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CYTOMEGALOVIRUS

PATHOGEN SAFETY DATA SHEET- INFECTIOUS SUBSTANCES

SECTION I-INFECTIOUS AGENT

NAME: Cytomegalovirus

SYNONYM OR CROSS REFERENCE: Human herpes virus 5 (HHV-5)Footnote 1, CMVFootnote 2 Footnote 3, HCMV.

CHARACTERISTICS: Member of the family Herpesviridae and subfamily BetaherpesvirinaeFootnote 1. The name cytomegalovirus is derived from the associated enlargement of cells following infection. Complete CMV particles have a diameter of 120-200 nm. They consist of a 235-kb double-stranded linear DNA genome enclosed within an icosahedral capsid, surrounded by a phospholipid rich envelope. Viral replication is slow and involves the expression of immediate- early, early, and late genes. Replication occurs in the nucleus of the host cell.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: CMV infection is common and usually asymptomatic in healthy children and adults, but can cause severe disease in newborns and immunocompromised children or adultsFootnote 1. CMV is the most common cause of congenital infection, affecting 0.2-2.4% of all infants, and also of viral-based mental retardation and hearing deficit in children of developing countriesFootnote 4. Infections are often recurrent, caused by reactivation of latent virus (especially in immunocompromised patients such as bone marrow or other transplant recipients), reinfection may also occur due to the antigenic diversity of the virusFootnote 5 Footnote 6. Infection may cause a mononucleosis-like-syndrome with prolonged fever (lasting 2-3 weeks), malaise, atypical lymphocytosis, cervical lymphadenitis, mild hepatitis, and encephalitisFootnote 1 Footnote 7-9.

Congenital infection: Congenital infection occurs when women acquire primary CMV infection during pregnancy. Some of these congenitally infected infants (10-15%) develop symptoms during the newborn period. Newborns with symptomatic disease present with a variety of congenital defects such as low birth weight, jaundice, hepatospleenomegaly, petechiae, thrombocytopenic purpura, myocarditis, pneumonitis, anemia, CNS abnormalities, retinitis, and chorioretinitisFootnote 1 Footnote 8 Footnote 9. These infants may die of complications within the first month of life or may survive with neurological complications. Approximately 6-25% of infants asymptomatic at birth develop complications such as sensory nerve hearing loss, psychomotor mental retardation, or both later on in their lives.

Neonatal infection: Perinatally infected infants do not usually have any apparent disease unless the infant is premature or immunocompromisedFootnote 1 Footnote 8. CMV infection in premature infants can result in hepatomegaly, thrombocytopenia, atypical lymphocytosis, or hemolytic anemia, and is associated with high mortality and morbidity.

CMV infection in immunocompromised people: Both primary CMV infection, or reactivation can cause serious illness in immunosuppressed patients (for example patients with AIDS, patients with leukemia or lymphoma who are receiving chemotherapy, and recipients of organ transplants on immunosuppressive therapy)Footnote 1 Footnote 8. The major symptoms of the disease in organ transplant recipients include fever, myalgia, malaise, arthralgia, leucopenia, thrombocytopenia, and hepatitis. Pneumonitis, caused by CMV infection in bone marrow transplant recipients is associated with significant morbidity and mortality (50-90%). CMV infection in HIV patients may spread to visceral organs, resulting in chorioretinitis, gastrointestinal infections (esophagitis, gastritis, and ulcerative colitis), polyradiculomyelopathy, and neurological disorders.

EPIDEMIOLOGY: Worldwide - Cytomegalovirus (CMV) is a universally distributed pathogen with approximately 40-100% of the world's population having CMV antibody present in blood as evidence of infectionFootnote 3 Footnote 11-12, the highest prevalence being in countries in the developing world. In the United States, >90% of healthy adults have become infected with CMV by the age of 80 years. Immunocompromised patients (AIDS patients or organ transplant recipients), premature infants, and newborns with congenital CMV are at a high risk of developing serious, life threatening illness with CMV infectionFootnote 3 Footnote 9 Footnote 11 Footnote 13. In the United States, approximately 30,000 children are born annually with congenital CMV infection, 20% of whom develop permanent disabilities. Transmission of infection has been reported to occur in day-care centersFootnote 1 Footnote 8. Furthermore, the majority of these congenital infections result from recurrent infections in pregnant womenFootnote 13.

HOST RANGE: Different strains affect humans (human cytomegalovirus) and animals such as rodents and rhesus macaqueFootnote 3.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Transmission can occur through direct contact with infectious tissues, secretions or excretions (urine, saliva, breast milk, cervical secretions, semen etc); during blood transfusion; and via organ transplantation. Infected mothers can transmit the virus to their fetus in utero (transplacental), to newborns at the time of delivery (intrapartum: by contact with the virus in the birth canal), or to infants through breast milkFootnote 1 Footnote 3 Footnote 8 Footnote 9. Sexual transmission has also been reported to occurFootnote 1. Transmission through aerosols has not been reportedFootnote 3.

