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HUMAN T-LYMPHOTROPIC VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Human T-lymphotropic virus (HTLV)

SYNONYM OR CROSS REFERENCE: HTLV, adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (1-3), Sezary’s disease (4).

CHARACTERISTICS: Human T-lymphotropic virus is a C-type retrovirus, family Retroviridae, genus Deltaretrovirus, with a central, electron dense nuclear core (1, 5). Genetic material is in the form of two positively charged single stranded RNA fragments. A reverse transcriptase is contained within the virion. Virions are round with a diameter of approximately 100 nm (3, 5, 6).

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Human T lymphotropic virus infection results in a lifelong infection (7). There are two known pathogenic strains of HTLV, HTLV-1 and HTLV-2. HTLV-1 primarily causes adult T-cell leukemia/lymphoma and topical spastic parapareis/HTLV-1 associated myelopathy. It also causes uveitis, infective dermatitis and lymphadenitis (3, 5, 7-10). HTLV-2 is a less pathogenic strain and has been associated with milder neurological disorders and chronic pulmonary infections. HTLV-3 and HTLV-4 have not been associated with specific illnesses. Acute HTLV infection is rarely suspected or diagnosed. Adult T-cell leukemia or lymphoma (ATLL) occurs in 1-2% of those infected. Symptoms present 20-30 years after infection (1, 2, 7). Of those who develop ATLL, more than two thirds develop leukemia while the remainder develop lymphoma (11). Prognosis is approximately 1 year after development of ATLL (12). ATLL has five types: asymptomatic, pre-leukemic, chronic/smouldering, lymphoma, and acute (7). The smouldering type presents with skin lesions and involvement of the bone marrow. The chronic stage is associated with elevated circulating leukemic cells and usually progresses to the acute type within two years. The acute phase is an aggressive form of leukemia and is accompanied by hypocalcaemia, elevated lactate dehydrogenase (LDH), skin lesions, lymphadenopathy, lymphomatous meningitis, lytic bone lesions, spleen or liver involvement and immunodeficiency. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has a shorter latency period than ATLL (5, 7). HAM/TSP is a progressive and chronic myelopathy, with preferential damage to the thoracic spinal cord. Symptoms include muscle weakness of lower limbs, hyperreflexia, sphincter disorders, impotence, sensory disturbances and lower back pain.

EPIDEMIOLOGY: Worldwide distribution, with an estimated 10-20 million people carrying the human T-cell lyphotropic virus (5-7). Endemic regions include southern Japan, Caribbean basin, central Africa, central and southern America, Melanesian Islands and the aboriginal population of Australia. Sporadic infections occur in at-risk groups, and metropolitan areas of Europe and the United States.

HOST RANGE: Humans and animals, including rabbits, rats and non-human primates (7).

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Infections can occur from blood and mucosal exposure (6). Virus is transmitted by sexual contact, intravenous drug abuse and blood transfusions (2, 3, 5, 7, 8, 10). Organ transplants, childbirth and breast feeding are also effective modes of transmission.

INCUBATION PERIOD: Unknown

COMMUNICABILITY: Human-to-human transmission is possible. Human T-lymphotropic virus is transmitted by sexual contact, intravenous drug abuse and blood transfusions (2, 3, 5, 7, 8, 10).

SECTION III - DISSEMINATION

RESERVOIR: Humans (2, 7, 8).

ZOONOSIS: None (13).

VECTORS: None.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: No established therapy (8). Combination therapy of Zidovudine (AZT) and interferon alpha (INF-α) is used with some success to improve prognosis.

SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% sodium hypochlorite, 2% glutaraldehyde, 4% chlorhexidine, 70% ethanol, 0.3% hydrogen peroxide, iodophores, phenolics, and quaternary ammonium compounds (14).

PHYSICAL INACTIVATION: Can be inactivated by steam sterilization at 121ºC for a minimum of 15 minutes and UV light (14).

SURVIVAL OUTSIDE HOST: HTLV-1 and HTLV-2 can survive in stored blood for 8-9 days (15).

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. HTLV is detected in blood serum by identifying antibodies using ELISA. Other methods of detection include particle agglutination assays and Western Blotting (5, 6). For the identification of specific viral sequences, PCR is used.

