4.

IMMUNIZATION STRATEGIES FOR PERTUSSIS

Pertussis Immunization in the Global Pertussis Initiative

European Region
Recommended Strategies and Implementation Considerations
Carl-Heinz Wirsing von König, MD,* Magda Campins-Marti,† Adam Finn, MD, PhD, Nicole Guiso,
Downloaded from https://journals.lww.com/pidj by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3tjcLwhL8g9bZhhig7WeJvugqboFLYwIlGE8McW184GwtaVCIsU6ySw== on 04/29/2019

PhD, Jussi Mertsola, MD,¶ and Johannes Liese, MD, MSc㛳

Key Words: Bordetella pertussis, pertussis, immunization,

Abstract: Approaches to pertussis diagnosis, surveillance and im-
munization vary widely across Europe. Nonetheless most countries
report high levels of vaccine coverage in infants and toddlers, and
significant reductions in infant morbidity and mortality have been
achieved. As a consequence of the effective protection of infants and
toddlers, the absolute incidence of pertussis has substantially de-
creased, but the relative proportion of older age groups, adolescents
and adults in particular, has increased. These groups, however, are a
relevant source of infection of unimmunized or incompletely immu-
nized infants. In addition to efficient childhood vaccination, other
approaches to pertussis immunization are required. Among the
various strategies evaluated, 3 were recommended by the European
participants in the Global Pertussis Initiative that might be adapted
to each country’s specific needs: the reinforcement of implementa-
tion of current schedules, the addition of an extra dose of vaccine to
current immunization schedules and the selective immunization of
health care workers, which is already included in a European
Commission directive. The main barriers to the acceptance of these
strategies are low awareness of pertussis in immunized populations,
poor recognition of the disease in adults and adolescents, lack of
standardized diagnostic criteria and poor access to laboratory con-
firmation of the diagnosis. These obstacles have led to underreport-
ing of pertussis and an underestimation of the disease burden.
Actions to overcome these issues are crucial to the implementation
of new or improved immunization strategies to combat pertussis in
Europe.
From the *Institut fur Hygiene und Laboratoriumsmedizin, Klinikum
Krefeld, Krefeld, Germany; the †Department of Preventive Medicine and
Epidemiology, Vall d’Hebron Hospital, Barcelona, Spain; the ‡Institute
of Child Health, UBHT Education Centre, Bristol, United Kingdom; the
§Department of Ecosystems and Epidemiology of Infectious Diseases,
Institut Pasteur, Paris, France; 㛳Universitäts-Kinderklinik, Dr. v. Haun-
ersches Kinderspital, München, Germany; and the ¶Department of Pedi-
atrics, Turku University Central Hospital, Turku, Finland
Address for correspondence: Institut fur Hygiene und Laboratoriumsmedi-
zin, Klinikum Krefeld, Lutherplatz 40, D-47805 Krefeld, Germany Fax
49-2151-32-2079. E-mail: wvk-hyg@klinikum-krefeld.de.
Copyright © 2005 by Lippincott Williams & Wilkins
ISSN: 0891-3668/05/2405-0087
DOI: 10.1097/01.inf.0000160920.75623.a3
adolescents, health care workers, Europe
(Pediatr Infect Dis J 2005;24: S87–S92)
A n accurate picture of the epidemiology of pertussis in
Europe is difficult to obtain because procedures for
diagnosing and reporting cases of pertussis disease vary
widely across Europe. Nevertheless some general epidemio-
logic trends have emerged. For example, the incidence of
pertussis increased in the 1990s in Finland,1 France,2 Spain,3
the Netherlands4 and the United Kingdom.5 Peak incidence
also shifted from infants to older age groups, such as school
age children and adults, in Finland,1 France,6 The Nether-
lands4 and Israel.7 In contrast, in the past decade, there has
been an increase in infant morbidity and mortality caused by
pertussis disease in France and the United Kingdom, possibly
as the result of increased parent-to-infant transmission, al-
though the incidence of the disease remains low.8,9 These
variations in incidence may be the result of the different
pertussis immunization schedules in each country.
In 2001, the Global Pertussis Initiative (GPI) was
established as an expert scientific forum to analyze the status
of pertussis disease globally and to evaluate various immu-
nization strategies to improve disease control. GPI partici-
pants from Europe considered strategies to improve disease
control and reduce the morbidity and mortality in unimmu-
nized or incompletely immunized infants.10 The initiative
participants have made recommendations to address specific
problems and explore the potential barriers to the implemen-
tation of such plans, and it is hoped that the appropriate
authorities may consider these recommendations.
CURRENT IMMUNIZATION SCHEDULES
Details of the current immunization schedules for Euro-
pean countries are outlined in Table 1. All the European coun-
tries represented on the GPI offer an initial course of 3 doses of

