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Table of Contents
Editorial
What is Whooping Cough?
Clinical Presentation
Why is Whooping Cough
Still a Problem?
Changing Epidemiology
Pre-vaccination era
Post-vaccination era
How Can the Resurgence of
Whooping Cough be Reversed? 15
Vaccination of Adolescents/Adults
The Global Response
Conclusions
Despite the worldwide introduction of effective induced immunity, and transmission of disease
combined diphtheria-tetanus-pertussis childhood
from adolescents and adults to young unprotected
vaccination programmes over 50 years ago,
infants, the most at-risk population for serious
whooping cough (pertussis), a highly contagious
pertussis-related complications, hospitalisation and
respiratory infection caused by the bacterium,
death. Furthermore, the accumulation of susceptible
Bordetella pertussis, is still endemic in many
adolescents and adults in any one region serves as
countries. Although the incidence of pertussis is
a reservoir for pertussis infection and outbreaks of
markedly lower since the introduction of routine
the disease that occur every 3−5 years.
infant and toddler pertussis vaccination in most countries, nevertheless it poses a considerable
Current optimal management for the prevention of
burden on healthcare systems with its associated
pertussis consists not only of adherence to primary
morbidity and mortality, especially among young
childhood vaccination and booster schedules, but
infants. In contrast, diphtheria and tetanus are
also the implementation of routine vaccination
largely controlled, including in numerous European
programmes for adolescents and adults. Routine
countries which have a >90% vaccination coverage
booster vaccination programmes are facilitated
rate in children.
by antigen-reduced acellular pertussis vaccines, for which safety, immunogenicity and efficacy have
Importantly, although the implementation of
been intensively studied and proven in the last
whole-cell pertussis vaccination programmes in the
1940s led to a significant decline in the incidence
Adults (usually parents) and adolescents become
of pertussis in infants and toddlers, in the last
an increasing focus for prevention since they are
two decades there has been a gradual resurgence
potential household contacts of newborns and young
in this vaccine-preventable disease, particularly
infants, and often present with only mild or atypical
in adolescents and adults, and also in very young
symptoms of pertussis infection. Nevertheless, they
unvaccinated infants. On the one hand, this may be
are the primary source of transmission to as yet
due to an increased awareness of pertussis in older
unimmunised or not fully immunised newborns
age groups and the greater sensitivity of laboratory
and young infants in the same household. Thus,
diagnosis by PCR and/or serology. On the other
although of benefit to the whole population, the
hand, this change in disease epidemiology, from an
use of safe and immunogenic pertussis boosters
infectious disease predominantly affecting infants
for adolescents and adults, as advocated in current
and children aged 1−6 years to one affecting infants
pertussis vaccination guidelines, will contribute to
<1 year and adolescents and adults aged ≥15 years
the protection of young infants, the most vulnerable
is also due to waning vaccine- and naturally-
Professor Johannes Liese
University Childrens Hospital
Würzburg, Germany
Whooping cough (pertussis), characterised by severe coughing spasms (paroxysmal), is a highly contagious
respiratory tract infection that is caused by the gram-negative bacillus Bordetella pertussis, a human-specific pathogen.(1) Pertussis, also referred to as the "100-day cough",(2) poses a significant healthcare burden,(1) and is a major cause of morbidity and mortality worldwide.(3) According to the World Health Organization (WHO), an estimated 50 million cases of pertussis occur each year, with 300 000 deaths attributed to the disease annually,(3) particularly in young infants.(1)
Bordetella pertussis, image reproduced with permission from Visuals Unlimited, Inc
Importantly, despite the implementation of
herd immunity against pertussis has not yet been
universal childhood immunisation programmes
over 40 years ago in most developed countries
The primary reason pertussis remains endemic
and a subsequent initial dramatic decline in the
worldwide, although at a markedly lower level
incidence of pertussis, since the 1980s in the
of incidence than in the pre-vaccine era, is that
USA and the 1990s in Canada, Australia, and in a
similar to naturally-acquired immunity, vaccine-
number of countries in Europe including Finland,
induced immunity to pertussis is not lifelong(1,9) but
France, Germany, Norway, Spain, Switzerland, the
rather wanes about 4−12 years after completion of
United Kingdom (UK) and Netherlands, there has
childhood vaccination,(8,9) and previously vaccinated
been a subsequent increase, with a shift in inci-
adolescents and adults are once again susceptible
dence from children to adolescents and adults.(2,4-7)
to pertussis.
