Introduction
Pneumococcal (Pnc) disease is caused by the bacterium Streptococcus pneumoniae
of which more than 90 serotypes are now recognised. Pnc is an important
cause of morbidity and mortality in Europe [1] – with the observed
burden varying geographically, due in part to differences in healthcare
factors such as blood culture practice and antibiotic use [2]. With large
reductions in the incidence of Haemophilus influenzae type b in many
European countries, Pnc is now one of the leading causes of meningitis
and invasive bacterial disease in children; Pnc is also one of the main
aetiological agents for community-acquired pneumonia in adults and for
otitis media in children [1]. Furthermore, in recent years antibiotic
resistant strains of Pnc have emerged as an increasing problem, with
rates of penicillin resistance ranging up to almost 50% of invasive isolates
in some European countries [1].
Two types of pneumococcal vaccine are now licensed in Europe,
and include a variable number of capsular serotypes: the older
23-valent Pnc polysaccharide vaccine (PPV) and the newer conjugated
7-valent Pnc vaccine (PCV). PPV provides protection against invasive
Pnc disease due to 23 serotypes in subjects older than two years
[3]. PCV protects against seven serotypes but also in those younger
than two years and provides longer lasting immunity against invasive
disease. Conjugate vaccine also protects against non-invasive
Pnc disease manifestations such as pneumonia [4]. Post-licensure
surveillance following introduction of PCV in the United States
in 1999 as a universal infant immunisation programme has shown
a large reduction in both invasive and non-invasive disease incidence
due to vaccine serotypes in both vaccinated and older unvaccinated
populations (‘herd immunity’). This reduction in
disease has also been accompanied by a fall in the rate of penicillin-resistant
Pnc [5]. However, a small increase in invasive disease due to
non-vaccine serotypes (termed ‘serotype replacement’)
has also been observed [6].
Historically, individuals at higher risk of Pnc infection such
as those with immune system impairment, and more recently, the
elderly, have been targeted with PPV in Europe. The licensure
of the new 7-valent Pnc conjugate vaccine in Europe by the European
Medicine Evaluation Agency (EMEA) in 2001 has re-ignited interest
in pneumococcal disease and the most appropriate vaccination
strategy in a European setting. A number of factors have contributed
to this decision making, including the potentially preventable
disease burden and the cost and effectiveness of alternative
intervention programmes. For European countries to be able to
design the most appropriate future vaccination strategies, it
will be important to understand local pneumococcal disease burden
in the context of current and past vaccination strategy. This
paper summarises the results of a survey of national Pnc vaccine
policy undertaken at the end of 2003 across the European Union
(EU) and the accession countries that constitute the current
EU,. This was undertaken within the framework of the EU funded
project Pneumococcal Disease in Europe (Pnc-EURO).
Methods
A standardised questionnaire was designed and sent to the national public
health institutes of each of the current 25 European Union member states
and Switzerland and Norway in late 2003, 10 of them in the accession
phase. Data from returned questionnaires were entered and analysed
in Excel.
Results
Twenty three of the 27 countries completed and returned the questionnaire.
Non-responders were Greece, Hungary, Poland and Spain.
Use of pneumococcal polysaccharide vaccine
A 23-valent PPV vaccine has been licensed in 22 of the 23 responding
countries (not in Malta) from the 1980s onwards [TABLE 1], with vaccine
from two manufacturers: Sanofi-Pasteur MSD and Wyeth-Lederle. With
the exception of Portugal, the remaining countries have developed national
recommendations for PPV.
All countries with national recommendations for PPV have implemented
strategies to target groups at higher risk of invasive pneumococcal
disease [TABLE 1].
The recommended vaccination schedule is generally a single dose,
although at least four countries recommend a booster dose after
three to six years, at least for certain groups, such as those
whose antibody levels decline rapidly.
Country specific risk-group recommendations are outlined in
Table 2. The number of risk groups (those individuals at higher
risk of invasive disease due to their underlying condition) ranged
from one to 12 (median nine groups, n=20) [TABLE 1]. Almost all
countries recommended vaccination of individuals with splenic
dysfunction (n=19), immunosuppression (n=17), chronic pulmonary
disease (CPD)(n=18), chronic cardiac disease (CCF)(n=16) and
chronic liver disease (n=15). Seventeen countries recommended
that the polysaccharide vaccine be administered to all those >65
years of age: three of these countries made this recommendation
for all those over 60 years of age.
