Wirsing von König, Carl-Heinz MD*; Campins-Marti, Magda†; Finn, Adam MD, PhD‡; Guiso, Nicole PhD§; Mertsola, Jussi MD¶; Liese, Johannes MD, MSc∥
An accurate picture of the epidemiology of pertussis in Europe is difficult to obtain because procedures for diagnosing and reporting cases of pertussis disease vary widely across Europe. Nevertheless some general epidemiologic trends have emerged. For example, the incidence of pertussis increased in the 1990s in Finland,1 France,2 Spain,3 the Netherlands4 and the United Kingdom.5 Peak incidence also shifted from infants to older age groups, such as school age children and adults, in Finland,1 France,6 The Netherlands4 and Israel.7 In contrast, in the past decade, there has been an increase in infant morbidity and mortality caused by pertussis disease in France and the United Kingdom, possibly as the result of increased parent-to-infant transmission, although the incidence of the disease remains low.8,9 These variations in incidence may be the result of the different pertussis immunization schedules in each country.
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. GPI participants from Europe considered strategies to improve disease control and reduce the morbidity and mortality in unimmunized or incompletely immunized infants.10 The initiative participants have made recommendations to address specific problems and explore the potential barriers to the implementation of such plans, and it is hoped that the appropriate authorities may consider these recommendations.
CURRENT IMMUNIZATION SCHEDULES
Details of the current immunization schedules for European countries are outlined in Table 1. All the European countries represented on the GPI offer an initial course of 3 doses of a combined diphtheria, tetanus, and either acellular pertussis (DTaP) or whole cell pertussis vaccine that is administered between the ages of 2 and 12 months. With the exception of Italy, Sweden and the United Kingdom, they also offer a further dose between the ages of 11 and 24 months. Some countries also recommend a fourth or fifth vaccine dose as a preschool booster for children 3–6 years of age (Belgium, Italy, The Netherlands, Spain, Switzerland and the United Kingdom) or an adolescent booster for children ∼11–18 years of age (Austria, France and Germany). Austria also recommends that adults be immunized every 10 years using a combined dTaP-inactivated poliovirus vaccine (IPV) vaccine, although no coverage data for adults are available and adult immunization is not binding across Europe.
The immunization programs used in Europe are effective and generally achieve in excess of 90% coverage of the infant population with the first 3 doses of vaccine. Such programs have proven successful in significantly reducing infant morbidity and mortality caused by pertussis.11 However, recent increases in the incidence of the disease and the apparent shift in some countries toward older age groups (school age children, adolescents and adults) suggest that new approaches are needed (and are already recommended in some countries) to improve pertussis control and develop herd immunity to protect unimmunized or incompletely immunized infants, who are at risk for complications and death.4 Given the particular problems in each country and the wide variation in approaches to childhood immunization, no single pan-European immunization schedule to combat pertussis disease is likely to be acceptable in all countries. Nevertheless broad strategies to reduce the impact of the disease could be adapted to each country's specific needs.
RECOMMENDED STRATEGIES TO OVERCOME PERTUSSIS IN YOUNG INFANTS
Of the strategies evaluated by the European GPI participants, the following were considered the most appropriate recommendations for countries that are not already implementing these approaches: reinforcement of the implementation of current immunization schedules; the administration of an extra dose of vaccine to children of preschool age (4–6 years) or adolescents, depending on the country; and selective immunization of health care workers (in accordance with EC Directive 2000/54/EC).12
Other groups of adults that might be targeted in the future include new mothers, child care workers, young adults and close contacts of newborns, if data can be obtained on the incidence of pertussis in these age groups and the role that these groups play in the transmission of pertussis to infants.
The selected strategies are discussed in more detail in this article, as are the possible obstacles to their implementation. Other strategies evaluated by the GPI participants and those recommended by the North American and international regions are described elsewhere in this issue.10,13,14
Reinforcing Current Immunization Schedules.
