http://www.health.gov.au/tga/docs/html/aadrbltn/aadr0108.htm#dtpa
The replacement of the
whole cell pertussis antigens (Pw) with acellular pertussis antigens (Pa) in
the combination diphtheria, tetanus and pertussis vaccines (DTPa) (Infanrix,
Tripacel) has been an important recent development. Clinical studies have shown
that DTPa causes fewer worrying reactions like inconsolable crying, high
fevers, hypotonic-hyporesponsive episodes and convulsions than DTPw.
As clinical experience with
the use of DTPa-containing vaccines has grown, it has been observed that there
is an increase in the rate of occurrence and severity of injection site
reactions with each successive dose.1 The fourth and fifth doses of
DTPa sometimes cause extensive limb swelling which may be associated with
redness and pain. These booster doses are recommended at 18 months (fourth
dose) and four years (fifth dose) in Australia and may be given into the arm or
the thigh. Of the 331 Australian reports of suspected adverse reactions to DTPa
vaccines received by ADRAC between late November 1997 and mid-June 2001, 103
described injection site reactions in children aged 18 months or older. In
contrast, only 37 described similar reactions in younger children. Of the 103
reports in the older children, forty-eight described extensive limb swelling or
included measurements of the swelling with at least one dimension greater than
10 cm. Descriptions like "swollen, red, hot from groin to ankle" and
"arm swollen from elbow to shoulder" are typical. Based on the
children's ages, 37 of the reports are likely to relate to a fourth dose of
DTPa and 11 to a fifth dose. The possibility of these reactions is mentioned in
the Australian product information for the vaccines.
This reporting needs to be
seen in the context of approximately 250,000 Australian children being eligible
each year to be given either a fourth or fifth dose of DTPa. The estimated
frequency of extensive limb swelling after booster doses of DTPa is about 2 %.1
The frequency with which extensive limb swelling was encountered with whole
cell pertussis-containing vaccines (DTPw) is less well documented as booster
doses were introduced in many countries without prior clinical studies, but in
one recent study was also 2%.2 Extensive local reactions involving most of the
upper arm or thigh have also been described following booster doses of
diphtheria-tetanus vaccine (DT) which does not contain pertussis.2
It has been proposed that DTPa-associated extensive limb swelling reactions
occur more commonly with those vaccines which contain larger amounts of
diphtheria antigens, but further study is needed.
In the forty-eight reports
to ADRAC of extensive limb swelling reactions to DTPa, the outcome was
"unknown" for 7 reports and "not yet recovered" for 14
reports. In all the other reports the child was said to have recovered without
sequelae. This is consistent with a published report of twenty cases of such swelling,
all of which subsided spontaneously, completely and without sequelae.1
To date there is insufficient information available about whether a child who
has experienced extensive limb swelling after the fourth dose of DTPa would be
likely to have a similar reaction to a fifth dose at four years of age.
DTPa generally causes far
fewer local reactions than DTPw, but extensive limb swelling seems to occur
with both vaccines with equal frequency. Parents should be warned of this
possible adverse reaction. As the swelling resolves without sequelae, and
pertussis continues to circulate in the community, it is recommended that a
child who develops extensive limb swelling after a fourth dose of DTPa be
offered a fifth dose of DTPa, with appropriate informed parental consent. This
recommendation is endorsed by the Australian Technical Advisory Group on
Immunisation (ATAGI).
References:
1. Rennels MB, Deloria MA,
Pichichero ME et al. Extensive swelling after booster doses of acellular
pertussis-tetanus-diphtheria vaccines. Pediatrics 2000; 105: e 1 - e 12.
2. Miller E, Rush M, Ashworth LAE et al. Antibody responses and reactions to
the whole cell pertussis component of a combined diphtheria/tetanus/pertussis
vaccine given at school entry. Vaccine 1995; 13: 1183-86.