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Pediatric Infectious Disease Journal:
4. Immunization Strategies for Pertussis

Pertussis Immunization in the Global Pertussis Initiative International Region: Recommended Strategies and Implementation Considerations

Forsyth, Kevin MD, PhD*; Nagai, Masaaki PhD†; Lepetic, Alejandro MD‡; Trindade, Evelinda MD§

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From the *Department of Paediatrics, Flinders Medical Centre, Flinders University, Adelaide, Australia; the †Research Center for Biologicals, The Kitasato Institute, Saitama, Japan; ‡Fundación del Centro de Estudios Infectológicos (FUNCEI), Buenos Aires, Argentina; and the §Brazilian National Agency for Health Surveillance, Brasilia, Brazil (ET)

Address for correspondence: Dr Kevin Forsyth, Department of Paediatrics, Flinders Medical Centre, Bedford Park 5042, South Australia, Adelaide, Australia. Fax (08) 8204 394; E-mail Kevin.Forsyth@flinders.edu.au.

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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.

In 2001, the Global Pertussis Initiative (GPI) was established as an expert scientific forum to analyze the status of pertussis disease globally and to evaluate various immunization strategies to improve disease control and reduce pertussis morbidity and mortality in infants too young to be fully immunized.1 Participants from 4 countries outside Europe and North America took part in the GPI: Argentina, Australia, Brazil and Japan. Collectively these countries were named the international region for the purposes of the GPI.1 The selected strategies are discussed in more detail in this article, as are the possible obstacles to implementation of the strategies. Other strategies evaluated by the GPI participants and those recommended by the European and North American regions are described elsewhere in this supplement.2–4 The GPI participants do not aim to implement changes to countries' immunization strategies. One of the main goals is to raise awareness of pertussis and the participants have made recommendations, which it is hoped will be considered by the appropriate authorities.

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OVERVIEW OF THE CURRENT EPIDEMIOLOGY

Although pertussis is a notifiable disease in Argentina, the data are of limited value because the diagnosis of pertussis infections is based on clinical criteria alone and underreporting is common in all age groups. Argentinian physicians have limited access to laboratory techniques to confirm the pertussis diagnosis.5 With the exception of outbreaks in the San Luis and Chubut provinces in 1999, the median incidence of pertussis disease was 1.6 cases/100,000 population in 2000 and 1.3/100,000 in 2001.5 As in many other countries, however, awareness of pertussis disease in adolescents and adults in Argentina is low, and the disease remains grossly underdiagnosed and underreported.

Pertussis has been a notifiable disease in Australia since 1990, and notification requires both clinical and laboratory diagnosis. Despite widespread immunization, the incidence of pertussis is high, at 22–58 cases/100,000 population, with peaks in children younger than 15 years of age and in adults 30–49 years of age. Australian epidemiologists also report high costs associated with the disease in adults older than 20 years of age, in whom it led to 15,200 lost work days (2260 cases), 8400 physician visits and 4300 prescriptions during 1998 in Western Australia.6 Nonetheless most Australian physicians still do not consider pertussis to be a disease of adulthood, and the disease is probably underreported in adults.

The epidemiology of pertussis in Brazil is less well understood than in other countries, because other communicable diseases (malaria and tuberculosis) are of greater prevalence. In Brazil, in 2000, the overall reported incidence of pertussis was 0.72/100,000 population.7 The number of confirmed cases presented a decreasing trend with age.

A national surveillance system has been in place in Japan since 1981, although it is not designed to identify all the cases of the disease that occur.8 Widespread pertussis immunization has significantly reduced the burden of the disease in the country during the past 50 years,9 although the incidence did rise sharply to ∼11 cases/100,000 population after reports of adverse reactions and a temporary suspension of diphtheria-tetanus-whole cell pertussis (DTwP) immunization in 1974 and 1975. The introduction of acellular pertussis (aP) vaccines in 1981 and a reduction in the age at which infants are immunized from 24 to 3 months have led to a further decrease in the incidence of the disease.10

The problem of waning vaccine-induced immunity and the relatively high incidence of pertussis disease among unimmunized or incompletely immunized infants was addressed by the GPI participants from the international region.

