Clinical implications of endotoxin concentrations in vaccines.
BACKGROUND
A previous study suggested that high concentrations of endotoxin may be present in whole-cell diphtheria/tetanus/pertussis (DTP) vaccine, and the scientific literature contains many studies examining the reactivity of whole-cell DTP vaccine. The medical and scientific communities have previously reported that the presence of endotoxin in commercial vaccines may have negative effects on vaccine recipients.


OBJECTIVE
To determine the endotoxin concentrations in whole-cell DTP, acellular DTP(DTaP), and DT vaccines and determine the clinical experience with each vaccine.


METHODS
To study the endotoxin concentrations in vaccines, the Limulus amebocyte lysate (LAL) assay was used. The vaccines analyzed with the LAL assay were whole-cell DTP vaccine lots manufactured by Connaught, Lederle, the Michigan and Massachusetts Departments of Health, and Wyeth; DTaP vaccine lots manufactured by Merieux and Takeda; and DT vaccine lots manufactured by Wyeth and Lederle. The incidence of adverse reactions following whole-cell DTP, DTaP, and DT vaccines were determined based on analysis of the Vaccine Adverse Events Reporting System (VAERS) database.


RESULTS
The results of the LAL assay showed that whole-cell DTP vaccines contained considerably more endotoxin than either DTaP or DT vaccines. The VAERS showed that statistically significantly more adverse reactions were associated with whole-cell DTP vaccine than DTaP or DT vaccines.


CONCLUSIONS
This analysis confirmed higher concentrations of endotoxin in whole-cell DTP vaccines compared with DTaP or DT vaccines. As high concentrations of endotoxin may be correlated with a higher incidence of adverse events, the switch from whole-cell DTP to DTaP for routine vaccinations in the US seems well justified.
Geier
David A
DA
Genetic Centers of America, 14 Redgate Court, Silver Spring, MD 20905-5726, USA.
Geier
Mark R
MR
D000293:Adolescent; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D001428:Bacterial Vaccines / Q000009:adverse effects* / Q000138:chemical synthesis; D002648:Child; D002675:Child, Preschool; D022422:Diphtheria-Tetanus Vaccine / Q000009:adverse effects / Q000138:chemical synthesis; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects / Q000138:chemical synthesis; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000009:adverse effects / Q000138:chemical synthesis; D004731:Endotoxins / Q000009:adverse effects* / Q000138:chemical synthesis; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008033:Limulus Test / Q000379:methods; D008297:Male; D011358:Product Surveillance, Postmarketing / Q000379:methods / Q000706:statistics & numerical data; D012640:Seizures / Q000139:chemically induced; D014611:Vaccination / Q000009:adverse effects
D001428:Bacterial Vaccines; D022422:Diphtheria-Tetanus Vaccine; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D004731:Endotoxins