Pathogen safety data sheets: Infectious substances - Epstein-Barr virus

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Section I: Infectious agent

Name: Epstein-Barr virus

Synonym or cross reference: Human herpesvirus 4 (HHV4); EBV, infectious mononucleosis (IM), glandular fever, Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC)Footnote 1Footnote 2.

Characteristics: Epstein-Barr virus belongs to genus lymphocryptovirus of the subfamily Gammaherpesvirinae in the Herpesviridae familyFootnote 1Footnote 2. It consists of a double-stranded 172 Kb DNA genome, enclosed within an icosahedral capsid, surrounded by a phospholipid rich envelopeFootnote 1Footnote 3. Epstein-Barr virus can be cultured in lyphoblastoid cell linesFootnote 4. The virus can infect B-cells and epithelial cellsFootnote 1Footnote 3Footnote 4.

Section II: Hazard identification

Pathogenicity/toxicity: Most EBV infections are acquired during childhood and are asymptomaticFootnote 1Footnote 5. Symptoms when produced are undistinguishable from other acute viral syndromes. Many benign and malignant diseases, however, have been associated with Epstein- Barr virus in both immunocompetent and immunocompromised patientsFootnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9.

Diseases in immunocompetent hosts

Infectious Mononucleosis (IM): IM is an acute, self limiting febrile illness in young adults, characterized by fever, sore throat, abdominal discomfort, pharyngitis, tonsillitis, tender generalized lymphadenopathy, palatal petechaie, and periorbital oedema)Footnote 1. Some patients also present with maculopapular rash, splenomegaly, hepatomegaly, and jaundice. Rashes are almost always present in patients who were given ampicillin or amoxicillinFootnote 1Footnote 5Footnote 9. The disease generally lasts 1 to 4 weeks; however, protracted illness or tiredness for up to one year can occur in some patientsFootnote 1. Many complications, including autoimmune hemolytic anemia, splenic rupture, hemophagocytic lymphohistiocytosis, and neurological complications have also been associated with infectious mononucleosisFootnote 1Footnote 5.

Burkitt's lymphoma: Burkitt's lymphoma may be endemic, sporadic or im munodeficiency associatedFootnote 3. Burkitt's lymphoma arises due to an early infection with EBV virus resulting in infected B cellsFootnote 4Footnote 8. Endemic Burkitt's lymphoma frequently affects the facial bones, particularly the jaw, maxilla, and orbit, in young childrenFootnote 8. The sporadic Burkitt's lymphoma arises in the lymphoid tissues of the gut and the upper respiratory tractFootnote 8.

Other malignant diseases in immunocompetent hosts include various B-cell or T-cell lymphomas, and epithelial or mesenchymal carcinomas such as classical Hodgkin's lymphoma and nasopharyngeal carcinomaFootnote 6Footnote 7Footnote 10.

Diseases in immunocompromised hosts: In AIDS patients or other immunosuppressed patients, many EBV-associated diseases may occur, such as oral hairy leukoplasia, interstitial lymphocytic pneumonia, B-cell or T-cell lymphomas and mesenchymal lymphomas (for e.g. leiomyosarcoma)Footnote 1Footnote 2Footnote 3Footnote 4Footnote 7. In transplant patients, early and late onset lymphoproliferative diseases are often caused by EBV.

Epidemiology: EBV infections are quite prevalent, affecting more than 90% of individuals during the first two decades of life worldwideFootnote 3. In developing countries, primary infections occur mainly in young children and are often asymptomaticFootnote 3Footnote 9. In developed countries, primary EBV infections are manifested mainly as infectious mononucleosis, and affect adolescents and young adultsFootnote 3Footnote 9. Endemic Burkitt's lymphoma occurs frequently in young children in the equatorial regions of Africa and Papua New Guinea and has an incidence of 50-100 cases per 1,000,000 individualsFootnote 7. In contrast, EBV-associated sporadic lymphoma occurs in children and young adults and has no specific geographic distribution, with an incidence of 2-3 cases per 1,000,000 individualsFootnote 7. It accounts for 40 and 50% of childhood non-Hodgkin's lymphomas (NHLs) and 1-2% of adult lymphomas in Western Europe and the United StatesFootnote 8. Endemic Burkitt's lymphoma is almost 100% associated with EBV, whereas, association of sporadic Burkitt's lymphoma with EBV is low (15-30% of cases)Footnote 7. Nasopharyngeal carcinoma (NPC) is most common in southern China, and accounts for approximately 20% of all adult cancersFootnote 6. It is extremely rare in Europe and North America, with an incidence rate is <1 per 100,000 populationFootnote 6.

