1 Department of Sera and Vaccines Evaluation, National Institute of Hygiene, 24 Chocimska Str., 00-791 Warsaw, Poland
2 Department of Medical Statistics, National Institute of Hygiene, 24 Chocimska Str., 00-791 Warsaw, Poland
Correspondence: Anna Gzyl, Department of Sera and Vaccines Evaluation, National Institute of Hygiene, 24 Chocimska Str., 00791 Warsaw, Poland. E-mail: agzyl{at}pzh.gov.pl
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Abstract |
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Methods Available data on notification, incidence, mortality, hospitalization, geographical distribution, incidence according to age, and diagnosis of pertussis were collected from national surveillance monographs and statistically evaluated.
Results Analyses performed in the study found two periods of rising and falling trends: in the incidence before and after 1989, respectively. Moreover, after 1989, the age-specific incidence among children aged 04 years decreased, and among 59, 1014, and 1519 year olds increased in comparison to the previous decade. The incidence rate of pertussis among infants was similar in both decades analysed. Clustering of pertussis incidence increase in provinces along a line from North East to South West was observed.
Conclusions As vaccination coverage did not decrease and diagnostics have not been improved since the 1980s, it is possible that waning immunity and the appearance of Bordetella pertussis vaccine escape mutants are involved in the changing pertussis epidemiological parameters. Further monitoring studies, together with improving diagnostics, might allow more precise epidemiological data to be obtained. An additional booster dose of acellular pertussis vaccine at age 6 years has been included in the current vaccination schedule.
Accepted 6 August 2003
Pertussis has been controlled successfully by routine mass immunization of infants and children with whole-cell vaccine for nearly 50 years. However, in many countries considerable media interest has been mixed with a fear of the possible re-emergence of pertussis.15 In some of countries recrudescence or persistence of pertussis has been recognized as being due to permanent or temporary exclusion of diphtheria-tetanus-pertussis (DTP) immunization from vaccination schedules, because of an underlying fear of possible local and general adverse events following immunization (AEFI) in vaccinated children.5 In some other countries, however, pertussis rates have increased despite the high vaccination coverage achieved over the course of many years.68 In these countries, changes in the surveillance system, a decrease in vaccination coverage and in vaccine quality, waning of vaccine-induced immunity, and the emergence of vaccine resistant strains (escape mutants) are proposed as possible factors for the increased incidence of pertussis.912 Reasons for the increase in pertussis have been studied intensively in the US12 and The Netherlands,13 but they are still not fully elucidated. In 19971998 in Polanda country with a population of 38.6 million14,15despite a 98% level of vaccination coverage with whole-cell pertussis vaccine, pertussis incidence rates were found to be similar to the rates registered 30 years earlier. In 1997 and 1998, 2082 and 2871 cases of pertussis were reported, accounting for an incidence/100 000 population of 5.4 and 7.4 respectively. Available national surveillance data on pertussis were collected and analysed in order to describe epidemiological changes in pertussis in Poland 19632000, and to identify factors of possible significance for the recent pertussis rates increase.
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Material and methods |
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Data of yearly notification, hospitalization, mortality, and incidence/100 000 population were collected for19502000 using data published in the Bi-weekly Reports on Infectious Diseases and Intoxications with Chemical Compounds bulletinsof the MOH for 19581968; the MOH together with the Public Health Laboratory, Warsaw for 19691983; and the Department of Epidemiology at NIH and the MOH for 19842000. Population-based incidence and incidence according to age refers to the number of recorded pertussis cases in correlation with specific census data, which is evaluated annually and published by the governmental Central Office of Statistics (CSO; www.stat.gov.pl).
Vaccination coverage data were collected from Szczepienia ochronne w Polsce (Vaccinations in Poland) monographs published yearly by NIH, MOH, and CSO. Vaccine coverage of pertussis with locally produced whole-cell pertussis (DTP) vaccine (Sera and Vaccines Manufacture BIOMED SA, Krakow, Poland) is routinely assessed by NIH. They determine the proportion of 2 year olds who received three or four doses of DTP, using obligatory yearly reports from Provincial Health Laboratories on all vaccinations performed at Health Institutions in each province.
