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Influenza is an important public health problem in Europe. It is associated
with higher general practice consultation rates (1), increased hospital
admissions (2) and excess deaths (2,3). Other aspects to be considered
are the number of increased days lost due to absence from work, its
seasonal impact on health care systems and the possibility of an influenza
pandemic (4). In England and Wales, the average number of excess deaths
during influenza epidemic periods (1989-1998) was estimated to be 12
554 per season (range 0-27, 587) (2). Extrapolating these figures to
the European Union (15 countries), the average number of excess deaths
during influenza epidemic periods between 1989 and 1998 was about 90
000, the total number in each country ranged from roughly 100 in Luxembourg
to 19 500 in Germany.
The European Influenza Surveillance Scheme (EISS) is a collaborative
project (5-7) that aims to contribute to a reduction in morbidity and
mortality due to influenza in Europe. The project has received funding
from the European Commission since November 1999 and adopted new objectives
at the beginning of the 2002-2003 season:
o To collect and exchange timely information on influenza activity in
Europe;
o To aggregate, interpret and make publicly available clinical and virological
data concerning influenza activity in Europe;
o To strengthen, and harmonise where appropriate, epidemiological and
virological methods, primarily based on the integrated sentinel surveillance
model, for assessing influenza activity in Europe;
o To contribute to the annual determination of the influenza vaccine
content;
o To monitor influenza prevention and control policies in Europe, including
influenza vaccine uptake;
o To contribute to European planning and response to pandemic influenza
through surveillance, investigation and provision of information;
o To promote research in support of these objectives.
During the 2002-2003 season, 22 surveillance networks (from 19 European
countries) were active members of EISS. The scheme aims to include all
member states of the European Union: the current 15 members and the
10 candidate countries (8). For full membership, networks must meet
the following criteria: 1) the surveillance network (consisting of sentinel
physicians providing clinical information and national reference laboratories
providing virological data) is nationally or regionally representative;
2) the authority of the network is recognised by the national or regional
health authority in the country or region; 3) clinical surveillance
and virological surveillance are integrated in the same population (community);
4) the network has functioned successfully for at least two years; and
5) the network can deliver data on a weekly basis.
Sixteen networks were full members of EISS and six were 'associate'
members (Lithuania, Northern Ireland, Poland, Romania, the Slovak Republic
and Sweden) during the 2002-2003 season, as they did not completely
fit the membership criteria. Poland, Romania, the Slovak Republic and
Sweden were 'associate' members because they did not combine clinical
and virological data in the same population; Northern Ireland and Lithuania
because they were new members to the scheme. Including all members,
the EISS project comprised 28 national influenza reference laboratories,
at least 10 600 sentinel physicians and presented surveillance data
during the 2002-2003 season for a total population of 441 million inhabitants.
Methods
EISS members actively monitored influenza activity from week 40/2002
(30/9/2002 - 6/10/2002) to week 20/2003 (12/5/2003 - 18/5/2003) during
the 2002-2003 season. In each of the countries, one or several networks
of sentinel physicians collected weekly (consultation) incidences of
cases of influenza-like illness (ILI) and/or acute respiratory infection
(ARI) (9). Sentinel physicians also obtained nasal, pharyngeal, or nasopharyngeal
specimens from a sample/subset of patients and these were sent to the
national reference laboratory-ies) for virological monitoring. Combining
clinical and virological data in the same population allows the validation
of clinical reports made by the sentinel physicians and provides virological
data in a clearly defined population (the general population that visits
their physician with an influenza-like illness or an acute respiratory
infection) (9).
The virological data included results from rapid diagnostic (immuno-enzymological
or immunofluorescence) tests and from cell cultures with specific identification.
Many laboratories also use reverse transcription polymerase chain reaction
(RT-PCR) routinely (10). In addition to specimens obtained from physicians
in the sentinel surveillance systems, the laboratories also collect
and report results on specimens obtained from other sources (e.g. from
hospitals or non-sentinel physicians). These data are collected as a
range of indices and used to monitor influenza activity and it allows
the validation of virological data obtained from the sentinel sources.
