Reactogenicity of infant whole cell pertussis combination vaccine compared with acellular pertussis vaccines with or without simultaneous pneumococcal vaccine in the Netherlands

Abstract

Background In addition to the routine enhanced passive safety surveillance of the Dutch National Vaccination Programme, RIVM (National Institute for Public Health and the Environment) started a large questionnaire study enrolling approximately 53,000 children from December 2003 until September 2007. Aim We intended to establish accurate frequency estimates for several more severe adverse events and to compare the incidence rates of three different infant vaccines that were used consecutively. Methods Whole cell pertussis (wP) DTP-IPV-Hib vaccine (NVI) was replaced by acellulair pertussis (aP) in 2005, first Infanrix-IPV-Hib (GSK) followed by Pediacel (Sanofi) in 2006. Pneumococcal vaccine, Prevenar (Wyeth), was added for children born from April 2006. Results Parents returned 28,796 questionnaires (response 54%), 15,069 for whole cell pertussis and 13,727 for acellular pertussis vaccine, including 4485 with pneumococcal vaccine. The OR for reported events was 3–6 for whole cell pertussis vaccine compared with acellular vaccine. This was true for prolonged crying for 3 h and more after the first dose (1.5% versus 0.4%; 95 CI 1.1–1.9 and 95% CI 0.2–0.7, respectively), and very high fever of 40.5 °C and over following the fourth dose (0.8% versus 0.2%; 95% CI 0.5–1.1 and 0.06–0.3, respectively), while possible febrile convulsions were diagnosed only twice after the fourth dose in the whole cell vaccine group and one after acellular pertussis vaccine. Pallor was significantly more frequent after the first dose of whole cell pertussis than after acellulair pertussis vaccination (18.3% versus 3.4%; 95% CI 17.2–19.5 and 95% CI 2.8–4.0 respectively) Collapse after the first dose was rare in both vaccine groups (5 after whole cell vaccine and 1 after acellular vaccine). The addition of conjugated pneumococcal vaccine did not result in statistically significant increased rates of adverse events in the acellular vaccine group. Conclusion Whole cell pertussis vaccine showed a significantly higher reactogenicity regarding the adverse events analysed, while addition of conjugated pneumococcal vaccine administered simultaneously with acellular pertussis showed no statistically different adverse event profile.