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CURRENT IMMUNIZATION SCHEDULES

Argentina, Australia, Brazil and Japan follow similar immunization schedules that include 3 doses of combined diphtheria-tetanus-acellular pertussis (DTaP) or a DTwP vaccine administered in the first year of life, followed by a fourth dose in the second year of life. Children in Argentina, Australia and Brazil also receive a preschool booster dose, and adolescents in Australia also receive a dTaP booster vaccination.

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RECOMMENDED STRATEGIES TO OVERCOME PERTUSSIS DISEASE

Argentina.

An adolescent booster would be a logical approach in Argentina. It would, in theory, reduce the morbidity caused by pertussis among adolescents, contribute to the development of herd immunity and possibly reduce transmission to young infants, although this has yet to be proven.

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Australia.

Health authorities in Australia recently introduced an adolescent pertussis booster. Future plans might therefore focus on the immunization of selected groups of adults, such as new mothers and health care workers, to reduce morbidity in these groups and to reduce transmission to young infants.

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Brazil.

By contrast, pertussis is not perceived to be a major threat to public health in Brazil. Pertussis immunization therefore does not receive the same level of funding as other communicable diseases, such as tuberculosis or malaria, although high levels of coverage of the initial pertussis immunization course are achieved. Reinforcement of the policy of preschool immunization is important.

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Japan.

In assessing new improved immunization strategies, a priority in Japan is to add a preschool booster to the current schedule and possibly also a booster in adolescence (11–12 years of age) to overcome waning immunity after the initial course of pertussis immunizations.

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RESEARCH NEEDED TO SUPPORT RECOMMENDED STRATEGIES

Certain key areas of research must be addressed, either before new strategies can be implemented or to measure the effectiveness of those strategies once in place. Such research includes evaluation of the duration of vaccine-induced immunity; the cost effectiveness of chosen immunization strategies; the role of population subgroups in the transmission of pertussis to infants; and the efficacy, safety and tolerability of aP vaccines formulated for adolescents and adults.

Vaccine-induced immunity is known to wane with time. The precise time period over which the decline in immunity occurs is not known, although a Japanese study suggests a period of 6–10 years.11 Data from the United States also support this time frame.12 If vaccine-induced immunity does wane after 6–10 years, a more cost-effective approach might be to omit the fourth dose of vaccine (usually administered in the second year of life) and to introduce a booster dose in adolescence to avoid the high incidence of the disease in this group, as implemented in Australia.13–15

Similarly governments, health authorities and insurers worldwide must be convinced of the cost effectiveness of new immunization strategies before they will agree to changes in current practice, particularly in countries with other pressing health priorities, such as Brazil. The relative cost effectiveness of acellular and whole cell vaccines, or indeed other new formulations, has yet to be determined. For example, in Australia, a dTaP vaccine formulated for adults has been granted marketing approval, but the Australian Government is awaiting cost effectiveness data before recommending its use in immunization schedules. In Argentina, the government must be convinced of the cost effectiveness of DTaP vaccines before it will sanction a switch from whole cell pertussis vaccines.

Determination of the role of key subgroups of the adult population in transmitting pertussis disease to unimmunized or incompletely immunized infants is crucial to the argument for future adult pertussis immunization in all countries. Groups of special interest are parents, other family members and other close contacts of newborn infants, such as health care and child care workers. If immunization of any or all of these groups can be shown to reduce infant morbidity and mortality and also morbidity in people in older age groups, the argument for immunization of these groups will be more compelling.

The reactogenicity of the newer aP vaccines must also be explored, specifically the reactogenicity of repeated doses in adolescents and adults. Such information is vital if adolescents and, in the future, adults are to be encouraged to undergo pertussis immunization.

