Prevention of pertussis: recommendations derived from the second Global Pertussis Initiative roundtable meeting.
ABSTRACT The Global Pertussis Initiative (GPI) was established in 2001 to assess the global extent of the ongoing problem of pertussis and to evaluate and prioritize pertussis control strategies. Exchange of data, knowledge, and experience, facilitated by discussion and debate, resulted in the formulation, in 2002, of the following recommendation: all countries should consider expanding existing vaccination strategies to include adding pertussis booster doses to pre-school children (4-6 years old), to adolescents, and to those specific adults that have the highest risk of transmitting Bordetella pertussis infection to vulnerable infants. The GPI met again in 2005, where it reinforced its previous recommendation for universal adolescent immunization. Additionally, the GPI recommended implementation of the cocoon strategy (immunization of family members and close contacts of the newborn) in countries where it is economically feasible, and encouraged efforts toward global standardization of pertussis disease clinical definitions and diagnostics. Universal adult vaccination is a logical goal for the ultimate elimination of pertussis disease, but feasibility issues remain obstacles to implementation.
Article: Pertussis immunization in the global pertussis initiative international region: recommended strategies and implementation considerations.[show abstract] [hide abstract]
ABSTRACT: Despite widespread immunization programs in most countries, pertussis disease continues to be a threat to public health. In particular, there has been a resurgence of pertussis disease in older children, adolescents and adults, creating a reservoir of infection, which poses a significant threat to infants who are either unimmunized or incompletely immunized. Global Pertussis Initiative participants from Argentina, Australia, Brazil and Japan considered the relative merits of several strategies to reduce the burden of pertussis disease and suggested strategies that might be implemented in these countries. Infants in these countries receive an initial course of 3 doses of vaccine in the first year of life followed by a fourth dose in the second year. Only children in Japan are not given a preschool booster (age 3-5 years). Of the strategies considered, the addition of a preschool booster is therefore a priority in Japan to overcome the problem of waning vaccine-induced immunity to pertussis in school children. Waning immunity also affects adolescents; Australia introduced an adolescent booster in 2003, and the addition of a booster in this age group was suggested for Argentina and Japan. Immunization of new mothers and other close contacts of young infants, such as child care and health care workers, might be appropriate in Australia in the future. Argentina also suggested a future possibility of immunizing health care and child care workers. Obstacles to new immunization strategies include poor access to standardized laboratory diagnostic techniques, inadequate resources to fund new immunization programs, low awareness of pertussis disease in adults and adolescents and inadequate surveillance techniques to assess the full extent of the problems caused by pertussis or the impact new vaccination strategies might have.The Pediatric Infectious Disease Journal 06/2005; 24(5 Suppl):S93-7. · 3.58 Impact Factor
Article: New pertussis vaccination strategies beyond infancy: recommendations by the global pertussis initiative.[show abstract] [hide abstract]
ABSTRACT: The Global Pertussis Initiative, an expert scientific forum, was established to address the ongoing problems associated with pertussis disease worldwide. The group analyzed pertussis disease trends, developed recommendations to improve disease control through expanded vaccination strategies, and proposed solutions to barriers to implementation and support of research activities. Bordetella pertussis infection is endemic and continues to be a serious problem among unvaccinated or incompletely vaccinated infants. In addition, the reported incidence of pertussis disease is increasing in adolescents and adults, who not only experience a considerable health burden themselves but also infect vulnerable infants. Current vaccination strategies need to be reinforced. Expanded vaccination should include adding booster doses to existing childhood schedules (preschool or adolescent) and booster doses for those specific adult subgroups that have the highest risk of transmitting B. pertussis infection to infants (i.e., new parents, other contacts of newborns, and health care workers). More epidemiological studies and studies of disease transmission and the cost-effectiveness of vaccination would be valuable, and surveillance, diagnostic improvements, and educational campaigns are needed for implementation. However, as a prelude to universal adult vaccination, immediate universal adolescent vaccination should be instituted in countries in which it is economically feasible.Clinical Infectious Diseases 01/2005; 39(12):1802-9. · 9.15 Impact Factor
Paediatrics & child health 04/2001; 6(4):184-6. · 0.78 Impact Factor
Vaccine 25 (2007) 2634–2642
Prevention of pertussis: Recommendations derived from the
second Global Pertussis Initiative roundtable meeting
Kevin D. Forsytha,∗, Carl-Heinz Wirsing von Konigb,
Tina Tanc, Jaime Carod, Stanley Plotkine,f
aDepartment of Pediatrics, Flinders Medical Centre and Flinders University, Adelaide, South Australia
bInstitut fur Hygiene und Laboratoriumsmedizin, Krefeld, Germany
cFeinburg School of Medicine, Northwest University and the Children’s Memorial Hospital, Chicago, Illinois, United States
dCaro Research Institute, Concord, Massachusetts, United States
eUniversity of Pennsylvania, Philadelphia, United States
fSanofi-Pasteur, Pennsylvania, United States
Received 29 June 2006; received in revised form 16 November 2006; accepted 10 December 2006
Available online 22 December 2006
The Global Pertussis Initiative (GPI) was established in 2001 to assess the global extent of the ongoing problem of pertussis and to evaluate
and prioritize pertussis control strategies. Exchange of data, knowledge, and experience, facilitated by discussion and debate, resulted in the
formulation, in 2002, of the following recommendation: all countries should consider expanding existing vaccination strategies to include
adding pertussis booster doses to pre-school children (4–6 years old), to adolescents, and to those specific adults that have the highest risk of
transmitting Bordetella pertussis infection to vulnerable infants. The GPI met again in 2005, where it reinforced its previous recommendation
for universal adolescent immunization. Additionally, the GPI recommended implementation of the cocoon strategy (immunization of family
of pertussis disease clinical definitions and diagnostics. Universal adult vaccination is a logical goal for the ultimate elimination of pertussis
disease, but feasibility issues remain obstacles to implementation.
© 2006 Elsevier Ltd. All rights reserved.
Keywords: Pertussis; Epidemiology; Immunization strategies; Transmission; Reporting; Infection; Infants; Adults; Adolescents; Health economics
The Global Pertussis Initiative (GPI) was established in
2001 with three main objectives: to raise the profile of per-
tussis as an important and preventable disease that warrants
greater global public health attention; to improve under-
standing of the increasing incidence of reported pertussis;
and to develop effective immunization strategies for pertus-
sis control. The GPI is composed of 37 experts in the field
of pertussis from 17 countries worldwide and its work is
supported by an unrestricted educational grant from sanofi
∗Corresponding author. Tel.: +618 8204 4459; fax: +618 8204 3945.
E-mail address: Kevin.Forsyth@flinders.edu.au (K.D. Forsyth).
pasteur. After in-depth evaluation of the available data, pri-
oritization of various immunization strategies, creation of
a health economic model to study the cost effectiveness
of the proposed strategies, and identification of potential
barriers to implementation of the recommendations and pos-
sible solutions to these barriers, the GPI concluded that
current vaccination strategies needed to be reinforced and
doses for adolescents in developed countries. Additionally,
the group recommended that immediate universal adolescent
vaccination and immunization of healthcare and childcare
workers should be instituted. Australia introduced an adoles-
0264-410X/$ – see front matter © 2006 Elsevier Ltd. All rights reserved.
K.D. Forsyth et al. / Vaccine 25 (2007) 2634–2642
tries, including, Austria, Canada, France, Germany, and the
United States, have incorporated an adolescent booster dose
into their current immunization schedules, as advocated by
the GPI .
