Minor adverse events in a comparative efficacy trial in Germany in infants receiving either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine : the pertussis vaccine study Group

Minor adverse events were evaluated in a comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP (DTP) or DT vaccine. Vaccinees received four doses (at three, four-and-a half, six and 15-18 months of age) of either DTP or DTaP vaccine or three doses (at three, four-and-a half and 15-18 months of age) of DT vaccine. The reactogenicity analysis included 4,273 DTaP, 4,259 DTP and 1739 DT vaccinees. Local reactions (erythema and induration) and systemic events (fever, fretfulness, drowsiness and anorexia) were more common after each dose of DTP vaccine than after the DTaP and DT vaccine doses. Erythema, induration and fever increased in frequency in DTaP and DT recipients with increasing series number. Erythema, induration and fever after the first two doses of vaccine were more frequent in DT recipients than DTaP vaccinees. Antipyretics were more commonly used in DTP recipients than in DTaP vaccinees

Polymerase chain reaction identification of Bordetella pertussis infections in vaccinees and family members in a pertussis vaccine efficacy trial in Germany

The polymerase chain reaction (PCR) was recently added to conventional culture and serology for the diagnoses of Bordetella pertussis infection in a large vaccine efficacy trial in Germany. In vaccinees or family members who had illnesses with cough, two nasopharyngeal swabs (calcium alginate for culture and Dacron for PCR) were taken and initial and follow-up clinical data were obtained. PCR was done using oligonucleotide primers PTp1 and PTp2 which amplify a 191-base pair DNA fragment of pertussis toxin operon. From December, 1993, to May, 1994, 555 pairs of swabs were processed; 28 grew B. pertussis and 9 grew B. parapertussis. Twenty-six of the 28 subjects with B. pertussis-positive cultures also had positive PCR results as did one of the 9 B. parapertussis cases and 82 additional samples were positive by PCR. PCR increased the identification of subjects with B. pertussis infections by almost 4-fold. Clinical characteristics were analyzed by laboratory category (Group 1, 28 culture-positive; Group 2, 82 culture-negative, PCR-positive; and Group 3, 436 culture- and PCR-negative). Group 1 subjects were more likely to have a diagnosis of definite or probable pertussis and to have paroxysmal cough, posttussive vomiting, whooping and a cough duration of < or = 4 weeks than Group 2 or 3 subjects. In contrast Group 2 subjects were more likely than Group 1 subjects to have had previous pertussis immunization or prior antibiotics. PCR identified many mild illnesses caused by B. pertussis that were not identified by culture

Comparative Efficacy of the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine and Lederle whole-cell component DTP vaccine in German children after household exposure : pertussis vaccine study group

BACKGROUND: A household contact substudy was performed as part of a prospective, cohort pertussis vaccine efficacy trial in Germany. DESIGN: Infants received four doses of either the Lederle/Takeda acellular pertussis component diphtheria-tetanus toxoids (DTP) vaccine (DTaP) or Lederle whole-cell component DTP vaccine at 3, 4.5, 6, and 15 to 18 months of age (Wyeth-Lederle Vaccines and Pediatrics, Pearl River, NY). An open control group received three doses of diphtheria and tetanus toxoids vaccine (DT) at 3, 4.5, and 15 to 18 months of age. Vaccine efficacy rates were calculated using a number of principal and ancillary case definitions for primary, secondary, and noncases by analyzing secondary attack rates in study infants after exposure to pertussis in the household using 7- to 28- and 7- to 42-day postexposure observation periods and the inclusion and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period. RESULTS: During a 3.5-year study period, 10271 infants (DTP or DTaP, n = 8532; DT, n = 1739) were enrolled and actively followed along with all household members for cough illnesses. Depending on the case definition, 160 to 519 household exposures to pertussis were identified. In general, secondary attack rates in DT recipients were low and this was primarily because of the frequent use of antimicrobial prophylaxis. Using the principal case definitions and the exclusion of noncases who received macrolide antibiotics or trimethoprim-sulfamethoxazole during the exposure period and the 7- to 42-day observation period, the efficacy of DTP against cough illness of greater than or equal to 7 days duration caused by Bordetella pertussis was 84% (95% confidence interval [CI] = 65-93) and that of DTaP was 58% (95% CI = 30-75). Using similar criteria, the efficacy against typical pertussis (greater than or equal to 21 days of cough with either paroxysms, whoop, or posttussive vomiting) was 94% (95 CI = 77-99) and 86% (95% CI = 62-95) for DTP and DTaP, respectively. The efficacy against any cough illness (with or without) laboratory confirmation was 54% (95% CI = 32-69) and 38% (95% CI = 13-56) for DTP and DTaP, respectively. CONCLUSION: This household contact substudy within our cohort study, with active investigator-generated surveillance, was a severe test of vaccine efficacy. Both vaccines (DTP and DTaP) are better at preventing typical pertussis than mild illness. When case definitions similar to those in other recent trials are used, the Lederle/Takeda vaccine has an efficacy similar to other multicomponent DTaP vaccines

A comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine

BACKGROUND. The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT. DESIGN. In a randomized, double-blind fashion, 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3, 4.5, 6, and 15 to 18 months of age. The controls received 3 doses (3, 4.5, 15 to 18 months of age) of DT vaccine. The DTP vaccine was Lederle adsorbed vaccine (licensed in the United States) and DTaP was Lederle/Takeda adsorbed vaccine. Follow-up for vaccine efficacy started 2 weeks after the third dose (DTP/DTaP) and at the same age (6.5 months) in DT recipients. Reactogenicity of all doses of all three vaccines was documented by standardized parent diary cards. In addition, all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls. RESULTS. From May 1991 to January 1993, a total of 10 271 infants were enrolled: 8532 received either DTP or DTaP and 1739 received DT. Specific efficacy against B pertussis infections with cough </=7 days duration was 83% (95% confidence interval [CI]: 76-88) and 72% (95% CI: 62-79) for DTP and DTaP, respectively; results for DTP and DTaP based on </=21 days of cough with either paroxysms, whoop or posttussive vomiting (PWV) were 93% (95% CI: 89-96) and 83% (95% CI: 76-88), respectively. For DTaP vaccine, efficacy was higher after the fourth dose as compared with its efficacy after the third dose (78% vs 62% for cough </=7 days and 85% vs 76% for cough </=21 days with PWV). For DTP vaccine, efficacy was less varied after the third and fourth dose (78% vs 85% for cough </=7 days and 93% vs 93% for cough </=21 days with PWV). In contrast with DTP, the DTaP vaccine had some efficacy against B parapertussis infection (point estimate for cough </=7 days: 31% [95% CI: -10-56]). All vaccines were generally well-tolerated. However, side reactions were significantly less after DTaP compared with DTP. CONCLUSIONS. Like other multicomponent acellular pertussis vaccines, the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussis infections. Interestingly, it also may have some efficacy against B parapertussis. Based on the results of this trial, the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country

Comparative study of Lederle/Takeda acellular and Lederle whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants in Germany

In preparation for a large efficacy trial in Germany, a pilot study was initiated in December 1990. In this study 149 infants were enrolled; with double-blind randomization 75 received Lederle/Takeda acellular pertussis component diphtheria-tetanus-pertussis vaccine (APDT) and 74 received Lederle whole-cell pertussis component diphtheria-tetanus-pertussis vaccine (DTP). The mean age at first dose was 3.5 months, and the second and third doses followed at 6-week intervals. Reactions were relatively mild with both vaccines; in general they were less frequent following APDT. The IgG antibody responses to lymphocytosis promoting factor (LPF) and fimbriae-2 were similar in both groups whereas the responses to pertactin and filamentous haemagglutinin (FHA) were greater in APDT recipients. DTP recipients had greater responses to tetanus and diphtheria toxoids. When age of first dose was examined (8-12 weeks versus 16-20 weeks), it was found that young age had a suppressive effect on antibody responses in DTP but not APDT recipients to LPF toxoid, pertactin, fimbriae-2, and tetanus and diphtheria toxoids. High values of transplacentally acquired antibody lessened the response to LPF toxoid and tetanus toxoid in DTP recipients and to tetanus toxoid in APDT vaccinees. The IgG immune response to LPF toxoid, FHA and fimbriae-2 was found to be more uniform in APDT recipients than in DTP vaccinees. An IgA antibody response to fimbriae-2 was noted in 13% of DTP recipients but in no APDT vaccinees. The broad immunogenicity and mild reactogenicity of this APDT vaccine justifies its use in the German efficacy trial