The Pediatric Infectious Disease Journal • Volume 24, Number 5, May 2005 S87
Wirsing von König et al The Pediatric Infectious Disease Journal • Volume 24, Number 5, May 2005

TABLE 1. Current Pertussis Immunization Schedules in Europe

Country Primary Series (Age, Vaccine) Boosters Coverage

Austria 2, 3, 4 mo DTaP-IPV-Hib-HB 13–18 mo DTaP-IPV-Hib-HB

14 –15 yr dTaP-IPV
Every 10 yr dTaP-IPV
Belgium* 2, 3, 4 mo DTaP-IPV-Hib 13–18 mo DTaP-IPV-Hib
5– 6 yr DTaP-IPV
Denmark 3, 5, 12 mo DTaP-IPV 5 yr DTaP-IPV
Finland* 3, 4, 5 mo DTwP 20 –24 mo DTwP 98% (4th dose)
6 yr DTaP
France* 2, 3, 4 mo DTaP-IPV-Hib or DTwP- 16 –18 mo DTaP-IPV-Hib 97% (3 doses and 87% (4 doses)
IPV-Hib
11–13 yr DTaP-IPV or dTaP-IPV
No data available yet, but ⬃50%
according to manufacturers
Germany* 2, 3, 4 mo DTaP-IPV-Hib-HB 11–14 mo DtaP-IPV-Hib-HB ⬎90% (primary series)
9 –17 yr dTaP or dTaP-IPV ⬍10% (final booster)
Greece 2, 4, 6 mo DTwP or DTaP 18 mo DTwP or DTaP-Hib
(DTaP-Hib at 6 mo) 4 – 6 yr DTaP or DTwP
Iceland 3, 5, 12 months DTaP-IPV 5 yr DTaP
Ireland 2, 4, 6 months DTaP-IPV-Hib 4 –5 yr DTaP-IPV
Israel* 2, 4, 6 months DTaP 12 mo DTaP ⬎90% (all 4 doses)
Italy* 2, 4, 10 months DTaP-IPV-Hib-HB 5– 6 yr DTaP ⬎90%
Luxembourg 2, 3, 4 months DTaP-IPV (DTaP-Hib- 11–12 mo DTaP-Hib-IPV
IPV at 3 months)
The Netherlands* 2, 3, 4 months DTwP-IPV-Hib 11 mo DTwP-IPV-Hib ⬎95% (primary series)
4 yr DTaP-IPV
Norway 3, 5, 11 months DTaP-IPV
Portugal 2, 4, 6 months DTwP 15–18 mo DTwP
5– 6 yr DTaP
Spain* 2, 4, 6 months DTaP-Hib or DTwP-Hib 15–18 mo DTaP-Hib or DTwP-Hib ⬎90% (primary series)
4 – 6 yr DTaP No data available for booster
coverage at 4 – 6 years
Sweden* 3, 5, 12 months DTaP-IPV-Hib ⬎98% (primary series)
Switzerland* 2, 4, 6 months DTaP-IPV-Hib 15–24 mo DTaP-IPV-Hib ⬎95% (primary series)
4 –7 yr DTaP-IPV
11–15 yr dTaP if 4th and/or 5th
dose missed
United Kingdom 2, 3, 4 mo DTaP-IPV-Hib 3–5 yr DTaP-IPV ⬎90% (primary series)
*Countries represented on the GPI.
DTaP, diphtheria, tetanus and acellular pertussis vaccine;
DTwP, diphtheria, tetanus and whole cell pertussis vaccine;
dTaP, diphtheria (low dose), tetanus and acellular pertussis vaccine;
IPV, inactivated polio vaccine;
Hib, Haemophilus influenzae type B vaccine;
HB, hepatitis B vaccine.