During the influenza season, the weekly clinical and virological data
are processed and analysed by the national centres and then entered
into the EISS database the following week via the internet (11). This
allows members to view data in neighbouring countries and the publication
of a weekly bulletin on influenza activity in Europe on the EISS website
each Friday.
This paper presents epidemiological and virological data collected between
week 40/2002 and week 16/2003.
Results
Figure 1 presents a graphic display of the two predominant influenza
viruses that circulated in Europe during the 2002-2003 season (influenza
B and A (H3N2)). The countries are ranked according to the week when
there was a steady circulation of each virus in the population (defined
as the isolation/detection of the virus in sentinel and/or non-sentinel
specimens with no more than one week interruption). Overall, influenza
B was reported earlier in the season and the period of influenza activity
was longer. Belgium, France and Spain had a mixed season, with influenza
B reported at the beginning of the season and influenza A (H3N2 in Belgium
and France and H1N1 in Spain) at the end of it.
The spread of influenza B first affected Portugal in week 43/2002 and
then moved to Spain, France and Belgium. The virus was detected in the
United Kingdom in weeks 50/2002 (Scotland) and 01/2003 (England), and
there was then a steady circulation in most of the rest of Europe. The
circulation of influenza A (H3N2) occurred later in the season, with
a steady circulation first reported in Germany in week 51/2002. It then
spread rapidly to England, France, Italy, Ireland, Denmark and most
of the rest of Europe. Some countries e.g. Northern Ireland, Slovenia
and Wales only reported sporadic cases of influenza B and A (H3N2).
On average, there was a better overlap of the peaks of clinical (sentinel
incidence data) and virological activity (sentinel and non-sentinel
laboratory reports) for influenza A (H3N2) than for influenza B.
The geographical spread and intensity of influenza activity in the member
countries varied during the 2002-2003 season (Table). The influenza
activity was sporadic in Ireland, Norway, Portugal, Sweden and the United
Kingdom. In the Netherlands, Lithuania, Poland, Romania and Spain it
was local or regional and in Belgium, the Czech Republic, Denmark, France,
Germany, Italy, Slovak Republic, Slovenia and Switzerland it was widespread.
The intensity of influenza activity (compared to historical data) ranged
from low in the Netherlands, Norway, Portugal and the United Kingdom
to high in the Czech Republic, Denmark, Germany and Poland.
The peak levels of clinical morbidity in Europe were reached between
week 02/2003 and 12/2003 (Figure 1 and Table), with the majority of
countries reporting peak levels from mid-February to mid-March (weeks
07/2003 to 11/2003). Overall, influenza B was predominant in the west
of Europe (Portugal, the United Kingdom and Ireland) and in Romania,
and influenza A (H3N2) was predominant in central and eastern Europe
(the Czech Republic, Denmark, Germany, Italy, Lithuania, the Netherlands,
Norway, Poland, the Slovak Republic, Slovenia and Switzerland). Belgium,
France and Spain had mixed seasons, with influenza B being predominant
at the beginning of the season and influenza A (H3N2 in Belgium and
France and H1N1 in Spain) at the end of the season.
During the 2002-2003 influenza season, a total of 17 302 respiratory
specimens were collected by the sentinel physicians and tested for influenza;
4613 (26.7%) were positive for influenza (17.0% for influenza A and
9.7% for influenza B). Figure 2 presents a pie chart of positive sentinel
specimens during the 2002-2003 season, broken down by type (the large
pie chart) and subtype (the smaller pie chart). Germany reported 46.5%
(2145/4613) of the positive specimens. In order to obtain a less skewed
distribution of types and subtypes in Europe, the data have been averaged
for all reporting countries (this means that each country has an equal
weight in the overall calculation of percentages). On average, 56% of
specimens were positive for influenza A and 44% for influenza B. Among
the influenza A subtyped specimens, on average, influenza A (H3N2) was
found among 78% of specimens, influenza A (H1N1) among 15% and influenza
A (H1N2) among 7%. The crude distributions, with no weighting, were:
64% influenza A and 36% influenza B [among the subtyped cases of influenza
A, 91% were A (H3N2), 8% influenza A (H1N1) and 1% influenza A (H1N2)].