Thus, for a vaccine-preventable disease, complete
• Pertussis (whooping cough) is a highly contagious respiratory disease
• Similar to naturally-acquired immunity, vaccine-induced immunity to
pertussis is not life-long but is limited to about 4−12 years
Clinical Presentation
The clinical presentation of pertussis varies widely
also associated with the common cold, thereby
according to a number of factors including age,
complicating diagnosis); paroxysmal, when the
vaccination status and concomitant infections.(9)
severity of the cough increases over 1−2 weeks and
However, in general, the duration of the illness lasts
is characterised by spasms, bursts or fits (paroxysms)
several weeks and has three clinical stages following
that may last for over a minute; and convalescent,
an incubation period of 7−10 (range 5−21) days(9):
which may last from 2−4 weeks to 3 months during
catarrhal, characterised by rhinorrhoea, and
which time the frequency and severity of coughing
mild non-productive cough (symptoms that are
episodes decrease.(1, 2)
1-2 weeks
2-4 weeks
2/4 weeks to 3 months
Clinical stages of pertussis
Subjects with pertussis are most infectious
may be broken with asymptomatic intervals,
during the catarrhal phase and the first 2 weeks
symptoms may occur in the absence of a fever.(2) Of
following the onset of cough, and this period
note, previously vaccinated adolescents and adults
of communicability is often before a diagnosis
often develop less typical pertussis characterised by
has been made.(10) Contact with airborne aerosol
the absence of whoop and manifesting as only a
droplets originating from the respiratory tract of an
protracted cough.(2) Studies show that 13−32% of
infected coughing subject is the presumed route of
adolescents and adults with a persistent cough of
direct transmission of B. pertussis.(10)
≥6 days have B. pertussis infection.(2,11) Nevertheless,
The WHO proposed definition of a "clinical case"
adults can also present with typical pertussis
is a case diagnosed as pertussis by a physician,
symptoms and have complications, including
or a person with a cough lasting at least 2 weeks
weight loss, seizures, incontinence, pneumothorax,
with at least one of the following symptoms:
rib fractures and hernia, which usually result from
paroxysm of coughing, inspiratory whooping, or
coughing spasms.
post-tussive vomiting without other apparent cause.(3) Nevertheless, the diagnosis of many cases
• Clinical manifestation of pertussis
of pertussis may not be captured by the WHO clinical
disease is highly variable
case definition(3) as there is much heterogeneity in disease expression.(9)
• Pertussis is often most contagious
before the typical coughing spasms
The manifestation of B. pertussis infection ranges
occur and a diagnosis has been
from a minimal symptomatic cough in children
and adults with residual immunity to more severe, generally among unvaccinated, unprotected
• Young infants aged <6 months
newborns and young infants.(9) Young infants
are at greater risk than older
aged <6 months may present with apnoea and
children for severe complications,
cyanosis the absence of the characteristic whoop(1,2)
hospitalisation or death
and are at greater risk than older children for
• Previously vaccinated adolescents
severe complications, hospitalisation or death.(2) In
and adults with waning immunity
unimmunised older children and adults, gasping
may develop less typical pertussis
for air between coughing defines the characteristic
characterised by a protracted
whoop, and coughing paroxysms are commonly
cough in the absence of whoop
associated with post-tussive vomiting which may lead to dehydration.(2) Although coughing spells
Complications arising from pertussis infection
and vomiting which can lead to dehydration and
may occur across all age groups and tend to vary
apnoea, nutritional problems and, rarely, death.(12)
in severity, although the most common is pneu-
In addition to the risk of pneumonia, adolescents
monia.(2) Not only are young infants (particularly
and adults with pertussis may also experience
those aged <6 months) the highest-risk group for
seizures, encephalopathy, sleep disturbances,
contracting pertussis, they are also at high-risk for
restricted activities of daily living, require time off
its associated complications including pneumonia,
school or work, and incur considerable direct and
seizures, encephalopathy, severe bouts of coughing
indirect costs.(13)
• Complications arising from pertussis, particularly pneumonia, occur
across all age groups and vary in severity
• Young infants are at greatest risk for contracting pertussis and for
developing complications such as apnoea, seizure and encephalopathy
Patients presenting with typical symptoms of
is mobilised). B. pertussis is particularly difficult
pertussis can be diagnosed following a clinical
to isolate from previously vaccinated individuals,
history; however, laboratory confirmation may be
hence the sensitivity of bacterial culture may
required. Available tests, albeit each with limitations,
