Haemophilus influenzae type b
vaccinebooster campaign
Hib exemplifies need for continued surveillance after
changesin vaccines
The chief medical officer has recently recommended that all
children in the United Kingdom aged 6 months to 4 years should
receive a single dose of Haemophilus influenzae type b vaccine.This is in response to a rise in the incidence of Hib disease
over the past four years. The reasons for the increase arecomplex,
but evidence points strongly to an effect of a temporary change to the use of a
Hib vaccine combined with diphtheria,tetanus, and acellular
pertussis (DTaP).
Before the Hib conjugate vaccine was introduced in 1992, Hibwas
the most common cause of bacterial meningitis in children.Rapid
control of Hib disease was achieved by combining routineinfant
immunisation at 2, 3, and 4 months of age with a catch-upprogramme
for children aged up to 4 years. Initially Hib vaccinewas given as a
separate injection, but in 1996 a combined DTP-Hib vaccine was introduced.
Uptake of the vaccine was high, andthe number of confirmed cases of
type b infection fell from855 in 1992 to 37 in 1998, but since 1999
a steady increasein cases has been seen (figure).
An analysis of Hib disease over the past 10 years shows a significant decline
in protection from the first two years after vaccinationin infancy.1 On the basis of this observation an increase
in cases might be expected in older children, but in 2002 themajor
increase was in vaccinated children between 1 and 2 yearsof age.2 The excess of younger cases in 2002 is consistentwith the observation of a lower level of protection for the
2000-1 birth cohort.1 A shortage of DTP-Hib
containing wholecell pertussis in late 1999 meant that another
vaccine wasrequired to ensure supply during 2000 and 2001. The
vaccineused was a Hib conjugate combined with DTP containing
acellularpertussis which, like the whole cell preparation, was givenas a single injection. Previous studies with this and most
other Hib combination vaccines containing acellular pertussishad
shown Hib antibody concentrations that were lower than expected.3 Licensure was permitted because of laboratory evidenceof high antibody quality and immunological memory,3
and these vaccines were being used successfully in a number of other countries.Further analysis of data from the United Kingdom has showna
significant association between receipt of vaccines containing
acellular pertussis and invasive Hib disease.4
Our experienceimplies that, at least at the schedule used in the
United Kingdom, the lower immunogenicity of such combinations is clinicallyrelevant.
The new campaign should have a rapid effect on Hib disease,and
the use of the whole cell pertussis DTP-Hib vaccine hasbeen resumed.
Global supplies of such vaccines have, however,fallen in recent
years, and large pharmaceutical companiesare expressing less
enthusiasm for continuing production. Howcould the United Kingdom
therefore use acellular pertussisvaccines without jeopardising the
control of Hib?
Three approaches are possible. One would be to offer Hib asa
separate injection. Although three injections at each visitmay be
acceptable as new vaccinessuch as pneumococcalconjugatescome into
routine use, novel combinationswill be required. One such
combination would be a meningitisvaccine, which includes Hib, MenC,
and pneumococcal conjugates,but this will also have potential for
immunological and chemicalinteractions, and studies adhering to the
schedule used inthe United Kingdom will be needed. All acellular
pertussisvaccines do not behave in the same way, and there is
evidencethat a five component acellular pertussis vaccine that usesa different adjuvant may be less likely to have a suppressive
effect in combination with Hib vaccine.5 Use of
this particularDTaP-Hib combination vaccine may be a second option.
Other conjugate vaccines given simultaneously but separately may also
influence Hib antibody concentrations, depending on which carrier
protein they use.6
The relatively small gap between vaccines in the schedule usedin
the United Kingdom results in a lesser, although usuallyadequate,
immunological response compared with schedules withlonger intervals.
There is evidence that the effect of acellularpertussis on Hib
combinations is less dramatic when more extendedschedules are used.7 The third option therefore may be toreview
the schedule used in the United Kingdom. Examples ofHib schedules
currently used in other industrialised countries include extended three dose
schedules (for example, at 3, 5,and 12 months of age) or three dose
accelerated schedules followedby a booster in late infancy or in the
second year of life (www.phls.org.uk/inter/eu_ibis/hib19992000.pdf).