A variety of other risk groups were also targeted including
individuals with cochlear implants (England), chronic renal disease
(Finland, Germany, Luxembourg and Ireland), travellers with certain
chronic conditions (Lithuania), those with repeated pneumococcal
infections (Norway) and those with Down’s syndrome (Sweden).
For those countries where the vaccine was recommended, in most
instances (n=14) the vaccine was either free or the cost refunded,
at least for some risk groups [TABLE 1]
Use of Pneumococcal conjugate vaccine
Twenty of the 23 responding countries had a pneumococcal conjugate vaccine
officially licensed, but not Estonia, Malta, or Slovenia [TABLE 3]. In
all cases, this was the 7-valent vaccine manufactured by Wyeth-Lederle
(Prevenar). No other PCV was commercially available at that time. By
2003, 13 of these 20 countries had developed and implemented national
recommendations for use of this vaccine since 2001. For seven countries,
mainly in central Europe and Scandinavia, the vaccine is licensed but
national recommendations are not yet in place or are being developed
(Czech Republic, Denmark, Latvia, Lithuania, Netherlands, Portugal and
Sweden). The recommended schedule is enerally three doses one to two
months apart from the second or third month of life. At least nine countries
recommend a booster dose after the age of one year.
At the time of the original questionnaire in 2003, no European
country recommended mass infant immunisation. In 2004, at least
one country (Luxembourg) recommended PCV for all children under
24 months of age (universal infant immunisation). In all countries
with national recommendations, conjugate vaccine was targeted
at specific risk groups. In many countries (at least seven),
use in target groups is restricted to children less than two
years of age, and in four countries to those under five years
of age (Belgium, England, Finland and Switzerland). The number
of risk groups range from one to 11 (median 8, n=13) [TABLE 3]:
the most common are individuals with asplenia (n=13), CCF (n=11),
CPD (n=11), diabetes (n=11), immune deficiency (n=11) and HIV
infection (n=12). Use in all persons over 65 years of age is
recommended in one country, Cyprus.
Other risk groups targeted include those with chronic renal
disease (Finland, Ireland, England and Germany) and children
with ventilatory tubes inserted (France). In France, young children
in families with more than three pre-school children or children
attending daycare are also targeted.
In the majority of countries where PCV is recommended (n=12),
the vaccine is reported to be free or the cost refunded, at least
for some risk groups [TABLE 4].
Discussion
This article provides a summary of pneumococcal vaccine policy in Europe
at the end of 2003 and illustrates differences in national pneumococcal
policy across Europe ranging from no licensure of any pneumococcal
vaccine to the more recent introduction of a universal Pnc conjugate
vaccine programme in infancy in 2004 in at least one country. These
variations in national vaccination policy have been previously well
documented for other vaccine programmes [7].
The Pnc polysaccharide vaccine, PPV, has been widely recommended
in some European countries for over two decades for groups perceived
to be at higher risk of invasive disease. The evidence base for
the true risk of Pnc in these groups may vary from country to
country, but has not been systematically collated. We demonstrate
that by 2003, the number of risk groups actually targeted ranges
dramatically across the countries of the EU. Furthermore, we
found that a large number of countries recently implemented programmes
for all individuals older than 65 years. There is limited published
evidence of the effectiveness of PPV targeted at populations
at higher risk of invasive infection [3,8], whereas a ‘universal’ elderly
PPV programme has been shown to be both effective [9] and cost-effective
[10] against invasive Pnc disease (at least in the United Kingdom).
We did not collate information on the uptake of these various
programmes, but ad hoc studies have suggested that targeted high-risk
programmes often have difficulty achieving high levels of coverage
[11], whereas ’universal’ programmes such as those
targeting all those over 65 years of age may be easier to implement.
It will be important to ensure surveillance systems are in place
to monitor the coverage, impact and effectiveness of these various
PPV programmes in Europe.