be low.(9) Serological testing determines whether
include isolation and culture of B. pertussis from
serum antibodies specific to components of
the nasopharyngeal aspirate, polymerase chain
B. pertussis such as pertussis toxin or filamentous
reaction (PCR)-based assay or serology.(9) A WHO
hemagglutinin are increased/high or exceed a cut-
laboratory confirmed case is one that meets the
off point (for the level of IgG against pertussis toxin
clinical case definition described above and is
or another antigen).(2,14) Alternatively, PCR assays
laboratory confirmed by culture, PCR or positive
can be done faster than culture, and are more
paired serology.(3)
sensitive as they facilitate the identification of the
Pertussis exhibits fastidious behaviour in culture,
genetic material of viable or non-viable B. pertussis
can be recovered only during the catarrhal or
from nasal secretions; however, false-positive
early paroxysmal stages and can only be isolated
results may be a problem. Serology or PCR are the
from a nasopharyngeal swab for a short period
preferred diagnostic tests for establishing pertussis
of time (a few days before the immune response
• Pertussis can be diagnosed clinically in patients with prolonged cough
disease of >2 weeks duration without any other explanation
• Pertussis can be diagnosed in 10−30% of adolescents and adults with
a cough lasting ≥7 days
• Serology or PCR are the preferred diagnostic tests for confirming
clinical suspected pertussis infection
Antibiotic treatment targeting B. pertussis can limit
primarily prescribed to eliminate B. pertussis from
the course of the disease and severity of the cough,
the nasopharynx and to limit transmission. Much
if administered early in the disease, as well as the
of the morbidity associated with pertussis stems
spread of B. pertussis to contacts if administered
from the paroxysmal cough. Although not proven
in the later stages of the disease.(15) Standard
to be effective, treatments recommended to reduce
antibiotics include a treatment of erythromycin
the cough while the disease runs its course include
(7−14 days) or a macrolide such as azithromycin
corticosteroids (e.g., dexamethasone), salbutamol,
(5 days) or clarithromycin (7 days). In reality, for
pertussis-specific immunoglobulin (antibodies to
most affected subjects, there is a delay in diagnosis
increase the body's resistance) or antihistamines
until the paroxysmal stage, and in the later stages,
antibiotics have little individual benefit and are
• Antibiotics can limit the course of coughing disease only when
administered early in the disease
• Nevertheless, antibiotics should be used in the first 3 weeks of
coughing disease to eliminate B. pertussis from the nasopharynx and
to limit transmission
Whooping Cough Still a Problem?
Changing Epidemiology
Pre-vaccination eraPrior to the availability of pertussis vaccines
Safety (alleged adverse reactions) and efficacy
(pre-1940) in the US, classical pertussis occurred
concerns regarding inactivated whole-cell pertu-
predominantly in children (85%) aged between
ssis vaccines (wP) led some countries to cease
1 and 9 years, while 10% of cases were in infants
established childhood vaccination programmes.
aged <1 year (Figure 1).(1,16) Furthermore, epidemics
For example, wP was withdrawn in Sweden in 1979
occurred every 3−5 years, most likely as a result
resulting in a large pertussis epidemic until the
of an accumulation of susceptible children.(1) The
introduction of less-reactogenic acellular pertussis
rate of pertussis among adults and in early infancy
(aP) vaccines from 1996.(17,18)
resulted from adults who had had pertussis infection
The epidemiology of pertussis in countries with poor
as children acquiring natural immunity that was
infant vaccination programmes against B. pertussis,
boosted by recurrent exposure, and mothers who
i.e., developing countries where resources are
were able to pass on protection to their offspring
limited, generally reflects the pre-vaccine era, while
through placental transfer of antibodies.(2)
in countries in which vaccination programmes were implemented, the epidemiology has changed over
• In the pre-vaccination era,
classical pertussis was considered
a classical childhood disease,
Proportion of cases (%)
occurring particularly in infants
and children aged between
1−9 years
Age distribution of reported pertussis cases in the USA
in the pre- and post-vaccine era. *1933−39 data from
Massachusetts.(1) Reproduced with permission from Yeh
Post-vaccination eraPertussis is preventable by routine childhood
pertussis vaccination in 1964 to ≈1/100 000 by the
vaccination and the introduction of widespread
mid-1980s(7); similarly, in England and Wales the
paediatric primary vaccination programmes using
rate declined after introduction of routine pertussis
inactivated wP combined with diphtheria and
vaccination in 1957 (Figure 2b).(20) Importantly, the
tetanus toxoids in the 1940s resulted in a dramatic
decline in incidence rates of pertussis following
decline in the mean incidence rate of pertussis.
