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CLOSTRIDIUM TETANI

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Clostridium tetani

SYNONYM OR CROSS REFERENCE: Tetanus Footnote 1; Lockjaw Footnote 2.

CHARACTERISTICS: Clostridium tetani is a motile, anaerobic, spore forming bacteria (terminal spores with drum stick appearance) Footnote 1, Footnote 2. Vegetative cells are rod shaped, pleomorphic, and occur in pairs or short chains Footnote 1. It is Gram positive in young cultures, but becomes Gram negative upon sporulation Footnote 1. It is catalase and superoxide dismutase negative. It produces a potent neurotoxin tetanospasmin (TeNT), which degrades the SNARE protein required for GABA-ergic neurotransmission Footnote 1.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Tetanus is caused by C. tetani, and has 4 different clinical manifestations: 1) local tetanus at the site of injury; 2) cephalic tetanus, which occurs due to head injuries or infections; 3) Generalized tetanus, which is the most common and represents 80% of the cases; 4) neonatal tetanus, which occurs in infants within 28 days of birth, due to infection of the umbilical stump Footnote 3.

C. tetani colonizes small, non serious wounds such as a puncture wound with a splinter, and releases TeNT at the site of injury. The toxin rapidly enters the CNS through retrograde transport and blocks postsynaptic inhibition of spinal motor reflexes resulting in prolonged spasmodic contractions of the skeletal muscles Footnote 1, Footnote 2. The first muscles to be affected are the neck and masseter muscles, causing rigidity of the neck and spasms of the jaw (lock jaw/trismus) Footnote 2, Footnote 3. This is followed by generalized spasms of the muscles involved in swallowing, respiration muscles, or back muscles (opisthotonos: characteristic body shape) Footnote 2. Renal failure can also occur due to muscle rigidity Footnote 3. Death results from exhaustion, respiratory failure, or cardiac arrest Footnote 2.

EPIDEMIOLOGY: Incidence of tetanus in developed countries is low and has been declining due to effective vaccination programs Footnote 3, Footnote 4. US Centers for Disease Control and Prevention (CDC) has reported 0.10 cases/million population overall, and 0.23 cases/million among individuals ≥65 years of age, between the years 2001 and 2008. The case-fatality rate was 13.2 percent overall, but was 31.3 percent among individuals ≥65 years of age Footnote 4. One million cases of tetanus occur each year, worldwide, with approximately 300,000-500,000 deaths Footnote 4. In Canada, the number of cases reported annually ranged from 1 to 10, with an average of 4 per year, between the years 1980 and 2004 Footnote 5. No infection was reported among neonates Footnote 5. Only 5 deaths due to tetanus have been reported in Canada between 1980 and 2004 Footnote 5. Tetanus, however, is still very common in the developing countries, with mortality rates exceeding 50% Footnote 3. Neonatal tetanus accounted for 59,000 deaths in 2008 in developing countries Footnote 4.

HOST RANGE:Humans, domestic and wild animals Footnote 2, Footnote 6.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Transmission occurs through contamination of wounds with soil or foreign bodies carrying C. tetani spores Footnote 2, Footnote 7.

INCUBATION PERIOD: 1-60 days Footnote 3. Length of the incubation period depends upon the distance between the wound and the CNS: the shorter the injury site is from the central nervous system, the shorter the incubation period Footnote 2.

COMMUNICABILITY: Not directly transmitted from person-person.

SECTION III - DISSEMINATION

RESERVOIR: Soil, feces, sewage, marine sediments, part of human’s indigenous microbiota (lower intestinal tract of humans) Footnote 1, Footnote 7. C. tetani spores can remain viable in soil for many years Footnote 2.

ZOONOSIS: Although disease occurs both in humans and animals, there is no evidence of direct transmission of the pathogen between the species, although indirect transmission through feces or decomposing animal tissues can occur Footnote 6.

VECTORS: None.

