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Epstein Barr Virus (EBV)
Frances A. Rosario FNP-S Suny Poly
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Epstein Barr Virus (EBV)
Epstein-Barr Virus is a herpesvirus that is transmitted via intimate contact between at risk individuals and asymptomatic EBV shedders EBV is the primary agent in pts with infectious mononucleosis (IM) EBV is assoc. with the development of several lymphomas such as B Cell lymphoma Hodgkin lymphoma T Cell lymphoma Nasopharyngeal carcinomas (Sullivan, 2013) Nasopharyngeal carcinomas --- only in certain pts
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Pathophysiology The only reservoir for Epstein-Barr virus are humans. Animals are not carriers HBV is present in oropharyngeal secretions & is most commonly spread via salvia. After infected the virus replicates within the nasopharyngeal epithelial cells. Cell lysis causes release of virions which spreads to the salivary glands and oropharyngeal lymphoid tissues. Continued viral replication results in worsening viremia affecting the lymphoreticular system: liver, spleen, & B lymphocytes in the peripheral blood. This results in a host response and the appearance of atypical lymphocytes in the peripheral. (Bennett, 2014b) Cell lysis is associated with a release of virions
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Pathophysiology The bodies host response includes CD8+ T lymphocytes with suppressor & cytotoxic functions T-lympocytes are cytotoxic to the EBV and will eventually decrease the no# of EBV (infected B-Cells) Primary infection is succeed by a latent infection during which the virus is found in lymphocytes & oropharyngeal epithelial cells as epitomes in the nucleus. Episomes seldom integrate into cell genome but some to replicate. Reactivation during latently is low (Bennett, 2014b)
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Etiology More than 95% of the worlds population have been infected with EBV/ human herpesvirus 4. The most common complication of EBV is mononucleosis (IM) Adolescents and young adults are most commonly effected by IM EBV in young children is usually asymptomatic (Bennett, 2014a) Breast milk may also contain the virus, but this is an uncommon route of vertical transmission
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Incidence 90% of all adults have antibodies to EBV indicating they have been infected at some point in their lives (Gequelin, Riediger, Nakatani, Biondo & Bonfim, 2011). Common in crowded populations such as military, college, and daycares Predominant age: All ages are effected by EBV Ages manifest as infectious mononucleosis Equally effects males & females By 20 yrs of age % of individuals have a life-long anti-EBV antibody present (5 Minute Clinical Consult, 2014) IM can happen to kids and elderly Also known as the "kissing disease” it is commonly a self-limiting disease, which means it evolves to a cure without specific treatment.
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Screening & Risk Factors
Currently there is no vaccine or specific tx for EBV (CDC, 2014a). Studies are being conducted to develop a vaccine for the EBV virus gp350 antigen is being studied as a possibility (Odumade, Hogquist & Balfour, 2011). Age Sociohygienic level Geographic location Close, intimate contact Immunocompromised (The 5 Minute Clinical Consult, 2014) Gp350/220 is one of the most abundant viral proteins present in lytically infected cell plasma membranes and the most abundant protein on the outer surface of the virus coat; binds to the CD21 receptor on the B cell which is responsible for the initiation of infection. In addition, most of the human EBV neutralizing antibody response is directed against gp350/220
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Transmission Transmitted mainly by contact with infected oropharyngeal secretions such as: Sharing of toothbrushes or kissing: the kissing disease Sharing drinks, cups, eating utensils & foods Contact with tools that have saliva on them (CDC, 2014) EBV is also transmitted via Blood Blood derivative transfusion Organ and Tissue transplants EBV can be present in breast milk and is present in the genital tract (Gequelin, Riediger, Nakatani, Biondo & Bonfim, 2011)
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Clinical Findings Sx of EBV include Fever & Fatigue Inflamed throat
Swollen lymph nodes in the neck Enlarged spleen and/or Swollen liver Sx usually only last about 2-4 wks, but some may continue to experience fatigue for several months or months After EBV infections (ex. IM) the virus become latent. Reactivation of the virus does not always cause sx-- unless immunocompromised (CDC, 2014a)
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Differential Dx Streptococcal Pharyngitis Diphtheria Blood dyscrasias
Rubella Measles Viral hepatitis Mononucleosis Cytomegalovirus (The 5 Minute Clinical Consult, 2014)
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Social/Environmental Considerations
EBV is more prevalent in low socioeconomic groups, occurs at an earlier age and is not as likely to result in acute infectious mononucleosis In developed nation EBV usually develops in adolescence and 50% results in acute mononucleosis EBV has no racial predictor and is equal found in men and women (Hellwig, Jude & Meyer, 2013)
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Laboratory/ Diagnostics