Argentina must improve its pertussis notification systems and obtain further data on the current coverage with DTaP primary immunization and the preschool booster. In Australia, the focus of interest will be the prospective monitoring of the epidemiologic effects of the introduction of adolescent immunization, in particular the effects on pertussis morbidity in young adults of child-bearing age.

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POTENTIAL OBSTACLES TO IMPLEMENTING RECOMMENDED IMMUNIZATION STRATEGIES

Availability of Appropriate Vaccines.

Availability of vaccines is not a significant obstacle to the new immunization strategies suggested for the countries in the GPI international region.

In Brazil and Japan, no licensed dTaP vaccine is yet available for use in adults. Moreover the vaccines currently available in Japan are suitable only for the primary course of childhood immunization, and new vaccines will be needed if preschool children and adolescents are to be immunized.

In Argentina, a dTaP vaccine for people older than 10 years of age was licensed in 2003. A dTaP vaccine is also available in Australia and since 2003 has replaced the diphtheria-tetanus (dT) booster administered at 15 years of age. This vaccine is also suitable for the immunization of the subgroups of adults in whom immunization is thought likely to be effective, new mothers and health care workers. However, no standalone aP vaccine is currently available to supplement the strategies of adolescent immunization and selective immunization of mothers, other close contacts of newborn infants and also health care workers. Such a vaccine is needed to ensure that all individuals with otherwise full immunization histories are also immunized against pertussis, especially as low dose diphtheria-tetanus (dT) immunization is recommended only at the ages of 15 and 50 years.

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Access to Target Populations and Delivery Infrastructure.

Japan is the only country in the GPI international region where a preschool pertussis booster is not administered. Because Japan already offers other preschool immunizations, the addition of a pertussis vaccine should not be a problem. The current DT immunization programs do not achieve high coverage rates in Brazil, particularly in rural areas where the delivery infrastructure is not well-organized. Japanese adolescents are easy to reach via schools, but universal adolescent immunization could present problems in Brazil, given that no universal delivery infrastructure exists within high schools, although adolescent dT and hepatitis boosters are recommended.

Although Argentinian adolescents are required to be immunized against diphtheria and tetanus before they can obtain an identity card at the age of 16, compliance is low. If the combined dT vaccine was replaced with a dTaP vaccine and the requirements performance improved, high levels of compliance could be achieved via the current delivery infrastructure. Moreover 10-yearly dT boosters are also recommended for adults. Therefore if adult pertussis immunization were agreed, it could easily be fitted into the currently recommended schedule. However, low compliance with adult vaccination must be recognized as an important problem by health authorities and a barrier for future interventions.

In Australia, new mothers could be relatively easily encouraged to be immunized by the various health care professionals involved in the antenatal and postnatal care of women and infants. Although new mothers are well-motivated to be immunized, other close contacts of the infants are likely to be more difficult to convince. Health care workers are also relatively easy to access via current occupational health programs.

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Diagnosis and Surveillance.

Physicians in all 4 of the international region countries need access to standardized and reliable laboratory techniques, such as polymerase chain reaction analysis of bacterial DNA, to confirm the diagnosis of pertussis because clinical signs alone can lead to misdiagnosis. Moreover, without such techniques, the full extent of the morbidity caused by pertussis disease cannot be accurately evaluated.

Access to computerized immunization records would also be valuable in the assessment of the effectiveness of immunization programs. Ideally national databases of information on all the cases of pertussis that occur should be improved. Argentina is in the process of evaluating a national surveillance net for pertussis.

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Resources, the Health Care Agenda and Policy Makers.

In Argentina and Brazil, funding is a significant barrier to extensions of current immunization programs. In the case of Argentina, where childhood DTwP immunizations are funded by the Government, health care resources have most recently been threatened by the ongoing economic crisis in the country. In Brazil, the resources available for pertussis immunization are limited by the fact that the disease is not seen as a priority for prevention. Also many people cannot afford private health care and are therefore unlikely to be able to pay for additional immunizations, if they can afford any at all.

