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Original Studies

Impact of a Pertussis Booster Vaccination Program in Adolescents and Adults on the Epidemiology of Pertussis in Austria

Rendi-Wagner, Pamela MD*; Paulke-Korinek, Maria MD*; Stanek, Gerold MD; Khanakah, Gelas MD; Kollaritsch, Herwig MD*

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The Pediatric Infectious Disease Journal: September 2007 - Volume 26 - Issue 9 - p 806-810
doi: 10.1097/INF.0b013e318124a9dd
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Abstract

Each year, an estimated number of 50 million cases of pertussis occur worldwide, accounting for about 300,000 deaths.1 Increasing incidences and a shift of infections to older age groups have been observed in several countries.2–14 In immunized persons, prolonged cough can be the only symptom of an infection with Bordetella pertussis. However, in 80% of adults with confirmed infection cough lasts 3 weeks, and 27% have symptoms for more than 90 days.4 Furthermore, it has been well documented that adolescents and adults are the major source of infection for infants and children.15

Waning natural immunity resulting from decreasing circulation of the pathogen and neglected booster vaccinations against pertussis in older age groups are thought to be responsible for the increasing occurrence of this disease.15 Moreover, a better awareness, improved surveillance, and better diagnostic features are discussed for increasing incidence rates of pertussis.4,16 In Austria, whole-cell vaccination against pertussis was introduced in the 1950s and has been routinely used from the early 1970s in children as a component in diphtheria-tetanus-pertussis vaccines. To improve vaccination coverage rates against pertussis, the less-reactogenic acellular pertussis vaccines were introduced in 1998 for universal primary immunization in Austria. This led to a rapid increase in infant immunization coverage rates from 80% in 1996 to 97% in 2003.14 Vaccination for infants is administered at 3, 4, and 5 months (since 2006 the schedule modified to 2, 4, and 6 months), and in the second year of life—since 1999, in the form of a hexavalent vaccine.

Since 2002, following complete primary immunization against B. pertussis in early childhood, consecutive regular booster vaccinations every 10 years until the age of 60 have been recommended by the Austrian Advisory Committee on Immunization. For vaccinees older than 60 years of age pertussis booster vaccinations have been suggested to be given every 5 years. Austria is the only country with existing recommendations for such regular booster vaccinations against whooping cough for adolescents and adults. Since 2004, in Austria, routine acellular pertussis booster vaccinations have been provided to all children free of charge, regardless of citizenship, between 6 and 16 years of age using a vaccination formulation containing tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis vaccine. Adults, however, must pay for their pertussis booster doses.

Participants of the Global Pertussis Initiative recommend the adolescent booster strategy to be implemented also in other regions; policy makers, however, warrant additional surveillance data demonstrating the effectiveness of such booster strategies by reduction in pertussis morbidity and mortality through reduced transmission.17–19

The aims of the present study were to monitor incidence rates of pertussis in the general population, including adults, to assess the disease trend of all age groups, and to evaluate current pertussis booster vaccination strategy.

MATERIALS AND METHODS

Study Design

The study is based on a 6-years prospective, nationwide, active surveillance of infection with B. pertussis diagnosed in Austrian laboratories. The observation period was January 1, 2000, to December 31, 2005. Data originated from a voluntary laboratory-based surveillance network, including the 6 principal nationwide microbiologic laboratories performing routine diagnosis on B. pertussis in Austria. The catchment area of these accredited laboratories reached >99% of the population. The geographic distribution of these diagnostic institutions was as follows: 2 in Vienna (2 institutes at the Medical University Vienna), 1 in Upper Austria (hospital-based), 1 in Tyrol (Medical University Innsbruck), 1 in Styria (Medical University Graz), and 1 in Vorarlberg (hospital-based). In the respective time interval, the mean population in Austria rose from 8,011,566 to 8,233,206.20

Information on case reports was obtained quarterly by dispensed standardized questionnaires. The reporting microbiologists or laboratory assistants were requested to provide the following data to the study notification center at the Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna: patient's age and gender, date of laboratory diagnosis, type of sample sending facility (ie, outpatient clinic, general practitioner/medical specialist, hospital ward), confirmation of positive laboratory diagnosis, and type of laboratory test system used. Active surveillance by personal contact to the designated reporting persons at either site completed incomplete reports. For confidentiality, only anonymous data were reported and used for any analysis.

