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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. References
1. Yeh SH, Mink CM. Shift in the epidemiology of pertussis infection: an indication for pertussis vaccine
boosters for adults? Drugs 2006;66:731-41.
2. Hewlett EL, Edwards KM. Pertussis - not just for kids. N Engl J Med 2005;352:1215-22.
3. WHO (World Health Organization). WHO-recommended surveillance standard of pertussis.
http://www.who.int/immunization_monitoring/diseases/pertussis_surveillance/en/index.html (last accessed November 2010). 4. Celentano LP, Massari M, Paramatti D et al. Resurgence of pertussis in Europe. Pediatr Infect Dis J 5. Baron S, Njamkepo E, Grimprel E et al. Epidemiology of pertussis in French hospitals in 1993 and 1994: thirty years after a routine use of vaccination. Pediatr Infect Dis J 1998;17:412-8.
6. Wirsing von Konig CH, Campins-Marti M, Finn A et al. Pertussis immunization in the global pertussis initiative European region: recommended strategies and implementation considerations. Pediatr Infect Dis J 2005;24:S87-92.
7. Hellenbrand W, Beier D, Jensen E et al. The epidemiology of pertussis in Germany: past and present. BMC Infect Dis 2009;9:22.
8. Broder KR, Cortese MM, Iskander JK et al. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;24:1-34.
9. Crowcroft NS, Pebody RG. Recent developments in pertussis. Lancet 2006;367:1926-36.
10. Schellekens J, von Konig CH, Gardner P. Pertussis sources of infection and routes of transmission in the vaccination era. Pediatr Infect Dis J 2005;24:S19-24.
11. Gilberg S, Njamkepo E, Du Chatelet IP et al. Evidence of Bordetella pertussis infection in adults presenting with persistent cough in a French area with very high whole-cell vaccine coverage. J Infect Dis 2002;186:415-8.
12. Stojanov S, Liese J, Belohradsky BH. Hospitalization and complications in children under 2 years of age with Bordetella pertussis infection. Infection 2000;28:106-10.
13. Edwards KM. Overview of pertussis: focus on epidemiology, sources of infection, and long term protection after infant vaccination. Pediatr Infect Dis J 2005;24:S104-8.
14. Guiso N, Berbers G, Fry NK et al. What to do and what not to do in serological diagnosis of pertussis: recommendations from EU reference laboratories. Eur J Clin Microbiol Infect Dis 2011;30:307-12.
15. Bettiol S, Thompson MJ, Roberts NW et al. Symptomatic treatment of the cough in whooping cough. Cochrane Database Syst Rev 2010:CD003257. 16. Cherry JD. The epidemiology of pertussis and pertussis immunization in the United Kingdom and the United States: a comparative study. Curr Probl Pediatr 1984;14:1-78.
17. Carlsson RM, Trollfors B. Control of pertussis - lessons learnt from a 10-year surveillance programme in Sweden. Vaccine 2009;27:5709-18.
18. Nilsson L, Rydevik G. Pertussis surveillance in Sweden - Twelve year report. http://www.smittskyddsinstitutet.se/upload/Publikationer/smirapport-01-2010.pdf (last accessed 5 January 2011).
19. Murphy TV, Slade BA, Broder KR et al. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2008;57:1-51.
20. Campbell H, Manikkavasagan G, Fry NK et al. What has happened to pertussis in England and Wales? Presented at the Ninth International Bordetella Symposium, Baltimore, MD, USA, September 30 - October 3, 2010 (poster).
21. Centers for Diseases Control and Prevention. Pertussis -United States, 1997-2002. MMWR 2002; 51: 73-6.
22. Tozzi AE, Pandolfi E, Celentano LP et al. Comparison of pertussis surveillance systems in Europe. 23. Cherry JD, Grimprel E, Guiso N et al. Defining pertussis epidemiology: clinical, microbiologic and serologic perspectives. Pediatr Infect Dis J 2005;24:S25-34.