In conjunction with wider immunization strategies, the reinforcement of ongoing programs will have a significant benefit in reducing infant morbidity and mortality caused by pertussis and in maintaining herd immunity, as had been demonstrated in Germany.15 All the countries represented on the GPI have effective childhood immunization programs in place, which have significantly reduced the incidence of pertussis in infants and toddlers and thus led to decreased awareness of the disease by vaccinating pediatricians or general practitioners. Therefore maintenance of these programs is proving difficult in some European countries.
An Additional Vaccine Dose.
To overcome the problem of waning vaccine-induced immunity to Bordetella pertussis in children and adolescents, a logical strategy for many European countries would be to add an extra vaccine dose to their existing schedules, either in preschool children at the age of 4–6 years or in adolescents, depending on the current schedule in each country.16–20
The preschool booster is a good opportunity to ensure that children are adequately immunized before entering school, and many European countries already implement this strategy.
An alternative approach has been taken in France and Germany, where adolescents are offered a booster dose of dTaP-IPV or DTaP-IPV vaccine and no preschool pertussis booster is given. If it could be demonstrated that the adolescent immunization in these countries induces a reduction in pertussis morbidity in adolescents and if it also reduces infant morbidity and mortality through reduced transmission, it could help to facilitate the introduction of adolescent immunization in other countries.21
Selective Immunization of Health Care Workers.
Certain groups of adults who are at a relatively high risk for infection, such as health care workers, might be protected from pertussis and therefore also prevented from transmitting the disease to other adults and unimmunized or incompletely immunized infants. Health care workers in pediatric and emergency departments, in particular, are important targets for this strategy.
EC Directive 2000/54/EC already strongly encourages European Union (EU) countries to protect health care workers through immunization.12 The Directive requires health care workers to be offered immunization against any disease for which an effective vaccine is available, which includes pertussis. However, individuals can choose whether or not they receive immunization, and experience suggests that health care workers are unwilling to comply with recommended immunizations for influenza immunization,22 despite proven benefits to workers and patients. Thus far, the Directive has been implemented only in Germany, since July 2001. The recent German recommendations (July 2003)23 suggest that health care workers in pediatric departments, those caring for pregnant women, those working in obstetrics and child care workers be immunized once with an acellular vaccine against pertussis. Although the EU implemented the immunization of health care and child care workers as a measure of its occupational health legislature, the implementation is also being monitored in respect to pertussis epidemiology. However, it is too soon to be able to confirm the effects of this strategy in terms of morbidity among health care workers or transmission to infants. Despite this, the GPI participants believed that it is important for this strategy to be implemented throughout Europe, given that countries that do not plan to implement the Directive will need to explain their reasons to the EU authorities.
POTENTIAL OBSTACLES TO IMPLEMENTING RECOMMENDED STRATEGIES
Access to Target Populations.
Access to the target populations can generally be obtained relatively easily, depending on the population being targeted. There will, however, be differences between countries.
Existing infant immunization programs could be given in a more timely fashion, to avoid postponing immunization due to the wrong contraindications. For the adolescent population, diphtheria-tetanus or diphtheria-tetanus-IPV boosters are recommended in many countries, and pertussis immunization could thus be introduced with relative ease, as is already the case in Austria, France and Germany. However, the vaccine coverage in these populations varies markedly. For health care workers, existing occupational health programs (ie, hepatitis B) can be used to meet the current requirements of EC Directive 2000/54/EC.
Availability of Appropriate Vaccines.
Because most European countries already implement childhood immunization programs (Table 1), access to appropriate infant vaccines is good. Two pertussis combination vaccines, with low dosage tetanus and pertussis components, are available in many European countries for use in adolescents and adults. The availability of appropriate vaccines will therefore not hinder the implementation of the strategies of giving an extra dose to children or adolescents or of immunizing health care workers. However, the availability of both combined and standalone pertussis vaccines would ensure that all groups can be fully immunized: some health care workers and adolescents, for example, might already have full diphtheria, tetanus and polio immunization histories and require only the acellular pertussis (aP) booster. Additionally many adults do not know their full immunization history.