SECTION IV - STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY/RESISTANCE: Forty-five isolates of C. tetani recovered from wounds of tetanus infected patients in the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were found to be susceptible to penicillin and metronidazole, but resistant to co-trimoxazole Footnote 7; however, C. tetani remained viable in the wounds despite the two week treatment with high doses of penicillin Footnote 4. Adequate wound debridement is crucial in tetanus infected patients Footnote 4.

SUSCEPTIBILITY/RESISTANCE TO DISINFECTANTS: Spores are resistant to most disinfectants and, when susceptible, they require longer contact time Footnote 2, Footnote 8.

Clostridium spores are resistant to ethyl and propyl alcohols Footnote 8. Spores of clostridium species can be killed by high level disinfectants such as 2% aqueous glutaraldehyde within 3 hours, 8% formaldehyde, 20 ppm sodium hypochlorite Footnote 8, Footnote 9.

PHYSICAL INACTIVATION: Spores of the genus Clostridium are generally heat resistant but enterotoxin is heat labile and can be inactivated by dry heat treatment at 60oC for 5 minutes. Vegetative cells can be rapidly killed by heat treatment at 160-170o C for 1-2 hours or moist heat at 121oC for 15 min-30 min Footnote 10.

SURVIVAL OUTSIDE HOST: Spores can survive in soil for many years Footnote 2.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Diagnosis is done mainly through monitoring of clinical symptoms (findings of rigidity, spasms, and trismus) Footnote 3. Cell culture or toxin assay are not as useful Footnote 2.

FIRST AID/TREATMENT: Treatment of tetanus is done with human tetanus immunoglobulin (HTIG). HTIG can neutralize unbound toxin, but has no effect on the toxin already present in neurons Footnote 2, Footnote 3. High dose of intrathecal HTIG has been reported to be more effective in reducing mortality than intramuscular HTIG Footnote 3. Adequate wound debridement is also necessary to remove spores and necrotic tissue where the bacteria multiply Footnote 4, Footnote 7. Management of tetanus also involves active immunization with a total of three doses of tetanus and diphtheria toxoid, immediately upon the diagnosis Footnote 4.

IMMUNISATION: Vaccination for control of tetanus is given as a combined DTaP vaccine of diptheria, pertussis, and tetanus toxoid Footnote 11. It is administered along with the vaccine for poliomyelitis and hemophilus influenzae type b (DTaP-IPV-Hib) at 2, 4, 6, and 18 months of age Footnote 11, Footnote 12. A booster dose of DTaP–IPV vaccine is also given between 4 and 6 years of age Footnote 11. Otherwise, routine booster doses every 10 years after last childhood vaccination are recommended. A single booster dose of dTpa (Boostrix TM) can be also be used to prevent diphtheria, tetanus, and pertussis in individuals aged ≥ 4years in Europe and Canada, in adolescents aged 10–18 years in the US, and in individuals aged ≥10 years in Australia Footnote 13. This vaccine contains the same toxoid as DTaP vaccine used for primary immunization, but in reduced quantities to prevent increased immunological reactions with consecutive doses Footnote 13.

PROPHYLAXIS: Human tetanus immune globulin (HTIG) can be used as a prophylactic in individuals with tetanus-prone wounds Footnote 2. Penicillin can be used along with HTIG for prophylaxis in individuals with serious or neglected wounds Footnote 2.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: 3 cases of tetanus infection among lab personnel have been reported Footnote 14.

SOURCE/SPECIMENS: Soil Footnote 1, Footnote 2, wound exudates Footnote 7.

PRIMARY HAZARDS: Accidental parenteral inoculation, ingestion of the toxin. Hazards associated with aerosols or droplets not confirmed Footnote 15.

SPECIAL HAZARDS: None.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 2 Footnote 16.

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 Footnote 17.

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 Footnote 17.

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.

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

STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labeled.

SECTION IX - REGULATORY AND OTHER INFORMATION

UPDATED: December 2011

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, 2011
Canada

REFERENCES:

Footnote 1
Johnson, E. A., Summanen, P., & Finegold, S. M. (2007). Clostridium. In P. R. Murray (Ed.), Manual of Clinical Microbiology (9th ed., pp. 889-910). Washington, D.C.: ASM Press.