The Austrian clinical case definition for statutory notification requires 2 weeks of cough—characterized by typical bouts of barking cough, by inspiratory “whooping,” or by vomiting after a coughing spell; however, no study-specific clinical case definition has been applied.

Laboratory Methods

Serology

Laboratory confirmation of B. pertussis infection was confirmed indirectly either by positive serology, with elevated concentrations of IgM and IgA antibodies to B. pertussis in a single sample or by significant increase (≥50%) of the antibody concentrations in paired samples. The tests were performed and interpreted according to the manufacturers instructions using CE-certificated commercial enzyme-linked immunosorbent assay kits (eg, Viron\Serion GmbH, Würzburg, Germany; Labsystems, Vantaa, Finland) or directly by positive culture of B. pertussis or detection of sequences of the pertussis toxin gene by real-time polymerase chain reaction (RT-PCR).

Culture.

Specimens collected from the posterior nasopharynx were plated on Bordetella agar (Oxoid, UK). The solid medium was incubated at 35°C for 3–5 days in a moist chamber under aerobic conditions and checked for tiny, small, characteristically mercury-silver appearing colonies. Nonmotile, gram-negative, coccobacilli that tested positive for catalase and oxidase were identified by polyclonal antiserum (Remel, UK) specific for B. pertussis.

Polymerase Chain Reaction.

DNA was extracted from the submitted specimens by the Qiagen tissue kit (Qiagen, Fremont, CA) for performing Taqman RT-PCR (Applied Biosystems; ABI Prism 7700 sequence detection system 7000) with primers derived from the toxin gene of B. pertussis (sequence obtained from the NCBI GenBank AJ006155).21 The detection limit was 10 copies per 5 μL of the sample extract.

Statistical Analysis

The 2000 through 2005 status of cases of B. pertussis infections was reported by the above-mentioned 6 microbiologic laboratories in every month of the observation period. Overall, 4636 notifications on cases of whooping cough were received. Two hundred and forty-one reports were excluded from further analysis because of identical initials, gender, date of birth, and report of disease of the same person within less than 100 days or within less than 100 days after a second report. Cases with identical personal data but 2 reports of disease, which were more than 100 days period apart, were treated as 2 cases (170 cases). Thus, 4395 cases remained for analysis.

Data on age, gender, type of sample sending facility (hospitalization rate), laboratory diagnostic system used, and season of disease were assessed. For age-specific analysis, cases were divided in 4 age groups, infants younger than 1 year of age, children from 1 to <6 years, children and adolescents from 6 to <16 years of age, as well as adolescents and adults 16 years of age and older.

Annual incidence rates were based on population rates of the respective age group at risk during the surveillance period. This number was obtained from Statistics Austria.20

Seasonality was studied examining the distribution of all cases by month of laboratory-based diagnosis of disease.

Based on sales figures of the corresponding producers of booster vaccinations against pertussis and detailed information on the number of state-paid vaccination doses for the booster vaccination program for 6-16-years olds in combination with population data,20 booster vaccination coverage per age group (6–16 years and >16 years) was calculated.

RESULTS

During the observation period, a total of 4395 laboratory-reported cases of pertussis were eligible for analysis. In 47% of these cases men were affected. The mean age of the reported cases was 38.6 years (±25.10 SD). Of all reported cases 3.6% (147 of 4392) were younger than 6 months of age, 13.5% (592 of 4392) were 70 years of age and older. Detailed data, including case numbers, mean age, and age-specific incidence rates per year of observation are summarized in Table 1.

