Case Reports, Case Series, and Uncontrolled Observational Studies

The North West Thames study by Pollock and Morris (1983), an uncontrolled cohort study, was a collection of reports of all reactions to vaccines in the North West Thames region of England and Wales. It was designed to intensify the reporting of severe manifestations, particularly neurologic complications, after childhood immunization between January 1975 and December 1981. Of 400,500 doses of DT and oral polio vaccine (OPV) (133,500 children completing a primary series of three doses of vaccine) and 221,000 single booster doses of DT given at school entry, seven children had seizures without neurologic damage and were well at follow-up. Three children with other neurologic conditions were identified; one child (9 months old) had infantile spasms predating vaccination, another child (9 years old) had a seizure with hemiplegia 1 day after receipt of DT but was normal on follow-up, and another child (7 months old) developed hemiparesis 14 days after receipt of DT and was normal on follow-up. None of these neurologic events was considered to be encephalopathic.

Because it was felt that reactions that occurred after vaccination with DT were being underreported in the first part of the North West Thames study (compared with the reporting of reactions that occurred after vaccination with DPT), an alternative method of study was undertaken on the basis of a hospital activity analysis of hospitals in the North West Thames region during 1979. Children under 2 years of age were included in the study if their diagnosis at the time of discharge included a neurologic event. No control group was used. Of 18,000 children who completed a primary series of DT (approximately 54,000 doses of DT were administered), 18 children had seizures (all febrile) within 28 days of DT immunization and 3 children had some other neurologic disease that developed within 28 days of DT immunization. Two of these children had focal seizures at 22 and 24 days after DT immunization, and the other child died of encephalopathy 28 days after DT immunization. Insufficient detail was given to describe the case of encephalopathy.

Several clinical trials compared DT and DPT (therefore, they are considered uncontrolled cohort studies for DT), and they showed that there were no serious neurologic adverse events after receipt of DT. Those studies, by Cody et al. (1981) and Barkin et al. (1985b), had only very small samples of those immunized with DT (784 and 40 subjects, respectively) and therefore do not provide much additional knowledge of the adverse events following immunization with DT.

Quast and colleagues (1979) found in the records of Behringwerke (a pharmaceutical firm in the former West Germany) a case report of a 36-year-old female who developed polyneuromyeloencephalopathy 5 days after receiving her first dose of aluminum-adsorbed tetanus toxoid in 1976. The

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