Viral Capsid antigen (VCA) Anti-VCA IgM appears early in EBV infection- disappears within 4-6 wks. + IgM=Active Infection Anti-VCA IgG is present in the acute stage of EBV infection & peaks at wks persist for life If VCA antibodies are not present then pt is susceptible to EBV A high or rising anti VCA IgG without a + EBNA = Strongly suggest primary infection after 4 wks of illness EBV Nuclear Antigen (EBNA): Antibody to EBNA: determined by the standard immunofluorescent test Not seen in acute infection, but appears 2-4 months after pt is symptomatic and is present life long The presence of VCA & EBNA= past infection from months to years (CDC, 2014b) EBNA on next slide
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Laboratory/ Diagnostics
Monospot Test – used to test for mononucleosis Is testing for heterophile antibodies. Heterophile is not always present in children with IM Antibodies (heterophile) detected by the Monospot can be caused by conditions other than EBV or Mononucleosis A + monospot may indicate that the pt has a typical case of IM, but it does not confirm an EBV infection (CDC, 2014b) EBV antibody tests are not usually needed to diagnose infectious mononucleosis. However, specific antibody tests may be needed to identify the cause of illness in people who do not have a typical case of infectious mononucleosis or have other illnesses that can be caused by EBV infection.
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treatment of EBV: Primary EBV is usually self-limiting and rarely requires more than symptom management Non pharmacological treatments include: Adequate fluids & nutritional intake is appropriate Adequate rest, but bed rest is unnecessary Tylenol & NSAIDS are recommended for fever, throat pain, and general malaise (CDC, 2014a) IM----infectious mononucleosis--- most common secondary EBV
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EBV Complications Primary complication is infectious mononucleosis
EBV complications include lymphoma’s such as: Hodgkin's & non-Hodgkin's lymphoma Burkett's lymphoma Post transplant lymphoproliferative disease Nasopharyngeal carcinoma (Gequelin, Riediger, Nakatani, Biondo & Bonfim, 2011) PCR is becoming an essential part of monitoring protocols in transplant pts as well as a predictor of post-transplant lymphoproliferative disease
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Symptoms of mononucleosis (Hellwig, Jude & Meyer, 2013)
Site Symptoms Central Throat Tonsils Lymph nodes Abdominal Systemic Fatigue, malaise, anorexia Soreness, reddening Swelling & exudate Swelling Splenomegaly, enlarged liver Fever, aches, & fatigue
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Antiviral used to tx IM Antiviral: Acyclovir
Inhibits the EBV infection by inhibition of EBV DNA polymerase (no effect on latent infection). Both PO & IV acyclovir have been studied A meta-analysis of 5 randomized controlled trials including 2 trials with IV acyclovir therapy, failed to show clinical benefit when compared to placebo Oropharyngeal shedding of virus greatly decreased by end of therapy in pts using acyclovir, but replication started again after tx ended (Hellwig, Jude & Meyer, 2013) These results are not surprising since there is little evidence that ongoing viral replication plays a role in the symptomatic phase of EBV-induced mononucleosis.
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Corticosteroids tx for Infectious mononucleosis (IM)
Corticosteroids: controversial Corticosteroids have traditionally been used to tx the sx of IM, but studies have shown no clinical significance Studies that have focused on steroid therapy alone have not perfect, but they indicated that steroids tx is able to induce modest improvement of lymphoid & mucosal swelling Steroid use not recomm. for routine cases of IM but have been used to manage the following sx: Severe Pharyngitis Swollen lymph nodes in the neck Enlarged spleen and/or Swollen liver (Hellwig, Jude & Meyer, 2013) Studies: meta anaylsis of 94 individuals, double blind studies, placebo-controlled trial of 94 patients.
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Follow up & Consultation/Referral
Normally referrals or follow- up are not needed unless complication such as Severe inflamed throat/ Pharyngitis that results in airway obstruction Swollen lymph nodes in the neck/ lymphoma’s Enlarged spleen and/or swollen liver (Hellwig, Jude & Meyer, 2013)
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Counseling/education
The EBV virus lives in saliva and commonly spread via kissing Do not share items such as eating utensils, drinking glasses, You can be tested for EBV or IM, but testing too early may result in a false negative. Treatment for EBV is geared toward symptoms management such as Tylenol (fever) NSIADS (sore throat) Rest and adequate fluid intake required May return to work/school when pt feels able to. It may wks to more than a month to feel back to normal Caution with return to sports: avoid splenic rupture. If possibility of enlarged spleen aviod contact sports till cleared by MD (Bennett, 2014) no specific guidelines that state when a patient with IM may return to athletic participation, but the general recommendation is roughly 3 weeks after initial symptom onset for athletes to resume activity in noncontact sports and at least 4 weeks after symptom onset for strenuous contact sports or activities that can lead to increased abdominal pressure
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10 Multiple questions
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Question # 1 Epstien-Barr is cause by which herpes virus ?
