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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) Footnote 1 Footnote 3, Sezary’s disease Footnote 4.

CHARACTERISTICS: Human T-lymphotropic virus is a C-type retrovirus, family Retroviridae, genus Deltaretrovirus, with a central, electron dense nuclear core Footnote 1 Footnote 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 Footnote 3 Footnote 5 Footnote 6.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Human T lymphotropic virus infection results in a lifelong infection Footnote 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 Footnote 3 Footnote 5 Footnote 7Footnote 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 Footnote 1 Footnote 2 Footnote 7. Of those who develop ATLL, more than two thirds develop leukemia while the remainder develop lymphoma Footnote 11. Prognosis is approximately 1 year after development of ATLL Footnote 12. ATLL has five types: asymptomatic, pre-leukemic, chronic/smouldering, lymphoma, and acute Footnote 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 Footnote 5 Footnote 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 Footnote 5Footnote 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 Footnote 7.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Infections can occur from blood and mucosal exposure Footnote 6. Virus is transmitted by sexual contact, intravenous drug abuse and blood transfusions Footnote 2 Footnote 3 Footnote 5 Footnote 7 Footnote 8 Footnote 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 Footnote 2 Footnote 3 Footnote 5 Footnote 7 Footnote 8 Footnote 10.

SECTION III - DISSEMINATION

RESERVOIR: Humans Footnote 2 Footnote 7 Footnote 8.

ZOONOSIS: None Footnote 13.

VECTORS: None.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: No established therapy Footnote 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 Footnote 14.

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

SURVIVAL OUTSIDE HOST: HTLV-1 and HTLV-2 can survive in stored blood for 8-9 days Footnote 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 Footnote 5 Footnote 6. For the identification of specific viral sequences, PCR is used.

FIRST AID/TREATMENT: Limited therapy is available for HTLV infections Footnote 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 Footnote 16. One reported infection with HTLV of a nurse after accidental inoculation of the finger with a needle containing a blood sample Footnote 17.

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

PRIMARY HAZARDS: Exposure of mucous membranes and accidental parenteral inoculation Footnote 18 Footnote 19.

SPECIAL HAZARDS: None

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3 pathogen Footnote 20.

CONTAINMENT REQUIREMENTS: Please refer to the Biosafety Directive for Human Immunodeficiency Virus (HIV) and Human T-cell Lymphotropic Virus Type 1 (HTLV-1)

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 Footnote 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 Footnote 18Footnote 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 Footnote 18.

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

STORAGE: Infectious material should be stored in sealed, leak-proof containers that are appropriately labelled Footnote 18 Footnote 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 2016

PREPARED BY: Centre for Biosecurity, 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, 2016

Canada

REFERENCES:

Footnote 1
Gessain, A., Dezzutti, C. S., Cowan, E. P., & Lal, R. B. (2007). Human T-Cell Lymphotropic Virus Types 1 and 2. In P. M. Murray, E. J. Baron, J. H. Jprgensen, M. L. Landry & M. A. Pfaller (Eds.), Manual of Clinical Mircobiology (9th ed., pp. 1330). Washington, DC: ASM Press.
Footnote 2
Larson, C. J., & Taswell, H. F. (1988). Human T-cell leukemia virus type I (HTLV-I) and blood transfusion. Mayo Clinic Proceedings.Mayo Clinic, 63(9), 869-875.
Footnote 3
Ryan, K. J., & Ray, C. G. (Eds.). (2004.). Sherris Medical Microbiology: An Introduction to Infectious Disease. (Fourth Edition. ed.). New York.: McGraw-Hill.
Footnote 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.
Footnote 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
Footnote 6
Lairmore, M. D., & Franchini, G. (2007). Human T-cell Leukemia Virus Types 1 and 2. In D. M. Knipe, & P. M. Howley (Eds.), Fields Virology (5th ed., pp. 2071). Philadelphia: Lippincott Williams & Wilkins.
Footnote 7
Johnson, J. M., Harrod, R., & Franchini, G. (2001). Molecular biology and pathogenesis of the human T-cell leukaemia/lymphotropic virus Type-1 (HTLV-1). International Journal of Experimental Pathology, 82(3), 135-147.
Footnote 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
Footnote 9
Sutton, R. E., & Littman, D. R. (1996). Broad host range of human T-cell leukemia virus type 1 demonstrated with an improved pseudotyping system. Journal of Virology, 70(10), 7322-7326.
Footnote 10
Koch, A. L. (2008). Stone age diseases and modern AIDS. Virology Journal, 5, 93. doi:10.1186/1743-422X-5-93
Footnote 11
Matutes, E. (2007). Adult T-cell leukaemia/lymphoma. Journal of Clinical Pathology, 60(12), 1373-1377. doi:10.1136/jcp.2007.052456
Footnote 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
Footnote 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.
Footnote 14
Disinfection, Sterilization, and Preservation (2001). In Block S. S. (Ed.), (5th ed.). Philadelphia: Lippincott Williams & Wilkins.
Footnote 15
Donegan, E., Lee, H., Operskalski, E. A., Shaw, G. M., Kleinman, S. H., Busch, M. P., Stevens, C. E., Schiff, E. R., Nowicki, M. J., & Hollingsworth, C. G. (1994). Transfusion transmission of retroviruses: human T-lymphotropic virus types I and II compared with human immunodeficiency virus type 1. Transfusion, 34(6), 478-483.
Footnote 16
Kataoka, R., Takehara, N., Iwahara, Y., Sawada, T., Ohtsuki, Y., Dawei, Y., Hoshino, H., & Miyoshi, I. (1990). Transmission of HTLV-I by blood transfusion and its prevention by passive immunization in rabbits. Blood, 76(8), 1657-1661.
Footnote 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
Footnote 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.
Footnote 19
Chosewood, L. C., & Decaudin, A. (Eds.). (2007). Biosafety in Microbiological and Biomedical Laboratories (5th ed.). Washington: US Government Printing Office.
Footnote 20
Human Pathogens and Toxins Act. S.C. 2009, c. 24. Government of Canada, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009, (2009).