was that interpretation of a "positive" Schick reaction to toxin required a control test with purified toxoid. Another implication was that pseudoreactions might predict clinically relevant hypersensitivity to further immunization with diphtheria toxoid (Pappenheimer, 1984). However, not all investigators found a high degree of correlation between Schick test results and adverse reactions (Settergren et al., 1986), and routine testing prior to immunization is impractical. Pappenheimer et al. (1950) demonstrated that a significant proportion of the delayed-type hypersensitivity reactions in previously immunized subjects were against the contaminants in the crude toxoid rather than against the highly purified diphtheria toxin. The role of bacterial cellular fractions in adverse reactions has been confirmed by Relyveld and colleagues (1979, 1980).
The problems of high rates of severe local and systemic reactions (fever, malaise, myalgia, headaches, and chills) noted in earlier studies with diphtheria toxoid in older children and adults have been alleviated by (1) the use of improved methods for purifying toxins, (2) reduction of the dose of toxoid (<2 Lf of diphtheria toxoid in Td versus 10-20 Lf in DPT and 10-12 Lf in DT), and (3) the use of adsorbed vaccine (Edsall et al., 1954; Levine et al., 1961; Myers et al., 1982; Smith, 1969). By this approach, the rates of adverse reactions related to hypersensitivity have been very low (Middaugh, 1979; Mortimer et al., 1986; Myers et al., 1982; Sheffield et al., 1978). Mild local reactions (tenderness and swelling at the injection site) occurred in 16 to 27 percent of vaccinees. Erythema, marked swelling, or systemic symptoms occurred in fewer than 2 percent of individuals.
Encephalopathy has been used in the literature to characterize a constellation of signs and symptoms reflecting a generalized disturbance in brain function often involving alterations in behavior or state of consciousness, convulsions, headache, and focal neurologic deficit. The annual incidence of encephalitis for the years 1950 to 1981 in Olmsted County, Minnesota was 7.4 per 100,000 (Beghi et al., 1984; Nicolosi et al., 1986). The incidence in children less than 1 year of age was 22.5, in children between 1 and 4 years of age it was 15.2, and in children between 5 and 9 years of age it was 30.2 per 100,000. Other estimates of encephalopathy for children less than age 2 years were somewhat lower than those reported by Beghi et al. (1984) and Nicolosi et al. (1986). Other estimates for annual incidence range from 5 per 100,000 children younger than age 2 years (Walker et al., 1988) to 10 per 100,000 children younger than age 2 years (Gale et al., 1990). For a more complete discussion of encephalopathy, see Chapter 3.