INCUBATION PERIOD: 1-4 months post-implant in the case of organ transplantation or blood transfusionFootnote 1, and 4-12 weeks for perinatal CMV infectionsFootnote 4.

COMMUNICABILITY: CMV virus can persist in body fluids such as urine, saliva, and seminal fluids for many years, or can remain dormant until reactivation of latent infectionFootnote 5 Footnote 6 Footnote 14. Transmission occurs through direct contact with body fluids from symptomatic or asymptomatic persons excreting the virusFootnote 3, thus infection may be transmitted between humans and from adults to children through childbirth and breastfeedingFootnote 15.

SECTION III-DISSEMINATION

RESERVOIR: Humans, CMV strains found in many animal species are not infectious for humansFootnote 9 Footnote 12.

ZOONOSIS: No, each CMV strain causes disease in its own natural host speciesFootnote 3.

VECTOR: None.

SECTION IV- STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Ganciclovir inhibits viral replication in vivoFootnote 8. Ganciclovir, Valganciclovir, Foscarnet, and Cidofovir have all been approved for treatment of CMV in immunocompromised patientsFootnote 3.

DRUG RESISTANCE: Both in vivo and in vitro resistant strains to antiviral drugs have been reportedFootnote 3, such as against ganciclovir, cidofovir, and foscarnet, and strains with multiple antiviral resistant have been observedFootnote 16.

SUSCEPTIBILITY TO DISINFECTANTS: Cytomegalovirus has been shown to be susceptible to 7.5% povidone-iodineFootnote 17. Although not much information is available on disinfectants specific for CMV, most herpes viruses are susceptible to 30% ethanol and isopropanol, 1% sodium hypochlorite, formaldehyde, 0.12% ortho phenylphenol, and 0.04% glutaraldehydeFootnote 18 Footnote 19.

PHYSICAL INACTIVATION: Inactivated by heat (56 °C for 30 min), low pH, UV light, cycles of freezing/thawingFootnote 1.

SURVIVAL OUTSIDE HOST: Cytomegalovirus can survive on dry inanimate surfaces (persistence varies from only a few hours up to 7 days)Footnote 2; blanket for 2 hours; plexiglass for 4-8 hoursFootnote 20.

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis of CMV infection mainly consists of: 1) Virus detection by demonstrating CMV cytopathic effects by inoculating fibroblasts cells with clinical specimens, viral antigen such as protein pp65 in peripheral blood leukocytes, or DNA in plasma or leukocytes (using PCR)Footnote 3 Footnote 8; 2) isolation of the virus from tissues, secretions or bloodFootnote 8; 3) serological tests to detect seroconversion and IgM antibody to CMVFootnote 3 Footnote 8. Demonstration of cytopathic effects is labour intensive, less sensitive, and may take 3-14 days. Detection of CMV antigen in leukocytes is more sensitive than culture of the blood to detect viremia.

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

FIRST AID/TREATMENT: Since CMV infection resolves spontaneously in normal healthy patients, antiviral treatment is not usually recommendedFootnote 3.

Congenital infection: Because of the potential side effects associated with anti-viral drugs, they have not been licensed for use in neonates and infantsFootnote 1 Footnote 12; however, intravenous Ganciclovir has been advocated for treatment of severe congenital CMV infectionFootnote 3. Other antiviral agents which can be used for treating severe congenital infection in neonates and infants include oral valganciclovir, intravenous foscarnet, and intravenous cidofovirFootnote 12. Passive immunization of a CMV infected pregnant women with CMV hyper immune globulin has also been suggested to be effective for both the treatment and prevention of congenital fetal infectionFootnote 21.

Infection in immunocompromised hosts (AIDS patients or organ transplant recipients): Intravenous ganciclovir or oral valganciclovir are the first line drugs for therapy for CMV infection in immunocompromised patientsFootnote 3). Intravenous cidofovir and foscarnet are used as alternatives. Once symptomatic improvement has been achieved, these drugs can also be used for chronic maintenance therapy in patients with CMV retinitis or neurological disease.

IMMUNISATION: No vaccine is licensed for prevention of cytomegalovirus infectionFootnote 1 Footnote 3.

PROPHYLAXIS: Prophylaxis with intravenous ganciclovir is recommended for HIV infected adults, children and adolescents who are CMV seropositive, and have CD4+ T-cell count less than 50 cells/μl, and for organ transplant recipientsFootnote 3. Hyper immune globulin preparations with high levels of antibody to CMV along with anti-viral agents such as ganciclovir can also be used for prophylaxis in organ transplant recipientsFootnote 3 Footnote 8.

SECTION VI-LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: No infections reported.

SOURCE/SPECIMENS: Urine, blood, breast milk, tears, stool, semen, respiratory secretions (nasopharyngeal secretions, saliva, throat washings, and bronchoalveolar lavage fluid) and cervical secretionsFootnote 1 Footnote 8.

PRIMARY HAZARDS: Inhalation of concentrated aerosolized materials, droplet exposure of mucous membranes of the eyes, nose, or mouth, ingestion, accidental parenteral inoculation are the primary hazards associated with herpes viruses including CytomegalovirusFootnote 22.

