Human Vaccines

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The global pertussis initiative: Meeting report from

the regional Latin America meeting, Costa Rica, 5-6
December, 2008

Rolando Ulloa-Gutierrez, Daniela Hozbor, Maria L. Avila-Aguero, Jaime Caro,

Carl-Heinz Wirsing von König, Tina Tan & Stanley Plotkin

To cite this article: Rolando Ulloa-Gutierrez, Daniela Hozbor, Maria L. Avila-Aguero, Jaime Caro,
Carl-Heinz Wirsing von König, Tina Tan & Stanley Plotkin (2010) The global pertussis initiative:
Meeting report from the regional Latin America meeting, Costa Rica, 5-6 December, 2008, Human
Vaccines, 6:11, 876-880, DOI: 10.4161/hv.6.11.13077

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 review

Human Vaccines 6:11, 876-880; November 2010; © 2010 Landes Bioscience

The Global Pertussis Initiative

Meeting report from the Regional Latin America Meeting,
Costa Rica, 5–6 December, 2008
Rolando Ulloa-Gutierrez,1,* Daniela Hozbor,2 Maria L. Avila-Aguero,3 Jaime Caro,4 Carl-Heinz Wirsing von König,5 Tina Tan6
and Stanley Plotkin7
1
Servicio de Infectología Pediátrica; Hospital Nacional de Niños; San José, Costa Rica; 2Instituto de Biotecnología y Biología Molecular; Universidad Nacional de La Plata; La
Plata, Argentina; 3Ministra de Salud; Ministerio de Salud; San José, Costa Rica; 4United BioSource Corporation; Lexington, MA USA; 5Institut fuer Hygiene und Labormedizin;
HELIOS Klinikum Krefeld; Krefeld, Germany; 6Northwestern University Feinberg School of Medicine; Children’s Memorial Hospital; Chicago, IL USA; 7University of Pennsylvania;
Philadelphia, PA USA

Key words: pertussis, incidence, Latin America

Pertussis remains endemic across the world, with an estimated
279,000 deaths in 2002, the majority in infants under 1 year
of age. Worldwide epidemiologic data indicates increasing
infection rates in older children and adults, which act as a
source of infection to young infants. The Global Pertussis
Initiative (GPI) is an expert scientific forum, which has
published consensus recommendations for the monitoring,
prevention and treatment of the disease. This paper reports
the proceedings of a regional meeting, held in Costa Rica
in December 2008. The meeting gathered information on
regional epidemiological, diagnostic capabilities and the
ability to introduce GPI recommended vaccine strategies in
Latin America. The capacity of Latin American countries to
conduct vaccination programs is high and there is considerable
government support. Whole-cell pertussis vaccines are used
across Latin America, which appear to be quite effective. A
4-dose schedule is typically used (2, 4, 6 and 18 months) and
a booster given at 4 to 6 years of age, with coverage often
above 90%, but with regions of low coverage due to political
and geographical difficulties. Adequate surveillance is lacking
in many countries, giving insufficient data to guide vaccination
policy. Improvements are being made, with countries such as
Costa Rica, Panama and Argentina introducing polymerase
chain reaction (PCR) diagnosis. Those countries that do
not currently use a preschool booster should launch one.
Implementing vaccination programs in adolescents and/or
adults to reduce exposure to infants would be beneficial and
possible in most countries, given their current infrastructure.
Introduction
The Global Pertussis Initiative (GPI) is an expert scientific
forum, set up in 2001 to assess the ongoing problem of pertussis
*Correspondence to: Rolando Ulloa-Gutierrez; Email: rolandoug@racsa.co.cr
Submitted: 07/14/10; Accepted: 07/20/10
Previously published online:
www.landesbioscience.com/journals/vaccines/article/13077
DOI: 10.4161/hv.6.11.13077
and to publish consensus recommendations for the monitoring,
prevention and treatment of the disease. The GPI consists of 35
global opinion leaders, chaired by Dr. Stanley Plotkin. The group
has previously developed and published specific recommenda-
tions for vaccinations beyond childhood to limit the impact of
the disease.1 In addition, a supplement was published that went
into further detail on various aspects of the disease.2 An update
meeting was held in Paris in 2005, with further recommenda-
tions that were also published.3
The GPI then considered how these recommendations could
be implemented, recognizing that this depended centrally on
regional problems and resources. With this in mind, GPI meet-
ings were held between 2006–2008 in Asia-Pacific, Eastern
Europe and Latin America.
This paper reports the proceedings of the meeting held in San
José, Costa Rica in December 2008. The meeting was opened by
the acting president of Costa Rica. Thirteen physicians represent-
ing countries all across Latin America attended, in addition to seven
members of the GPI. The meeting had three aims: (1) to gather
information about the regional epidemiology of pertussis and the
regional means for diagnosis; (2) to consider regional issues about
suggested vaccine strategies; and (3) to discuss regional implemen-
tation issues and regional cost-effectiveness issues.
Global Pertussis Incidence
All three regional meetings shared similar themes, which have
been discussed previously by the GPI.1-3 Pertussis remains
endemic across the world and remains one of the most common
infections leading to death in infants. In 2002, approximately
17.6 million cases of pertussis occurred worldwide, 90% of which
were in developing countries and about 279,000 people died
from the disease.4 The majority of these deaths were in infants
≤1 year old. Epidemiologic data from across the globe, in both
resource-rich and -poor countries, indicates a reduced burden of
disease in infants, which is to be welcomed, but also increasing
infection rates in older children and adults.5 Furthermore, there
has been a shift from siblings to parents as sources of infection
for young infants.

