Sabina Schmitt-Grohé

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 pertussisinfections 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 parapertussisinfection (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 pertussisinfections. Interestingly, it also may have some efficacy againstB 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.

Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis

In conjunction with a pertussis vaccine efficacy trial in Germany, nasopharyngeal specimens were collected from May, 1992, to March, 1993, from patients with cough illnesses. Clinical data were obtained by initial and follow-up questionnaires. Bordetella parapertussis was isolated from 38 patients (mean age, 3.5 years; 68% girls). Clinical characteristics in these cases were compared with those of 76 patients (matched by age and sex) with illness caused by Bordetella pertussis during the same period. Findings were: (B. pertussis/B. parapertussis): cough > 4 weeks 57%/37% (P = 0.06); whoop 80%/59% (P = 0.07); whoop > 2 weeks 26%/18% (P = 0.05); paroxysms 90%/83% (P = 0.5); body temperature > or = 38 degrees C 9%/0% (P = 0.17); vomiting 47%/42% (P = 0.69); and mean leukocyte and lymphocyte counts 12,500/mm3 and 7600/mm3 (P < 0.0001) and 7800/mm3 and 3500/mm3 (P < 0.0001), respectively. Illness caused by B. parapertussis was typical of pertussis but less severe than that caused by B. pertussis. In contrast with B. pertussis infection, lymphocytosis is not a characteristic of B. parapertussis infection. This is most likely a result of the lack of production of lymphocytosis-promoting factor toxin by B. parapertussis.

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 diagnosis 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

Inzidenz und Symptomatik von hospitalisierten Gastroenteritiden in einer Kohorte von 10.271 Säuglingen und Kleinkindern

ZusammenfassungFragestellung: Eine prospektive Pertussisimpfstudie mit engmaschiger Überwachung des gesamten Kollektivs erlaubte uns, erstmals das Risiko von Säuglingen und Kleinkindern, wegen einer Gastroenteritis hospitalisiert zu werden, in einer umfangreichen Kohorte zu bestimmen. Methode: Die Kohorte aus 10.271 gesunden Kindern wurde, beginnend im Alter von 2–4 Monaten, über einen mittleren Zeitraum von 2,5 Jahren beobachtet (Gesamtbeobachtungsdauer 25.284 Jahre). Dabei wurden u.a. alle Krankenhausbehandlungen erfaßt. Ergebnisse: Bei 173 Kindern (1,7%) registrierten wir insgesamt 179 Gastroenteritisepisoden, die stationär behandelt wurden. Dies entspricht einer mittleren Inzidenz von 7,1/1000 Beobachtungsjahren mit einem Maximum von 11,2/1000 im 7. bis 12. Lebensmonat und einer Abnahme mit steigendem Lebensalter. Die beiden am häufigsten nachgewiesenen Erreger waren Rotaviren (34%) und Salmonellen (20%). Rotavirus-Infektionen traten gehäuft in der kalten Jahreszeit auf, die höchste Inzidenz lag bei Säuglingen im 7. bis 12. Lebensmonat. Die Symptomatik war geprägt von Enteritis (90%), Erbrechen (85%) und Zeichen der Dehydratation (58%). Demgegenüber trat der Großteil aller Salmonellosen in den Monaten Juli-September auf, mit einem Altersgipfel im 19. bis 24. Lebensmonat, charakterisiert durch Enteritis (92%), hohes Fieber (56%, >39°C) und erhöhte Werte des C-reaktiven Proteins (68%). Bei 5% bzw. 12% der wegen Rotavirus- bzw. Salmonelleninfektionen hospitalisierten Kinder war ein Fieberkrampf Anlaß für die Klinikeinweisung. Schlußfolgerung: Gastroenteritiden führen bei primär gesunden Kindern in den ersten Lebensjahren häufig zu Krankenhausbehandlungen. Rotaviren und Salmonellen sind dabei die prädominierenden Erreger.SummaryObjective: A pertussis vaccine efficacy trial included a prospective follow up of all hospitalizations involved. This allowed us to calculate the rates of hospitalization due to acute gastroenteritis in a large cohort of infants and children in Germany. Methods: 10271 healthy children were enrolled at the age of 2–4 months and followed up for a mean of 2.5 years. All hospitalizations during follow-up of the study were registered and letters of discharge from hospital in children with gastroenteritis were evaluated for the present analysis. Results: A total of 179 episodes of hospitalization due to a gastroenteritis were reported in 173 children (total observation years 25284). The mean calculated incidence was 7.1/1000 observation years, with a maximum of 11.2/1000 years in 7–12 month old children. Rotavirus and Salmonella spp. were the most frequently identified agents. Rotavirus infections were most prevalent during the cold season and the maximum incidence was between 7 and 12 months of age. Characteristic symptoms of rotavirus infections were diarrhea (90%), vomiting (85%) and signs of dehydration (58%). In contrast most Salmonella infections occurred between July and September with a peak between 19 and 24 months of age. Salmonella infections were characterized by enteritis (92%), high fever (56% >39°C) and significantly increased values for the c-reactive protein (68%). In this study rotavirus and Salmonella infections leading to hospitalization were associated with febrile seizures in 5% and 12% of cases, respectively. Conclusion: Gastroenteritis frequently leads to hospitalization in previously healthy infants and young children. Rotavirus and Salmonella spp. are the predominant causative agents.