Herpes simplex 1 Herpes simplex 2 Herpes virus 3 Herpes virus 4 # 3 varicella-zoster virus. 4Epstein-Barr virus 5 cytomegalovirus (CMV). 6 Human herpes virus 6 (HHV6) is a recently observed agent found in the blood cells of a few patients with a variety of diseases. It causes roseola 7 HHV7 can also cause roseola, but it is not clear what other clinical effects that this virus causes. 8 Human herpes virus 8 (HHV8) was recently discovered in the tumours called Kaposi's Sarcoma (KS).
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2. The Epstein-Barr virus is spread via?
Question # 2 2. The Epstein-Barr virus is spread via? Blood Oropharyngeal secretions Salvia All of the above
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3. A complication of EBV includes multiple lymphoma?
Question # 3 3. A complication of EBV includes multiple lymphoma? True False Hodgkin’s & non-Hodgkin’s lymphoma Burkett's lymphoma Post transplant lymphoproliferative disease Nasopharyngeal carcinoma
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4. The most common complication of EBV is?
Question # 4 4. The most common complication of EBV is? Hodgkin's lymphoma Nasopharyngeal carcinomas Viral hepatitis Mononucleosis A & B are also caused by EBV C is a Diff Dx for EBV
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5. There is a vaccine for the EBV virus
Question # 5 5. There is a vaccine for the EBV virus True False False but studies are being conducted looking at gp350 antibody
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6. IM is most often seen in what age groups?
Question # 6 6. IM is most often seen in what age groups? Young children Elderly Middle-aged Adolescents Can be seen in all age groups but mostly in adolscents
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7. Symptoms of EBV include?
Question # 7 7. Symptoms of EBV include? Fever & Fatigue Pharyngitis Nausea/Vomiting A & B
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8. A definitive diagnosis for EBV can be made by testing for?
Question # 8 8. A definitive diagnosis for EBV can be made by testing for? Monospot- heterophile Viral Capsid Antigen (VCA) EBV Nuclear Antigen (EBNA) B & C
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9. When does a positive Anti-VCA IgM appear?
Question # 9 9. When does a positive Anti-VCA IgM appear? 4-6 wks after infection Very early in infection 2- 4 months after infection Late in the infection
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10. The presence of VCA & EBNA indicates?
Question # 10 10. The presence of VCA & EBNA indicates? Acute infection Immunity None of the above D. Past infection from months to years
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References Bennett, J. (2014a). Pediatric mononucleosis and epstein-barr virus infection: Background. Retrieved from Bennett, J. (2014b). Pediatric mononucleosis and epstein-barr virus infection: Pathophysiology. Retrieved from Center for Disease Control and Prevention (CDC). (2014a). Epstein-barr virus and infectious mononucleosis. Retrieved from ebv.html Center for Disease Control and Prevention (CDC). (2014b). Laboratory testing. Retrieved from Gequelin, L., Riediger, I., Nakatani, S., Biondo, A., & Bonfim, C. (2011). Epstein-barr virus: general factors, virus-related diseases and measurement of viral load after transplant. US National Library of Medicine National Institutes of Health, 33(5), doi: / Hellwig, T., Jude, K., & Meyer, B. (2013). Management options for infectious mononucleosis. Retrieved from Hellwig, T., Jude, K., & Meyer, B. (2013). Management options for infectious mononucleosis. Retrieved from
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References Odumade, O., Hogquist, K., & Balfour, H. (2011). Progress and problems in understanding and managing primary epstein-barr virus infections. Retrieved from Sullivan, J. (2013). Clinical manifestations and treatment of epstein-barr virus infection. Retrieved from manifestations-and-treatment-of-epstein-barr-virus- infection?source=search_result&search=epstein barr&selectedTitle=1~150 The 5 Minute Clinical Consult Stanard (2014). Epstein-barr virus infections. (23rd ed.). Lippincott Williams & Wilkins.
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