876 Human Vaccines Volume 6 Issue 11

 review meeting report

Table 1. Summary of pertussis immunization schedules

Maternal Adolescent
2, 4, 6 months 18 months 4–6 years
­postpartum (10–12 years)
Argentina# - DTwP Hib HB DTwP Hib DTwP Tdap
Brazil - DTwP DTwP DTwP *
-
Chile - DTwP DTwP DTwP** -
Colombia - DTwP DTwP DTwP -
Costa Rica TdaP DTwP DTwP DTwP** -
Guatemala - DTwP DTwP DTwP -
Mexico - DTaP DTaP DTaP -
Panama - DTwP DTwP DTwP Tdap
Paraguay - DTwP DTwP DTwP -
Venezuela - DTwP DTwP DTwP -
DTaP, diphtheria/tetanus/acellular pertussis; DTwP, diphtheria/tetanus/whole-cell pertussis. DTaP is given to children with special problems or those
*

with adverse events to DTwP. **It is planned to change to DTaP soon (Costa Rica, 2nd semester 2010). #Argentine National Immunization Schedule estab-
lished from the second half of 2009.

Table 2. Vaccine coverage per country
Country Surveillance methods
Argentina DTP3, over 90%; but in some regions below 80%
Brazil 95%, approaching 100% in some regions
Chile DTP3, 93%–95% between 1999–2006
Colombia 90%, although some local areas with 60%
Costa Rica 90%
Guatemala 80%–86%; 50% for 18-month booster
Mexico 93%
Panama 80%–90%
Paraguay Generally 80%, recent drop to about 60%
Optimal DTP3 coverage, 42% in 1990; 18% in 2007
Venezuela
DTP coverage per year, 60%–90%
Pertussis Vaccination in Latin America
The capacity of Latin American countries to conduct vaccina-
tion programs is very high and there is considerable government
support. The most commonly used vaccine against pertussis
across Latin America is whole-cell pertussis vaccine combined
with tetanus and diphtheria (DTwP) or tetanus, diphtheria and
other vaccines such as Hib (DTwP Hib) or Hib and hepatitis
B (DTwP Hib HB), with a 3-dose schedule, given at 2, 4, and
6 months (Table 1). Some countries include the first booster
dose at 18 months of age. A fifth dose at age 4 to 6 years has
been implemented in only 6 of the 10 Latin American coun-
tries represented at the meeting. Only Mexico uses acellular
vaccine (DTaP diphtheria/tetanus/acellular pertussis) routinely,
using the same dosing schedule. Adolescent immunization with
Tdap is only in place in Argentina and Panama, to reduce the
potential source of infection to infants from older age groups. In
2009, Panama extended the vaccination program to postpartum
maternal immunization and health care workers (reported to the
GPI following the meeting), as a recent outbreak occurred.6 In
2007 in Costa Rica, following outbreaks of pertussis disease,
a nationwide postpartum maternal Tdap vaccination program
was launched to immunize mothers within 48 hours of giving
birth.7,8 This is an example of the cocoon strategy recommended
by the GPI and the outcome of this strategy in Costa Rica is
awaited with interest.
Three-dose pertussis coverage is high, typically 90%, across
the region, with the highest coverage reported in Brazil (95%)
(Table 2). According to the Ministry of Health, in Argentina
DTP3 coverage in 2008 was 92.5% (91.3% in 2007), but this
value is not for the whole country because there are some regions
with coverage below 80%. Argentina is aiming to focus con-
trol of pertussis outbreaks by increasing vaccine coverage in all
regions, and to induce herd immunity using Tdap boosters for
adolescents and child health care workers. In Paraguay coverage
is typically 80% but has recently dropped to 60%, due to diver-
sion of resources to other diseases like dengue and yellow fever.
In Venezuela DTP3 coverage was only 60% by 2008, but has
improved in 2009 up to 80% (reported to the GPI post-meet-
ing). Across Latin America, there are some rural and urban areas
without sufficient coverage, with political issues often influenc-
ing resources.
Whole-cell pertussis is generally used in Latin America, and
there was overall satisfaction with its effectiveness, shown by
lower levels of clinical cases compared with the pre-vaccination
era. However, there is recognition that there are issues of repro-
ducibility and reactogenicity with whole-cell vaccines. This is
evident particularly in Chile, where a high rate of adverse events
occurred in 2005 upon the introduction of a new vaccine. A com-
parison between 2 DTwP vaccines, used at ages 18 months and
4 years, demonstrated that children who received one of these
vaccines showed a higher risk of presenting with adverse reac-
tions (relative risk = 2.9; p < 0.001), of which high fever was the
most common. There was also a greater probability of consult-
ing at emergency rooms for severe adverse reactions, particularly
among 4-year-old children (odds ratio = 18.9; p < 0.001).9 It is
likely that acellular vaccines will be introduced across the region
in the future.