The GPI held its second roundtable meeting in December
2005 to re-evaluate previous recommendations and to dis-
cuss the progress made in pertussis control since their first
meeting in 2002. Twenty-three members of the GPI, led by
met for 2 days to present the latest developments on the epi-
demiology and diagnosis of pertussis and to examine various
vaccination strategies with the aim of proposing updated rec-
from the meeting and presents the group’s recommendations
for adolescent and selective adult immunization.
2. Epidemiology of pertussis
Although progress has been made since the first GPI
meeting in 2002 toward gaining a better understanding of
the transmission and control of pertussis, in 2006 the dis-
ease remains an important public health concern. The World
Health Organization (WHO) estimates that at least 27 mil-
294,000 deaths from pertussis in children under age 5 (2002
data) could have been preventable by vaccines . It contin-
ues to be endemic worldwide, with an estimated 50 million
cases occurring annually, 90% of which are in developing
countries [4,5]. Infants remain the most vulnerable group.
From 1997 to 2000 in the United States, 20% of all pertussis
cases required hospitalization; 90% of those patients were
infants <1 year old . Incidence rates vary widely, but the
general resurgence of reported pertussis, especially among
the adolescent and adult populations, indicates that current
immunization schedules, among other factors, inadequately
protect against the disease.
In the pre-vaccine era, pertussis was universally present
with cyclic peaks every 2–5 years. Reported cases averaged
157 per 100,000 in the United States and occurred almost
exclusively in unvaccinated children [7,8]. The early use of
whole-cell vaccines and the implementation of an immu-
nization schedule in the United States were highly effective,
reducing the incidence of reported pertussis to <1 case per
100,000 during the 1970s. Since 1984, there has been a
modest increase, although some would say a resurgence,
in reported pertussis, to 9 per 100,000, with cyclic peaks
still occurring at 2–5-year intervals [7,9]. It is believed that
endemic adolescent and adult disease is likely to be respon-
2.1. Evolution of Bordetella pertussis
To determine whether B. pertussis is polymorphic or
evolving, members of the GPI roundtable agreed that the
parison of clinical isolates in different parts of the world;
analysis and comparison of clinical isolates collected before
and after introduction of vaccination in the region of inter-
est; and analysis of the epidemiology of the disease in the
the mid-1980s on the evolution of B. pertussis generally
concluded that some strains were subject to rapid muta-
using typing techniques such as multi-locus enzyme elec-
pertussis exhibits very restricted genetic diversity compared
with other bacterial species [12,13].
Results obtained with the use of more recent typ-
ing techniques that allow analysis of portions of the
bacterial genome, such as restriction fragment length poly-
morphism (RFLP), multi-locus sequence typing (MLST),
multiple antigen sequence typing (MAST), and multiple-
concurred that B. pertussis shows very restricted genetic
diversity, but some differences are seen between vaccine
strains and circulating isolates . Small and seasonal dif-
the whole genome . In a study where pulsed-field gel
electrophoresis was used to type B. pertussis strains isolated
from children with severe versus mild illness, no significant
differences in PFGE patterns were found between groups
. This indicates that variability in severity of pertussis
could not be attributed to specific hypervirulent clones of B.
ponents included in several acellular component pertussis
(aP) vaccines . Data on duration of immunity in France
after wP or aP vaccines show that the level of protection has
not changed in the past 10 years although circulating isolates
were shown to have changed [17,18]. Data on isolates col-
lected in Japan, a country using aP vaccines for more than 20
years, indicate that the antigenic divergence found between
B. pertussis vaccine strains and circulating strains have not
affected the efficacy of pertussis vaccination in Japan .
2.2. New data on pertussis in Europe
period during which data were collected on the epidemiol-
and to assess the burden of disease in adolescents and adults
[20,21]. The study pooled national surveillance data from
1998 to 2002, and showed a wide variation in reported inci-
dence, from 0.1 per 100,000 population for Portugal (a total
of 47 reported cases) to 123.9 per 100,000 for Switzerland
(a total of 845 reported cases). Countries north of Germany
were shown to have a higher incidence of reported pertussis
than countries in southern Europe. The incidence tended to
K.D. Forsyth et al. / Vaccine 25 (2007) 2634–2642
increase from 1998 to 2002 in adults and possibly in infants.
