Epstein-Barr Virus (EBV)
Erika Guevara, Elly Nagata and Bin Yang
Case Study
17-year-old high school student
No prior major illnesses
Low grade fever
Malaise- several days
Sore throat
Swollen cervical lymph nodes
Increasing fatigue
Discomfort in left upper quadrant of abdomen
Sore throat, lymphadenopathy and fever
resolve over next two weeks
Full energy level does not return for another
six weeks
Herpesviruses
Linear genome
dsDNA with nicks or gaps
Enveloped
Icosahedral capsid
Infect humans
Remain latent within host
cell after primary infection
and may become activated
EBV vs. Cytomegalovirus (CMV)
CMV Infection EBV Infection
Human herpesvirus Human herpesvirus
type 5 type 4
Severe systemic Usually asymptomatic
disease can develop in infants
in infants Severe pharyngitis
Negative heterophile
antibody test and
serology
Tests Performed:
CBC count
Liver function test
Heterophile antibody test
- differential absorption
- heterophile antibody titers
- monospot
EBV serology
Imaging Studies
CBC count
40%-70% of patients have leukocytosis with a WBC
count of 10,000-20,000 cells/mL. 10% of patients
will have a WBC count greater than 25,000 cells/mL
by the second week.
80-90% of patients have lymphocytosis with more
than 50% lymphocytes. 20-40% of the lymphocytes
are atypical. The illness typically lasts for 2-6 weeks.
The atypical lymphocytes appear larger, have a
lower nuclear-to-cytoplasmic ratio, and have a
nucleus that is less dense than that of normal
lymphocytes.
Liver function test
80-100% patients have elevated liver function
test results.
Alkaline phosphatase, aspartate
aminotransferase (AST), and bilirubin levels
peak 5-14 days after onset, and gama-
glutamyltransferase (GGT) levels peak at 1-3
weeks after onset.
Lactic acid dehydrogenase (LDH) levels are
increased in approximately 95% of patients.
Most liver function test results return to normal
within 3 months.
Differential absorption test
Bovine RBCs absorb infectious
mononucleosis heterophile antibodies, but
Guinea pig kidney cells do not.
Serum from a patient with infectious
mononucleosis agglutinates sheep RBCs
after absorption with guinea pig cells, but
no agglutination occurs after absorption
with bovine RBCs.
Heterophile antibody titers
The titer of heterophile antibody is determined with tube
dilution. A titer of 1:40 after absorption with guinea pig
cells is considered positive for acute infectious
mononucleosis.
60-90% of patients have test results that are positive for
heterophile antibodies in the second or third weeks.
Then it begins to decline until less than 1:40 within 2-3
months.
As many as 20% of patients still have positive titer
resutls within 1-2 years. 75% of patients have positive
horse RBC agglutinin findings at 1 year.
10-30% of children younger than 2 years and 50-75%
of children aged 2-4 years develop heterophile
antibodies with primary EBV infection.
EBV serology
Antibodies to EBV antigens include antibodies to viral
capsid antigen (VCA), early antigens (EAs), and EBNA.
They are measured with enzyme immunoassays, indirect
immunofluorescence assays, and immunoblot assays.
Antibody to the restricted component of early antigens
(EA/R) is measurable in children younger than 4 years
with primary EBV infection or in patients with
nonsymptomatic infection.
80% of the patients with infectious mononucleosis have
antibodies to the diffuse-staining component of EA
(EA/D).
Patients who are immunocompromised and have
persistent or reactivated EBV infections often have high
levels of antibodies to EA/D or EA/R.
EBV serology
In patients with a more prolonged symptomatic
illness, EA/D may become umeasurable, and
EA/R results may become positive.
The antibody pattern in 3-12 months includes
positive findings for VCA-IgG and EBNA
antibodies, negative VCA-IgM antibodies, and
positive EA antibodies.
After 12 months, EA antibodies are not present.
EBV serology
Kit Components
Peptide-coated paddles, IgM Enzyme
conjugate, IgG Enzyme conjugate,
Substrate 1, Substrate 2, Substrate mixing
vial, Wetting agent /wash solution, Stop
solution, Paddle storage bag. Positive and
negative controls available separatly.
Indirect immunofluorescence assay
designed for qualitative and/or semi-
quantitative detection of IgM
antibodies to Epstein-Barr Virus viral
capsid antigen (EBV-VCA) in human
serum.
Monospot
Slide tests use either horse RBCs or bovine
RBCs.
Bovine RBCs are specific for acute infectious
mononucleosis heterophile antibodies, while
horse RBCs are more sensitive.
Low sensitivity (63%-84%), with a negative
predictive value of more than 10%.
Rarely yield false-positive results in patients.
Monospot test
Qualitative or semi-quantitative differential slide agglutination
test for detection of infectious mononucleosis heterophile
antibodies in human serum or plasma. The test is based on
fresh horse RBC.
Kit Components
Guinea Pig Antigen (Reagent I), Beef RBC
Antigen (Reagent II), Horse RBC (Indicator
cells), Positive control, Negative control,
Glass Slide, Microcapillary Pipettes, Rubber
Bulbs, Plastic Pipettes, Wooden Applicators
Imaging Studies
Not for diagnosing acute infectious
mononucleosis.
Chest radiography can detect lymph node
enlargement, but should prompt consideration
of other diagnoses.
Abdominal CT scanning can reveal splenic
rupture.
Ultrasonography, radionuclide scanning or the
spleen may assist diagnosis.
Diagnosis
Symptoms and age of
patient
Increased percentage
of atypical
mononuclear cells
Positive reaction to
“mono spot” test
- Positive for
heterophile
antibodies
Serology results:
-Positive EA, VCA-IgM,
VCA-IgG, EBNA
Epstein-Barr Virus
Also known as Human Herpesvirus 4
Infectious mononucleosis; hepatitis;
retinitis; pneumonia; colitis; Burkitt’s
lymphoma, certain B-cell tumors;
nasopharyngeal carcinoma
EBV remains dormant or latent
throughout lifetime
Affects 95% of the population
Only 5% of patients acquire EBV from
someone who has an acute infection
More transmission in areas of lower
socioeconomic groups and crowded
conditions
Patients that are immunocompromised
(organ allograft recipients or HIV-
infected) are at greater risk.
Infections do not occur in epidemics
Infectious Mononucleosis
Transmission:
-Intimate contact of oral saliva; usually between
an uninfected person and EBV-seropositive person
who is shedding the virus asymptomatically
-Transfusion of blood products
Widespread; infection apparent chiefly in young
adults
Symptoms:
Fatigue- usually lasts 2-3 weeks.
Splenomegaly- occurs in about 50%
of cases in 2nd-3rd week and lasts 6-8
weeks. This can cause anemia =
fatigue.
Fever- peaks in afternoon
Pharyngitis- may be severe and
painful
Lymphadenopathy- usually
symmetric, involves group of nodes;
may be the only manisfestation Palatal petechiae, erosions and a greyish exudate in a
patient with infectious mononucleosis.
Cardiac, jaundice, periorbital edema,
palatal enanthema, maculopapular
eruptions, CNS problems (rare)
Complications: neurological,
hematologic, splenic rupture,
respiratory, and hepatic
Incubation period is about 30-50 days
Asymptomatic in young children
Not fatal
Treatment:
No specific treatment
Rest
No specific antiviral drug
Corticosteroids can be used for swelling of
pharyngitis, airway obstruction, severe
thrombocytopenia, and hemolytic anemia.
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