a combined diphtheria, tetanus, and either acellular per-
tussis (DTaP) or whole cell pertussis vaccine that is
administered between the ages of 2 and 12 months. With
the exception of Italy, Sweden and the United Kingdom,
they also offer a further dose between the ages of 11 and
24 months. Some countries also recommend a fourth or
fifth vaccine dose as a preschool booster for children 3– 6
years of age (Belgium, Italy, The Netherlands, Spain,
Switzerland and the United Kingdom) or an adolescent
booster for children ⬃11–18 years of age (Austria, France
and Germany). Austria also recommends that adults be
immunized every 10 years using a combined dTaP-inacti-
vated poliovirus vaccine (IPV) vaccine, although no cov-
erage data for adults are available and adult immunization
is not binding across Europe.
The immunization programs used in Europe are ef-
fective and generally achieve in excess of 90% coverage of
the infant population with the first 3 doses of vaccine. Such
programs have proven successful in significantly reducing
infant morbidity and mortality caused by pertussis.11 How-
ever, recent increases in the incidence of the disease and
the apparent shift in some countries toward older age
groups (school age children, adolescents and adults) sug-
gest that new approaches are needed (and are already
recommended in some countries) to improve pertussis
control and develop herd immunity to protect unimmu-
nized or incompletely immunized infants, who are at risk
for complications and death.4 Given the particular prob-
lems in each country and the wide variation in approaches
to childhood immunization, no single pan-European im-
munization schedule to combat pertussis disease is likely
to be acceptable in all countries. Nevertheless broad strat-
egies to reduce the impact of the disease could be adapted
to each country’s specific needs.

