Introduction

Pertussis immunization has had a turbulent history.1-5 Effective vaccines have been available for 50 years, but controversy relating to true and perceived reactogenicity has limited their use in many areas of the world. Historically pertussis was a devastating disease; even today more than 355 000 deaths occur every year in unvaccinated young children. All whole cell, pertussis component diphtheria-tetanus toxoids-pertussis (DTP) vaccines are reactogenic (mainly because of their endotoxin content), which led to concern about their safety, particularly during the 1970s. A substantial number of "experts," as well as the public, in many European countries and Japan concluded that the risk of pertussis immunization was greater than the risk of the disease. Epidemiologic studies in the late 1970s and the 1980s clearly demonstrated that DTP vaccines had a favorable risk:benefit ratio and found no evidence that DTP vaccines caused sudden infant death syndrome or brain damage.1-5 Nonetheless without new scientific evidence, and based on the same old testimonial information, the media regularly recycle the same concerns about the safety of DTP vaccines.3, 5-7 The new era with acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) is exciting. These vaccines are effective and significantly less reactogenic than currently available whole cell pertussis component DTP vaccines. With the universal use of DTaP vaccines, one would assume that the past safety issues will disappear, but I believe an important warning is necessary. The major adverse events (sudden infant death syndrome and the first seizure of infantile epilepsy), which DTP vaccine has been accused of causing, will still occur in young children in temporal relationship to DTaP immunization, and this will lead those without epidemiologic training, those looking for an acceptable scapegoat and those who can make money from such unfortunate circumstances (plaintiff lawyers and their "experts," the media, anti-vaccine groups and the parents of children who experience these events) to assume that DTaP vaccines are at fault. The scientific medical community must be alert to this inevitable association, and meaningful postmarketing research must continue. It has been an honor for me to be the editor of this symposium. The other three authors and I have been extensively involved in biologic and epidemiologic studies relating to Bordetella pertussis, as well as DTP and DTaP vaccines. In our investigative endeavors we all have conducted studies that have been supported by the various vaccine manufacturers, including Smith-Kline Beecham, whose grant supported this symposium. In addition we have occasionally been consultants to one or more of the manufacturers. Four articles make up this symposium. Dr. Erik Hewlett presents an update on molecular microbiologic aspects of the pathogenesis of B. pertussis as it relates to the prevention of pertussis with new acellular vaccines. Dr. Steven Black presents data on the epidemiology of the disease pertussis, as well as the organism B. pertussis, and Drs. Kathryn Edwards and Michael Decker review the prospects and status of combination vaccines that contain acellular pertussis components. Finally I have analyzed the efficacy and reactogenicity data relating to the licensed and candidate acellular pertussis component DTP vaccines. Controversy relating to pertussis and pertussis immunization will not end with the universal use of DTaP vaccines. There is still much to be learned. Even though millions of dollars have been spent on recent efficacy trials with new vaccines, we still have no laboratory correlate of immunity (a laboratory test that indicates a person is immune, such as the specific antibody tests we have for measles, rubella, hepatitis B, etc.). Until a correlate or correlates become available, it will be difficult to improve upon the present acellular pertussis vaccines. All health care professionals who vaccinate children and all parents want to obtain immunity in children with as few injections as possible. To this end we currently have DTP, DTP-Haemophilus influenzae type b (Hib), measles-mumps-rubella vaccine and other combination vaccines. As pointed out by Drs. Edwards and Decker, however, combining DTaP with Hib and other antigens has been difficult, and our desire for combined products will be delayed, negating some of the appeal of DTaP vaccines. Finally the general acceptance of new evidence relating to the epidemiology of B. pertussis has been slow. Dr. Black suggests that the resurgence of pertussis in the United States in recent years is the result of the growth of a more susceptible adult population because of waning vaccine-induced immunity. The data of our group, however, as well as studies by others, suggest that immunity after infection is no more long-lasting than that after immunization.1, 8 In my opinion the modest increase in reported pertussis in the United States is caused at least in part by an increased awareness of the disease (particularly in adults) and the loss of potency of one of the two DTP vaccines available throughout the United States.9, 10