EISS received no sentinel reports of influenza A (H7N7).
Figure 3 presents the results of the strain characterisations of influenza
virus isolates reported by the national reference laboratories in EISS.
These data were collected for the first time during the 2002-2003 season
and combine sentinel and non-sentinel data. The pie chart percentages
have not been weighted and this means that the data from Germany (a
network that reported 69% of the isolates) makes a disproportionate
contribution to the pie chart. Over 99% of the isolates characterised
by the reporting networks were covered by the 2002-2003 vaccine. There
were 26 reports of non-vaccine strain A/Fujian/411/02(H3N2)-like viruses
(13 in Norway and 13 in Switzerland; reported at the end of the season)
and these isolates represented less than 0.75% of all characterised
isolates. In Norway, where A/Fujian/411/02-like viruses were the most
numerous (more than 70 per cent of characterised H3N2 strains), the
circulation of these viruses failed to cause significant outbreaks (Olav
Hungnes, personal communication).
Figure 4 presents age-specific weekly incidence rates for four countries
that reported cases of ILI and two countries that reported cases of
ARI during the 2002-2003 season. These countries were chosen as they
reported age-specific data (some EISS networks do not report these data)
and because there were sufficient data to present the rates (England,
the Netherlands and Portugal did not have sufficient cases of ILI each
week to present meaningful graphs). The virological results for influenza
positive sentinel specimens are also presented to demonstrate the temporal
relationship between clinical and virological activity.
The incidence rates were highest, in all countries, among those aged
0-4 and 5-14 years. The lowest rates, in all six countries, were reported
in the 65+ age group. The age-specific incidence rates in each country
varied considerably. In Denmark, the Slovak Republic and Switzerland,
the peak incidence rates in the age groups 0-4 and/or 5-14 were 3-5
times higher than in those aged 65+. In the other countries, the differences
were larger and even rose to 16 times higher in Spain (38 ILI consultations
per 100 000 in persons aged 65+ compared to 611 ILI consultations per
100 000 in persons aged 5-14).
Discussion
The 2002-2003 influenza season in Europe was a heterogeneous one in
terms of intensity and type/subtype diversity. Some countries reported
high levels of influenza activity (the Czech Republic, Denmark, Germany
and Poland) whilst others had very quiet seasons (Ireland, the Netherlands,
Norway, Sweden and the United Kingdom). Some countries had activity
that was driven by the influenza B virus (mainly in the western part
of Europe), whilst in other countries it was influenza A (usually influenza
A (H3N2)). Influenza B activity was generally earlier in the season
(weeks 49/2002-08/2003), it lasted a longer time period, and was associated
with lower weekly incidence rates.
The weekly incidence rates of ILI and ARI collected and presented by
EISS provide valuable information on the dynamic spread of influenza
in the population and are an important indicator for the evaluation
of national influenza vaccination campaigns (other indicators include
the availability of vaccines before the start of the season and vaccination
uptake rates). The results (see Figure 4) indicate that the lowest incidence
rates were observed in persons aged 65+, a population group that the
vaccination campaigns target (12) - in all six countries.
Comparisons of age-specific incidence rates across Europe (e.g. the
rates in Denmark compared to those in Spain) must be made with care.
The differences in incidence rates observed among the four countries
reporting ILI incidences (see Figure 4) can probably be explained by
a number of different factors, including: different case definitions
(13), changes in the surveillance systems over time (the sentinel physicians
in the Slovak Republic began reporting cases of ILI (instead of ARI)
during the 2001-2002 season, and some of the physicians may have still
been reporting cases of ARI during the 2002-2003 season) and different
consultation behaviours e.g. due to cultural differences and the need
to have a medical certificate to be absent from work (14).