Availability of Appropriate Delivery Infrastructures.
Immunization programs are operated in Europe through various delivery channels. School immunization programs are an efficient way of immunizing children and adolescents, and the target population can be accessed easily. Where immunization programs do not exist in schools, public health services should take action to introduce or reintroduce them. In many countries, however, immunization programs are based on individual pediatricians and/or general practitioners and the political direction seems to favor these routes of immunization.
Because health care workers in several European countries (including France, Germany and the United Kingdom) already receive other immunizations via occupational health programs, including immunizations against diphtheria, tetanus, influenza and hepatitis, the addition of a pertussis immunization would be relatively simple. However, vaccine coverage in health care workers is generally very low; it is important to obtain a better understanding of the reasons for this, to ensure that immunization is successful.
Diagnosis and Surveillance.
The typical form (paroxysmal cough, whoop and posttussive vomiting) of pertussis is now less common than the atypical form (mild or severe, persistent cough), which usually affects adolescents and adults. As a result, diagnosis can no longer rely on the clinical signs and symptoms and needs laboratory confirmation.
Polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) techniques are now widely available. However, neither polymerase chain reaction techniques nor the various ELISAs are standardized. For ELISA standardization, an international reference serum for serology is a prerequisite.
Diagnosis with the use of ELISA can be made with sufficient specificity with a single sample assay.24–26 Sample collection techniques, particularly sample collection from infants, must also be standardized, because poor sampling technique and sample storage can affect the results of laboratory analysis.27
Accurate surveillance studies require health care professionals to be aware of pertussis disease. In particular, health care professionals must be more aware of the disease in adults and have a higher index of suspicion for the disease when patients present with either typical or atypical symptoms. Health professionals must also be more aware of the laboratory techniques available to confirm the diagnosis of pertussis and should have ready access to such techniques.
Surveillance would be significantly improved with mandatory registration of vaccine distribution and administration, passive and active safety surveillance and monitoring of vaccine uptake in infants, children and adults. Vaccine registries are already in place in some countries such as France and the United Kingdom.
Resources, the Health Care Agenda and Policy Makers.
The implementation of strategies to extend immunization programs primarily needs enough data for policy makers to demonstrate the benefits of a new strategy and the need for additional funding.
Regarding the addition of an extra dose in preschool children or adolescents, vaccine efficacy and cost effectiveness data from countries where these strategies are already in place will help to convince decision makers in other European countries of the benefits of a booster dose. One U.K. study has predicted that the introduction of an aP booster at the age of 4 years will reduce morbidity and mortality in the younger age groups by 40–100%28; however, the United Kingdom does not give a booster dose during the second year of life.
EU policy makers are already convinced of the need to protect health care workers from vaccine-preventable diseases, including pertussis.12 In Germany, health care workers undergo pertussis immunization; data confirming the effectiveness of this strategy in terms of reducing morbidity among this group of people and in reducing transmission to infants may help to convince other European countries to institute similar programs.
Health insurance and reimbursement systems vary from country to country in Europe, and decisions on funding will be made at the country or regional level. However, robust epidemiologic and health-economic data on the effects of adding an extra dose of vaccine to current childhood immunization schedules (eg, data on adolescent immunization from Austria, France and Germany) may help support the introduction of an additional booster dose, although direct comparisons will be difficult because immunization schedules vary between countries.
Under the EC Directive, vaccines must be offered free of charge to health care workers. The cost of immunizing health care workers is expected to be met by employers because this approach is seen as protecting workers from occupational hazards.
Other costs must also be taken into account. For example, in the United Kingdom, a system of financial incentives has encouraged general practitioners to effect childhood immunizations and has improved the coverage and success of these programs. The addition of an extra dose could also increase the cost of these incentives. In other countries, the cost of setting up school-based adolescent immunization must also be met, as must the cost of health education campaigns to support the new strategies.
Improving Education and Awareness.
