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Dispatch
Bordetella pertussis,
Finland and France
Valérie Caro,*
Annika Elomaa,† Delphine Brun,* Jussi Mertsola,† Qiushui He,† and Nicole
Guiso*
*Institut Pasteur, FRE-CNRS 2849, Paris, France; and †National Public Health Institute and University of Turku, Turku, Finland
Suggested
citation for this article
We used pulsed-field
gel electrophoresis analysis and genotyping to compare clinical isolates
of Bordetella pertussis recovered since the early 1990s in Finland
and France, 2 countries with similar histories of long-term mass vaccination
with whole-cell pertussis vaccines. Isolates from both countries were
similar genetically but varied temporally.
The introduction of whole-cell pertussis vaccines (wP) from the 1940s
to the 1960s in many countries resulted in a dramatic decrease in illness
and death from pertussis. However, pertussis remains a considerable public
health problem worldwide. Indeed, the disease continues to be endemic
in vaccinated populations in Europe, Australia, Canada, and the United
States, with cyclic increases at 3- to 5-year intervals, despite high
vaccination coverage (1,2). One of the major causes
is waning of vaccine-induced immunity with time (1,3),
but increased disease surveillance and use of biologic diagnosis are also
implicated. However, changes in the agent of the disease, Bordetella
pertussis, are of some concern. This bacterium expresses adhesins
such as filamentous hemagglutinin, pertactin, fimbriae (FIM), and toxins
such as pertussis toxin, and adenylate cyclase-hemolysin (4).
Recently, circulating isolates were found to differ from the strains used
for the wP vaccines in the world (5–13). These
observed changes might modify the properties of the isolates and affect
the efficacy of pertussis vaccines.
In Europe, heterogeneity is high in epidemic situations with respect
to wP vaccines used and vaccination history and strategy. However, Finland
and France have implemented similar mass wP vaccination programs with
high coverage for several decades. Since 1952, children in Finland have
been vaccinated with combined diphtheria-tetanus wP vaccine (DTwP) at
3, 4, and 5 months and from 20 to 24 months of age. The wP vaccine contains
2 strains and has remained unchanged since 1976. Since 1959, children
in France have been vaccinated with DTwP-inactivated polio vaccine at
3, 4, and 5 months and from 16 to 18 months of age. The vaccine calendar
for primary vaccination was changed to 2, 3, and 4 months of age in 1995.
The same wP vaccine, composed of 2 strains, has been used for >40 years.
In both Finland and France, incidence of pertussis has increased and the
disease has shifted to older age groups, especially adolescents and adults.
The cycles of pertussis disease are observed every 3–5 years (5,13).
The aim of this study was to analyze and compare the isolates circulating
in the 2 European countries with long-term and intensive vaccination.
B. pertussis isolates were selected from collections of the Finnish
Pertussis Reference Laboratory of the National Public Health Institute
(Turku, Finland) and the French Pertussis National Center of Reference
(Paris, France). Of the 503 Finnish isolates recovered from 1991 to 2004,
64 were selected either because they represent all available isolates
from 1 community (Paimio) or they were recovered from a geographic area as wide as possible. In addition, 6 isolates from a school outbreak that occurred
in Heinavesi (Finland) in 1982 were included to study the changes over
time. Of the 1,049 French isolates recovered from 1991 to 2004, we selected
61 because they are representative of the French collection from a temporal
and geographic viewpoint and they correlate with the different cycles
of pertussis observed in France and Finland.
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Figure. A) Pulsed-field gel electrophoresis
profile repartition of Bordetella pertussis isolates by year
and by country... |
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Appendix
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![Appendix Figure.](images/05-1283_appt.gif) |
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Appendix Figure. Genomic analysis of Finnish
and French Bordetella pertussis isolates. From left to right,
chromosomal DNA profiles... |
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All Finnish and French isolates showed a high similarity with a minimum
of 80.3% overall relatedness by using pulsed-field gel electrophoresis
(PFGE) analysis after digestion of B. pertussis genomic
DNA with
XbaI restriction enzyme (14) (Appendix
Figure [ 122
KB, 1 page]). Most Finnish and French isolates fell into
PFGE groups III, IV, and V (Appendix Figure [ 122
KB, 1 page]and Figure,
panel A) corresponding to the isolates circulating in Europe from 1999
to 2001 (14). A new PFGE group (VII) was
identified among Finnish isolates recovered in 2004 (Appendix
Figure [ 122
KB, 1 page] and Figure, panel A).
This new profile, with 97.3% level of relatedness (Appendix
Figure [ 122
KB, 1 page]),
might represent an emerging group. The new profile was further confirmed
with PFGE by using the second restriction endonuclease SpeI
(data not shown), as previously recommended (5,14).
