PEDIATRICS Vol. 91 No. 6 June 1993, pp. 1158-1165
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Severe Reactions Associated With Diphtheria-Tetanus-Pertussis Vaccine: Detailed Study of Children With Seizures, Hypotonic-Hyporesponsive Episodes, High Fevers, and Persistent Crying

Dean A. Blumberg MD1, Patricia Chatfield PNP1, James D. Cherry MD, MSc1, ChrisAnna M. Mink MD2, Karen Lewis MD2, and Peter D. Christenson PhD3

1 From the Department of Pediatrics, UCLA School of Medicine, and UCLA Center for Vaccine Research, Los Angeles, CA.
2 From the Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA.
3 From the Department of Biomathematics, UCLA School of Medicine, Los Angeles, CA.

Objective. The pathophysiology of severe reactions to diphtheria-tetanus-pertussis (DTP) vaccine is not well understood. Active pertussis toxin in DTP vaccine has been proposed to cause severe DTP vaccine reactions. Large doses of pertussis toxin cause hyperinsulinemia and hypoglycemia as well as leukocytosis with a predominant lymphocytosis in animal models. To learn more about the causes of and risk factors for severe DTP vaccine reactions, children experiencing severe DTP vaccine reactions were studied.

Design. Prospective, referral-based surveillance.

Setting. Los Angeles, CA.

Subjects. Children experiencing severe reactions within 48 hours of DTP immunization and evaluated within 24 hours of the reaction. Severe reactions included encephalopathy, persistent crying ge3 hours, hypotonic-hyporesponsive episodes (collapse episodes), fever ge40.5°C, or seizures. Some comparisons were made between children with DTP vaccine-associated seizures and a comparison group of children experiencing febrile seizures unrelated to immunization.

Outcome measures. A history and physical examination were performed. Follow-up examinations were performed 1 month later. Blood was collected for complete blood cell count with leukocyte differential count, serum chemistry measurements, and insulin and glucose values. Serum was assayed for active pertussis toxin, both in free and immune-complex masked states.

Results. Sixty children experienced severe reactions within 48 hours of DTP immunization: 32 children had seizures only, 14 subjects had hypotonic-hyporesponsive episodes, 2 subjects had fever ge40.5°C only, 4 subjects had persistent crying ge3 hours, 6 children had seizures and fever ge40.5°C, and 2 children had persistent crying and seizures. The children with seizures had a high rate of personal and family histories of seizures, and 90% had documented fevers (ge38°C). Persistent crying was associated with painful local reactions. Effects that may have been due to vaccine pertussis toxin were not found. Lymphocytosis did not occur, nor did hypoglycemia. Some relatively elevated insulin values were noted; however, this finding was also noted in the comparison group of children experiencing febrile seizures unrelated to immunization. No biologically active pertussis toxin was found in the acute sera of children experiencing severe DTP vaccine reactions.

Conclusions. Seizures associated with DTP vaccine have similar clinical characteristics as febrile seizures, and persistent crying is initiated by painful local reactions. Vaccine endotoxin is a cause of febrile DTP vaccine reactions. We found no evidence that DTP vaccine pertussis toxin plays a role in severe DTP vaccine reactions.

Key Words: pertussis • vaccine reactions • seizures • hypotonic-hyporesponsive episodes • diphtheria-tetanus-pertussis vaccine • fever • crying • insulin • glucose • immune complex • pertussis toxin

Submitted on December 7, 1992
Accepted on February 8, 1993




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