www.landesbioscience.com Human Vaccines 877

 Surveillance and Diagnosis
Complete surveillance is lacking in many countries, giving insuf-
ficient data to guide vaccination policy (Table 4). In Costa Rica,
an observed increase in pertussis, including 18 deaths, drove
improvements in surveillance and diagnosis and led to the intro-
duction of the cocoon strategy. The country now has compul-
sory surveillance, wide availability and use of polymerase chain
reaction (PCR) for diagnosis of pertussis. Panama also uses PCR
diagnosis, but in general across the region, specific laboratory
diagnosis by PCR and serology are lacking and this is the major
technology gap in the capacity for Latin America to deal with
pertussis effectively.
Argentina uses intensive surveillance, diagnosing clinically
with laboratory confirmation. Probable cases are defined on clini-
cal signs, with confirmed cases assessed by culture, PCR or serol-
ogy, or by epidemiologic linkage to a laboratory-confirmed case.
Chile and Colombia use a similar system, with clinical diagnosis
and laboratory confirmation, mainly using immunofluorescence
(IF) due to its low cost and availability in the public sector diag-
nostic laboratories. However, using IF may hinder laboratory
confirmation and indeed in Colombia the confirmation rate is
low, e.g., in 2007, 387 suspected cases were reported, but only 28
were confirmed.
Guatemala, Panama and Paraguay all stated that their cur-
rent passive surveillance systems were inadequate and there was
a need to move toward active surveillance. Brazil recognizes that
its laboratory facilities need to improve, with diagnoses mostly
made by clinical criteria (62%), with the remainder diagnosed
by leukocytosis or lymphocytosis, epidemiologic link or culture.
Improvements in laboratory diagnoses, however, are ongoing in
other countries in the region, with Panama (and Costa Rica,
see above) reporting the introduction of PCR. It was men-
tioned that professional workshops on laboratory diagnosis may
be helpful. The Pan American Health Organization (PAHO;
devserver.paho.org)10 is currently funding an initiative of this
type in three countries (Panama, Mexico, and Argentina) in the
first instance.
The World Health Organization has developed a generic pro-
tocol for estimation of disease burden of pertussis in neonates
and school-age children that may have utility in Latin America.
One feature of the protocol was information to set up for diag-
nostic laboratories and hospital-based surveillance (www.who.
int/immunization_monitoring/diseases/pertussis_surveillance/
en/index.html).4 Hospital surveillance is particularly important,
because this is where disease in infants is observed, and gener-
ally levels of hospital care are good in Latin America, albeit with
regions lacking facilities in areas of extreme poverty.
Incidence
In Argentina, incidence rates were 1.8 per 100,000 inhabitants in
2003, increased to 2.7 in 2004, then to 5.7 in 2005 and declined
to 4.4 in 2006 (Table 3).11,12 Most of the detected cases are in
infants <6 months, who have not received or only received 1 dose
(the median age of hospitalized children was <3 months). There
878 Human Vaccines Volume 6 Issue 11
Table 3. Reported incidence rates
Country Reported incidence
2 per 100,000 inhabitants until 2003; 4.4 per 100,000 in
Argentina
2006
17,349 reported cases, with 6,887 confirmed cases in last
reportable year
Brazil Highest incidence in the North: 10 per 100,000
inhabitants
Epidemics reported in Sao Paulo and Rio Grande do Sul
25 per 100,000 in 1996; 6–7 per 100,000 in 2007–2008
In children aged >1 year, 330 per 100,000; 6–9 deaths/
Chile
year
Aysén region: 122 per 100,000 in 2007
Colombia In 2007, 387 suspected cases, only 28 confirmed
Seasonality and cyclic patterns are observed
Outbreaks in 1997–1998, 2001–2002 and 2006–2007 (83