Host range: Humans

Infectious dose: Not known

Mode of transmission: For infectious mononucleosis, transmission occurs mainly via sexual contact or contact with saliva of infected persons (oral route)Footnote 1Footnote 2Footnote 9. Possible spread via blood transfusion can also occur (not an important route)Footnote 1Footnote 9. For Burkitt's lymphoma, EBV transmission occurs early in life through saliva and then the lymphoma develops later after malaria infection. HIV-AIDS is also a possible cofactorFootnote 11.

Incubation period: The incubation for IM is 30-50 daysFootnote 5Footnote 9. For BL, the incubation period is longer ranging from 4.7-9.2 yearsFootnote 12Footnote 13.

Communicability: The virus is contracted after repeated contact with the infected person, or asymptomatic person shedding the virusFootnote 4. Shedding decreases during the year following infection but persists throughout lifeFootnote 14. Peaks in transmission occur between 1-6 and 14-20 years of age and over 95% of adults are asymptomatic carriers of the virusFootnote 15.

Section III: Dissemination

Reservoir: Asymptomatic humans shedding the virusFootnote 4.

Zoonosis: None

Vector: None

Section IV: Stability and viability

Drug susceptibility: Nucleoside analogues such as acyclovir, ganciclovir, and famciclovir, and pyrophosphate analogues, such as foscarnet can inhibit viral replicationFootnote 1Footnote 4.

Susceptibility to disinfectants: Most herpes viruses are susceptible to 30% ethanol and 20% isopropanol, 2000 ppm sodium hypochlorite, 0.12 % orthophenyl phenol, and 0.04% glutaraldehydeFootnote 16.

Physical inactivation: Herpes viruses can be inactivated by heating in solution at 60°C to 80°C, by freeze drying, and heating at 100°C for 30 minutesFootnote 10.

Survival outside host: Unknown

Section V: First aid and medical

Surveillance: Monitor for clinical symptomsFootnote 4. Direct detection of the viral antigen can be done by staining for EBNA 1 using anti complement immunofluorescence; viral RNA or DNA can be identified using in situ hybridization, dot-blot hybridization, nucleic acid amplification testing (NAAT), and southern blottingFootnote 1. Tests for heterophile antibodies in mononucleosis, antibodies against viral capsid antigen (VCA), antibodies to EBV nuclear antigen (EBNA) can also be usedFootnote 1Footnote 2Footnote 4.

Note: All diagnostic methods are not necessarily available in all countries.

First aid/treatment: Treatment of infectious mononucleosis is mainly supportive Footnote 4. Viral replication can be inhibited by nucleoside analogues which can reduce or terminate viral shedding, but have no effect on the symptomsFootnote 1Footnote 4. Airway obstruction is treated with a high dose of corticosteroid and nasopharyngeal airwayFootnote 1Footnote 4Footnote 9. Gamma interferon treatment has been shown to be effective for patients lacking this interferonFootnote 1. Lymphoproliferative disorders associated with EBV can be treated with anti-CD20 monoclonal antibodies and EBV specific cytotoxic T lymphocytes along with anti-viral drugsFootnote 1.

Immunisation: No registered vaccine is available for preventing Epstein-Barr virus infection; however, a glycoprotein gp340 vaccine is in clinical trialsFootnote 1.

Prophylaxis: None

Section VI: Laboratory hazards

Laboratory-acquired infections: Low risk of laboratory acquired infectionFootnote 17. No reports of laboratory acquired infection were found in the literature.

Source/specimens: Clinical specimens - blood, saliva and throat specimensFootnote 1Footnote 4.

Primary hazards: Ingestion, accidental parenteral inoculation, direct exposure of mucous membranes of the eyes, nose, or mouth, or inhalation of aerosolized materials are risks associated with herpes virusesFootnote 17.

Special hazards: None

Section VII: Exposure controls and personal protection

Risk group classification: Risk group 2Footnote 18.

Containment requirements: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashesFootnote 19.

Other precautions: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activitiesFootnote 19.

Section VIII: Handling and storage

Spills: Allow aerosols to settle, then, wearing protective clothing, gently cover the spill with absorbent paper towel and apply an appropriate disinfectant, starting at the perimeter and working towards the center. Allow sufficient contact time before starting the clean up.

