Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after Hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM

Objective: The hemophilus vaccine has been linked to the development of autoimmune type 1 diabetes, insulin dependent diabetes (IDDM) in ecological studies. Methods: We attempted to determine if the Hemophilus influenza B (HiB) vaccine was associated with an increased risk of IDDM by looking for clusters of cases of IDDM using data from a large clinical trial. All children born in Finland between October 1st, 1985 and August 31st, 1987, approximately 116,000 were randomized to receive 4 doses of the HiB vaccine (PPR-D, Connaught) starting at 3 months of life or one dose starting after 24 months of life. A control-cohort included all 128,500 children born in Finland in the 24 months prior to the HiB vaccine study. Non-obese diabetic prone (NOD) mice were immunized with a hemophilus vaccine to determine if immunization increased the risk of IDDM. Results: The difference in cumulative incidence between those receiving 4 doses and those receiving 0 doses is 54 cases of IDDM/100,000 (P = 0.026) at 7 years, (relative risk = 1.26). Most of the extra cases of IDDM appeared in statistically significant clusters that occurred in periods starting approximately 38 months after immunization and lasting approximately 6-8 months. Immunization with pediatric vaccines increased the risk of insulin diabetes in NOD mice. Conclusion: Exposure to HiB immunization is associated with an increased risk of IDDM. NOD mice can be used as an animal model of vaccine induced diabetes.