S88 © 2005 Lippincott Williams & Wilkins

The Pediatric Infectious Disease Journal • Volume 24, Number 5, May 2005
RECOMMENDED STRATEGIES TO OVERCOME
PERTUSSIS IN YOUNG INFANTS
Of the strategies evaluated by the European GPI par-
ticipants, the following were considered the most appropriate
recommendations for countries that are not already imple-
menting these approaches: reinforcement of the implementa-
tion of current immunization schedules; the administration of
an extra dose of vaccine to children of preschool age (4 – 6
years) or adolescents, depending on the country; and selective
immunization of health care workers (in accordance with EC
Directive 2000/54/EC).12
Other groups of adults that might be targeted in the
future include new mothers, child care workers, young adults
and close contacts of newborns, if data can be obtained on the
incidence of pertussis in these age groups and the role that
these groups play in the transmission of pertussis to infants.
The selected strategies are discussed in more detail in
this article, as are the possible obstacles to their implemen-
tation. Other strategies evaluated by the GPI participants and
those recommended by the North American and international
regions are described elsewhere in this issue.10,13,14
Reinforcing Current Immunization Schedules. In conjunction
with wider immunization strategies, the reinforcement of
ongoing programs will have a significant benefit in reducing
infant morbidity and mortality caused by pertussis and in
maintaining herd immunity, as had been demonstrated in
Germany.15 All the countries represented on the GPI have
effective childhood immunization programs in place, which
have significantly reduced the incidence of pertussis in in-
fants and toddlers and thus led to decreased awareness of the
disease by vaccinating pediatricians or general practitioners.
Therefore maintenance of these programs is proving difficult
in some European countries.
An Additional Vaccine Dose. To overcome the problem of
waning vaccine-induced immunity to Bordetella pertussis in
children and adolescents, a logical strategy for many Euro-
pean countries would be to add an extra vaccine dose to their
existing schedules, either in preschool children at the age of
4 – 6 years or in adolescents, depending on the current sched-
ule in each country.16 –20
The preschool booster is a good opportunity to ensure
that children are adequately immunized before entering
school, and many European countries already implement this
strategy.
An alternative approach has been taken in France and
Germany, where adolescents are offered a booster dose of
dTaP-IPV or DTaP-IPV vaccine and no preschool pertussis
booster is given. If it could be demonstrated that the adoles-
cent immunization in these countries induces a reduction in
pertussis morbidity in adolescents and if it also reduces infant
morbidity and mortality through reduced transmission, it
© 2005 Lippincott Williams & Wilkins
European Immunization Strategies
could help to facilitate the introduction of adolescent immu-
nization in other countries.21
Selective Immunization of Health Care Workers. Certain
groups of adults who are at a relatively high risk for infection,
such as health care workers, might be protected from pertus-
sis and therefore also prevented from transmitting the disease
to other adults and unimmunized or incompletely immunized
infants. Health care workers in pediatric and emergency
departments, in particular, are important targets for this strat-
egy.
EC Directive 2000/54/EC already strongly encourages
European Union (EU) countries to protect health care work-
ers through immunization.12 The Directive requires health
care workers to be offered immunization against any disease
for which an effective vaccine is available, which includes
pertussis. However, individuals can choose whether or not
they receive immunization, and experience suggests that
health care workers are unwilling to comply with recom-
mended immunizations for influenza immunization,22 despite
proven benefits to workers and patients. Thus far, the Direc-
tive has been implemented only in Germany, since July 2001.
The recent German recommendations (July 2003)23 suggest
that health care workers in pediatric departments, those car-
ing for pregnant women, those working in obstetrics and
child care workers be immunized once with an acellular
vaccine against pertussis. Although the EU implemented the
immunization of health care and child care workers as a
measure of its occupational health legislature, the implemen-
tation is also being monitored in respect to pertussis epide-
miology. However, it is too soon to be able to confirm the
effects of this strategy in terms of morbidity among health
care workers or transmission to infants. Despite this, the GPI
participants believed that it is important for this strategy to be
implemented throughout Europe, given that countries that do
not plan to implement the Directive will need to explain their
reasons to the EU authorities.
POTENTIAL OBSTACLES TO IMPLEMENTING
RECOMMENDED STRATEGIES
Access to Target Populations. Access to the target popula-
tions can generally be obtained relatively easily, depending
on the population being targeted. There will, however, be
differences between countries.
Existing infant immunization programs could be given
in a more timely fashion, to avoid postponing immunization
due to the wrong contraindications. For the adolescent pop-
ulation, diphtheria-tetanus or diphtheria-tetanus-IPV boosters
are recommended in many countries, and pertussis immuni-
zation could thus be introduced with relative ease, as is
already the case in Austria, France and Germany. However,
the vaccine coverage in these populations varies markedly.
For health care workers, existing occupational health pro-
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Wirsing von König et al The Pediatric Infectious Disease Journal • Volume 24, Number 5, May 2005
grams (ie, hepatitis B) can be used to meet the current
