Infectious mononucleosis

Ahmed Alwassief, MDAlazhar University

Herpes Virus Group

Produce a variety of diseases. May result in sub-clinical infections May be reactivated under

appropriate conditions.

Herpes Virus Group

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

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

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.

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.

Infectious Mononucleosis

Downey cells may be present

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.

CLINICAL MANIFESTATIONS

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

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.

Infectious Mononucleosis

IM with rash after treatment with amoxicillin or ampicillin

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.

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.

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.

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.

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.

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.

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

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.

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.

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 .

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.

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

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

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

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.

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