Seasonality data suggest a synchronization of cases in chil-
definition among the 16 participating countries, or stringent
surveillance processes, there was likely significant under-
study. The EUVAC-NET data did not include information on
vaccination coverage for all the countries, but sub-analyses
of the available data for Denmark (a total of 997 cases from
cases), and Norway (12,748 cases) indicated that one dose of
less than 1 year of age .
Comparison of the data between the EUVAC-NET coun-
tries may not be appropriate due to the high variability of
the surveillance systems and diagnostic and reporting meth-
ods, but EUVAC-NET was the first pertussis surveillance
study that might allow for an examination of incidence data
between European countries. In contrast, there is a serious
lack of information regarding the incidence of pertussis in
and India. Better diagnostic tools and better reporting will
likely prove that current numbers grossly underestimate the
true incidence. For epidemiologically and clinically valuable
data to be collected, there is a need to enhance and harmo-
nize surveillance systems among countries worldwide, using
anti-PT IgA may provide a better approximation of true rates
of infection in adolescent and adult populations.
Clearly, there are different surveillance systems, different
and seeks to find some process to enhance standardization
globally. Policy issues around infectious disease and immu-
GPI would consider convening a pertussis standardization
summit to begin a process of harmonization of pertussis pro-
tocols internationally. Only then can true comparisons be
undertaken and better understanding of pertussis disease be
3. Differential diagnosis
Correct diagnosis of pertussis can be a challenge because
of the overlap of symptoms with other respiratory infections
caused by viruses and other bacteria. Differential diagnosis
of prolonged cough, even with paroxysms, may include Bor-
detella parapertussis, Bordetella bronchiseptica, Chlamydia
pneumoniae, Mycoplasma pneumoniae, adenoviruses, respi-
ratory syncytial virus (RSV), human parainfluenza viruses,
influenza viruses A and B, rhinovirus, and human metapneu-
Although culture is now less frequently used than in years
past for laboratory confirmation of causative pathogens, bac-
terial isolates are still needed for genotypic and phenotypic
tages include offering a result within a few hours, and no
requirement for samples to be handled post-amplification,
which will reduce the risk of contamination. The Euro-
pean Research Programme for Improved Pertussis Strain
Characterization and Surveillance (EUpertstrain) published
a consensus paper in 2005 that addressed the methodology
DNA . It concluded that real-time PCR is more sensitive
than culture for the detection of B. pertussis and B. para-
pertussis, especially after the first 3–4 weeks of coughing
and after antibiotic therapy has been started. There are still
problems with quality control and standardization; a good
working model for global use is still 2–4 years away from
There is good evidence that PT IgG geometric mean
titre correlates with severity of symptoms , and that an
IgG–PT cut-off of 100U/ml for serodiagnosis is reliable in
all age groups. Furthermore, an IgG–PT of <10U/ml is asso-
ciated with increased risk of re-infection . Serology is
therefore a reliable test for clinicians to diagnose B. pertussis
primarily in relation to anti-PT IgG. A reference serum pre-
pared by the FDA is currently generally accepted, but a new
one being tested is expected to become the WHO reference
serum. The serological cut-off for confirmation of diagnosis
will probably be similar worldwide.