Other relevantconsiderations include ensuring control of early
pertussis and preservation of high vaccine coverage, both reasons for theinitial adoption of the current schedule used in the United
Kingdom.
A different approach includes the one currently being useda
catch-up campaign. In many developing countries regular mass
campaigns have been effective in controlling poliomyelitisand have
also been used for measles.8 Mathematical modelsof Hib transmission may help in deciding whether this optionis
feasible. Our experience emphasises the importance of continuedhigh
quality surveillance for vaccine preventable diseaseseven long after
their apparent control. Such surveillance isincreasingly critical
after the introduction of new vaccines,vaccine combinations, or new
formulations and will help toinform the best future strategy for the
control of vaccine preventable diseases.
Paul T Heath, consultant in paediatric infectious
diseases
Vaccine Institute and Department of Child Health, St George's
Hospital Medical School, London SW170RE (pheath@sghms.ac.uk)
Mary E Ramsay, consultant epidemiologist
Immunisation Division, Health Protection Agency Communicable
Disease Surveillance Centre, London NW9 5EQ
We wish to acknowledge the contributions of colleagues to thiseditorial through a recent meeting held under the auspicesof
the Royal College of Paediatrics and Child Health Immunisationand
Infectious Disease Standing Committee.
Competing interests: PH and MR have received research grantsand reimbursements for attending symposiums from vaccine manufacturersincluding Aventis Pasteur and Glaxo SmithKline. PH has received
fees for consulting from Glaxo SmithKline.
References
Ramsay ME, McVernon J, Andrews N, Heath PT, Slack MPE.
Estimating Hib vaccine effectiveness in England and Wales using the
screening method. J Infect Dis (in press).
Trotter CL, Ramsay ME, Slack MPE. The epidemiology of
Haemophilus influenzae type b disease in England and Wales, 1990-2002.
Commun Dis Public Health 2003;6: 55-8.
Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist C.
Combined vaccination of Haemophilus influenzae type b conjugate and
diphtheria-tetanus-pertussis containing acellular pertussis. Lancet
1999;354: 2063-8.[CrossRef][ISI][Medline]
McVernon J, Andrews N, Slack MPE, Ramsay ME. Risk of vaccine
failure after Haemophilus influenzae type b (Hib) combination vaccines
with acellular pertussis. Lancet 2003;361: 1521-3.[CrossRef][ISI][Medline]
Mills E, Gold R, Thipphawong J, Barreto L, Guasparini R,
Meekison W, et al. Safety and immunogenicity of a combined five-component
pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus b
conjugate vaccine administered to infants at two, four and six months of
age. Vaccine 1998;16: 576-85.[CrossRef][ISI][Medline]
Dagan R, Eskola J, Leclerc C, Leroy O. Reduced response to
multiple vaccines sharing common protein epitopes that are administered
simultaneously to infants. Infect Immun 1998;66: 2093-8.[Abstract/Free Full Text]
Vidor E, Hoffenbach A, Fletcher MA. Haemophilus influenzae
type b vaccine: reconstitution of lyophilised PRP-T vaccine with a
pertussis-containing paediatric combination vaccine, or a change in the
primary series immunisation schedule, may modify the serum anti-PRP
antibody responses. Curr Med Res Opin 2001;17: 197-209.[CrossRef][ISI][Medline]
Global measles mortality reduction and regional elimination.
2000-1. Wkly Epidemiol Rec 2002;77: 50-5.
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information, data, and material contained, presented, or provided here is for
general information purposes only and is not to be construed as reflecting the
knowledge or opinions of the publisher, and is not to be construed or intended
as providing medical or legal advice. The decision whether or not to vaccinate
is an important and complex issue and should be made by you, and you alone, in
consultation with your health care provider.
"A foolish faith in authority is the worst enemy of truth."
-- Albert Einstein, letter to a friend, 1901
"I know of no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."
-- Thomas Jefferson, letter to William C. Jarvis, September 28, 1820
"What's the point of vaccination if it doesn't protect you from the unvaccinated?"
-- Sandy Gottstein
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