We cannot say whether PFGE VII isolates are actually emerging or
whether evidence for their emergence is anecdotal, as is the case
with French PFGE VI isolates, which represent only 0.6% of French
isolates (data not shown).
We previously showed that the major PFGE group circulating in Europe
from 1999 to 2001 is group IV (14). In
France and in Finland, the PFGE group IV was overrepresented from
1992 to 2004 with 85.3% level of relatedness, confirming the limited
polymorphism of B.
pertussis. PFGE group IV was subdivided into 3 subgroups, α,
β, and γ, whose frequencies varied between countries (14).
In our study, we show that, as in France (5)
the PFGE groups of the isolates circulating in Finland vary temporally
with the cycles of the disease (Appendix Figure [ 122
KB, 1 page] and
Figure, Panel A). However, the frequency of the
isolate subgroups circulating in Finland and France was different. In
fact, the major subgroup detected in Finland between 1992 and 1999 was
IVγ; since 2000, subgroups
IVα and IVβ have been found (Figure,
panel A). This circumstance is well illustrated among the isolates recovered
in Paimio, where 99% of isolates with IVγ were circulating in
1992 whereas in 2004, 42% of subgroup IVβ, 33% of subgroup IVα,
and 25% of the new group VII and none of IVγ were circulating
in Paimio. Subgroups IVα and β, absent from 1992 to 1994,
are now circulating. However, subgroup IVα is not a new subgroup
in Finland since the 6 isolates collected in Heinavesi in 1982 exhibit
this profile (Appendix
Figure [ 122
KB, 1 page]).
The analysis also included genotyping of the genes encoding pertussis
toxin S1 subunit (ptxA) and pertactin (prn) and
serotyping of FIM, performed as described previously (5,13).
The sequence of ptxA is the same (ptxA allele
type 1) for all Finnish and French isolates. The same types of prn alleles
are also harbored by Finnish and French isolates (Appendix
Figure [ 122
KB, 1 page]). The emergence of isolates harboring ptxA1 and prn2
or prn3 alleles in both countries might be explained by the
fact that the wP vaccine strains used in both countries harbor ptxA2
or A4 and prn1 alleles (13,15).
A similar hypothesis might be proposed for the expression of FIM. In
fact, most of the Finnish isolates collected from 1991 to 2004 express
FIM2, whereas in France most of the isolates express FIM3 (Figure,
panel B). The differences in the expression of FIM between Finnish and
French isolates might reflect the difference in strains used for Finnish
and French wP vaccines. The Finnish wP vaccine contains 2 strains expressing
FIM2,3 and FIM3, whereas the French wP vaccine includes 2 strains expressing
FIM2,3 and FIM2 (13,15). A marked shift of
predominant serotype from FIM2 to FIM3 has been observed in Finland
since 1999, although the wP vaccine remained the same. The emergence
of isolates with FIM3 and PFGE subgroup IVβ, a new subgroup found
in Finland, might be due to the increase in the frequency of this subgroup
in the neighboring countries and the increased mobility of people within
the European Union in the last decades.
We show that the B. pertussis isolates circulating in 2 countries
with a long history of wP vaccination are genetically close. In the 2
countries, similar PFGE groups and subgroups are present, but their frequencies
were different in the 1990s. Further, the subgroup emerging according
to the cycles of pertussis in each country varies. The difference observed
in frequency of subgroups could be due to herd immunity or human density
of the populations concerned. Does this herd immunity vary depending on
the human genetic population concerned or are the vaccine strains used
expressing similar factors but not at the same level (e.g., FIM2 vs. FIM3)?
This question needs further investigation.
These 2 countries have started using acellular pertussis vaccines, France
since 2002 and Finland since 2005. Continued monitoring of the circulating
isolates will be important.
We thank the European
Commission of Life Program (QLK2-CT-2001-01819, EUpertstrain), GlaxoSmithKline,
and Sanofi-Pasteur laboratories for supporting this work financially.
This work was also financially supported by Institut Pasteur Foundation
and FRE-CNRS 2849 for France and the Special Governmental Fund for University
Hospitals (EVO) for Finland.
Dr Caro is assistant
director of the French National Center of Reference of Whooping Cough
and Other Bordetelloses and researcher in the Molecular Prevention and
Therapy of Human Diseases Unit, Institut Pasteur, Paris, France. Her
research interests focus on the molecular evolution of Bordetella
in relation to clinical and public health problems, comparative genomic
analysis, and new molecular diagnostic methods.
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Suggested citation
for this article:
Caro V, Elomaa A, Brun
D, Mertsola J, He Q, Guiso N. Bordetella pertussis, Finland and
France. Emerg Infect Dis [serial on the Internet]. 2006 Jun [date cited].
Available from http://www.cdc.gov/ncidod/EID/vol12no06/05-1283.htm
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