4. Prevention of pertussis: vaccination strategies
Since it was established in 2001, GPI members have
reviewed the international literature and exchanged data,
knowledge, experience, and opinion through teleconfer-
ences, a password-protected interactive Web site, and the
two roundtable meetings. With the goal of identifying and
addressing potential barriers to pertussis control, they evalu-
immunization of adolescents; universal immunization of
adults; selective immunization of new mothers, and family
and close contacts of newborns (cocoon strategy); selective
immunization of healthcare workers; selective immuniza-
tion of childcare workers; implementation of a fourth or
fifth booster dose for all pre-school children (4–6 years
of age); and improvement of current infant and toddler
immunization strategies. An outcome of the first major
GPI symposium was a clear recognition that adolescent
vaccination was an important additional step to help con-
trol pertussis disease in the adolescent populations. This
second GPI symposium has expanded on this earlier rec-
ommendation, in that the ongoing problems of severe
pertussis disease in the neonatal and infant populations
have been better clarified and understood, with a particu-
lar focus on possible intervention strategies to address this
K.D. Forsyth et al. / Vaccine 25 (2007) 2634–2642
4.1. Adolescent vaccination
The GPI previously noted that the incidence of pertus-
sis in adolescents appears to be increasing, as shown in
studies from regions as diverse as Canada, Poland, and the
United States [26–29]. Pertussis is a particularly serious ill-
and adolescents have been shown to be an important source
of infection for young infants. A recent Centers for Disease
Control and Prevention (CDC) study of 774 infant cases of
reported pertussis from four states showed that among 264
infants for whom a source could be identified, 56% were
adults ≥20 years of age and 20% of the sources were 10–19
years of age . Adding boosters to existing childhood
adult subgroups at highest risk of transmitting B. pertussis
infection to infants were expanded immunization strategies
recommended previously by the GPI.
Pertussis continues to be a worldwide problem even
though immunogenic and effective vaccines are available
and can be safety administered beyond childhood [31–33].
A study in Prince Edward Island in Canada explored the
immunogenicity of Tdap after different vaccination intervals
(2–9 years) in cohorts who had previously been vaccinated
The results showed that Tdap was well tolerated by adoles-
cents who were immunized after intervals of 2 to ≥10 years
after receiving a previous DTwP/DTaP/Td-containing vac-
cine and that it can be safely administered at intervals as
short as 18 months after prior tetanus, diphtheria, or per-
tussis vaccination. A more recent study to assess the safety
and immunogenicity of a sixth dose of Tdap vaccine in ado-
lescents showed that, regardless of the prior DTaP/DTwP
vaccination history, a sixth sequential dose of Tdap appears
safe and immunogenic .
The Advisory Committee on Immunization Practices
(ACIP) of the CDC has recently recommended routine Tdap
vaccination for adolescents, based on the following: “evi-
dence regarding the burden of pertussis among adolescents;
negative effects of pertussis outbreaks involving adolescents
on the community and the public health system; studies
suggesting use of Tdap among adolescents will likely be
safe, effective, and economical; and the established infras-
tructure for adolescent vaccination” . Other countries,
including Canada, Austria, Australia, France, and Germany,
evidence suggests that they are effective, but surveillance
will be required to confirm this . The duration of pro-
tection (and need for an adult booster after the adolescent
one) is not known. Some studies indicate that antibody lev-
els may decrease after 3 years, but they remain significantly
higher than pre-booster immunization levels . As more
data from vaccinated cohorts become available, it will be
GPI recommendation of universal adolescent immunization
programs is still valid based on the continued high rates of
after school entry.
4.2. Adult vaccination
There are two potential approaches to vaccinating adults:
universal adult vaccination to build up herd immunity and
eradicate B. pertussis infection; and selective vaccination
of those adults who are at highest risk of transmitting B.