Disposal: All wastes should be decontaminated before disposal either by steam sterilization, incineration or chemical disinfection.

Storage: The infectious agent should be stored in a sealed and identified container.

Section IX: Regulatory and other information

Regulatory information: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

Updated: October 2010

Prepared by: Pathogen Regulation Directorate, Public Health Agency of Canada Although the information, opinions and recommendations contained in this Pathogen Safety Data sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Public Health Agency of Canada, 2010



Footnote 1

Linde, A., & Falk, K. I. (2007). Epstein-Barr Virus. In P. R. Murray (Ed.), Manual of clinical microbiology (9th ed., pp. 1564-1573). Washington, D.C.: ASM Press.

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Footnote 2

Rickinson, A. B., & Kieff, E. (2007). Epstein-Barr Virus. In D. M. Knipe, & P. M. Howley (Eds.), Fields of virology (5th ed., pp. 2655-2700). Philadelphia, PA: Lippincott Williams & Wilkins.

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Footnote 3

Ng, S. B., & Khoury, J. D. (2009). Epstein-Barr virus in lymphoproliferative processes: an update for the diagnostic pathologist. Advances in Anatomic Pathology, 16 (1), 40-55.

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Footnote 4

Drew, W. L. (2004). Herpesviruses. In K. J. Ryan, & C. G. Ray (Eds.), Sherris medical microbiology: An introduction to infectious diseases (4th ed., pp. 555-576). USA: McGraw Hill.

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Footnote 5

Griffiths, P. D. (2009). Herpesviruses. Medicine, 37 (12), 668-672.

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Footnote 6

Shah, K. M., & Young, L. S. (2009). Epstein-Barr virus and carcinogenesis: beyond Burkitt's lymphoma. Clinical Microbiology & Infection, 15 (11), 982-988.

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Footnote 7

Kutok, J. L., & Wang, F. (2006). Spectrum of Epstein-Barr virus-associated diseases. Annual Review of Pathology, 1, 375-404.

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Footnote 8

Yustein, J. T., & Dang, C. V. (2007). Biology and treatment of Burkitt's lymphoma. Current Opinion in Hematology, 14 (4), 375-381.

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Footnote 9

Papesch, M., & Watkins, R. (2001). Epstein-Barr virus infectious mononucleosis. Clinical Otolaryngology & Allied Sciences, 26 (1), 3-8.

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Footnote 10

Sofer, G., Lister, D. C., & Boose, J. A. (2003). Virus inactivation in the 1990s - And into the 21st century: Part 6, inactivation methods grouped by virus. BioPharm International, 16 (4), 42-52+68.

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Footnote 11

Orem, J., Mbidde, E. K., Lambert, B., de Sanjose, S., & Weiderpass, E. (2007). Burkitt's lymphoma in Africa, a review of the epidemiology and etiology. African Health Sciences, 7(3), 166-175. doi:10.5555/afhs.2007.7.3.166

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Footnote 12

Armenian, H. K., & Lilienfeld, A. M. (1974). The distribution of incubation periods of neoplastic diseases. American Journal of Epidemiology, 99 (2), 92-100.

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Footnote 13

Beral, V., Peterman, T., Berkelman, R., & Jaffe, H. (1991). AIDS-associated non-Hodgkin lymphoma. Lancet, 337 (8745), 805-809.

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Footnote 14

Luzuriaga, K., & Sullivan, J. L. (2010). Infectious mononucleosis. The New England Journal of Medicine, 362 (21), 1993-2000. doi:10.1056/NEJMcp1001116

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Footnote 15

Perera, R. A., Samaranayake, L. P., & Tsang, C. S. (2010). Shedding dynamics of Epstein- Barr virus: A type 1 carcinogen. Archives of Oral Biology, doi:10.1016/j.archoralbio.2010.06.009

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Footnote 16

Prince, H. N., & Prince, D. L. (2001). Principles of viral control and transmission. In S. S. Block (Ed.), Disinfection, sterilization and preservation (5th ed., pp. 543-571). Philadelphia, PA: Lippincott Williams & Wilkins.

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Footnote 17

Viral agents: Human herpes virus. (1999). In J. Y. Richmond, & R. W. Mckinney (Eds.), Biosafety in microbiological and biomedical laboratories (BMBL) (4th ed., pp. 161). Washington, D.C.: CDC & NIH.

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Footnote 18

Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009, (2009).

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Footnote 19

Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.

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