At the end of the 2002-2003 season (late February 2003), the Netherlands
experienced an epidemic of highly pathogenic avian influenza A (H7N7)
in poultry that also went on to affect Belgium and Germany (the regions
bordering the Netherlands). As of 30 August 2003, there were 89 cases
(15) of H7N7 influenza among poultry workers and their families, causing
mainly mild conjunctivitis, sporadically ILI, but also one case (a veterinarian
who had visited one of the affected farms) of severe fatal pneumonitis.
Epidemiological and virological studies indicated that there were three
cases of human to human transmission: from two poultry workers to three
of their family members. Fortunately, the epidemic in poultry in the
Netherlands and the outbreaks in Belgium and Germany were contained.
The last human case of H7N7 influenza (laboratory confirmed) in the
Netherlands occurred on 19 April 2003 (15), indicating that the outbreak
among humans was also over.
The identification of circulating viruses within the population and
the recognition of virological changes are important tasks for EISS.
There is a particular need to detect and monitor the emergence or re-emergence
of viruses with pandemic potential and viruses that have a 'mismatch'
with the vaccine strain components. The emergence of two 'novel' viruses
during the 2001-2002 season (influenza A (H1N2) and B/Victoria/2/87
lineage) were carefully documented by EISS and have exemplified the
benefit of having a surveillance system to facilitate the rapid exchange
of information across Europe (6). During the 2002-2003 season, another
'novel' virus was detected: the influenza A/Fujian/H3N2-like virus.
Fortunately, only sporadic cases were detected and patients had normal/typical
clinical symptoms.
The composition of the influenza vaccine for the 2003-2004 season (northern
hemisphere winter) was announced by the World Health Organization (WHO)
in March 2003 (16). The strains are unchanged compared to the 2002-2003
season. The WHO delayed the announcement of the strains due to the detection
of some cases at the end of the season that had a reduced reactivity
to the A/Panama/2007/99 antiserum (and appeared to be similar to A/Fujian/411/2002)
(16). Considering there was no A/Fujian/411/2002-like virus suitable
as a vaccine strain candidate isolated in embryonated eggs, the composition
of the 2003-2004 influenza vaccine in the northern hemisphere will remain
the same as the current season.
The European influenza vaccine (17) for the 2003-2004 season contains:
o an A/New Caledonia/20/99 (H1N1)-like virus
o an A/Moscow/10/99 (H3N2)-like virus (the widely used vaccine strain
is A/Panama/2007/99)
o a B/HongKong/330/2001-like virus (currently used vaccine strains include
B/Shandong/7/97, B/Hong Kong/330/2001, B/Hong Kong/1434/2002)
The emergence of the influenza A (H3N2) Fujian-like virus at the end
of the 2002-2003 season in Norway and Switzerland and its wide circulation
in Australia and New Zealand during the southern hemisphere winter (2003)
(18), mean that there is the possibility of a 'mismatch' occurring between
the H3N2-vaccine strain component and the circulating H3N2 virus strains
during the 2003-2004 season (15). The current data from Australia indicate
that only sporadic cases of influenza-like illness were observed in
immunised (i.e. vaccinated) individuals and there does not appear to
have been a major reduction in vaccine protection (18). It is very difficult
to predict which virus(es) will circulate in Europe during the 2003-2004
season (e.g. there could be a co-circulation of influenza A (H3N2) viruses)
and which age groups will be affected. Influenza vaccination is therefore
extremely important; even if the Fujian-like virus circulates in Europe
during the 2003-2004 season, vaccination will offer some cross protective
immunity. The spread of virus strains in Europe during the 2003-2004
season will be carefully monitored by the virological, epidemiological
and clinical experts within EISS. Assessments of the influenza activity
will be made in collaboration with the WHO Collaborating Centre in London
and will be reported on the EISS website on a weekly basis.