Additionally, case-surveillance on collected case-standardized epidemiological questionnaires collected from Provincial Health Laboratories is performed by the Department of Epidemiology, NIH, and results of these are published yearly in Przegld Epidemiologiczny (Epidemiological Reviewa Polish scientific journal published quarterly since 1920). The incidence rate according to age has been calculated by NIH using Polish CSO data. Data on specific incidence rate according to age and vaccination status on 12 174 cases 19762000 (no data 1982) were collected from Epidemiological Review publications.
The distribution of notifications of pertussis and incidence rates within 49 provinces from 19801998 were collected from Epidemiological Review publications and Vaccinations in Poland monographs.
Pertussis definition
Pertussis is defined by the presence of the following symptoms: cough with whooping lasting for >2 weeks or cough followed by vomiting in combination with such symptoms as apnoea, cyanosis, subconjunctival bleeding, leukocytosis, lymphocytosis, or contact with a confirmed or suspected pertussis case during the previous 3 weeks.16 For confirmation of clinical diagnosis, bacteriology, immunofluorescence, or serology tests are recommended. Serological confirmation of clinical diagnosis of pertussis is based on a passive haemagglutination test (PHT) with pertussis endotoxin or ELISA assay with pertussis toxin and whole Bordetella pertussis cells as antigens. PHT performed on patient sera at 2-weekly intervals is used to correlate specific antibody level dynamics with clinical features of pertussis, onset of clinical symptoms, or vaccination status. The ELISA test is considered positive when a high titre of IgA against B. pertussis in a single serum or 100% rise of IgG antibodies against pertussis toxin in the second of the paired serum sample is seen.
Statistical analysis
Incidence rates in 04 (0, 1, 2, 3, 4), 59, 1014, and 1519 age groups within the periods 19761989 and 19902000 were analysed using linear regression.17 Pooled estimate of slope for each group incidence was obtained by averaging age group specific incidence estimates with inverse variance as a weight. Averages of pertussis incidence/100 000 population calculated for the periods 19801989 and 19901998 in 49 provinces were compared using a t-test, and the significance of incidence increase found in 11 provinces was calculated after application of the Bonefferoni correction. The Bonefferoni correction was applied to avoid problems associated with multiple comparisons.18 Notification averages within particular months were calculated from 1990 to 2000. All calculations were performed using the statistical package Splus 2000.19
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Results |
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The reported yearly incidence generally decreased over time from >100200 cases/100 000 population in the pre-vaccine decade (19501960) to <1 case/100 000 population within the 19811990 period (Figure 1).
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The decrease in pertussis notification and incidence rates commenced from 1989. In 1992 the increase in pertussis incidence in comparison to 1991 and 1989 was twofold and fivefold, respectively. In 1997, a sixfold increase in comparison to 1996 was noted (Figure 1). Within the period of 19972000 the yearly incidence/100 000 population was 5.4, 7.4, 2.3, and 5.9, respectively.
Although the highest increase in morbidity/year has been noted since 1997, analysis of notification rates/month within the last 10 years evidently shows that pertussis has been on the increase since June 1995. Arithmetic means of the monthly registered cases within the last 10 years show that pertussis cases were periodically more prevalent from September to March (Figure 2). Analysis of quarterly registered case rates 19572000 found lower pertussis rates, with easily seen longer inter-epidemic periods during 19752000 in comparison with the period 19571974.
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Vaccination coverage
Children in Poland have, from 1960, been continuously immunized with three primary doses and 1 booster dose at the ages of 2, 34, 5, and 1618 months with a locally manufactured DTP vaccine. Vaccination coverage with three and four doses of the DTP vaccine for children born in particular years between 19791999, oscillated in ranges of 98.299.5% and 94.998.7%, respectively.
Vaccination status
Analysis of the vaccination status of 12 174 registered case-patients between 19762000 revealed, from 1990 onwards, an increase in the incidence of pertussis in those vaccinated in comparison to the non-vaccinated. However, there were no major changes observed in the proportions of children vaccinated with one, two, or three doses of DTP vaccine, who got pertussis.
