A placebo-controlled trial of a pertussis-toxoid vaccine

N Engl J Med. 1995 Oct 19;333(16):1045-50. doi: 10.1056/NEJM199510193331604.

Abstract

Background: Although many whole-cell vaccines have been effective in preventing pertussis, these vaccines are difficult to standardize and can produce side effects. In Sweden, pertussis became endemic during the 1970s despite vaccination. Because of its limited efficacy, the Swedish-made whole-cell vaccine was withdrawn in 1979.

Methods: To evaluate the efficacy of an acellular vaccine consisting of pertussis toxin inactivated by hydrogen peroxide (pertussis toxoid), we conducted a randomized, double-blind, placebo-controlled trial in Sweden. Infants were vaccinated with either diphtheria and tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria, tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at 3, 5, and 12 months of age.

Results: There were no serious reactions. With the pertussis vaccine there were slightly more local reactions than with the DT toxoids alone, but the rates of postvaccination fever were the same. The main period of surveillance, which began 30 days after the third vaccination, continued for a median of 17.5 months. There were 312 cases of pertussis (72 in the DTP-toxoids group and 240 in the DT-toxoids group) that met the clinical criterion (paroxysmal cough lasting > or = 21 days) and laboratory criteria for pertussis as defined by the World Health Organization. The efficacy of this acellular vaccine was 71 percent (95 percent confidence interval, 63 to 78 percent). The recipients of DTP toxoids who had pertussis had cough of shorter duration than the recipients of DT toxoids, and fewer had whooping and vomiting. The vaccine efficacy after two doses was 55 percent (95 percent confidence interval, 12 to 78 percent), on the basis of 14 cases in the DTP-toxoids group and 31 in the DT-toxoids group that met the definition of the World Health Organization.

Conclusions: A pharmacologically inert, acellular pertussis-toxoid vaccine that is easily standardized is safe and confers substantial protection against pertussis.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Diphtheria Toxoid / adverse effects
  • Diphtheria Toxoid / therapeutic use
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Diphtheria-Tetanus-Pertussis Vaccine / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Pertussis Vaccine / adverse effects
  • Pertussis Vaccine / therapeutic use*
  • Sweden / epidemiology
  • Tetanus Toxoid / adverse effects
  • Tetanus Toxoid / therapeutic use
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / therapeutic use
  • Whooping Cough / diagnosis
  • Whooping Cough / epidemiology
  • Whooping Cough / prevention & control*

Substances

  • Diphtheria Toxoid
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Pertussis Vaccine
  • Tetanus Toxoid
  • Vaccines, Combined