In Australia, the omission of the 18-month DTaP vaccine dose and the inclusion of an adolescent dose in its place is unlikely to incur extra costs and might reduce overall health care costs through reduced adolescent morbidity and reduced transmission to unimmunized or incompletely immunized infants. Similarly the need to protect health care workers from vaccine-preventable diseases could be influential and could encourage the introduction of pertussis immunization for this group or, at least, for those at particular risk, such as pediatric or emergency medicine staff. Whether cost benefit studies will support this strategy remains to be seen.

In Japan, the costs of private health care are high and government funding of immunization programs is difficult to obtain. Data that confirm the effectiveness, safety, tolerability and cost effectiveness of the addition of preschool and adolescent pertussis boosters are therefore needed to convince policy makers and insurance companies of the benefits of expanded pertussis immunization programs. Moreover additional firm evidence of the benefits of pertussis immunization to the individual is also needed to convince the general public of the need for immunization.

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Improved Education and Awareness.

Pertussis is generally perceived to affect only infants and children, and awareness of the disease in adolescents and adults is low. As a consequence, neither the public as a whole nor selected subgroups of adults are likely to comply with pertussis immunization programs. Low awareness of pertussis disease among adolescents and adults is likely to present particular problems in Japan, where a high degree of public approval of new immunization strategies is required before the Government will alter policy. Thus in the GPI international region, wide-ranging public health awareness campaigns are necessary, both in advance of and after the inception of new immunization strategies. Specific occupational health campaigns will also be needed in Argentina and Australia if the strategy of immunizing health care workers and/or child care workers is to succeed. In general, educational programs will need to meet the following objectives: improve recognition of pertussis as a health problem extending beyond childhood; raise awareness of the impact of infected adolescents and young adults as a source of transmission of pertussis to young infants; convincingly demonstrate the benefits of immunizing young adults; increase awareness of pertussis problems and prevention measures; obtain information about the immunogenicity and safety aspects of new vaccines; and increase recognition of health care workers or others (family members/close contacts of newborns) as possible sources of infection.

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IMPLEMENTATION TIMETABLE

Universal adolescent immunization of adolescents using a dTaP vaccine is already implemented in Australia. The program may be extended to selected groups of adults once a standalone aP vaccine becomes available. In Argentina, a dTaP vaccine is licensed for use in people older than 10 years of age. Currently this vaccine is used only partially, in private practice, as a replacement of the dT vaccine. No similar program of adolescent immunization is yet planned in Japan. Indeed the requirement for extensive public health education campaigns to increase awareness of the need for pertussis immunization will slow the introduction of such a strategy in Japan.

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CONCLUSION

The purpose of the GPI is to suggest new approaches to control pertussis and to raise awareness of the overall burden of pertussis. In particular, the strategies suggested for the GPI international region are aimed at overcoming waning vaccine-induced immunity, which occurs in late childhood in countries where no preschool booster is administered or in adolescence where children already receive a preschool booster dose of vaccine. In addressing this problem, it is hoped that pertussis morbidity among adolescents and transmission to young infants will be reduced and herd immunity developed. The additional strategy of immunizing selected groups of adults, such as new mothers, other close contacts of young infants and health care and/or child care workers, might also be considered in countries where children and adolescents are adequately immunized.

Key obstacles to the introduction of new immunization strategies include the lack of adequate surveillance and cost-benefit data in each country, a lack of widely available laboratory services to confirm the diagnosis of pertussis and poor awareness of the disease incidence in adolescents and adults who could transmit the disease to each other and to young infants. Without such facilities and data, it is impossible to make an accurate assessment of the burden that pertussis presents.

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REFERENCES

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Keywords:

Bordetella pertussis; pertussis; immunization

© 2005 Lippincott Williams & Wilkins, Inc.

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