Vaccine 28 (2010) 7215–7220
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Post-licensure comparison of the safety profile of diphtheria/tetanus/whole cell
pertussis/haemophilus influenza type b vaccine and a 5-in-1
diphtheria/tetanus/acellular pertussis/haemophilus influenza type b/polio
vaccine in the United Kingdom
Nick Andrews
a,*
, Julia Stowe
b
, Lesley Wise
c
, Elizabeth Miller
b
a
Statistics Unit, Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, United Kingdom
b
Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency, Centre for Infections, United Kingdom
c
Vigilance Risk Management of Medicines, Pharmacovigilance Risk Management Group, Medicines and Healthcare products Regulatory Agency, United Kingdom
article info
Article history:
Received 9 June 2010
Received in revised form 10 August 2010
Accepted 11 August 2010
Available online 26 August 2010
Keywords:
DTP
Acellular pertussis combinations
Safety
abstract
General practitioner consultation data were used to compare the reactogenicity in infants of a 5-in-1
acellular pertussis vaccine (DTaP
5
/Hib/IPV) introduced in the United Kingdom in 2004 to the 4-in-1 whole
cell-pertussis vaccine (DTwP/Hib) that it replaced. For each vaccine the incidence in the week following
vaccination was compared to other periods to obtain a relative incidence. A lower relative incidence of
crying, fever and local reactions was seen with DTaP
5
/Hib/IPV than DTwP/Hib. Although there were no
other significant differences between vaccines the relative incidence was significantly above one on the
day of vaccination for convulsions following DTwP/Hib and for apnoea/collapse following DTaP
5
/Hib/IPV.
© 2010 Elsevier Ltd. All rights reserved.
1. Introduction
In September 2004 a combined diphtheria, tetanus, 5 compo-
nent acellular pertussis, Haemophilus influenza type b, inactivated
poliovirus vaccine (DTaP
5
/Hib/IPV) manufactured by Sanofi Pas-
teur MSD (Pediacel
TM
) replaced the combined whole cell pertussis
(wP) containing DTwP/Hib vaccine formerly given for primary
immunisation with oral poliovirus vaccine in the United Kingdom
(UK). DTaP
5
/Hib/IPV is the acellular pertussis combination vaccine
of choice for the UK immunisation programme as it achieves a
satisfactory antibody response to the Hib component under the
accelerated UK primary schedule of 2/3/4 months [1], unlike some
other DTaP/Hib combination vaccines used in the UK [2,3]. Further-
more it contains five purified pertussis antigens—a formulation that
has been shown in clinical trials to provide protection equivalent
to that of the wP-containing vaccine previously used in the UK [4].
In a pivotal randomised trial that compared the immunogenic-
ity [1] and reactogenicity [5] profile of DTaP
5
/Hib/IPV with that of
the existing UK DTwP/Hib vaccine, local redness and swelling, and
common systemic symptoms, occurred at a significantly lower
rate after DTaP
5
/Hib/IPV. In the current study we have assessed
*
Corresponding author. Tel.: +44 020 8327 7419; fax: +44 020 8200 7868.
E-mail address: nick.andrews@hpa.org.uk (N. Andrews).
the impact that the reduction in common and generally mild
symptoms measured in clinical trials has on consultations for
suspected vaccine reactions seen in general practice. For this, the
General Practice Research Database (GPRD) was used to compare
the incidence of consultations for events compatible with a vaccine
reaction in children under 1 year of age in DTaP
5
/Hib/IPV and
DTwP/Hib vaccinated cohorts.
2. Methods
We identified consultations for events of interest and details
of vaccinations from the GPRD, which is one of the world’s largest
primary care databases [6]. It holds data on consultations, referrals,
prescriptions and vaccinations for over 3 million active patients in
practices throughout the UK (5.7% of the population). We selected
children in the GPRD whose practice record had an ‘acceptable’ sta-
tus and with an ‘up to standard’ date earlier than the child’s date
of birth. The ‘up to standard’ date is the date when the practice
complied with specific quality measures based on completeness,
continuity and plausibility in key areas. Acceptable status is given
to a patient when certain data quality conditions have been met,
such as no events recorded before birth date, age is less than 115
years and the gender field is completed. Children included in the
analysis were those born from January 2003 to March 2006 who
were registered from birth until the age of 12 months or death if
earlier. This gave an estimated cohort size of 121,700 children from
0264-410X/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2010.08.062