TABLE 1
TABLE 1:
Reported Number of Pertussis Cases, Mean Age (±SD), and Annual Incidence Rates (per 100,000 Population) With Respect to Age Groups, 2000–2005

In almost 98% (4299 of 4395) of all reported cases serology was performed, which was positive in 97% of this subgroup. PCR was done in 2% (83 of 4395) of all case reports. In 84.3% of these cases DNA of B. pertussis was present. Bacteriologic cultivation was prepared in 4.3% of all laboratory-reported cases (188 of 4395) and positive for B. pertussis in 55.3%. In 187 cases more than one test system was applied. Of PCR or culture-positive cases, 25.3% were confirmed by positive serology results.

The estimated coverage rate regarding booster vaccination against whooping cough among Austrian children and adolescents between 6 and 16 years of age rose to almost 10% (start of vaccination program in 2002). Persons older than 16 years had an average booster vaccination coverage of less than 2%.

Incidence Rate.

The mean annual incidence of reported cases of infections with B. pertussis in the Austrian population was 9.02, increasing from 6.38 in 2000 to 11.14 per 100,000 population in 2005. As expected, the highest rates (39.07 per 100,000) were observed for the youngest age group (<1 year) and the lowest for the age group between 1 and 6 years (7.31 per 100,000). Table 1 and Figure 1 summarize age-specific incidence rates per years of observation.

FIGURE 1.
FIGURE 1.:
Incidence rates of reported cases of pertussis per 100,000 population by age group and year of observation, 2000–2005.
Hospitalization Rate.

In 89.8% (3945 of 4395) of all reports information on the type of facility sending the samples to the reporting laboratories was available. Fifty-five percent of these samples were sent by general practitioners or medical specialists, 12.7% were sent by outpatient clinics, and 32.4% of the samples were from hospitalized patients. Comparing single years of observation, a decreasing trend from 41% inpatients of the annual cases in 2000 to 26.7% in 2005 was observed. For infants younger than 6 months of age the reported hospitalization rate was 86%. Hospitalization rates were 79% for children less than 1 year of age (group 1), 48% for children 1–6 years of age (group 2), 19.2% for those between 6 and 16 years of age (group 3), and 33% for persons 16 years and older (group 4). Hospitalization rates for persons older than 60 years of age suffering from whooping cough were 54.7%. Figure 2 illustrates the temporal trend of age-specific hospitalization rates.

FIGURE 2.
FIGURE 2.:
Proportion of hospitalized pertussis cases by age group and years of observation (grouped: 2000–2001; 2002–2003; and 2004–2005).
Seasonality.

On average most cases of pertussis disease occurred during the months January, May, October, and December (66.0–68.5 cases per month). The smallest numbers of cases were observed in February, June, and July (50.7–53.3 cases per month). No distinctive seasonal occurrence of pertussis was noticed. However, when analyzing seasonality according to age groups, a peak of case numbers in August and September in children below 1 year of age (group 1) was evident. This season-depended fluctuation was not observed in persons 6 years and older. Standard deviation of average monthly percentage of cases per age group and year was 3.4 in group 1. In groups 3 and 4 this standard deviations were 1.4 and 1.6, respectively.

DISCUSSION

This study provides nationwide surveillance data on pertussis covering 3 years before and during given recommendation of pertussis booster vaccination in adolescents and adults. On the basis of our observation, an increasing incidence of laboratory-reported pertussis had been observed since 2000, rising from 6 cases per 100,000 population in 2000 to 11 per 100,000 population in 2005. At the same time a trend toward older affected age groups was evident. Increasing incidences and this shift in age was also observed in other countries such as the United States,5,7–9 Poland,6 Israel,10 Canada,11,12 or Australia.13 The decreasing disease rates observed for children in Austria are certainly because of a national infant vaccination coverage of more than 95%,14 whereas the rate for pertussis booster vaccination settled at an unsatisfactory level of 2% for adults and 10% for the 6–16 years olds.