FIRST AID/TREATMENT: Limited therapy is available for HTLV infections (1). ATL treated with chemotherapy. Zidovudine (AZT) and alpha interferon have shown some response and improved the ATL prognosis. Other treatments are currently under investigation including arsenic, trioxide, proteasome inhibitors, retenoids, angiogenesis inhibitors and cellular immunotherapy. Antiretroviral treatments using lamivudine and high dose interferon alpha and interferon beta is used for HTLV-1-associated myelopathy/tropical spastic parparesis. Uveitis is treated with topical and systemic corticoids to improve sight. Infective dermatitis is treated with antibiotics.

IMMUNIZATION: None

PROPHYLAXIS: None

SECTION VI - LABORATORY HAZARD

LABORATORY-ACQUIRED INFECTIONS: One reported infection with HTLV-1 of a physician after a syringe containing a blood sample pierced the foot (16). One reported infection with HTLV of a nurse after accidental inoculation of the finger with a needle containing a blood sample (17).

SOURCES/SPECIMENS: Blood samples and bodily fluids (ie. CSF, blood,etc) (6).

PRIMARY HAZARDS: Exposure of mucous membranes and accidental parenteral inoculation (18, 19).

SPECIAL HAZARDS: None

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3 pathogen (20).

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities and equipment for work involving clinical specimens and non-culture procedures. Containment Level 3 facilities, equipment, and operational practices for all work culturing HTLV and for activities involving non-human primates and any animals experimentally infected or inoculated with HTLV (18).

PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes (20).

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animals or large scale activities (18-20).

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (18).

DISPOSAL: Decontaminate all materials before disposal using steam sterilization, incineration, and/or chemical disinfection (18, 19)

STORAGE: Infectious material should be stored in sealed, leak-proof containers that are appropriately labelled (18, 19).

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: September 2011

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Material 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, 2011

Canada

REFERENCES:

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  3. Ryan, K. J., & Ray, C. G. (Eds.). (2004.). Sherris Medical Microbiology: An Introduction to Infectious Disease. (Fourth Edition. ed.). New York.: McGraw-Hill.

  4. Poiesz, B. J., Ruscetti, F. W., Reitz, M. S., Kalyanaraman, V. S., & Gallo, R. C. (1981). Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sezary T-cell leukaemia. Nature, 294(5838), 268-271.

  5. Verdonck, K., Gonzalez, E., Van Dooren, S., Vandamme, A. M., Vanham, G., & Gotuzzo, E. (2007). Human T-lymphotropic virus 1: recent knowledge about an ancient infection. The Lancet Infectious Diseases, 7(4), 266-281. doi:10.1016/S1473-3099(07)70081-6

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  8. Bagossi, P., Bander, P., Bozoki, B., & Tozser, J. (2009). Discovery and significance of new human T-lymphotropic viruses: HTLV-3 and HTLV-4. Expert Review of Anti-Infective Therapy, 7(10), 1235-1249. doi:10.1586/eri.09.97

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  11. Matutes, E. (2007). Adult T-cell leukaemia/lymphoma. Journal of Clinical Pathology, 60(12), 1373-1377. doi:10.1136/jcp.2007.052456

  12. Satou, Y., Nosaka, K., Koya, Y., Yasunaga, J. I., Toyokuni, S., & Matsuoka, M. (2004). Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro. Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K, 18(8), 1357-1363. doi:10.1038/sj.leu.2403400

  13. Krauss, H., Schiefer, H. G., Weber, A., Slenczka, W., Appel, M., von Graevenitz, A., Enders, B., Zahner, H., & Isenberg, H. D. (2003). Viral Zoonoses. Zoonoses: Infectious Disease Transmissible from Animals to Humans (3rd ed., pp. 1). Washington D.C.: ASM Press.

  14. Disinfection, Sterilization, and Preservation (2001). In Block S. S. (Ed.), (5th ed.). Philadelphia: Lippincott Williams & Wilkins.

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  17. Menna-Barreto, M. (2006). HTLV-II transmission to a health care worker. American Journal of Infection Control, 34(3), 158-160. doi:10.1016/j.ajic.2005.12.002

  18. 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.

  19. Chosewood, L. C., & Decaudin, A. (Eds.). (2007). Biosafety in Microbiological and Biomedical Laboratories (5th ed.). Washington: US Government Printing Office.

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