24. Wendelboe AM, Njamkepo E, Bourillon A et al. Transmission of Bordetella pertussis to young infants. Pediatr Infect Dis J 2007;26:293-9.
25. Bonmarin I, Bouraoui L, Guiso N et al. Pertussis: data collection and vaccinal strategy. Med Mal Infect 26. Bonmarin I, Levy-Bruhl D, Baron S et al. Pertussis surveillance in French hospitals: results from a 10 year 27. ECDC (European Centre for Disease Prevention and Control). ECDC Guidance: Scientific panel on childhood immunisation schedule: Diphtheria-tetanus-pertussis. (DTP) vaccination. http://www.ecdc.europa.
eu/en/publications/Publications/0911_GUI_Scientific_Panel_on_Childhood_Immunisation_DTP.pdf (last accessed 5 January 2011).
28. CDC (Centers for Disease Control and Prevention). Pertussis (Whooping Cough): Outbreaks. http://www.cdc.gov/pertussis/outbreaks.html (last accessed 26 November 2010).
29. Floret D. Les décès par infection bactérienne communautaire. Enquête dans les services de réanimation pédiatrique français (Pediatric deaths due to community-acquired bacterial infection. Survey of French pediatric intensive care units). Arch Pediatr 2001;8:705s-11s.
30. Kretsinger K, Broder KR, Cortese MM et al. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR 2006;55:1-37.
31. Schmitt-Grohe S, Cherry JD, Heininger U et al. Pertussis in German adults. Clin Infect Dis 1995;21:860-6.
32. Lee LH, Pichichero ME. Costs of il ness due to Bordetella pertussis in families. Arch Fam Med 2000;9:989-96.
33. Purdy KW, Hay JW, Botteman MF et al. Evaluation of strategies for use of acellular pertussis vaccine in adolescents and adults: a cost-benefit analysis. Clin Infect Dis 2004;39:20-8.
34. Lee GM, Riffelmann M, Wirsing von Konig CH. Cost-effectiveness of adult pertussis vaccination in Germany. Vaccine 2008;26:3673-9.
35. Tan T, Trindade E, Skowronski D. Epidemiology of pertussis. Pediatr Infect Dis J 2005;24:S10-8.
36. Liese JG, Rieber N, Malzer T et al. Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents. Pediatr Infect Dis J 2010;29:1067-71.
37. Forsyth KD, Wirsing von Konig CH, Tan T et al. Prevention of pertussis: recommendations derived from the second Global Pertussis Initiative roundtable meeting. Vaccine 2007;25:2634-42.
38. Lopalco PL, de Carvalho HG, Kreidl P et al. Childhood vaccination schedules in Europe vary widely. Is this a problem? Bundesgesundheitsblatt 2009;52:1095-8.
39. Vaccination de l'adulte CSS 2009 Belgique n° 8547.
http://www.health.belgium.be/internet2Prd/groups/public/@public/@shc/documents/ie2divers/13036470_fr.pdf (last accessed 27 January 2011).
40. BEH 22 avril 2010/n°14-15. http://www.invs.sante.fr/beh/2010/14_15/beh_14_15.pdf (last accessed 27 January 2011). 41. Epidemiologisches Bulletin Nr. 30. 2 August 2010. http://www.rki.de/cln_091/nn_1270420/DE/Content/ Infekt/EpidBul /Archiv/2010/30_10,templateId=raw,property=publicationFile.pdf/30_10.pdf (last accessed 27 January 2011).
42. Scott LJ. Tdap5 vaccine (Covaxis): a review of its use as a single-booster immunization for the prevention of tetanus, diphtheria, and pertussis in children (aged 4 years), adolescents, and adults. BioDrugs 2010;24:387-406.
Sanofi Pasteur MSD S.N.C. au capital de 60 000 000 Euros – RCS LYON B 392 032 934 - 4015390 / CO00646 - Avril 2011

Source: http://www.vacinas.com.pt/conteudos/02/94/00/01/Bordetella-Pertussis_Need-for-expanded-immunisation-programme-Wolters-Kluwer-2011_5253.pdf

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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.

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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.