SPECIAL HAZARDS: None.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 2Footnote 23.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materialFootnote 24.

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 24.

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 24.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, while wearing protective clothing, cover spill with absorbent paper towel. Apply an appropriate disinfectant, and, starting from perimeter and wipe towards the center. Allow sufficient contact time before cleaning up.

DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism before disposing by autoclave, chemical disinfection, gamma irradiation, or incinerationFootnote 24.

STORAGE: Properly labeled and sealed containers.

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

REFERENCES:


Footnote 1
Hodinka, R. L. (2007). Human Cytomegalovirus. In P. R. Murray (Ed.), Manual of clinical microbiology (9th ed., pp. 1549-1563). Washington, D.C.: ASM Press.
Footnote 2
2. Kramer, A., Schwebke, I., & Kampf, G. (2006). How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infectious Diseases, 6
Footnote 3
Mocarski, E. S., Shenk, T., & Pass, R. F. (2007). Cytomegalovirus. In D. M. Knipe, & P. M. Howley (Eds.), Fields of virology (5th ed., pp. 2701-2772). Philadelphia PA: Lipincott Williams & Wilkins.
Footnote 4
Kim, C. S. (2010). Congenital and perinatal cytomegalovirus infection. Korean Journal of Pediatrics, 53 (1), 14- 20.
Footnote 5
Tegtmeier, G. E. (1986). Transfusion-transmitted cytomegalovirus infections: significance and control. Vox Sanguinis, 51 Suppl 1 , 22-30.
Footnote 6
Cornalba, G. P., Dore, R., & Colombo, E. (1994). Abdominal manifestations in immunocompromised patients. [Manifestazioni addominali nei pazienti immunocompromessi] La Radiologia Medica, 87 (5 Suppl 2), 52-61.
Footnote 7
Pantoni, L., Inzitari, D., Colao, M. G., De Mayo, E., Marini, P., & Mazzota, F. (1991). Cytomegalovirus encephalitis in a non-immunocompromised patient: CSF diagnosis by in situ hybridization cells. Acta Neurologica Scandinavica, 84 (1), 56-58.
Footnote 8
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.
Footnote 9
Ross, D. S., Dollard, S. C., Victor, M., Sumartojo, E., & Cannon, M. J. (2006). The epidemiology and prevention of congenital cytomegalovirus infection and disease: activities of the Centers for Disease Control and Prevention Workgroup. Journal of Women's Health, 15 (3), 224-229.
Footnote 10
Lentz, E. B., Dock, N. L., McMahon, C. A., Fiesthumel, S. R., Arnold, C. B., & Lamberson, H. V.,Jr. (1988). Detection of antibody to cytomegalovirus-induced early antigens and comparison with four serologic assays and presence of viruria in blood donors. Journal of Clinical Microbiology, 26 (1), 133-135.
Footnote 11
Freeman, R. B.,Jr. (2009). The 'indirect' effects of cytomegalovirus infection. American Journal of Transplantation, 9 (11), 2453-2458.
Footnote 12
Marshall, B. C., & Koch, W. C. (2009). Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events. Paediatric Drugs, 11 (5), 309-321.
Footnote 13
Cannon, M. J. (2009). Congenital cytomegalovirus (CMV) epidemiology and awareness. Journal of Clinical Virology, 46 (SUPPL. 4), S6-S10.
Footnote 14
Biggar, R. J., Andersen, H. K., Ebbesen, P., Melbye, M., Goedert, J. J., Mann, D. L., & Strong, D. M. (1983). Seminal fluid excretion of cytomegalovirus related to immunosuppression in homosexual men. British Medical Journal (Clinical Research Ed.), 286 (6383), 2010-2012.
Footnote 15
Mosca, F., Pugni, L., Barbi, M., & Binda, S. (2001). Transmission of cytomegalovirus. Lancet, 357 (9270), 1800. doi:10.1016/S0140-6736(00)04914-X
Footnote 16
Erice, A. (1999). Resistance of human cytomegalovirus to antiviral drugs. Clinical Microbiology Reviews, 12 (2), 286-297.
Footnote 17
Numazaki, K., & Asanuma, H. (1999). Inhibitory effect of povidone-iodine for the antigen expression of human cytomegalovirus. In Vivo, 13 (3), 239-241.
Footnote 18
Laboratory Safety Manual (1993). (2nd ed.). Geneva: World Health Organization.
Footnote 19
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.
Footnote 20
Faix, R. G. (1985). Survival of cytomegalovirus on environmental surfaces. Journal of Pediatrics, 106 (4), 649-652.
Footnote 21
Adler, S. P., & Nigro, G. (2009). Findings and conclusions from CMV hyperimmune globulin treatment trials. Journal of Clinical Virology, 46 (Suppl 4), S54-7.
Footnote 22
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.
Footnote 23
Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57- 58 Elizabeth II, 2009. (2009).
Footnote 24
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.