introduction of pertussis vaccines was not
For example, the rate declined from 150/100 000
sustained.(13) For instance, in the US, epidemic
to ≈1/100 000(13) by 1980 in the US (Figure 2a),(19)
cycles still occur every 3−5 years with outbreaks,
from about 140/100 000 in former West Germany
indicating incomplete immunity and an ongoing
prior to the introduction of mandatory childhood
circulation of B. pertussis in the population.(1)
Number (in thousands)
Number (in thousands)
Fig. 2a Annual number reported pertussis cases in the United States from 1922−2006 (inset depicts
cases occurring between 1990−2006 by age group).(19)
Coverage by 2nd birthday
Total notifications
Fig. 2b Annual number reported pertussis cases in England and Wales from 1940−2005
(vaccine coverage levels in England are shown from 1970 onwards).(20) Reproduced with
permission from Campbell et al.(20) Data from the Health Protection Agency (Colindale).
As discussed above, withdrawal of the wP vaccine
of pertussis in Sweden from 1997 to 2009
from childhood vaccination programs in Sweden
(Figure 3).(18) Thus, as seen with the initiation of
in 1979 led to a 17-year endemic situation.(18)
childhood vaccination, reintroduction of pertussis
However, the introduction of aP vaccines in 1996,
vaccination also resulted in a certain degree of herd
with two primary doses and an early booster
immunity, dramatically reducing rates of pertussis
dose administered at 3, 5 and 12 months of age
in children and in vaccinated and unvaccinated
resulted in a large decline in the overall incidence
individuals of all ages.(18)
of pertussis per month
Culture and PCR confirmed cases
1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006
Case reports/100 000
Lab reports/100 000
Overall pertussis incidence in Sweden. Case reports were obtained from general practitioners until the
mid-1980s, and according to the communicable disease act of 1997, lab reports from 1980 (inset depicts
cases occurring between 1986−2006).(17,18) Adapted with permission from Nilsson et al.(17) and Carlsson et al.(18)
Current immunisation programmes against per-
aged >10(1,2,20) or >14−15 years.(4,20) For example,
tussis have provided stable or increasing vaccination
from 1997 to 2000 in the US, infants aged
coverage rates; in Europe, >90% of the infant
<1 year (29%) and children aged 10−14 years
population is captured with primary vaccination
(29%) comprised the highest proportion of all
with the first three doses of vaccine.(6) Nevertheless,
cases of pertussis, followed by subjects aged >15
there has been a worldwide resurgence in the
years (20%) (Figure 1);(1,21) a similar trend in this
incidence of pertussis, with the highest incidence
age-related shift in incidence has also been reported
now seen in the least immunised age group,
in Europe in the last decade, e.g., in England and
infants aged <1 year,(4) and adolescents and adults
Wales (Figure 4)(20) and Germany.(7)
Age distribution of reported pertussis cases in England
and Wales in 4-year periods from 1998−2009 (laboratory-
confirmed).(19) Reproduced with permission from Cam-
pbell et al.(20) Data from the Health Protection Agency
The worldwide change in the epidemiology of the
from a surveillance study in France,(25,26) parents
disease from one regarded as a childhood disease to
were the predominant source (about 55%);(24-26) in
most cases occurring in adolescents and adults,(22,23)
the French study in 2878 cases of pertussis (1882
or in very young infants (unimmunised or not fully
were in infants aged <6 months), siblings were
immunised) reflects that vaccine-induced immunity
the next greatest source of infection (about 25%)
to pertussis fails to provide lifelong immunity and
(Figure 5 shows data from 2004-2007).(25,26) Very
wanes approximately 4−12 years after completion
young infants (aged <6 months) are most vulnerable
of childhood vaccination, a duration less than
as they may not be fully vaccinated,(4) and may not
that gained from naturally-acquired immunity
have received transplacental antibodies to pertussis
(≈7−20 years).(9) It is apparent that universal
antigens from their mothers.(13,27)
childhood vaccination is highly effective in protecting children and has resulted in a dramatic reduction in overall disease burden; however,
because immunity is not lifelong and adherence to vaccination recommendations has been suboptimal,