Costa Rica adult, 132 infant cases, 8 deaths)
Detected incidence increased in 2006, following PCR
introduction
Limited data. Highly endemic, 30 deaths in 2004 out-
break
Guatemala Outbreak in 2007/8, with ~30 cases in infants aged <1
year and further cases detected in individuals up to age
20 years
Epidemiologic surveillance for pertussis in Mexico is
poor. An epidemiological study done in Mexico showed
Mexico
that 32.8% of adolescents with cough lasting more than
14 days were positive for Bordetella pertussis by PCR.
The highest incidence rates reach 233 per 100,000 in
some regions
Panama Between 2003–2007, 113 cases of pertussis in infants <3
months old - 66% of reported total, but surveillance of
older age groups is very poor
93 cases of pertussis-like syndrome in 2008
Paraguay
93% were in infants aged <1 year, 65% <3 months old
Venezuela 1,183 in 2006, using WHO clinical criteria
has been an increase in school-age cases (aged 10–14 years) but
this is less well documented.
Brazil had 17,349 reported cases, of which 6,887 were con-
firmed cases, mostly by clinical criteria (62%) in the last report-
able year. Incidence varies regionally with the greatest incidence
in the north (~10 per 10,000). The majority of pertussis cases
occur before the first vaccine dose has been received. Despite a
remarkable decrease in the number of cases, pertussis is still a
serious problem in Brazil, chiefly in the first months of life. An
epidemic has been reported in Sao Paulo and the State of Rio
Grande do Sul.13
Incidence rates in Chile reduced from 25 per 100,000 in 1996
to 6 per 100,000 in 2007 to 2008. Approximately 75% of cases
are detected in children aged <5 years and 56% in infants aged
<1 year. In infants <1 year, the incidence rate is 330 per 100,000,
with 6 to 9 deaths/year. There are some geographic variations,
with the Aysén region reporting 122 cases per 100,000 in
2007. Forty percent of the cases are confirmed by the National
Reference Laboratory. No outbreaks have been experienced in
the last 2 years. Adolescents and adults are the primary contacts
for infection of infants.
 Table 4. Surveillance and diagnostic methods, by country
Country Surveillance methods
Probable case defined clinically. Laboratory
Argentina c­ onfirmation (by culture, PCR or serology), or
­epidemiologic linkage to a laboratory-confirmed case
62% confirmed by clinical criteria. Remainder
Brazil diagnosed by leukocytosis or lymphocytosis,
­epidemiologic link or culture
Suspected case by clinical symptoms. Confirmed by
laboratory diagnosis or epidemiologically linked to a
Chile
laboratory-confirmed case. Immunofluorescence the
most commonly used diagnostic tool
Clinical diagnosis and laboratory confirmation by
Colombia
immunoflorescence or culture. Low confirmation rate
Clinical diagnosis. Culture available, but little used
PCR and direct immunofluorescent testing (for B.
Costa Rica
­pertussis and B. parapertussis)
Serology is not used
Passive clinical reporting. Culture at 1 central
Guatemala
­laboratory
Culture and immunoflorescence are the most com-
Mexico
mon diagnostic tools. PCR found only in research labs
Suspected cases detected by clinical diagnosis. PCR
Panama
available at a National Reference Laboratory
Passive surveillance of outbreaks. Central laboratory
Paraguay culture, very low positivity rate, most from samples
geographically close to the laboratory
Venezuela Almost entirely by clinical symptoms
In Costa Rica, there have been outbreaks in 1997 to 1998,
2001 to 2002 and 2006 to 2007, including 8 deaths in 2007 and
seasonal and cyclic patterns are observed. An increase in 2006
was believed to be due to the use of PCR whereas the less sensitive
IF and culture were used before.
Limited diagnostic ability has restricted reporting in
Guatemala, but there have been outbreaks in 2004 (where 30