United States and elsewhere, disease prevention in adults is
not widely practiced: for example, although annual flu vacci-
nation is recommended for healthcare workers, CDC survey
data for 2004 indicated a vaccination coverage level of only
42% . Experts and supporting models support the notion
that universal vaccination would markedly reduce the inci-
dence of pertussis disease among all ages [32,41,42]. In the
past, pertussis did not have a sufficiently high profile to drive
a change in preventive medicine practices. However, some
recent events have led to an increased public awareness of
adolescent and adult pertussis and also the need for a more
universal approach to adult immunization. Specifically, the
dramatic increase in reported pertussis in adolescents and
adults has resulted in extensive media coverage and dissem-
ination of the information that new vaccines are available
[43,44]. In the opinion of the GPI, the concern about avian
influenza and the publicity surrounding new human papil-
lomavirus (HPV) vaccines that can prevent cervical cancer
have led to an increased general awareness about vaccines
policy bodies are advocating ‘whole-of-life’ immunization
The Adult Pertussis Trial (APERT), sponsored by the
National Institutes of Health (NIH), has demonstrated the
efficacy of acellular pertussis vaccines in preventing pertus-
sis disease in adolescents and adults [45,46]. Subjects who
received either a dose of a tricomponent acellular vaccine
(n=1391) or a hepatitis A vaccine (controls, n=1390) were
tussis vaccine met the primary case definition (culture, PCR,
cacy of 92% (95% confidence interval, 32–99%). Among
cases that were confirmed by culture or PCR assay, five were
in the control group and none were in the vaccine group. The
duration of protection and prevention of secondary disease
were not assessed in this study.
The safety of vaccination in adolescents and adults is well
doses of Tdap. Pertussis prevention advocacy will be key
to overcoming implementation issues, but payment will be
an issue in many countries (particularly developing coun-
tries). For an adult vaccination program to be successful,
key components must include education and public aware-
ness. Advocacy among healthcare providers is important
K.D. Forsyth et al. / Vaccine 25 (2007) 2634–2642
in driving vaccine coverage and needs to be emphasized
in most countries. Because there is a moral imperative for
healthcare workers to protect themselves and those in their
employees. With education, childcare workers and parents
tion more quickly than the general population. Furthermore,
adults with chronic underlying lung disease, such as chronic
obstructive pulmonary disease (COPD), may also benefit
from pertussis immunization. Findings from one study in
patients with COPD indicated that as much as 31% of acute
exacerbations might be caused by Bordetella infections .
The new ACIP recommendations to replace Td with Tdap
among adults in the United States are highly significant.
This indicates a policy shift to adult pertussis disease pre-
vention, and although it may not have an immediate effect,
the leadership in immunization provided by the ACIP will
likely lead to increased adult immunization uptake over time
. Twelve European countries currently recommend Td
vaccination every 10 years.
4.3. Cocoon strategy
Several recent studies indicate that adults – mothers, in
particular – are an important source of B. pertussis infec-
tion to unvaccinated or incompletely vaccinated infants. A
national active monthly surveillance program of child health
specialists conducted in 2001 in Australia revealed that 140
infants (median age at diagnosis, 8 weeks) were hospitalized
with pertussis and 4 infants (<6 weeks old) died . Of 97
(69%) infants who had not been vaccinated for pertussis, 63
vaccine (<8 weeks old). A coughing contact was identified
for half the cases, and 68% of those were adults, usually one
of the infant’s parents. Other studies have confirmed these
results and indicate that parents act as primary vectors in
30–57% of infant cases [9,30,50,51].
siblings) of newborns, known as the cocoon strategy, should
be considered as a first step toward (or a component of)
universal adult vaccination. A study designed to evaluate
the impact of five adolescent/adult immunization strategies
showed that although the cocoon strategy leads to only a
9–17% reduction in typical adult cases, there is a strong indi-
rect effect on infants and young children: a decrease by 70%,
65%, and 69% was noted in cases among the 0–3-month-
old, 4–23-month-old, and 2–4-year-old groups, respectively
the cocoon strategy should be recommended, even though it
can only reduce (but not eliminate) the risk of infants acquir-
strategies have not been successful for the control of other
infectious diseases, it is considered that the cocoon strategy
is worthy of implementation for pertussis [53,54]. Even pro-
tecting just some infants would be considered a success. The
cocoon strategy is recommended in Australia, France, Ger-
many, and Austria, although there are no requirements in
these countries to enforce this policy, and vaccine coverage
is currently low [38,55].
4.4. Maternal vaccination
that cause substantial morbidity and mortality worldwide.
