Transcript EPSTEIN-BARR VIRUS INFECTIONS

dr.Mohsen Meidani
INCLUDING
INFECTIOUS
MONONUCLEOSIS
Dr.Meidani
dr.Mohsen Meidani
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Epstein-Barr virus (EBV) is the cause of
heterophile-positive infectious mononucleosis (IM),
which is characterized by fever,sore throat,
lymphadenopathy, and atypical lymphocytosis.
dr.Mohsen Meidani
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EBV is also associated with several human tumors,
including nasopharyngeal carcinoma, Burkitt’s
lymphoma, Hodgkin’s disease, and (in patients with
immunodeficiencies) B cell lymphoma.
The virus, a member of the family Herpesviridae,
consists of a linear DNA core surrounded by a
nucleocapsid and an envelope that contains
glycoproteins.
dr.Mohsen Meidani
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EBV infections occur worldwide.
These infections are most common in early
childhood, with a second peak during late
adolescence.
By adulthood, more than 90% of individuals have
been infected and have antibodies to the virus.
IM is usually a disease of young adults.
dr.Mohsen Meidani
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EBV is spread by contact with oral secretions.
The virus is frequently transmitted from
asymptomatic adults to infants and among young
adults by transfer of saliva during kissing.
Transmission by less intimate contact is rare.
EBV has been transmitted by blood transfusion and
by bone marrow transplantation.
More than 90% of asymptomatic seropositive
individuals shed the virus in oropharyngeal
secretions.
dr.Mohsen Meidani
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EBV is transmitted by salivary secretions.
The virus infects the epithelium of the oropharynx
and the salivary glands and is shed from these cells.
The virus then spreads through the bloodstream.
dr.Mohsen Meidani
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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.
If T cell immunity is compromised, EBV-infected B
cells may begin to proliferate.
dr.Mohsen Meidani
dr.Mohsen Meidani
dr.Mohsen Meidani
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The incubation period for IM in young adults is 4 to
6 weeks.
A prodrome of fatigue, malaise, and myalgia may
last for 1 to 2 weeks before the onset of fever, sore
throat, and lymphadenopathy.
Fever is usually low-grade and is most common in
the first 2 weeks of the illness; however, it may
persist for1 month.
dr.Mohsen Meidani
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Lymphadenopathy and pharyngitis are most
prominent during the first 2 weeks of the illness,
while splenomegaly is more prominent during the
second and third weeks.
Lymphadenopathy most often affects the posterior
cervical nodes but may be generalized.
Enlarged lymph nodes are frequently tender and
symmetric but are not fixed in place.
dr.Mohsen Meidani
dr.Mohsen Meidani
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Pharyngitis, often the most prominent sign, can be
accompanied by enlargement of the tonsils with an
exudate resembling that of streptococcal pharyngitis.
A morbilliform or papular rash, usually on the arms
or trunk, develops in 5% of cases.
Most patients treated with ampicillin develop a
macular rash; this rash is not predictive of future
adverse reactions to penicillins.
dr.Mohsen Meidani
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The white blood cell count is usually elevated and
peaks at 10,000 to 20,000/L during the second or
third week of illness.
Lymphocytosis is usually demonstrable, with >10%
atypical lymphocytes.
atypical lymphocytes are enlarged lymphocytes that
have abundant cytoplasm, vacuoles, and
indentations of the cell membrane.
CD8 cells predominate among the atypical
lymphocytes.
dr.Mohsen Meidani
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Low-grade neutropenia and thrombocytopenia are
common during the first month of illness.
Liver function is abnormal in more than 90% of
cases.
Serum levels of aminotransferases and alkaline
phosphatase are usually mildly elevated.
the serum concentration of bilirubin is elevated in
40% of cases.
dr.Mohsen Meidani
dr.Mohsen Meidani
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Most cases of IM are self-limited.