people died, prompting a vaccination campaign), and in 2007.
There have been reported incidence rates of 50 per 100,000 in
adolescents in public schools in Mexico City, with 61 adolescents
identified who had a cough for longer than 2 weeks. This was the
first time rates this high have been reported in this age group in
the region, and the authors pointed out the danger of asymptom-
atic or unrecognized infections to infants.14
Obstacles to Vaccination
In the majority of countries, there is a general lack of aware-
ness of pertussis as a health problem, except in expert groups.
Furthermore, most people are unaware that pertussis can infect
older age groups such as adolescents and adults. Often this is due
to countries lacking good epidemiologic data as a result of poor
surveillance and diagnostic resources. It was acknowledged by
the group that it is difficult to introduce adolescent or adult pro-
grams without data to prove that pertussis is problematic in a
particular country. The group agreed that detection of disease
in adults was inadequate, normally only being recorded if there
www.landesbioscience.com Human Vaccines 879
was documented contact with a child with pertussis disease. The
recognition of the importance of adult infection as a source for
infant disease is recognized in some countries (Brazil, Argentina,
Costa Rica, Panama, Mexico),15-18 but not in others due to lack of
data (Colombia, Paraguay). Other countries (Chile, Guatemala,
Venezuela) recognize that adults are increasingly infected, but
have not made the connection to infant disease.
The committee agreed that increased education and public
awareness campaigns on the natural history of pertussis infection
would be a powerful argument to improve existing vaccination
programs, although epidemiologic data was most important.
Additionally, there were concerns over timely vaccination for
the primary series of 3 doses, particularly in larger countries with
inherent geographic constraints (Brazil, Argentina). Despite this,
both countries achieve good rates of vaccine coverage. Costa Rica
was alone in citing budgetary limitations as the greatest obstacle
to introducing greater adolescent and adult vaccination.
Regional Implementation of GPI Recommendations
There was general agreement by committee members that the
GPI-recommended strategies could be applied throughout the
regions, given adequate resources and political will. Countries
that do not use a preschool dose should launch one as soon as
possible. Every country cited adolescent booster programs as a
priority to advance pertussis vaccination, and it was felt that this
would be possible in most countries using the current infrastruc-
ture. Many country representatives felt that this could be fol-
lowed by the introduction of the cocoon strategies, followed by
full adult vaccination, but some countries expressed uncertainty
regarding the feasibility and implementation of these strategies,
particularly the cocoon strategy.
Representatives from Costa Rica argued strongly for the
cocoon strategy, but emphasized that for it to be effective in post-
partum women, high postdelivery coverage is necessary, requir-
ing full logistics to be in place. Maternal vaccination would be
ideal but studies are needed to show that vaccination late in preg-
nancy does protect the infant.19,20 This has the potential to be a
highly effective strategy so it is recommended that these studies
be performed in Latin America.
Another approach which could have a large effect is simply
to change from a Td to a Tdap vaccine booster in adults, which
should be a relatively inexpensive way of impacting pertussis.
Conclusions
1. In many Latin American countries, improvements in labora-
tory epidemiological surveillance and specific diagnosis by PCR
and serology would be beneficial.
