may appear later in the
course of illness.

EBV-Specific Antibodies
In addition to the transient heterophile
antibodies, infection with EBV results in the
development of virus specific antibodies.
Antibodies to viral capsid antigen (VCA)
measured by immunofluorescence arise early in
the course of the illness and are demonstrable at
presentation in the majority of cases. IgG
antibodies to VCA are usually present at titers of
80 or greater on the first visit to a physician.

 On the other hand, IgM antibodies to VCA are

sensitive
and
specific
for
infectious
mononucleosis but are difficult to measure.
Antibodies to EBNA appear late in the course of
all cases of infectious mononucleosis and persist
for life.
The appearance of EBNA antibodies in a patient
who was previously VCA positive and EBNA
negative, is strong evidence of recent EBV
infection.

Detection of EBV
Epstein-Barr virus may be cultured from
oropharyngeal washings or from circulating
lymphocytes of 80-90 percent of the patients
with infectious mononucleosis.
Cultivation of the virus is, however, not routinely
in most diagnostic virology laboratories.
Rapid diagnostic techniques based on DNA
hybridization
or
monoclonal
antibody
techniques are currently under development.

DIFERENTIAL DIAGNOSIS
CMV Infection (CMV is the most common cause of
heterophile-negative mononucleosis , usually
presenting in older patients)
Acute infection with
Toxoplasma
HIV
Human herpes virus 6
Hepatitis viruses
drug hypersensitivity reactions
rubella
lymphoma or leukemia

TREATMENT
Treatment of infectious mononucleosis is largely
supportive since more than 95 percent of the
patients recover uneventfully without specific
therapy.
Contact sports or heavy lifting should be avoided
during the first 2-3 weeks of illness, especially
splenomegaly is present.

 Aspirin or acetaminophen, are helpful in

relieving the sore throat and in suppressing the
fever.
Corticosteroids are often advocated, but their
use in uncomplicated illness is still controversial.
Most infectious disease consultants prefer not to
administer corticosteroids in this self-limited
disease of certain specific indications.

Corticosteroids are generally used in the following

situations:
Impending airway obstruction
Severe thrombocytopenia
Hemolytic anemia
CNS involvement
Myocarditis
Pericarditis

 Acyclovir has had no significant clinical impact

on IM in controlled trialls.
Acyclovir, at a dosage of 400-800 mg five times
daily, has been effective for the treatment of oral
hairy leukoplakia .