requirements of EC Directive 2000/54/EC.
Availability of Appropriate Vaccines. Because most Euro-
pean countries already implement childhood immunization
programs (Table 1), access to appropriate infant vaccines is
good. Two pertussis combination vaccines, with low dosage
tetanus and pertussis components, are available in many
European countries for use in adolescents and adults. The
availability of appropriate vaccines will therefore not hinder
the implementation of the strategies of giving an extra dose to
children or adolescents or of immunizing health care workers.
However, the availability of both combined and standalone
pertussis vaccines would ensure that all groups can be fully
immunized: some health care workers and adolescents, for
example, might already have full diphtheria, tetanus and polio
immunization histories and require only the acellular pertus-
sis (aP) booster. Additionally many adults do not know their
full immunization history.
Availability of Appropriate Delivery Infrastructures. Immu-
nization programs are operated in Europe through various
delivery channels. School immunization programs are an
efficient way of immunizing children and adolescents, and
the target population can be accessed easily. Where immuni-
zation programs do not exist in schools, public health services
should take action to introduce or reintroduce them. In many
countries, however, immunization programs are based on
individual pediatricians and/or general practitioners and the
political direction seems to favor these routes of immuniza-
tion.
Because health care workers in several European coun-
tries (including France, Germany and the United Kingdom)
already receive other immunizations via occupational health
programs, including immunizations against diphtheria, teta-
nus, influenza and hepatitis, the addition of a pertussis im-
munization would be relatively simple. However, vaccine
coverage in health care workers is generally very low; it is
important to obtain a better understanding of the reasons for
this, to ensure that immunization is successful.
Diagnosis and Surveillance. The typical form (paroxysmal
cough, whoop and posttussive vomiting) of pertussis is now
less common than the atypical form (mild or severe, persis-
tent cough), which usually affects adolescents and adults. As
a result, diagnosis can no longer rely on the clinical signs and
symptoms and needs laboratory confirmation.
Polymerase chain reaction and enzyme-linked immu-
nosorbent assay (ELISA) techniques are now widely avail-
able. However, neither polymerase chain reaction techniques
nor the various ELISAs are standardized. For ELISA stan-
dardization, an international reference serum for serology is a
prerequisite.
Diagnosis with the use of ELISA can be made with
sufficient specificity with a single sample assay.24 –26 Sample
collection techniques, particularly sample collection from
S90
infants, must also be standardized, because poor sampling
technique and sample storage can affect the results of labo-
ratory analysis.27
Accurate surveillance studies require health care pro-
fessionals to be aware of pertussis disease. In particular,
health care professionals must be more aware of the disease
in adults and have a higher index of suspicion for the disease
when patients present with either typical or atypical symp-
toms. Health professionals must also be more aware of the
laboratory techniques available to confirm the diagnosis of
pertussis and should have ready access to such techniques.
Surveillance would be significantly improved with
mandatory registration of vaccine distribution and adminis-
tration, passive and active safety surveillance and monitoring
of vaccine uptake in infants, children and adults. Vaccine
registries are already in place in some countries such as
France and the United Kingdom.
Resources, the Health Care Agenda and Policy Makers. The
implementation of strategies to extend immunization pro-
grams primarily needs enough data for policy makers to
demonstrate the benefits of a new strategy and the need for
additional funding.
Regarding the addition of an extra dose in preschool
children or adolescents, vaccine efficacy and cost effective-
ness data from countries where these strategies are already in
place will help to convince decision makers in other Euro-
pean countries of the benefits of a booster dose. One U.K.
study has predicted that the introduction of an aP booster at
the age of 4 years will reduce morbidity and mortality in the
younger age groups by 40 –100%28; however, the United
Kingdom does not give a booster dose during the second year
of life.
EU policy makers are already convinced of the need to
protect health care workers from vaccine-preventable dis-
eases, including pertussis.12 In Germany, health care workers
undergo pertussis immunization; data confirming the effec-
tiveness of this strategy in terms of reducing morbidity
among this group of people and in reducing transmission to
infants may help to convince other European countries to
institute similar programs.
Health insurance and reimbursement systems vary from
country to country in Europe, and decisions on funding will
be made at the country or regional level. However, robust
epidemiologic and health-economic data on the effects of
adding an extra dose of vaccine to current childhood immu-
nization schedules (eg, data on adolescent immunization from
Austria, France and Germany) may help support the intro-
duction of an additional booster dose, although direct com-
parisons will be difficult because immunization schedules
vary between countries.
Under the EC Directive, vaccines must be offered free
of charge to health care workers. The cost of immunizing
health care workers is expected to be met by employers
© 2005 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 24, Number 5, May 2005
because this approach is seen as protecting workers from
occupational hazards.
Other costs must also be taken into account. For exam-
ple, in the United Kingdom, a system of financial incentives