Following the recent licensure of the 7-valent PCV in Europe,
we found that the majority of countries have now included the
new vaccine in their national recommendations. In 2003, PCV was
targeted at certain groups of children under two years of age
who are at higher risk of invasive infection (under five years
in some countries), with the number of recommended risk groups
varying dramatically from country to country from very limited
to very extensive indications including children attending daycare,
such as in France. In this article, we have gathered information
only on national recommendations: the coverage and impact of
these programmes has not been collated and remain largely unreported.
The factors that influence the coverage achieved (and thus the
eventual impact) in any one country are manifold. However, it
is important to note that in a number of countries, a large proportion
of all vaccination may be administered through the private sector,
where insurance schemes may (or may not) reimburse cost of vaccination.
Clearly, this raises issues of equity and access to healthcare.
It will be important to ensure that national surveillance schemes
fully capture the programmatic impact of PCV administered through
both the public and private sectors.
No country in the European Union had implemented a universal
PCV programme at the time of the original questionnaire in 2003.
Future decisions on the use of pneumococcal vaccines in Europe,
in particular PCV, will be decided on the basis of a number of
factors: disease burden and the effectiveness and cost effectiveness
of alternative interventions. The Pnc disease burden in European
settings is recognised to vary across the continent [2] due both
to differences in healthcare factors affecting observed rates
of disease (such as use of antibiotics and blood culture [12,13]),
and also to real differences in pneumococcal epidemiology (such
as Pnc serotype distribution and the prevalence of antibiotic
resistance [2,14]). High quality pre-vaccination surveillance
data will be critical for informed national decision making for
local vaccination policy. Secondly, the impact of the universal
PCV programme in North America is increasingly evident, particularly
the size of the herd immunity effect with evidence of significant
protection for older, unvaccinated populations (together with
evidence of serotype replacement – the emergence of non-vaccine
serotypes, for instance, as observed in acute otitis media [15]).
Finally, the cost-effectiveness of any PCV programme (compared
to PPV programme) will be influenced by recent clinical trial
evidence of the effectiveness of alternative primary immunisation
schedules involving fewer doses of vaccine [16]. Indeed, at least
one European country, Luxembourg, introduced a universal infant
immunisation programme in 2004, with a three dose primary course
and a booster dose in the first year of life.
We have demonstrated a diversity of Pnc vaccination programmes
in Europe, and these are rapidly evolving. It will be critical
for countries to ensure that high quality surveillance systems
are in place to monitor the impact and effectiveness of these
programmes and to ensure future interventions, particularly in
relation to possible introductions of PCV, are undertaken in
an informed fashion based on local Pnc disease epidemiology.
Acknowledgements
We thankfully acknowledge all the national gatekeepers
who kindly completed and returned the questionnaires. Pnc-EURO
was a EU funded project (Project number QLG4-CT-2000-00640).
The European Pneumococcal group included: R
Strauss (FM for Health and Women, Vienna, Austria), G Hanquet
(Scientific Institute for Public Health, Brussels, Belgium),
P Protopapa (Medical and Public Health Services, Nicosia, Cyprus),
S Samuelsson (Statens Serum Institut, Copenhagen, Denmark), K
Kutsar (Health Protection Inspectorate, Tallinn, Estonia, A Perrocheaux
(Institut de Veille Sanitaire, Paris, France), J O’Donnell
(National Disease Surveillance Centre, Dublin, Ireland) , Jurijs
Perevoscikovs (State Public Health Agency, Riga, Latvia), N Kupreviciene
(Centre for Communicable Disease Prevention and Control, Vilnius,
Lithuania), M Micallef (Department of Public Health, Malta),
S van den Hof (Rijksinstitut voor Volksgezondheid en Milieu,
Bilthoven, the Netherlands), H Nokleby (Institute of Public Health,
Oslo, Norway), M Slacikova (National Public Health Institute,
Bratislava, Slovak Republic), A Kraigher (Institute of Public
Health, Ljubljana, Slovenia), K Ekdahl (Institute for Infectious
Disease Control, Stockholm, Sweden), T Fernandes (Ministry of
Health, Lisbon, Portugal), B Kriz (National Institute of Public
Health, Prague, Czech Republic), J Mossong (Laboratoire National
de Santé, Luxembourg).
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