tective level of antibody could not be assessed directly in human subjects (by challenge with active toxin), two early workers in this field immunized themselves with the tetanus toxoid and then challenged themselves with two to three fatal doses of tetanus toxin. They were protected by their prechallenge serum levels of 0.007 and 0.01 American units of tetanus toxoid per ml (Wolters and Dehmel, 1942). In 1950, the World Health Organization (WHO) reset the international unit (IU) to equal the American unit (see the section Biologic Events Following Immunization below).

Two types of tetanus toxoid are available in the United States: fluid and adsorbed. The adsorbed vaccines contain less than 1.25 mg of aluminum and 4 to 10 flocculation units (Lf) of toxoid per 0.5-ml dose. (The quantity of toxoid is measured by in vitro flocculation when toxoid is mixed with a known amount of antitoxin, and the results are recorded as the limit of flocculation [Lf].) The fluid preparations contain 4 to 5 Lf of toxoid. All tetanus toxoids in the United States contain 0.02 percent formaldehyde and 0.1 percent thimerosal. Some investigators have noted an increased rate of severe local reactions and abscess formation when adsorbed diphtheria toxoid or diphtheria and tetanus toxoids for pediatric use (children under 7 years of age) (DT) were used (e.g., 30 percent adsorbed versus 8 percent fluid) (Collier et al., 1979; Holden and Strang, 1965). However, others have not corroborated these findings and note that adsorbed toxoids have similar reaction rates as long as the injections are given intramuscularly rather than subcutaneously. In addition, adsorbed toxoids offer the benefit of enhanced immunogenicity (Jones et al., 1985; Relihan, 1969; Trinca, 1965; White, 1980; White et al., 1973).

Diphtheria

Diphtheria is an acute respiratory infection caused by Corynebacterium diphtheriae. In a nontoxigenic form, the organism may colonize the throat of asymptomatic individuals or may produce mild pharyngitis. However, when the bacterium is infected with a bacteriophage carrying the structural gene for biosynthesis of the toxin responsible for clinical disease, classic diphtheria can result. The clinical presentation includes a fibrinous, adherent pharyngeal membrane and complications of severe systemic toxicity, myocarditis, and peripheral neuritis. Case fatality rates were commonly in the range of 50 percent prior to the availability of antitoxin therapy. It is now known that diphtheria toxin is one of a family of A and B toxins. The A and B fragments of diphtheria toxin are part of a single polypeptide chain. Fragment A ("active") is a potent enzyme that acts intracellularly to block protein synthesis. The only known substrate for fragment A is elongation factor 2, which is involved in catalyzing the movement of ribosomes



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