2. Those countries that do not currently use a preschool dose
should launch one.
3. Implementing vaccination programs in adolescents to reduce
exposure to infants would be beneficial and possible in most
countries, given their current infrastructure.
4. Costa Rica is introducing postpartum immunization. Other
Latin American countries should also consider this approach.
5. Physicians should endeavor to increase awareness of pertussis,
to health care workers, government health officials and the gen-
eral public. It should be emphasized that pertussis infection can
occur in any age group, which can be source of serious infection
in infants.
6. Whole-cell pertussis vaccines are used across Latin America
which appear to be quite effective. However, the introduction
of an acellular vaccine would be a step forward to avoid issues of
reproducibility and reactogenicity.
Latin American countries vary in their approaches to vac-
cination against pertussis and in the programs they adopt. The
sharing of ideas and data among Latin American experts at the
meeting was well received and there was a shared commitment
toward reducing the impact of pertussis disease. Costa Rica has
initiated one approach, using a cocoon strategy which will be
monitored closely, while other countries continue to face many
obstacles. In the majority of countries, there is a lack of awareness
of pertussis as a problem and this is often due to the lack of good
epidemiologic data as a result of poor surveillance. Diagnosis and
surveillance generally need improvement, particularly the avail-
ability of PCR and specific serology. Nevertheless, there have
been some great success stories across the region. Latin America
has a tradition of mobilizing resources to produce successful
vaccination campaigns, and it is clear that this tradition is con-
tinuing to help combat pertussis.
Financial Disclosure
The Global Pertussis Initiative is supported by an unrestricted
educational grant from Sanofi Pasteur. Dr. Ulloa-Gutierrez
has served as a speaker for Sanofi Pasteur, GSK, Wyeth, Pfizer,
Merck; on Advisory Boards for Sanofi Pasteur, GSK, Wyeth;
and as Chairman-Co-chairman for Sanofi Pasteur and GSK. Dr.
Hozbor’s and Dr. Avila-Aguero’s salaries are financed by their
respective governments and they have no conflicts of interest to
report. Dr. Caro works for United BioSource Corporation, a con-
sulting company that has received grants for research work and
contracts from multiple vaccine manufacturers. Dr. Wirsing von
Koenig has no conflicts of interest to report. Dr. Tan has received
unrestricted research grants from Sanofi Pasteur and Merck;
she has done speaking and teaching and has served on advisory
committees for Sanofi Pasteur, Merck and Wyeth; she serves as
a consultant for Sanofi Pasteur and on advisory committees for
GSK. Dr. Plotkin is a consultant to most major manufacturers
of pertussis vaccines, including Sanofi Pasteur. Writing support
was provided by Phil Matthews, Ph.D., of PAREXEL and was
funded by Sanofi Pasteur.

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Appendix Rolando Ulloa-Gutierrez (Costa Rica). Note: Due to an outbreak

Meeting Attendees: Regional attendees: Katia Abarca (Chile);
Antonio Arbo (Paraguay); Edwin Asturias (Guatemala); María
L. Avila-Aguero (Costa Rica); Fernando de la Hoz (Colombia);
Angela Gentile (Argentina); Daniela Hozbor (Argentina);
Reinaldo Menezes (Brazil); Ana Morice (Costa Rica); Javier
Nieto (Panama); Sonia Ramos (Brazil); Jaime Torres (Venezuela);
of Dengue Fever in Mexico, the invited Mexican health officials
could not attend this meeting.
GPI members: Stanley Plotkin, Chairman (USA); Jaime
Caro (USA); James Cherry (USA);Nicole Guiso (France); Scott
Halperin (Canada); Carl-Heinz Wirsing von König (Germany);
Tina Tan (USA).

880 Human Vaccines Volume 6 Issue 11