This age trend is also reflected by the rising mean age of pertussis cases from 30 years in 2000 to 44 years in 2005 corresponding to an increasing proportion of pertussis patients treated by general practitioners or medical specialists.

In Austria, 86% of infants 6 months of age and younger with pertussis were hospitalized, the highest hospitalization rate of all age groups. The rate for children in the second year of age was 66% and then steadily declined to 12% in adolescence and adulthood. A second peak was seen in the elderly. Persons older than 60 years were hospitalized in 55% of the cases. This age-dependent shift of hospitalization rates were reported by Güris et al. also.7 These numbers show that infant vaccination have an impact not only on incidence of pertussis, but also on hospitalization rates as reported by others.22

A rising proportion of cases with milder manifestations were observed in the age groups between 1 and 70 years, which could be explained by the increasing awareness during the respective time period.

It seems noteworthy that immunization against pertussis of older age classes is of increasing importance, not only to provide an indirect protection for the youngest, particularly those younger than 6 months old, but also to directly protect elderly persons because disease severity is increasing with age as reflected by high pertussis-associated hospitalization rates in these age groups.

At the same time, lack of typical pertussis symptoms such as whoop, being higher for older children, adolescents and adults than for younger children, may contribute to a considerable degree of underreporting in older age groups.2,23 Besides, it needs to be pointed out that the incidence rates reported here refer to laboratory-initiated reports of pertussis and may therefore not be interpreted as an accurate reflection of the true incidence of infection or disease in the Austrian population.

Seasonality of whooping cough with a distinct late summer peak was observed for infants younger than 1 year of age, and a similar, but alleviated seasonal trend was given in children 1–6 years of age. However, in older age groups, there was no evidence of seasonality. Similar observations have been described by Celentano et al.22 Interestingly, contrary to infants, older children and adults seem to be affected by whooping cough irrespective of the season, thus supporting the role of adolescents and adults as a reservoir for the bacteria.

In the present study, detection of B. pertussis or antibodies against the pathogen was performed according to local laboratory standard procedures, mostly by serology (98%). However, serology is limited in expressiveness. There is no possibility to distinguish between antibody levels originating from infection and titers in a period of a year after vaccination. More meaningful PCR tests, which have proved to be highly sensitive and specific,24 are more complex and difficult to be performed.1 Culture, still considered the WHO standard, is specific but lacks sensitivity because pertussis confirmation is often considered too late. To date, worldwide existing recommendations on laboratory diagnosis of pertussis are not standardized. Obviously, this important topic has to be further focused on.

Undoubtedly, missing standardized laboratory diagnostic techniques pose a shortcoming of the present data. Moreover, our data sources provided no information regarding pertussis deaths. However, in the respective time interval only one death caused by pertussis has been officially reported to the Austrian Federal Ministry of Health.25 Besides, one has to admit that the present evaluation of the novel booster strategy is partially hampered by the low booster immunization coverage reached so far in the targeted age groups, particularly adults. Furthermore, incidence rates are to some extent influenced by increasing awareness during the years of observation.

Taken together, our findings reveal that laboratory-reported pertussis incidence in Austria remains high among adults implying that coverage rates regarding booster vaccination of adolescents and adults still is far too low. Hence, these findings clearly support the reinforced application of the current booster strategy to efficiently limit disease spread in all age groups.

ACKNOWLEDGMENTS

We thank all participating laboratories that provided clinical data, for their continuing support. Moreover, the skilful technical assistance of Dr. Michael Hofer is gratefully acknowledged. This study was financially supported by a grant of the Research Foundation of the Austrian National Bank (No. 6165), the Centre for Travel Medicine, Vienna, and by a research grant of the Austrian Green Cross for Preventive Medicine.

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Keywords:

pertussis; epidemiology; vaccination; adults; adolescents

© 2007 Lippincott Williams & Wilkins, Inc.