This article was written on behalf of all EISS members: Alexandrescu
V (RO), Aymard M (FR), Bartelds AIM (NL), Buchholz U (DE), Burguiere
A-M (FR), Brydak L (PL), Cohen JM (FR), Domegan L (IE), Dooley S (IE),
Falcao I (PT), Fleming DM (UK), Grauballe P (DK), Haas, W (DE), Hagmann
R (CH), Havlickova M (CZ), Heckler R (DE), Heijnen M-L (NL), Hungnes
O (NO), Iversen B (NO), de Jong JC (NL), Kennedy H (UK), Kristufkova
Z (SK), Libotte M-L (BE), Lina B (FR), Linde A (SE), Lupulescu E (RO),
Machala M (PL), Manuguerra J-C (FR), de Mateo S (ES), Meijer A (NL),
McMenamin J (UK), Meerhoff T (NL), Mosnier A (FR), Meijer A (NL), Nolan
D (IE), O'Flanagan D (IE), O'Neill H (UK), Opp M (LU), Paget WJ (NL),
Penttinen P (SE), Perez-Brena P (ES), Pierquin F (BE), Pregliasco F
(IT), Prosenc K (SI), Rebelo de Andrade H (PT), Rokaite D (LT), Samuelsson
S (DK), Schweiger B (DE), Socan M (SI), Thomas D (UK), Thomas Y (CH),
Tumova B (CZ), Uphoff H (DE), Valette M (FR), Vega T (ES), van der Velden
K (NL), van der Werf S (FR), Watson J (UK), Wilbrink B (NL), Yane F
(BE) and Zambon M (UK).
Acknowledgements
EISS would not exist without the regular participation of sentinel
physicians across Europe. We would like to thank them for making this
surveillance scheme possible.
*Participants
Belgique / Belgium
Scientific Institute of Public Health, Bruxelles
République Tchèque / Czech Republic
National Institute of Public Health, Praha; National Influenza Centre,
Praha
Danemark / Denmark
Statens Serum Institut, Copenhagen
France
Groupes Régionaux d'Observation de la Grippe, Open Rome, Paris;
Institut Pasteur, Paris; Centre Hospitalo-Universitaire, Lyon
Allemagne / Germany
ArbeitsGemeinschaft Influenza, Marburg; Robert Koch Institute, Berlin;
Niedersächsisches Landesgesundheitsamt, Hannover
Irlande / Ireland
Irish College of General Practitioners, Dublin; National Disease Surveillance
Centre, Dublin; National Virus Reference Laboratory, University College
Dublin
Italie / Italy
Istituto di Virologia, Milano; Dipartimento di Scienze della Salute,
Genova; Istituto Superiore di Sanita, Roma
Lituanie / Lithuania
Centre for Communicable Disease Prevention and Control, Vilnius
Pays-Bas / Netherlands
Netherlands Institute for Health Services Research, Utrecht; National
Institute for Public Health and the Environment, Bilthoven; Erasmus
University, Rotterdam
Norvège / Norway
National Institute of Public Health, Oslo
Pologne / Poland
National Institute of Hygiene, Warsaw
Portugal
Instituto Nacional de Saude, Lisboa
Roumanie / Romania
Cantacuzino Institute, Bucharest
Slovaquie / Slovak Republic
State Health Institute of the Slovak Republic, Bratislava
Slovénie / Slovenia
Institute of Public Health, Ljubljana
Espagne / Spain
Instituto de Salud Carlos III, Madrid; Sentinel Networks of Madrid,
Castilla y Leon, C. Valenciana, Pais Vasco, Guadalajara, Andalucia,
Aragon y Baleares.
Suède / Sweden
Swedish Institute for Infectious Disease Control, Solna
Suisse / Switzerland
Swiss Federal Office of Public Health, Bern; National Centre for Influenza,
Hôpital Cantonal Universitaire, Geneva
Royaume-Uni / United Kingdom
Royal College of General Practitioners, Birmingham; HPA Communicable
Disease Surveillance Centre, London; HPA Central Public Health Laboratory,
London; Scottish Centre for Infection and Environmental Health, Glasgow,
Scotland; HPA Communicable Disease Surveillance Centre, Cardiff, Wales;
HPA Communicable Disease Surveillance Centre, Belfast, Northern Ireland
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