Infectious Mononucleosis

By: Shiva Ram Naga Bsc MLT 5th Semester Nobel college, Sinamangal

Introduction
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Also called glandular fever

Benign, self-limiting lymphoproliferative disease caused by Epstein-Barr Virus The mode of transmission is not known, but may be facilitated by saliva exchange The virus is shed in the throat during the illness and for up to a year after infection

After the initial infection, the virus tends to become dormant for a prolonged period and can later reactivate and be shed from the throat again.

Introduction
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

The virus is spread by person-to-person contact, via saliva. In rare instances, the virus has been transmitted by blood transfusion or transplacentally
Recognized more often in high school and college students. The disease usually runs its course in two to four weeks, although cases may be as brief as a week or last six to eight weeks After recovery, weakness may continue for several months

Epstein-Barr virus
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Epstein-Barr virus (EBV) is a human herpes DNA virus.

The structure of EBV is typical for a member of herpesvirus family : Inner core of DNA surrounded by a nucleocapsid, tegument, and an envelope. The virus affects B-lymphocytes. Initiates infection of B cell by binding to viral receptor Also cause: Burkitts lymphoma Nasopharyngeal carcinoma

Epstein-Barr virus
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

EBV infected B-lymphocytes express a variety of new antigens encoded by the virus. Infection with EBV results in expression of: 1. Viral Capsid Antigen (VCA) 2. Early Antigen (EA) 3. Nuclear Antigen (NA) Each antigen expression has corresponding antibody responses.

Pathogenesis
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

The virus in the contaminated saliva invades and replicates within epithelial cell of salivary gland
Enters into B cells in lymphoid tissue Infection spread throughout the body via blood stream or by infected B cell

Viraemia or death of infected cells cause an acute febrile illness

Appearance of specific Ab (peak about 2 week after infection)

Appearance of Ab marks the disappearance of virus from the blood

Pathogenesis
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

EBV-infected cell continue to be present in circulation as latent infection EBV-infected cells undergoes polyclonal activation and proliferation

They secrete the antibody

Activate CD8+ T lymphocyte

Pathogenesis
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Proliferation of cells is responsible for generalised lymphoadenopathy and hepatosplenomegaly

The sore throat in IM may be cause either by necrosis of B cell or due to viral replication within the savilary epithelial cells in early stage

Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Most common
Fatique and malaise 1-2 wks Sore throat, Pharyngitis

Retro-orbital headache
Fever Myalgia Nausea Abdominal pain Generalized lymphadenopahy Hepatosplenomegaly
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Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Rare sign and symptom

Thrombocytopenia Pancytopenia

Splenic rupture
Splenic hemorrhage, Upper airway obstruction

Pericarditis
Pneumonitis

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Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Pharyngitis is the most consistent physical finding. 1/3 of patients : exudative pharyngitis.
25-60% of patients : petechiae at the junction of the hard and soft palates. Tonsillar enlargement can be massive, and occasionally it causes airway obstruction.

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Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Lymphadenopathy : 90% symmetrical enlargement. mildly tender to palpation. posterior cervical lymph nodes. anterior cervical and submandibular nodes. Axillary and inguinal nodes. Enlarged epitrochlear nodes are very suggestive of infectious mononucleosis.

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Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Hepatomegaly : 60% jaundice is rare. Percussion tenderness over the liver is common. Splenomegaly : 50% palpable 2-3 cm below the left costal margin and may be tender. rapidly over the first week of symptoms, usually decreasing in size over the next 7-10 days. spleen can rupture from relatively minor trauma or even spontaneously

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Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

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Sign and symptoms

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Exudative pharyngitis

Cervical lymphadenopathy
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Laboratory findings
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Diagnosis of Infectious Mononucleosis is made by: Haematological findings

Serological diagnosis
Liver function test

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Haematological findings
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

TLC: moderate rise during 2nd to 3rd week of infection

DLC: absolute lymphocytosis rise in normal as well as atypical lymphocyte

Atypical T cell
presence of at least 10-12% atypical T cells(or mononucleosis) Usually size of large lymphocyte Nucleus is oval , kidney shaped or slightly lobate due to indentation of nuclear membrane and contain relatively fine chromatin with out nucleoli Cytoplasm is more abundant, basophilic and finely granular and may contain vacuole
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Atypical lymphocyte
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

High power showing reactive lymphocytes

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Haematological findings
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

CD 4+ and CD 8+ T cell count

Reversal of CD4+/CD8+ cell ratio Marked decrease in CD4+ T cell while substantial rise in CD8+ cells

