This document discusses infectious mononucleosis and Epstein-Barr virus (EBV). It states that EBV is spread through oral secretions and is a cause of infectious mononucleosis. Infectious mononucleosis presents as enlarged lymph nodes, sore throat, fever, and extreme tiredness. EBV is also associated with African Burkitt's lymphoma, nasopharyngeal carcinoma, and B cell lymphomas. Treatment for infectious mononucleosis involves rest and supportive care.

1. Infectious
mononucleosis
Ahmed Alwassief, MD
Alazhar University

2. Herpes Virus Group
 Produce a variety of diseases.
 May result in sub-clinical infections
 May be reactivated under appropriate
conditions.

3. Herpes Virus Group
 We will discuss the following:
– Epstein-Barr virus
– Cytomegalovirus
– Herpes simplex virus type I and II
– Varicella-zoster virus

4. Epstein-Barr Virus (EBV)
 Spread through oral transmission
 Cause of Infectious Mononucleosis.
 Other Diseases include:
– African or Burkitt’s lymphoma
– Nasopharyngeal carcinoma
– B cell lymphoma

5.  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.

6. Infectious Mononucleosis
 4 to 7 week incubation
 Acute self-limiting infection of the RE system
 Enlarged lymph nodes in the neck.
 Sore throat, fever, rash
 Malaise, lethargy, extreme tiredness
 Liver and spleen involvement and enlargement
 Hematology: High WBC, over 20% atypical
reactive lymphocytes also known as Downey
cells.

7. Infectious Mononucleosis
 Downey cells may be present

8. EPIDEMIOLOGY
EBV infections occur worldwide.
 EBV 90% of acute IM
 Etiology of most EBV-negative IM : unknown
 These infections are most common in early
childhood 3-6 y developing , with a second
peak during late adolescence 12-15 y.
 By adulthood, more than 90% of individuals
have been infected and have antibodies to the
virus.
 IM is usually a disease of young adults.

9. CLINICAL MANIFESTATIONS
Enlarged lymph nodes are frequently tender and symmetric but are not
fixed in place.

10.  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.

11. Infectious Mononucleosis
IM with rash after treatment with amoxicillin or ampicillin

12. Complications
 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.

13.  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.

14.  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.

15. Laboratory Findings
 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.

16.  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.

17.  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.

18. EBV Specific Antibodies
 EBV specific antibodies may be measured.
 Pattern of appearance of EBV antigens.
 Most valuable is IgM antibody to viral capsid
antigen (VCA), indicates a current infection (best
marker), lasts about 12 weeks.
 Can also detect anti-early antigen (EA) (recent
infection) and anti EB nuclear antigen (EBNA)
(older infection).
 ELISA and IFA most commonly used

19. TREATMENT
 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.

20.  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.

21.  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 .

22.  Interferon .
 antibody to CD20.
 Infusions of donor lymphocytes are often effective for stem cell
transplant recipients.
 Infusions of EBVspecific cytotoxic T cells.
 Infusion of autologous EBV-specific cytotoxic T lymphocytes
 The isolation of patients with IM is unnecessary.

23. Epstein-Barr virus
 African or Burkitt’s Lymphoma
– malignant B-cell neoplasm
– presents as a rapidly growing tumour of the
jaw, face or eye
– grows very quickly, and without treatment
most children die within a few months
– Epstein-Barr virus (EBV) has been strongly
implicated

24. African or Burkitt’s Lymphoma
 Although BL is a very rapidly growing tumour it
responds well to treatment.
 Three pictures: before treatment, 3 days and 6
days after treatment

25. Nasopharyngeal Carcinoma
 Endemic in South China, Africa, Arctic Eskimos
 This is a malignant tumour of the squamous
epithelium of the nasopharynx.
 100% contain EBV DNA
 Rates are less than 1 per 100,000 in most
populations
 Nasopharyngeal carcinomas are found in
association with reactivation of latent Epstein-
Barr Virus.
 The exact mechanisms of association are
unknown

26. B-Cell Lymphoma
 In most individuals infected with EBV, the virus
is present in the B-cells, which are normally
controlled by T-lymphocytes
 When T-cell deficiency exists, one clone of
EBV-infected B-lymphocytes escapes immune
surveillance to become autonomously
proliferating.
 EBV induced B cell lymphomas are most
prevalent in immunocompromised patients.

27. Oral Hairy Cell Leukoplakia
 Viral infection of the oral cavity.
 Indicator of HIV infection as well as of a
person's lessening or weakening immunity