Pertussis distribution within 49 provinces (19801998)
Among 49 provinces, 20 during 19801989 and 22 during 19901998 have maintained an average incidence of <1/100 000 population. Moreover, 18 provinces reported no changes in the average incidence at a level <1, 16 provinces at a level lower than 12, and one province at a level lower than 25/100 000 population. Five provinces in both periods recorded fluctuations between 1 and 12. Thus, in 30 provinces the incidence remained at
2/100 000. Among 19 others there were incidence increases in 19901998 observed in comparison with 19801989, and in 11 it was statistically significant (P < 0.05). However, statistical significance of the incidence increase after application of the Bonefferoni correction has been found only in a single province. A clustering of pertussis incidence increase has been observed along a line from North East to South West (Figure 3).
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The frequency of pertussis cases among 59 and 1014 year olds increased threefold and sevenfold, respectively, when comparing 1985 and 1998. There was a 33% increase in infections among those >10 years old out of the total number of pertussis cases registered in 1997. Generally, the frequency of pertussis increased 0.5, 3, and 6 times for 59, 1014, and 1519 year olds when comparing 19901996 to 19972000. In 19851992 only a few pertussis cases were registered in the age group 1519 years. However, in 1997 and 2000 as many as 77 and 158 cases, respectively, were registered.
A significant decrease (P = 0.028) and increase (P = 0.045) in pooled incidence rates calculated from data relating to all age groups compared between 19761989 and 19902000 respectively, were found.
A non-statistically significant downward trend between 1976 and 1989 in the age group <1 year old was found in comparison with a statistically significant decrease found when 1 (P = 0.001), 2 (P = 0.002), 3 (P = 0.001), and 4 (P = 0.001) year old children within the total 04 age group were analysed (Figure 4A). During 19902000, in the total 04 age group, a statistically significant incidence increase was found only for 3 (P = 0.009) and 4 year old (P = 0.008) and not for 0, 1, and 2 year old children (Figure 4B). A statistically significant morbidity decrease within 19761989 was seen in all age groups analysed (P
0.003) (Figure 5A). Among individuals in the four age groups analysed, a significant increase in incidence rates was found between 19902000 for 59 (P = 0.006), 1014 (P = 0.005), and 1519 (P = 0.016) year olds, but not in the 04 year old age group (Figure 5B). Regressive analysis of the data revealed that the most aggressive slopes for morbidity increase have been found for 59 and 1014 year olds, and for 3 and 4 year old children among the 04 group as a whole (Figures 4B and 5B).
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Discussion |
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In Poland, before the introduction of pertussis immunization to the vaccination programme, pertussis was mainly registered in 24 year old children. As little as 10 years after the introduction of DTP, when incidence was lowered in groups covered by vaccination, a decrease of incidence rates in all age groups as an effect of increased herd immunity was notified. The rise in incidence registered in Poland since 1997, after 36 years of continuously successful DTP immunization, was unexpected for the following two reasons. Firstly, the DTP vaccination programme has been performed with success continuously since 1960. Secondly, the success of this programme has been easily seen since the 1970s, when cycles with epidemic and endemic peaks every 35 years were recognized, but generally pertussis incidence during 19821991 was <1/100 000.
Average vaccine coverage in the period 19852000 has not changed, reaching 9698% for children aged 1 year,5 and thus a possible role of the occurrence of a large pool of susceptible individuals in the population can be excluded. Vaccination coverage was maintained thus at a high stable level even in the 1980s; much higher than registered in the US in the 1990s.12
The increased rate of pertussis found among 59, 1014, and 1519 year olds in Poland in the last decade may be related to the reduced circulation of B. pertussis due to long-term vaccination with subsequent less frequent exposure to the bacteria, and therefore a lower possibility of natural boosting. The risk of pertussis among infants, many of whom may be too young to receive primary doses of DTP, remained at similar levels during 19761989 and 19902000. Additionally, the incidence of pertussis in children aged 4 years old also remained stable within both periods analysed. A similar picture was found in the US, where the average incidence for children <5 years has not increased, but among those aged 59, 1019, and older the increase was pronounced.12,20 In The Netherlands, a decrease in the proportion of pertussis cases among infants <1 year old was also found. However, an increase of pertussis cases among children aged 14, and adults, together with a decrease in cases among 59 year old children was observed. No changes were observed among 1014 and 1519 year old children.13