Platelet count
Thrombocytopenia

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Serological diagnosis
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Test for heterophile antibody EBV specific antibody test EBV antigen detection

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Test for heretophile antibody

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Every infected cell contains viral capsid antigens, which give rise to specific heterophile antibodies

Paul-Bunnell test
Unabsorbed serum agglutinated sheep red cells to titres of 40 to 1,280

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Test for heretophile antibody

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Monospot test
Reagents Sera. Patient's serum (fresh or inactivated by heating at 56C for 30 min) and positive and negative control sera. Red cell suspension. 20% suspension of horse blood in 109 mmol/l (32 g/l) trisodium citrate. Before use, the suspension must be well mixed by repeated inversion. For the screening test, it is unnecessary to wash the cells. Guinea pig kidney emulsion. Ox red cell suspension.

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Test for heretophile antibody

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Method
Place 1 large drop (c 30 l) of guinea pig kidney emulsion and 1 large drop of ox-cell suspension on two adjacent squares on an opal glass tile Add 1 drop of patient or control serum adjacent to each Deliver 10 l of horse-blood suspension to the corner of each square by means of a disposable plastic micropipette With a wooden applicator stick, mix the reagents

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Test for heretophile antibody

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Interpretation
Positive Agglutination is stronger in the square containing guinea pig kidney emulsion than in the square containing ox-cell suspension. Negative Agglutination is absent in both squares.

Slide screening test for infectious mononucleosis. Top row: guinea pig kidney. Middle row: ox-cell suspension. Bottom row: saline

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Test for heretophile antibody

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Davidsohn Differential
Heterophil Antibody -----------------------Infectious Mononucleosis Kidney Extract -----------------Not Absorbed Beef Erythrocyte --------------------Absorbed

Forssman

Absorbed

Not Absorbed

Serum Sickness

Absorbed

Absorbed

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EBV specific antibody test

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Specific antibody against EBV capsid antigen

Elevated titers in over 90% of cases Most useful for diagnosis of acute infection

Antibody against EBV nuclear antigen

Detects 3-6 weeks after infection Persist throughout life

Antibody to early antigen

Less useful for diagnosis Remains elevated for 3-6 months

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EBV antigen detection

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Detection of EBV DNA or proteins can be done in blood or CSF by PCR method

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Liver function test

Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Elevated serum Transaminases Rise is serum Alkaline Phosphatase

Mild elevation in serum bilirubin

95% of patients : elevated LDH GGT peaks at 1-3 weeks. Occasionally, GGT remains mildly elevated for up to 12 months

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Treatment
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

As this is a viral condition, it is not usual to undergo any specific treatment. The condition is self-limiting and will usually subside in 6-8 weeks Patients may suffer fatigue for a much longer period of time (3 months to 1 year)

Bed rest, fluids and analgesia

Salt water or OTC gargles to relieve throat pain

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Treatment
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Acyclovir (10 mg/kg/dose IV q8h for 7-10 d) inhibit viral shedding from the oropharynx clinical course is not significantly IVIG (400 mg/kg/d IV for 2-5 d) immune thrombocytopenia associated with

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Complication
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Secondary Throat Infections Splenic Rupture (Rare)

Seizures
Bells Palsy Hearing loss

Hepatitis
Hemolytic Anaemia Death in immunocompromised patients
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Prevention
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Isolation is not required : low transmission. Avoid contact with saliva. Do not kiss children on the mouth. Maintain clean conditions : day care, avoid sharing toys. EBV can be transmitted by blood transfusion and by bone marrow transplantation.

Vaccine development is proceeding, although the role of a vaccine is unclear

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Conclusion
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

In addition to clinical signs and symptoms, laboratory testing is necessary to establish or confirm the diagnosis of IM. This can provide important information for both the diagnosis and management of EBVassociated disease

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Refrences
Introduction Epstein-Barr virus Pathogenesis Clinical features Laboratory findings Treatment Complication Conclusion References

Mohan H. Textbook of Pathology, sixth edition. Jaypee Brothers Medical publishers (P) Ltd. 2010
Lewis S M, Bain B J, Bates I. Dacie and Lewis Practical Hematology, tenth edition, Elsevier Ltd.2006 Cheesbrough M. District Laboratory Practice in Tropical Countries, second edition, Cambridge University Press. 2006 Godkar P B, Godkar D P. Textbook of Medical Laboratory Technology, second edition. Bhalani Publishing House. 2011 Forbes.A B et al. Bailey & Scotts Diagnostic Microbiology,12th edition ,Mosby Elseiver.2007. http://en.wikipedia.org/wiki/Infectious_mononucleosis

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 2012, shv

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