EPSTEIN-BARR VIRUS

PATHOGEN SAFETY DATA SHEET- INFECTIOUS SUBSTANCES

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)^(1,2)

CHARACTERISTICS: Epstein-Barr virus belongs to genus lymphocryptovirus of the subfamily Gammaherpesvirinae in the Herpesviridae family^(1,2). It consists of a double-stranded 172 Kb DNA genome, enclosed within an icosahedral capsid, surrounded by a phospholipid rich envelope^(1,3). Epstein-Barr virus can be cultured in lyphoblastoid cell lines⁽⁴⁾. The virus can infect B-cells and epithelial cells^(1,3,4).

SECTION II- HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Most EBV infections are acquired during childhood and are asymptomatic^(1,5). 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 patients^(1-9).

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)⁽¹⁾. Some patients also present with maculopapular rash, splenomegaly, hepatomegaly, and jaundice. Rashes are almost always present in patients who were given ampicillin or amoxicillin^(1,5,9). The disease generally lasts 1 to 4 weeks; however, protracted illness or tiredness for up to one year can occur in some patients⁽¹⁾. Many complications, including autoimmune hemolytic anemia, splenic rupture, hemophagocytic lymphohistiocytosis, and neurological complications have also been associated with infectious mononucleosis^(1,5).

Burkitt's lymphoma: Burkitt's lymphoma may be endemic, sporadic or im munodeficiency associated⁽³⁾. Burkitt's lymphoma arises due to an early infection with EBV virus resulting in infected B cells^(4,8). Endemic Burkitt's lymphoma frequently affects the facial bones, particularly the jaw, maxilla, and orbit, in young children⁽⁸⁾. The sporadic Burkitt's lymphoma arises in the lymphoid tissues of the gut and the upper respiratory tract⁽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 carcinoma^(6,7,10).

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)^(1-4,7). 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 worldwide⁽³⁾. In developing countries, primary infections occur mainly in young children and are often asymptomatic^(3,9). In developed countries, primary EBV infections are manifested mainly as infectious mononucleosis, and affect adolescents and young adults^(3,9) . 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 individuals⁽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 individuals⁽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 States⁽⁸⁾. Endemic Burkitt's lymphoma is almost 100% associated with E BV, whereas, association of sporadic Burkitt's lymphoma with EBV is low (15-30% of cases )⁽⁷⁾. Nasopharyngeal carcinoma (NPC) is most common in southern China, and accounts for approximately 20% of all adult cancers⁽⁶⁾. It is extremely rare in Europe and North America, with an incidence rate is <1 per 100,000 population⁽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)^(1,2,9). Possible spread via blood transfusion can also occur (not an important route)^(1,9). 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 cofactor⁽¹¹⁾.

INCUBATION PERIOD: The incubation for IM is 30-50 days^(5,9). For BL, the incubation period is longer ranging from 4.7-9.2 years^(12,13).

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

SECTION III-DISSEMINATION

RESERVOIR: Asymptomatic humans shedding the virus⁽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 replication^(1,4).

SUSCEPTIBILITY TO DISINFECTANTS: Most herpes viruses are susceptible to 30% ethanol and 20% isopropanol, 200 ppm sodium hypochlorite, 0.12 % orthophenyl phenol, and 0.04% glutaraldehyde⁽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 minutes⁽¹⁰⁾.

SURVIVAL OUTSIDE HOST: Unknown

SECTION V-FIRST AID / MEDICAL

SURVEILLANCE: Monitor for clinical symptoms⁽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 blotting⁽¹⁾. Tests for heterophile antibodies in mononucleosis, antibodies against viral capsid antigen (VCA), antibodies to EBV nuclear antigen (EBNA) can also be used^(1,2,4).

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

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

IMMUNISATION: No registered vaccine is available for preventing Epstein-Barr virus infection; however, a glycoprotein gp340 vaccine is in clinical trials⁽¹⁾.

PROPHYLAXIS: None

SECTION VI-LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: Low risk of laboratory acquired infection⁽¹⁷⁾. No reports of laboratory acquired infection were found in the literature.

SOURCE/SPECIMENS: Clinical specimens - blood, saliva and throat specimens^(1,4).

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 viruses⁽¹⁷⁾.

SPECIAL HAZARDS: None

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk group 2⁽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 splashes⁽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 activities⁽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.

Copyright ©
Public Health Agency of Canada, 2010
Canada

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