The immune system of neonates is immature and relatively
ineffective, and a US study by Healy et al. has shown that
babies born during recent years have low levels of pertussis-
specific antibody . They found that although placental
transfer of pertussis antibodies is efficient, low maternal lev-
els and their rapid decay in infant sera leave infants with
little protection against life-threatening pertussis in early
infancy. Although Healy’s data provide some support for the
rationale of maternal immunization with acellular pertussis
vaccines, there is clearly a role for cellular immunity in per-
any biological agent, it is unlikely maternal immunization
alone will significantly reduce the incidence of B. pertussis
infection in infants; it needs to be part of a broader vac-
cination strategy, including adolescents and at least those
During the 1930s and 1940s, the possibility of protecting
ing pregnancy was investigated, but no further work in that
area was published until recently. Some animal and human
traindication to Tdap or Td vaccination, and guidance on the
use of Tdap during pregnancy is currently under considera-
tion . Immunization during pregnancy has the potential
to protect both mother and infant during a vulnerable period
in their lives. Transplacental transfer of antibodies is safer
and less expensive than administration of immunoglobulin
preparations to the infant. There is proven antibody transfer
sufficient to protect the neonate from B. pertussis infection.
There is also uncertainty about whether maternal immuniza-
tion could affect the immunogenicity and efficacy of primary
and/or booster vaccination in infants/children [60–62].
4.5. Neonatal vaccination
In the United States from 1938 to 1940, there were
more than 10,000 recorded pertussis deaths, 70% of which
occurred in infants (most were younger than 4 months) .
In recent years, there has been a resurgence of reported per-
tussis in infant populations, as demonstrated by studies in
Canada, France, Germany, and the Netherlands [9,64–66].
In Australia over the past 20 years, hospitalization rates for
K.D. Forsyth et al. / Vaccine 25 (2007) 2634–2642
infants <5 months have remained unchanged despite exten-
sive immunization coverage .
Several studies conducted during the past decade have
confirmed earlier findings of acceptable safety, efficacy, and
immunogenicity of pertussis vaccination (DTwP), in full-
term and pre-mature infants [67,68]. A study by Englund
et al. showed that there was no suppression of subsequent
vaccine immunogenicity in infants born to mothers with
high antibody levels after primary immunization with Tdap
(although after whole-cell pertussis vaccine, higher levels
of pre-existing antibody were associated with substantial
(28–56%) reductions in the subsequent antibody response
to pertussis toxin) . Neonatal and maternal vaccinations
are similar ways to achieve the same goal, but maternal vac-
cination has fewer implementation issues, although will not
rounding neonatal vaccination are complex. It is practice in
some countries to give hepatitis B vaccine at birth. However,
the uptake is relatively low, partly because the immunization
delivery infrastructure has not traditionally included mid-
wives. It is unclear if newborn pertussis immunization will
induce sufficient and timely immunity. Clearly further trials
are needed, and the GPI strongly endorses such trials to be
5. Utilization of Tdap in 4–6 year olds
Booster doses of DTaP vaccines given at 4–6 years of
age are commonly followed by large injection site reactions,
with an increase in redness, swelling, and pain compared to
previous reactions . Several studies have shown that the
adolescent/adult formulation diphtheria, tetanus, and acel-
lular pertussis combination vaccine with lower pertussis and
togenic and slightly less immunogenic than the pediatric
formulation combination vaccine (DTaP) when given as a
booster to 4–6-year-old children [71–73].
As booster responses to all antigens appear adequate with
Tdap, it might be preferable to use Tdap or Tdap-IPV (inac-
tivated poliomyelitis viruses vaccine) from mid-childhood
onwards. Where both Tdap and DTaP are licensed, coun-
tries need to determine which vaccine to use. Australia and
Switzerland currently use DTaP for primary immunization
and the pre-school booster. Germany has recently introduced
Tdap as a fifth dose, given at 5–6 years of age, while contin-
uing to recommend Tdap-IPV at 9–17 years (previously the
fifth dose, but now the sixth dose).
