Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.

Efficacy of acellular pertussis vaccine in early childhood after household exposure.

OBJECTIVE: To evaluate the efficacy of a three-dose primary vaccination with a diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical" pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of Bordetella pertussis infection by culture or serology. DESIGN: Passive monitoring for suspected first household (index) cases of typical pertussis in six areas in Germany comprising 22,505 children vaccinated with study vaccine at 3, 4, and 5 months of age. Blinded, prospective follow-up of household contacts of index cases for incidence and progression of pertussis. SETTING: Six areas in Germany with a high incidence of pertussis. SUBJECTS: Four hundred fifty-three households with index cases comprising 360 evaluable contacts eligible for analysis of vaccine efficacy. MAIN OUTCOME MEASURE: Vaccine efficacy from attack rates of pertussis in household contacts classified by vaccination status. RESULTS: Of the 173 nonvaccinated household contacts, 96 developed typical pertussis, compared with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6% to 94.6%). Protection did not wane until at least the time recommended for booster vaccination. None of the analyzed potential confounding factors--age, socioeconomic status, erythromycin treatment, household composition, center effect, and selection bias--influenced study results in favor of the vaccine. CONCLUSIONS: Under conditions of intense household exposure, primary vaccination with acellular vaccine protected against pertussis until at least the time recommended for booster vaccination. The vaccine can be expected to be equally or more effective in settings with lower infectious pressure.