Footnote 2
Ryan, J. R. (2004). Clostridium, Peptostreptococcus, Bacteroids, and other Anaerobes. In K. J. Ryan, & C. G. Ray (Eds.), Sherris Medical Microbiology: An Introduction to Infectious Diseases (4th ed., pp. 309-326). USA: McGraw-Hill.

Footnote 3
Gibson, K., Bonaventure Uwineza, J., Kiviri, W., & Parlow, J. (2009). Tetanus in developing countries: a case series and review. Canadian Journal of Anaesthesia, 56(4), 307-315.

Footnote 4
Sexton, D. J.Tetanus. www.uptodate.com

Footnote 5
Public Health Agency of Canada. (2007). Vaccine preventable diseases: Tetanus. Retrieved April, 9, 2010, from http://www.phac-aspc.gc.ca/im/vpd-mev/tetanus-eng.php

Footnote 6
Songer, J. G. (2010). Clostridia as agents of zoonotic disease. Veterinary Microbiology, 140(3-4), 399-404.

Footnote 7
Campbell, J. I., Lam, T. M., Huynh, T. L., To, S. D., Tran, T. T., Nguyen, V. M., Le, T. S., Nguyen, V. C., Parry, C., Farrar, J. J., Tran, T. H., & Baker, S. (2009). Microbiologic characterization and antimicrobial susceptibility of Clostridium tetani isolated from wounds of patients with clinically diagnosed tetanus. American Journal of Tropical Medicine & Hygiene, 80(5), 827-831.

Footnote 8
Rutala, W. A. (1996). APIC guideline for selection and use of disinfectants. American Journal of Infection Control, 24(4), 313-342.

Footnote 9
Russel, A. D. (2001). Chemical Sporicidal and Sporostatic Agents. In S. S. Block (Ed.), Disinfectaion, Sterilization and Preservation (5th ed., pp. 529-541). Philadelphia PA: Lippincott Williams and Wilkins.

Footnote 10
Pflug, I. J., Holcomb, R. G., & Gomez, M. M. (2001). Principles of the thermal destruction of microorganisms. In S. S. Block (Ed.), Disinfection, Sterilization, and Preservation (5th ed., pp. 79-129). Philadelphia, PA: Lipincott Williams and Wilkins.

Footnote 11
Galanis, E., King, A. S., Varughese, P., & Halperin, S. A. (2006). Changing epidemiology and emerging risk groups for pertussis. Canadian Medical Association Journal, 174(4), 451-452.

Footnote 12
Greenberg, D. P., Doemland, M., Bettinger, J. A., Scheifele, D. W., Halperin, S. A., Waters, V., & Kandola, K. (2009). Epidemiology of pertussis and haemophilus influenzae type b disease in Canada with exclusive use of a diphtheria-tetanus-acellular pertussis- inactivated poliovirus-haemophilus influenzae type b pediatric combination vaccine and an adolescent-adult tetanus-diphtheria-acellular pertussis vaccine: Implications for disease prevention in the United States. Pediatric Infectious Disease Journal, 28(6), 521-528.

Footnote 13
Frampton, J. E., & Keating, G. M. (2006). Reduced-antigen, combined diphtheria, tetanus, and acellular pertussis vaccine (Boostrix): a review of its use as a single-dose booster immunization. Biodrugs, 20(6), 371-389.

Footnote 14
Collins, C. H., & Kennedy, D. A. (1999). Laboratory acquired infections. Laboratory acquired infections: History, incidence, causes and prevention (4th ed., pp. 1-37). Woburn, MA: BH.

Footnote 15
Agent Summary Statements:Bacterial Agents. (1999). In J. Y. Richmond, & R. W. Mckinney (Eds.), Biosafety in Microbiological and Biomedical Laboratories (BMBL) (4th ed., pp. 88-117). Washington, D.C.: Centres for Disease Control and Prevention.

Footnote 16
Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009. (2009).

Footnote 17
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.