As the pertussis incidence rate among the whole 04 year old group has not increased, the recent increase in the incidence of pertussis in Poland is related neither to a decrease in vaccination coverage nor to a significant reduction in DTP efficacy. The whole-cell vaccine produced in Poland meets international standards and there was no sign of a gradual deterioration of the vaccine quality as determined for product release using a mouse-protection test. However, our unpublished data show lower potency levels (but still fulfilling accepted lower limits) in the DTP lots released 19921997 correlated to the lower IOU number/single human dose in comparison with vaccine lots produced in another periods. It could be suspected that lower vaccine immunogenicity might cause a lower protective immunization level than previously achieved, resulting in higher incidence rates among 3, 4, and 59 year old children, as observed in the study. However, the increase of pertussis incidence rates observed among >10 year olds suggests the involvement of other factors. The increase in pertussis rates in vaccinated people, with a subsequent decrease in the pertussis rate among the non-vaccinated from 1990 onwards, might be related to an increase in infections among children of school age and older. Such a trend is to be expected when there is a high proportion of vaccinated people in a population together with no significant decrease in vaccine efficacy. In the study, an expected association between school opening and a peak in pertussis (similar to data from the US20) was seen since pertussis is spread by the airborne route. However, we could not specify differences in monthly recorded prevalence according to age. American data correlated increased pertussis for 1019 year olds with a peak in October/December, and for 5 year olds with a peak in June/September.20
Pertussis cases were reported from all 49 provinces within the period studied and the annual incidence of pertussis varied greatly between provinces (similar to the US), although vaccination coverage oscillated around approximately 9098%. The highest rate of incidence increase occurred in the North East border and in the centrally located provinces. It might be speculated that the higher rates of pertussis (oscillating around 4/100 000) reported by Lithuania, Belarus, and Ukraine may bear a relation to increased rates observed in the eastern part of Poland. Moreover, the Russian Federation reported to the WHO between 19972000 pertussis rates accounting for morbidity around 18/100 000.
In Poland, similarly to The Netherlands and the US, an occurrence of epidemics is thought to be at least in part explained by a genetic shift in B. pertussis strains involving pertactin and pertussis toxin genes.68,10 It has been suggested that genetic change in B. pertussis shortens the duration of vaccine-induced immunity and increases incidence.11 At present, isolates of B. pertussis containing non-vaccine variants of ptxS1 and prn alleles comprise approximately 30% of all strains isolated in Poland.
Changes in the epidemiology of pertussis observed in Poland are similar to the changes observed in the other highly vaccinated populations. Waning immunity among infrequently naturally boosted adolescents and adults who may get only a mild form of the disease, might thus create a reservoir and a source of infection for under immunized children.9 Moreover, it has been suggested that vaccinated people become susceptible to pertussis 510 years after vaccination, depending on the type or brand of vaccine.12 Strebel et al.21 and De Serres et al.22 indicated that a booster dose for 1112 year olds might be an effective strategy to prevent pertussis among US adolescents. In Europe, France and Germany implemented additional reinforcing booster doses of acellular pertussis vaccine at age 11 years.23 Pertussis seroprevalence studies in Poland determined protective antibody levels against pertussis in 70%, 58%, and 45% of children aged 6, 7, and 8, respectively. It shows that a decrease of immunity may cause an increase in the number of pertussis cases among children >5 years.24 An additional booster (fifth) dose of acellular pertussis vaccine before entering school has now been introduced in Poland.
In Poland, contrary to the US, underestimation of the true incidence due to surveillance and diagnostic improvements resulting from increased awareness of pertussis in adolescents and adults has not been suspected.11,12 However, underreporting might be involved, similar to the pertussis increase in 1996 in The Netherlands, due to improved compliance with the notification system.13 Pertussis cases in Poland were reported based on clinical definition up to 1980, and still are. However, after 1980, because of the availability of serological tests, many of them were laboratory confirmed. Following a current WHO Expert Committee case definition,25 laboratory confirmation of pertussis is advised in Poland. Recently as many as 90% of registered pertussis cases have been laboratory confirmed. However, only half have used methods according to the WHO recommendations.26,27 The remaining half has unfortunately been confirmed with an old-fashioned PHT method, frequently performed only once.
Although there are some weaknesses in surveillance influencing absolute validity of the data, epidemiological trends of pertussis in Poland are similar to other highly vaccinated populations. However, the laboratory aspects of pertussis diagnosis present several drawbacks and improving these is essential for real estimation of the burden of pertussis.
KEY MESSAGES
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Acknowledgments |
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Notes |
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References |
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