Deaths are very rare and most often are due to
central nervous system (CNS) complications, splenic
rupture, upper airway obstruction, or bacterial
superinfection.
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Autoimmune hemolytic anemia occurs in 2% of cases
during the first 2 weeks.
Nonspecific antibody responses may also include
rheumatoid factor,antinuclear antibodies, anti–
smooth muscle antibodies, antiplatelet antibodies, and
cryoglobulins.
IM has been associated with red-cell aplasia, severe
granulocytopenia, thrombocytopenia, pancytopenia,
and hemophagocytic syndrome.
Splenic rupture is more common among males than
among females and may be manifest as abdominal
pain, referred shoulder pain, or hemodynamic
compromise.
dr.Mohsen Meidani
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Hypertrophy of lymphoid tissue in the tonsils or
adenoids can result in upper airway obstruction, as
can inflammation and edema of the epiglottis,
pharynx, or uvula.
Other rare complications associated with acute EBV
infection include hepatitis (which can be fulminant),
myocarditis or pericarditis with electrocardiographic
changes, pneumonia with pleural effusion,
interstitial nephritis, genital ulcerations, and
vasculitis.
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EBV-associated lymphoproliferative disease.
The X-linked lymphoproliferative syndrome
(Duncan’s disease).
Oral hairy leukoplakia.
chronic fatigue syndrome.
Chronic active EBV infection.
Burkitt’s lymphoma.
Hodgkin’s disease.
CNS lymphomas in AIDS patients.
dr.Mohsen Meidani
dr.Mohsen Meidani
dr.Mohsen Meidani
dr.Mohsen Meidani
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The heterophile test is used for the diagnosis of IM in
children and adults.
A titer of 40-fold or greater is diagnostic of acute
EBV infection in a patient who has symptoms
compatible with IM and atypical lymphocytes.
Tests for heterophile antibodies are positive in 40%
of patients with IM during the first week of illness
and in 80 to 90% during the third week.
Therefore, repeated testing may be necessary,
especially if the initial test is performed early.
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Tests usually remain positive for 3 months after the
onset of illness, but heterophile antibodies can persist
for up to 1 year.
These antibodies usually are not detectable in
children <5 years of age, in the elderly, or in patients
presenting with symptoms not typical of IM.
False-positive monospot results are more common in
persons with connective tissue disease, lymphoma,
viral hepatitis, and malaria.
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acute infection with cytomegalovirus.
Toxoplasma.
HIV.
human herpesvirus 6.
hepatitis viruses .
drug hypersensitivity reactions.
Rubella.
acute infectious lymphocytosis in children.
lymphoma or leukemia.
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Therapy for IM consists of supportive measures,
with rest and analgesia.
Excessive physical activity during the first month
should be avoided to reduce the possibility of splenic
rupture.
If splenic rupture occurs, splenectomy is required.
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Glucocorticoid therapy: Prednisone (40 to 60 mg/d
for 2 to 3 days, with subsequent tapering of the dose
over 1 to 2 weeks):
airway obstruction
autoimmune hemolytic anemia
severe thrombocytopenia.
Glucocorticoids have also been used in a few selected
patients with :
severe malaise and fever
severe CNS
cardiac disease.
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Acyclovir, at a dosage of 400 to 800 mg five times
daily, has been effective for the treatment of oral
hairy leukoplakia (despite common relapses) and
some cases of chronic active EBV disease.
The posttransplantation EBV lymphoproliferative
syndrome generally does not respond to antiviral
therapy.
When possible, therapy should be directed toward
reduction of immunosuppression .
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Interferon .
antibody to CD20.
Infusions of donor lymphocytes are often effective for stem
cell transplant recipients.
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Infusions of EBVspecific cytotoxic T cells.
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Infusion of autologous EBV-specific cytotoxic T lymphocytes
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The isolation of patients with IM is unnecessary.
dr.Mohsen Meidani
dr.Mohsen Meidani