has encouraged general practitioners to effect childhood im-
munizations and has improved the coverage and success of
these programs. The addition of an extra dose could also
increase the cost of these incentives. In other countries, the
cost of setting up school-based adolescent immunization must
also be met, as must the cost of health education campaigns
to support the new strategies.
Improving Education and Awareness. Health care profession-
als, including physicians, nurses and midwives, are particu-
larly influential with respect to childhood immunization and
are therefore important targets for education and awareness
campaigns. These groups will need to understand the benefits
of an extra dose of vaccine not only for their patients but also
for themselves. Education and awareness programs should
also extend to improving the diagnosis of pertussis.
Across Europe, antivaccine campaigners have a strong
presence; clear and simple education programs are needed to
counter unfounded antivaccine claims and highlight the con-
tinuing problems associated with pertussis, to persuade public
and health professionals of the benefits of immunization.29
RESEARCH NEEDED TO SUPPORT
RECOMMENDED STRATEGIES
Data on Current Immunization Programs. Although many
European countries operate systems to monitor the coverage
of national immunization programs, little official information
is available on adherence to immunization schedules, such as
the number of infants who are immunized at the ages recom-
mended, or on local obstacles to immunization, such as social
deprivation and religious or other philosophical opposition to
immunization.29 Such information would be useful in guiding
the development of local immunization strategies and would
provide valuable baseline data for comparison.
Transmission Studies. Because of the differences in immuni-
zation schedules and organization of child care across Eu-
rope, a key area for research is investigations into the trans-
mission of pertussis to young infants by specific groups
(adolescents and adults in general and more specifically
health care and child care workers, parents and other close
contacts of young infants).
Sudden Infant Death Syndrome (SIDS) Studies. Given that
pertussis may contribute to SIDS mortality,30,31 it would also
be useful to try including pertussis diagnosis in ongoing SIDS
studies in the various countries.
Diagnosis and Surveillance. Other areas that would benefit
from new or more comprehensive data are the clinical and
laboratory diagnosis of pertussis and surveillance of the
disease. Such information would enable a more accurate
© 2005 Lippincott Williams & Wilkins
European Immunization Strategies
picture of the extent of the morbidity caused by pertussis to
be produced. In particular, studies in adults and adolescents,
in whom underreporting is most common, are warranted to
assess and raise awareness of the need for immunization in
these groups. Studies addressing these problems are ongoing,
with very different study designs, in Sweden, France and
Germany.
Vaccine Effectiveness and Safety Studies. It would be desir-
able to obtain data on the effectiveness of vaccines to reduce
not only clinical disease but also transmission.32 The duration
of protection induced by the different vaccines should also be
clarified, as should the reactogenicity of repeated doses of
vaccine. Based on the results of these studies, further research
can be conducted into the interval of administration of aP
boosters, in addition to the safety of repeated aP vaccine
doses. Because of the demonstrated long term effectiveness
of the acellular vaccines,33,34 the feasibility of eliminating a
vaccine dose between infancy and adolescence could also be
studied, to address the potential problem of increased reac-
togenicity with multiple vaccine doses. The possibility of
immunizing pregnant women in the third trimester could also
be considered (although there are ethical issues associated
with immunizing pregnant women), as should immunization
of infants immediately after birth with a standalone aP vac-
cine or a combined aP-hepatitis B vaccine. The impact of
bacterial polymorphisms on the effectiveness of aP vaccines
should be continually monitored in all countries.
CONCLUSION
A combination of strategies to reinforce the implemen-
tation of current childhood immunization programs, increase
the number of vaccine doses given in childhood and adoles-
cence and target specific groups of high risk adults is cur-
rently considered to be the first step to reduce morbidity and
mortality caused by pertussis in young infants and reduce the
health burden in older age groups because of waning immu-
nity. In particular, it is hoped that these strategies will
increase herd immunity among adults and adolescents. Sev-
eral countries have recently expanded their immunization
programs. Austria, France and Germany now offer an ado-
lescent pertussis booster. Austria also recommends that adults
be immunized every 10 years with a combined aP vaccine.
Various obstacles must be addressed to support the
implementation of these strategies, including low awareness
of pertussis disease in adults and adolescents, inconsistent
diagnostic criteria and poor access to standardized laboratory
techniques to confirm the diagnosis. It is currently difficult to
obtain an accurate picture of the epidemiology of pertussis
disease in Europe, or of the effectiveness and cost benefits of
particular immunization schedules. Therefore epidemiologic
studies of the true extent of the morbidity and mortality
caused by pertussis disease and its effects are a top priority.
Cost effectiveness data on the results of adolescent immuni-
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Wirsing von König et al The Pediatric Infectious Disease Journal • Volume 24, Number 5, May 2005
zation in Austria, France and Germany will also be valuable
in establishing expanded immunization strategies in other
European countries.
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