Clustering of Cases of Insulin Dependent Diabetes (IDDM) Occurring Three Years After Hemophilus Influenza B (HiB) Immunization Support Causal Relationship Between Immunization and IDDM JOHN BARTHELOW CLASSEN a, * and DAVID C. CLASSEN b a Classen Immunotherapies Inc., 6517 Montrose Avenue, Baltimore, MD 21212 USA; b Division of Infectious Diseases, University of Utah School of Medicine, 561 East Northmont Way, Salt Lake City, UT 84103, USA (Submitted 21 March 2002; Accepted 26 March 2002) 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 ðP ¼ 0:026Þ at 7 years, (relative risk ¼ 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. Keywords: Insulin dependent diabetes; Vaccines; Immunization; Hemophilus INTRODUCTION We discovered a rise of type 1, insulin dependent diabetes (IDDM) occurred in Finland following the introduction of the Hemophilus influenza B (HiB) vaccine. [1] Due to the low relative risk associated with a single vaccine, we wanted to determine if we could identify specific clusters of cases of IDDM associated with the hemophilus vaccine. We initiated toxicity studies in non-obese diabetic prone (NOD) mice to determine if the vaccine could increase the risk of diabetes in the mice and if the findings in mice correlated with the findings in humans. METHODS We followed upon a clinical trial described in detail earlier. [2] 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 (3, 4, 6, 18 months) or 1 dose starting at 24 months of life. In the latter group, the mean age of immunization was approximately 26 months of life. By design of the original study, historical controls were designated as the unvaccinated controls for long-term safety studies. ISSN 0891-6934 print/ISSN 1607-842X online q 2002 Taylor & Francis Ltd DOI: 10.1080/08916930290028175 *Corresponding author. Tel.: þ 1-410-377-4549. Fax: þ 1-410-377-8526. E-mail: classen@vaccines.net Autoimmunity, 2002 Vol. 35 (4), pp. 247–253 Autoimmunity Downloaded from informahealthcare.com by Universitat de Barcelona on 07/09/15 For personal use only.