Clostridium tetani is a spore-forming anaerobic bacillus. Spores are present in the environment, particularly in the soil of warm and moist areas, and may be carried in the intestinal tracts of humans and animals. Maternal tetanus is a consequence of unclean deliveryand poor postnatal hygiene when the umbilical cord becomes infected. Tetanus in children and adults following injuries may also constitute a considerable public health problem.
Under favourable anaerobic conditions, such as in dirty, necrotic wounds, this ubiquitous bacillus may produce an extremely potent neurotoxin which causes muscular stiffness and spasm. Characteristically, early spasms of the facial muscles ("lockjaw") are followed by spasm of the back muscles and sudden, generalized tonic seizures and causes disease. Immunity to tetanus is antibody-mediated and depends upon the ability of antitoxin antibodies to neutralize tetanus toxin. Recovery from clinical tetanus does not result in protection against future disease, and immunity can be obtained only by active or passive immunization such as vaccination, immunoglobulin therapy, or transfer of maternal antibodies through the placenta.
Tetanus vaccines are based on inactivated tetanus toxin. Toxigenic strains of C. tetani are grown in liquid media, the toxin is purified, and then inactivated by treatment with formaldehyde to produce the toxoid antigen. After purification and sterilization, tetanus toxoid is formulated with aluminum or calcium salts and administered by intramuscular injection. On the international market, tetanus toxoid vaccine is available as a single antigen vaccine (TT), in combination with diphtheria toxoid in infant and adult doses (DT and Td), and in combination with diphtheria and whole-cell or acellular pertussis (DTP). DTP-containing multi-antigen vaccines (with Hep B, Hib, or IPV) are increasingly in use in national immunization campaigns.
Tetanus vaccine Standardization
The WHO requirements for the production and quality control of tetanus toxoid vaccine were originally formulated in 1964 and revised and incorporated into recommendations for DTP in 1978. A major revision for the multi-antigen DTP vaccine was undertaken in 1989. The 2003 amendment updated the recommendations on potency testing to reduce the number of animals needed for batch (lot) release purposes and amended the section on international reference materials.
Recommendations to assure the quality, safety and efficacy of tetanus vaccines (adsorbed), Technical Report Series 980, 2012
- WHO Manual for Quality Control of Diphtheria, Tetanus and Pertussis Vaccines
Recommendations to assure the quality, safety and efficacy of DT-based combined vaccines, WHO Technical Report Series 980, Annex 6
WHO reference materials for tetanus toxoid (adsorbed) and tetanus toxoid for flocculation testing are available to qualified applicants:
WHO Working Group meetings on revision of the Manual laboratory methods for testing DTP vaccines, Geneva, Switzerland, 20-21 July 2006 and 28-30 March 2007
WHO Consultation on DT Potency Assay and Consistency, December 2002
Prequalified tetanus vaccines
Tetanus (T) vaccines in combination with Diphtheria (D) or Diphtheria and Pertussis (wP) vaccines are prequalified for procurement by UN organizations. DTwP vaccines in combination with Hib and/or hepatitis B are also are prequalified for procurement by UN organizations.