outpatient controls. The study did not show a statistically significant association between receipt of DT and coma or complicated convulsions (matched OR, 1.6; 95 percent CI, 0.54-4.74). However, the outpatient controls were randomly selected from records of vaccinated children. This would inflate exposure rates among the outpatient control group and perhaps create a negative bias in the odds ratio. Unpublished information provided by the authors permitted a separate (unmatched) analysis for the cases and inpatient controls, which revealed an unmatched OR of 2.16 (95 percent CI, 0.37-12.49). A meta-analysis combining the data from the NCES and the cases and inpatient controls from the study of Crovari et al. (1984) yields a Mantel-Haenszel OR of 0.95 (95 percent CI, 0.68-1.34).

Controlled Clinical Trials

No controlled clinical trials have compared DT recipients with an appropriate control.

Causality Argument

There is some biologic plausibility that tetanus toxoid-containing preparations might cause encephalopathy, on the basis of the evidence of Illis and Taylor (1971) that tetanus toxin has been associated with CNS sequelae. The case reports and case series reviewed above offer no convincing evidence for the occurrence of encephalopathy following immunization with DT. Three case-control studies addressed the question of a possible relation between DT immunization and encephalopathy. The best of the controlled observational studies is the NCES (Alderslade et al., 1981). The authors of that study did not detect an association between the occurrence of acute neurologic illness and receipt of DT (OR, 0.92; 95 percent CI, 0.64-1.30), nor did a meta-analysis combining the NCES results with those based on cases and inpatient controls in the study by Crovari et al. (1984) (OR, 0.95; 95 percent CI, 0.68-1.34). Therefore, the combined evidence strongly suggests that no relation exists between immunization with DT and the onset of acute neurologic illness. The possibility of lot-specific reactions to DT, as has been demonstrated for DPT preparations (Baraff et al., 1989), suggests that studies could be more revealing if the vaccines were tracked by lot. (See Chapter 11 for suggestions for further research.)

If the evidence favors rejection of a causal relation between DT and acute encephalopathy, then in the committee's judgment the evidence favors rejection of a causal relation between DT and chronic encephalopathy and between Td and tetanus toxoid alone and encephalopathy.



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