Further studies would be useful to confirm that Tdap
(±IPV) vaccines are not inferior in immunogenicity and are
less reactogenic compared to full-content DTaP (±IPV) vac-
cines. Because Tdap vaccines may be significantly better
tolerated, more studies are warranted on their routine use
for children 4–6 years of age. These studies should be done
with vaccines from both major manufacturers (sanofi pasteur
and Glaxo SmithKline).
6. Economic assessment
An understanding of the impact of vaccination on disease
transmission (i.e., capturing herd immunity) is a key to being
able to assess the economic value of adult strategies. A mod-
eling study conducted by Drs. A. Van Rie and J. Caro was
designed to provide transmission probabilities data to better
assess the impact of the following adolescent and adult vac-
cination strategies in the United States: routine adolescent
vaccination; the cocoon strategy; and routine adult vaccina-
tion every 10 years (unpublished data presented at the GPI
Roundtable Meeting, December 9, 2005, Paris, France). Pre-
liminary results of that study, using an updated computer
simulation incorporating the most current US epidemiologi-
cal information, indicate the following:
• If vaccinations were introduced using any of the three
strategies above, the overall incidence of infection would
• Routine adolescent vaccination would have an important
effect on the incidence of pertussis in the 0–19 year olds,
reducing infection to 40% of its current level.
• The cocoon strategy plus routine adolescent vaccination
would effect a further 50% reduction in infant pertussis,
but would have no substantial additional impact on the
incidence of pertussis infection in the general population.
school or work) associated with reported pertussis in adoles-
the infected adults are healthcare workers, serious adverse
health (transmission to patients, colleagues, and family) as
well as economic consequences can result . Although
there are limited new data examining both direct and indirect
to use models to examine adolescent and adult vaccination
strategies, and utility estimates have also been developed.
Computer simulations predict that the cocoon strategy will
and extent of herd immunity are accurate, and implemen-
tation of the vaccination schedule is feasible), although the
relative ranking of the various adolescent/adult vaccination
these models persist: cost data are scanty, especially for mild
cases; the extent of herd immunity is unknown; no data exist
from outside Europe, North America, and Australia; and the
long-term effectiveness of the vaccines is uncertain.
7. Conclusions and recommendations
Since 2001, there has been notable progress in the under-
standing of B. pertussis disease, but it continues to affect
millions of people worldwide and is a major cause of infant
mortality, especially in developing countries. Previously, the
GPI recommended that an acellular pertussis vaccine be
incorporated into the current dT vaccine schedule for adoles-
K.D. Forsyth et al. / Vaccine 25 (2007) 2634–2642
countries have incorporated that recommendation into their
immunization schedule . The GPI also recommended
increased and improved surveillance, improved detection,
and greater awareness of pertussis as a major public health
problem in order to arrive at a measure of the true incidence
of the disease and the effectiveness of any immunization
strategy. At their second meeting, the GPI acknowledged
and reinforced their previous recommendations for expand-
ing pertussis vaccination to adolescents. They emphasized
second meeting addressed quite specifically the problems of
neonatal and infant pertussis disease, and after reviewing
and discussing available data the GPI has further endorsed
implementation of the cocoon strategy in countries where it
is economically possible, as well as selective vaccination of
healthcare workers and childcare workers. Universal adult
vaccination may be justified by the available epidemiologi-
cal data, but its feasibility is currently in question. As new
data continue to support the immunogenicity and safety of
Tdap vaccines in adolescents and adults, an efficient way to
immunize these populations would be to substitute Tdap or
ommended in many countries. Standardization of diagnostic
tests, reagents and clinical criteria are urgently required; the
GPI is willing to support or generate such a process.
will focus on issues that must be resolved with the aim of
preventing infant morbidity and mortality from pertussis and
tailoring strategies to fit the needs of each country. The GPI
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