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Epstein Barr Virus (EBV) Frances A. Rosario FNP-S Suny Poly 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 • T Cell lymphoma • Hodgkin lymphoma Nasopharyngeal carcinomas (Sullivan, 2013) 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) 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) 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) 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 10-19 manifest as infectious mononucleosis • Equally effects males & females • By 20 yrs of age 60-90 % of individuals have a life-long anti-EBV antibody present • (5 Minute Clinical Consult, 2014) Screening & Risk Factors Screening • Currently there is no vaccine or specific tx for EBV (CDC, 2014a). • Studies are being conducted to develop a vaccine for the EBV virus • Risk Factors • Age • Sociohygienic level • Geographic location • Close, intimate contact • Immunocompromised gp350 antigen is being studied as a possibility • (Odumade, Hogquist & Balfour, 2011). (The 5 Minute Clinical Consult, 2014) 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) 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) Differential Dx • Streptococcal Pharyngitis • Diphtheria • Blood dyscrasias • Rubella • Measles • Viral hepatitis • Mononucleosis • Cytomegalovirus • (The 5 Minute Clinical Consult, 2014) 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) 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 2-4---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) 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) 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) 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) Symptoms of mononucleosis (Hellwig, Jude & Meyer, 2013) Site Symptoms • Central • Fatigue, malaise, anorexia • Throat • Soreness, reddening • Tonsils • Swelling & exudate • Lymph nodes • Swelling • Abdominal • Splenomegaly, enlarged liver • Systemic • Fever, aches, & fatigue 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) 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) 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) 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) 10 Multiple questions Question # 1 1. Epstien-Barr is cause by which herpes virus ? A. Herpes simplex 1 B. Herpes simplex 2 C. Herpes virus 3 D. Herpes virus 4 Question # 2 2. The Epstein-Barr virus is spread via? A. Blood B. Oropharyngeal secretions C. Salvia D. All of the above Question # 3 3. A complication of EBV includes multiple lymphoma? A. True B. False Hodgkin’s & non-Hodgkin’s lymphoma Burkett's lymphoma Post transplant lymphoproliferative disease Nasopharyngeal carcinoma Question # 4 4. The most common complication of EBV is? A. Hodgkin's lymphoma B. Nasopharyngeal carcinomas C. Viral hepatitis D. Mononucleosis Question # 5 5. There is a vaccine for the EBV virus A. True B. False Question # 6 6. IM is most often seen in what age groups? • Young children • Elderly • Middle-aged • Adolescents Question # 7 7. Symptoms of EBV include? A. Fever & Fatigue B. Pharyngitis C. Nausea/Vomiting D. A & B Question # 8 8. A definitive diagnosis for EBV can be made by testing for? A. Monospot- heterophile B. Viral Capsid Antigen (VCA) C. EBV Nuclear Antigen (EBNA) D. B & C Question # 9 9. When does a positive Anti-VCA IgM appear? A. 4-6 wks after infection B. Very early in infection C. 2- 4 months after infection D. Late in the infection Question # 10 10. The presence of VCA & EBNA indicates? A. Acute infection B. Immunity C. None of the above D. Past infection from months to years References • Bennett, J. (2014a). Pediatric mononucleosis and epstein-barr virus infection: Background. Retrieved from http://emedicine.medscape.com/article/963894-overview • Bennett, J. (2014b). Pediatric mononucleosis and epstein-barr virus infection: Pathophysiology. Retrieved from http://emedicine.medscape.com/article/963894-overview • Center for Disease Control and Prevention (CDC). (2014a). Epstein-barr virus and infectious mononucleosis. Retrieved from http://www.cdc.gov/epstein-barr/aboutebv.html • Center for Disease Control and Prevention (CDC). (2014b). Laboratory testing. Retrieved from http://www.cdc.gov/epstein-barr/laboratory-testing.html • 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), 383-388. doi: 10.5581/1516-8484.20110103 • 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 http://www.medscape.com/viewarticle/805511_8 References • Odumade, O., Hogquist, K., & Balfour, H. (2011). Progress and problems in understanding and managing primary epstein-barr virus infections. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021204/ • Sullivan, J. (2013). Clinical manifestations and treatment of epstein-barr virus infection. Retrieved from http://www.uptodate.com/contents/clinicalmanifestations-and-treatment-of-epstein-barr-virusinfection?source=search_result&search=epstein barr&selectedTitle=1~150 • The 5 Minute Clinical Consult Stanard 2015. (2014). Epstein-barr virus infections. (23rd ed.). Lippincott Williams & Wilkins.