optimal control of pertussis has not been achieved and previously vaccinated adolescents and adults
are again susceptible to pertussis.(10)
Importantly, adolescents and adults,
(23) particularly
household members with pertussis, are a
significant source of transmission to infants. In one international study that included 95 index
cases and 404 contacts from February 2003 to
October 2004, 73−82%(24) of infections in infants aged ≤6 months were transmitted from household
Yearly source of potential pertussis contamination in
infants in France (Renacoq, 2004-2007).(25)
members, and as seen in 12-year data (1996-2007)
• In the post-vaccination era, where good control of pertussis in children
has been achieved in countries with high infant vaccine coverage,
the epidemiology of pertussis has changed
• Pertussis outbreaks still occur every 3−5 years indicating incomplete
immunity and ongoing circulation of B. pertussis in the population
• There has been a worldwide resurgence in the incidence of pertussis,
with the increasing incidence now seen in the least immunised age
group, infants aged <1 year and adolescents and adults aged ≥15 years
• Optimal control of pertussis has not been achieved and previously
vaccinated adolescents and adults may again be susceptible to pertussis
• Up to 73−82% of infections in infants aged ≤6 months are
transmitted from household members
In infantsThe clinical complication rate of pertussis is greatest in young infants in whom it is a potential life-threatening disease. The Renacoq data which included information on 1688 cases of pertussis in infants aged <6 months collected from 10 years of surveillance (1996−2005) of pertussis in French hospitals clearly showed a high hospitalisation (96%) and mortality (2%) rate; the greatest proportion (88%) of these deaths occurring in those aged <3 months (Figure 6a and 6b), i.e., infants who are too young to have been fully vaccinated.(26)
Number of cases 200
Fig. 6a Cases of pertussis (n=1688) by age (months) in infants
Fig. 6b Age distribution of pertussis-related mortality in infants
aged <6 months in France: Renacoq, 1996−2005.(26)
aged <6 months in France: Renacoq, 1996−2005.(26)
In the US, the pertussis-related mortality rate
aged ≤2 months.(29) Among 100 cases of childhood
among infants has been reported as 2.4 deaths/
(aged between 10 days and 18 years) mortality
1 million, with pertussis-related fatalities in infants
with no known risk factors, although Neisseria
accounting for >90% of all pertussis-related
meningitidis (34%) and Streptococcus pneumoniae
deaths.(2) A higher than usual level of disease and
(28%) were the 1st and 2nd highest pathogenic
death from an outbreak of pertussis was reported
causes of death, B. pertussis was the third (13%).
in California during 2010; >6700 cases between
Of note, for the cohort of 30 infants aged between
January and mid-November including 10 infant
10 days and 2 months, which represented one
deaths.(28) This is the highest number of cases
third of the fatalities, B. pertussis was the number
reported in the region in 63 years, 9934 cases were
one bacterial pathogenic cause of death (Figure 7)
reported in 1947, and the highest incidence in 52
and was responsible for 3 deaths in 1999 (0.1% of
years; in 1958 the rate was 26.0 cases/100 000.
fatalities in this age group) and 10 in 2000 (33%).(29)
During the previous peak in 2005 there were 3182 cases. Such compelling statistics highlight the need to protect infants who are too young to be eligible for vaccination.
Although the number of cases of pertussis in France has been stable since 1996, a 2-year (1999−2000) retrospective study conducted in 60% of paedia-tric intensive care units in France showed that B. pertussis was the primary source of bacterial infection causing mortality in newborns and infants
Streptococcus pneumoniae 1
Streptococcus, group B
Staphylococcus aureus 1
Streptococcus, group A
Escherichia coli
Clostridium perfringens 1
≤2 months (n=30)
>2 months (n=70)
Mycoplasma pneumoniae 1
Bacteriological causes of mortality from a retrospective survey of 100 paediatric deaths due
to community-acquired bacterial infections in paediatric intensive care units.(29) *Includes
10 cases in the >2 month age group of non-documented purpura fulminans considered to
be caused by Neisseria meningitidis.