Health care professionals, including physicians, nurses and midwives, are particularly influential with respect to childhood immunization and are therefore important targets for education and awareness campaigns. These groups will need to understand the benefits of an extra dose of vaccine not only for their patients but also for themselves. Education and awareness programs should also extend to improving the diagnosis of pertussis.
Across Europe, antivaccine campaigners have a strong presence; clear and simple education programs are needed to counter unfounded antivaccine claims and highlight the continuing problems associated with pertussis, to persuade public and health professionals of the benefits of immunization.29
RESEARCH NEEDED TO SUPPORT RECOMMENDED STRATEGIES
Data on Current Immunization Programs.
Although many European countries operate systems to monitor the coverage of national immunization programs, little official information is available on adherence to immunization schedules, such as the number of infants who are immunized at the ages recommended, or on local obstacles to immunization, such as social deprivation and religious or other philosophical opposition to immunization.29 Such information would be useful in guiding the development of local immunization strategies and would provide valuable baseline data for comparison.
Because of the differences in immunization schedules and organization of child care across Europe, a key area for research is investigations into the transmission of pertussis to young infants by specific groups (adolescents and adults in general and more specifically health care and child care workers, parents and other close contacts of young infants).
Sudden Infant Death Syndrome (SIDS) Studies.
Given that pertussis may contribute to SIDS mortality,30,31 it would also be useful to try including pertussis diagnosis in ongoing SIDS studies in the various countries.
Diagnosis and Surveillance.
Other areas that would benefit from new or more comprehensive data are the clinical and laboratory diagnosis of pertussis and surveillance of the disease. Such information would enable a more accurate picture of the extent of the morbidity caused by pertussis to be produced. In particular, studies in adults and adolescents, in whom underreporting is most common, are warranted to assess and raise awareness of the need for immunization in these groups. Studies addressing these problems are ongoing, with very different study designs, in Sweden, France and Germany.
Vaccine Effectiveness and Safety Studies.
It would be desirable to obtain data on the effectiveness of vaccines to reduce not only clinical disease but also transmission.32 The duration of protection induced by the different vaccines should also be clarified, as should the reactogenicity of repeated doses of vaccine. Based on the results of these studies, further research can be conducted into the interval of administration of aP boosters, in addition to the safety of repeated aP vaccine doses. Because of the demonstrated long term effectiveness of the acellular vaccines,33,34 the feasibility of eliminating a vaccine dose between infancy and adolescence could also be studied, to address the potential problem of increased reactogenicity with multiple vaccine doses. The possibility of immunizing pregnant women in the third trimester could also be considered (although there are ethical issues associated with immunizing pregnant women), as should immunization of infants immediately after birth with a standalone aP vaccine or a combined aP-hepatitis B vaccine. The impact of bacterial polymorphisms on the effectiveness of aP vaccines should be continually monitored in all countries.
A combination of strategies to reinforce the implementation of current childhood immunization programs, increase the number of vaccine doses given in childhood and adolescence and target specific groups of high risk adults is currently considered to be the first step to reduce morbidity and mortality caused by pertussis in young infants and reduce the health burden in older age groups because of waning immunity. In particular, it is hoped that these strategies will increase herd immunity among adults and adolescents. Several countries have recently expanded their immunization programs. Austria, France and Germany now offer an adolescent pertussis booster. Austria also recommends that adults be immunized every 10 years with a combined aP vaccine.
Various obstacles must be addressed to support the implementation of these strategies, including low awareness of pertussis disease in adults and adolescents, inconsistent diagnostic criteria and poor access to standardized laboratory techniques to confirm the diagnosis. It is currently difficult to obtain an accurate picture of the epidemiology of pertussis disease in Europe, or of the effectiveness and cost benefits of particular immunization schedules. Therefore epidemiologic studies of the true extent of the morbidity and mortality caused by pertussis disease and its effects are a top priority. Cost effectiveness data on the results of adolescent immunization in Austria, France and Germany will also be valuable in establishing expanded immunization strategies in other European countries.
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