A Placebo-Controlled Trial of a Pertussis-Toxoid Vaccine
Birger Trollfors, M.D., John Taranger, M.D., Teresa Lagergård, Ph.D., Lena Lind, M.D., Valter Sundh, B.Sc., Gunilla Zackrisson, M.D., Charles U. Lowe, M.D., William Blackwelder, Ph.D., and John B. Robbins, M.D.
Background Although many whole-cell vaccines have been effectivein preventing pertussis, these vaccines are difficult to standardizeand can produce side effects. In Sweden, pertussis became endemicduring the 1970s despite vaccination. Because of its limitedefficacy, the Swedish-made whole-cell vaccine was withdrawnin 1979.
Methods To evaluate the efficacy of an acellular vaccine consistingof pertussis toxin inactivated by hydrogen peroxide (pertussistoxoid), we conducted a randomized, double-blind, placebo-controlledtrial in Sweden. Infants were vaccinated with either diphtheriaand tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria,tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at3, 5, and 12 months of age.
Results There were no serious reactions. With the pertussisvaccine there were slightly more local reactions than with theDT toxoids alone, but the rates of postvaccination fever werethe same. The main period of surveillance, which began 30 daysafter the third vaccination, continued for a median of 17.5months. There were 312 cases of pertussis (72 in the DTP-toxoidsgroup and 240 in the DT-toxoids group) that met the clinicalcriterion (paroxysmal cough lasting >21 days) and laboratorycriteria for pertussis as defined by the World Health Organization.The efficacy of this acellular vaccine was 71 percent (95 percentconfidence interval, 63 to 78 percent). The recipients of DTPtoxoids who had pertussis had cough of shorter duration thanthe recipients of DT toxoids, and fewer had whooping and vomiting.The vaccine efficacy after two doses was 55 percent (95 percentconfidence interval, 12 to 78 percent), on the basis of 14 casesin the DTP-toxoids group and 31 in the DT-toxoids group thatmet the definition of the World Health Organization.
Conclusions A pharmacologically inert, acellular pertussis-toxoidvaccine that is easily standardized is safe and confers substantialprotection against pertussis.
Source Information
From the Departments of Pediatrics (B.T., J.T.), Medical Microbiology and Immunology (T.L.), Clinical Bacteriology (L.L., G.Z.), and Geriatric Medicine (V.S.), Göteborg University, Göteborg, Sweden; and the National Institute of Child Health and Human Development (C.U.L., J.B.R.) and the National Institute of Allergy and Infectious Diseases (W.B.), National Institutes of Health, Bethesda, Md.
Address reprint requests to Dr. Trollfors at the Göteborg Pertussis Vaccine Trial, St. Paulig 6, S-416 60 Göteborg, Sweden.
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