• The clinical complication rate including apnoea, seizures, pneumonia and
high lymphocytosis is greatest in infants aged 1−3 months who are yet
too young to have been fully vaccinated
In adultsEven in adults, pertussis can lead to complications requiring hospitalisation, particularly in individuals aged ≥65 years (Table 1);(30) in addition, weight loss, urinary incontinence, pneumothorax, rib fractures, hernia,
and otitis media have also been reported. There is much variation in the symptoms of pertussis in adults, from minor coughing (as seen with the common cold) through to serious disease.(31) Although paroxysmal cough manifests in the majority of infected adults, the characteristic whoop generally only occurs in a third of this population, nevertheless, post-tussive vomiting can be troublesome. In addition to the raised rate of hospitalisation in older adults infected with pertussis, the rate of pneumonia is also raised in the elderly, contributing to their mortality risk.
Clinical characteristics and complications in adults with pertussis in the US excluding Massachusetts, 1996-2004.(30)
Clinical characteristics an complications
% of adults aged 19-64 years
% of adults aged ≥65 years
Post-tussive vomiting
Pneumonia (X-ray confirmed)
• Even in adults, pertussis can lead to complications, some requiring
hospitalisation, including weight loss, seizures, incontinence,
pneumothorax, rib fractures, hernia, otitis media and pneumonia
In addition to the clinical burden of pertussis,
associated with individuals aged ≥10 years was due
pharmacoeconomic analyses indicate that there is
to indirect costs, including time lost from work and/
also a considerable economic burden to individuals
or recreational activities.(33)
and society; a cost-effective management strategy
Of note, a recent cost-benefit analysis utilising a
is warranted. One prospective study in 69 families
Markov model and assessed from the German health
determined that for a household with at least one
payer perspective, estimated that a single adult
case of pertussis, the direct medical cost of illness
(aged 20−64 years) booster dose of a combined
($US) was $181 per adult (costed for an average
tetanus toxoid, reduced diphtheria toxoid and aP
of 6 lost working days), $254 per adolescent, $308
vaccine (Tdap) would be cost effective.(34) Based
per child, and $2822 per infant, averaging a total
on a disease incidence of 165/100 000, a single
medical cost of $2115 per family with a case of
booster dose vaccination strategy in
(32) Based on data from the CDC for infants
adults (at a total cost of 366 million) would prevent
and prospective studies for adults, it was estimated
498 000 cases and result in cost-effectiveness ra-
(based on 2002 values) that the direct and indirect
tios of €5800 per quality-adjusted life year (QALY)
cost burden of pertussis over a 10-year period
saved, or €160 per pertussis case prevented.
would be $17 billion. The majority (88%) of the cost
• Pertussis poses a considerable economic burden to individuals and society
Resurgence of Whooping Cough be Reversed?
Vaccination of Adolescents/Adults
Although pertussis vaccination coverage in
adolescents/adults to prolong vaccine immunity
infants is generally high in developed countries,(6)
and reduce transmission.(10)
B. pertussis is still circulating, albeit at markedly
Most countries in Europe and other developed
lower levels than in the pre-vaccination era, af-
countries including the US have replaced wP
fecting incompletely or unvaccinated infants, and
vaccines with less reactogenic aP vaccines that
even pre- or unvaccinated adolescents and adults.
contain various numbers of purified pertussis anti-
Waning immunity post vaccination and high rates
gens, e.g., pertussis toxin, and provide the option
of transmission from adolescents/adults to infants
of booster vaccination in individuals aged >6 years,
too young to be fully vaccinated support the
which is not possible with the wP vaccine.(35, 36)
importance of adhering to the current childhood immunisation schedules whilst concurrently in-troducing and/or reinforcing booster dose(s) to
• Waning immunity and high rates of transmission from adolescents/adults
to young unprotected infants strongly support adherence to current
childhood immunisation schedules, including a preschool booster at
5−6 years of age plus booster dose(s) for adolescents/adults
The Global Response
The global response to the changing epidemiology of pertussis is gathering momentum. In the last
decade, the Global Pertussis Initiative (GPI) for
the European region recommended three broad
strategies for tailoring as required by individual countries: the reinforcement of implementation
of current childhood immunisation schedules, the
addition of an extra dose of vaccine to current
immunisation schedules (either in preschool child-
Number of countries
ren aged 4−6 years or in adolescents, depending
on current schedules), and in recognition of their
high transmission risk, the selective vaccination
of healthcare and childcare personnel (also a
European Commission directive).(6,27,37) Nevertheless, there is much variation in childhood vaccination
