Corynebacterium diphtheriae) is a slender, club-shaped, Gram-positive bacillus. The most important virulence factor of C. diphtheriae is the exotoxin. In addition to this exotoxin, cell-wall components such as the O- and K-antigens are important in the pathogenesis of the disease. Humans are the only natural host for C. diphtheriae. Transmission occurs through droplets and close physical contact. Throughout history, diphtheria has been one of most feared childhood diseases, characterized by devastating outbreaks. Although most infections are asymptomatic or run a relatively mild clinical course, many patients succumb to airway obstruction caused by laryngeal diphtheria or toxic myocarditis. During a major diphtheria epidemic in Europe and the United States in the 1880s, the case-fatality rates reached 50% in some areas. Diphtheria is still a significant child health problem in countries with poor vaccine coverage. Where vaccine coverage is high and natural boosting low, as in most industrialized countries, a large proportion of the adult population is gradually rendered susceptible to diphtheria as a result of waning immunity.
Diphtheria vaccines are based on diphtheria toxoid, a modified bacterial toxin that induces protective antitoxin antibodies of the IgG type. Toxin-producing C. diphtheriae is grown in liquid media and the toxin converted to the inactive toxoid by treatment with formalin. This toxoid is adsorbed to aluminium salt as an adjuvant and thiomersal added as a preservative for multi-dose vials. Diphtheria toxoid combined with tetanus and pertussis vaccines (DTP) has been part of the WHO Expanded Programme on Immunization (EPI) since its inception in 1974. A reduced dose formulation is generally administered to individuals over 7 years of age. Diphtheria toxoid is one of the safest vaccines available. Individuals with an anti-diphtheria toxin antibody level of more than 0.1 IU/mL are considered fully protected from disease. DTP-containing multi-antigen vaccines (with Hep B, Hib, or IPV) are increasingly being used in national immunization campaigns.
Diphtheria Vaccine Standardization
WHO recommendations for the production and quality control of diphtheria vaccines were first formulated in 1964 and further revised and incorporated into recommendations for DTP in 1978. The 1989 revision updated the recommendations in important areas regarding toxin purification and potency determination. 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 for DTP and combined vaccines, Amendments 2003, Annex 5, WHO Technical Report Series No. 927
Requirements for DTP, WHO Technical Report Series No. 800, 1990
WHO Reference materials for Diphtheria toxoid for use in flocculation tests, toxoid (adsorbed vaccine) and other reagents for testing vaccines 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, Bilthoven, The Netherlands, 16-17 December 2002
Prequalified Diphtheria vaccines
Diphtheria (D) vaccines in combination with tetanus (T) or tetanus 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.