Number of doses of pertussis-containing vaccines recom-
schedules throughout Europe and the total number
mended to use in children aged <18 years in 29 European
countries (27 EU + Norway and Iceland).(38)
of pertussis doses ranges between 3−6 (Figure 8).(38)
In response to the GPI(37) and other current
that adults receive a single dose of a combined
vaccination guidelines,(8,30) a number of European
aP vaccine.(6,8,27,30) In addition in Austria, a booster
countries including Belgium,(39) France,(40) and
dose for adults every 10 years with a combined aP
Germany,(41) the US,(30) and other countries, intro-
vaccine is recommended.(6)
duced the "cocoon strategy" for the prevention of
Although initial pertussis vaccines used in infant
morbidity and mortality associated with pertussis
and childhood vaccination programmes conta-
in young infants too young to have started/
ined wP and were associated with reactogeni-
completed a primary immunisation programme;
city concerns, these have been largely over-
that is, administration of pertussis booster vaccines
come with the introduction of aP vaccines in the
to their parents, families, healthcare and childcare
1990s.(42) Similar to infant and childhood vaccin-
workers to prevent pertussis transmission to these
ation, pertussis vaccination for adolescents and
high-risk infants, which may finally facilitate herd
adults may be administered in combination with
immunity and control pertussis infections. However,
tetanus and diphtheria vaccination, and in some
to date, the cocoon strategy has only rarely been
countries, with poliovirus vaccination.(42) Currently
successfully implemented, possibly due to missing
available pertussis vaccines in Europe consisting
vaccination opportunities and unclear definition
of combined tetanus toxoid, reduced diphtheria
of contacts. Of note, several European countries
toxoid and aP booster vaccines (Tdap) for the
(including France [the first to do so in 1998](24),
immunisation of older children, adolescents and
Germany, Belgium, and Austria) and other regions
adults have shown, and consistently show efficacy,
(e.g., US, Canada, and Australia) now recommend
assessed as robust immune responses, and are well
an adolescent booster dose in immunisation
schedules,(6,8,27) and some of these countries (France, Germany, and the US) specifically recommend
• There is much variation in childhood vaccination schedules throughout
Europe − total number of pertussis doses range between 3−6
• A number of European countries utilise the "cocoon strategy"
(administration of pertussis booster vaccines to all household contacts
including adolescent/adult contacts) to prevent pertussis transmission
to infants too young to have been fully immunised
• A number of European countries follow guideline-recommended use of
aP booster vaccines for adolescents/adults
• In Europe, currently available aP vaccines are consistently proving to
be well tolerated and effective
The initiation of mass immunisation programmes over 50 years ago with the use of wP vaccines in
infants and toddlers largely reduced the circulation of the bacterium in the childhood population and the incidence of pertussis disease. However, neither natural nor vaccine-induced immunity is life-long and the worldwide resurgence of the bacterium in the last two decades in adolescents and adults, the primary source of transmission to at-risk young infants, has seen a change in epidemiology of the disease which remains a global healthcare problem. The complementary strategies of universal primary childhood vaccination schedules and adolescent/adult booster vaccination using less-reactogenic aP vaccines will facilitate the control of the disease and reduce pertussis-associated morbidity and mortality amongst adolescents, adults and high-risk young infants.
Preparation of this brochure was supported by Sanofi Pasteur MSD, and editorial assistance was provided by Nila Bhana of inScience Communications, a Wolters Kluwer business.
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Sanofi Pasteur MSD S.N.C. au capital de 60 000 000 Euros – RCS LYON B 392 032 934 - 4015390 / CO00646 - Avril 2011
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"Little Women?": Karen JoyFowler's Adventure inAustenland Edward Neill has published widely in journals and periodicals, and is the author of four books: Trial by Ordeal?: Hardy and the Critics, The Politics of Jane Austen, The Secret Life of Thomas Hardy, and "The Waste Land" Revisited: Modernism, Intertextuality and the French Connection.
REPORT NR. 01/2016 FÜNDIGKEITSRISIKEN AUTOREN Allegra Seipp, Christine Grüning und Ulf Moslener * Die Studie stellt die persönliche Meinung der Autoren dar und nicht die der Institutionen, mit denen wir verbunden sind. Wir danken zahlreichen Interviewpartnern für die vielen Informationen und hilfreichen Kommentare. Ganz besonders: Kai Imolauer, Stephan A. Jacob, Matthias Kliesch, Christian Müller-Wagner, Kirsten Offermanns, Thorsten Schneider, Matthias Tönnis, Wesly Urena Vargas, Arndt Wierheim, und Jens Wirth.