Immunity to Poliomyelitis in the Netherlands

Marina A. E. Conyn-van Spaendonck1, Hester E. de Melker1, Frithjofna Abbink1, Nazrin Elzinga-Gholizadea2, Tjeerd G. Kimman3 and Ton van Loon4

1 Department of Infectious Diseases Epidemiology, National Institute of Public Health and the Environment, Bilthoven, the Netherlands.
2 Laboratory for Control of Biological Products, National Institute of Public Health and the Environment, Bilthoven, the Netherlands.
3 Research Laboratory for Infectious Diseases, National Institute of Public Health and the Environment, Bilthoven, the Netherlands.
4 Department of Virology, Eijkman Winkler Institute, University Medical Center Utrecht, Utrecht, the Netherlands.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Despite a vaccination coverage rate of 97%, several poliomyelitis outbreaks occurred in the Netherlands during the last three decades, all among sociogeographically clustered, unvaccinated persons. Therefore, to eradicate polio, insight into poliomyelitis immunity is particularly useful. In 1995–1996, the authors conducted a population-based study and determined neutralizing antibodies against poliovirus types 1, 2, and 3 in 9,274 sera from the general population and from religious groups rejecting vaccination. In the general population, the antibody prevalence (>=1:8) was 96.6% (95% confidence interval (CI): 95.9, 97.2), 93.4% (95% CI: 92.3, 94.5), and 89.7% (95% CI: 88.3, 91.0) for poliovirus types 1, 2, and 3, respectively. Antibodies persisted for long periods in persons with natural immunity as well as in persons whose immunity was induced by inactivated polio vaccine. In Orthodox Reformed persons, the antibody prevalence of poliovirus types 1, 2, and 3 was 65.0% (95% CI: 57.2, 72.9), 59.0% (95% CI: 40.1, 77.9), and 68.7% (95% CI: 65.2, 72.2), respectively. The recent outbreaks clearly affected the seroprevalence profiles of Orthodox Reformed groups but not the general population. At present, there is an insufficient social and political basis for mandatory vaccination; therefore, global eradication of poliovirus seems to be the only way to protect these Orthodox Reformed persons against future poliomyelitis outbreaks.

antibodies; immunity; poliomyelitis; polioviruses; seroepidemiologic studies; vaccination

Abbreviations: CI, confidence interval


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In the 10 years after the World Health Organization launched the initiative to eradicate poliomyelitis by the year 2000, major progress was made worldwide (1Go). As a result of increased global vaccination coverage, the incidence of reported cases of poliomyelitis dropped from over 35,000 in 1988 to approximately 6,000 in 1998 (2Go, 3Go). Surveillance plays a major role in directing vaccination efforts and, in the process, toward eventually certifying that the world is free of poliovirus. Surveillance is based on registration and examination of clinical cases compatible with poliovirus infection. Although immunosurveillance is not required by the World Health Organization, it will provide insight into the protective immunity of (sub)populations. Immunosurveillance will be of added value in eradicating polio, particularly in countries with pockets of unvaccinated persons (4GoGo–6Go).

Poliovirus vaccination was introduced in the Netherlands in 1957 and was offered to all those persons born in 1945 and thereafter. Children are vaccinated at age 3, 4, 5, and 11 months with diphtheria, tetanus, pertussis, and inactivated polio vaccine and at age 4 and 9 years with diphtheria, tetanus, and inactivated polio vaccine. The rate of coverage for receiving at least three vaccinations by age 12 months has been 97 percent in past decades (7Go, 8Go). Major outbreaks similar to those that developed in the previous decades did not occur in the 1960s and early 1970s. Smaller outbreaks did occur in the first 10–15 years after vaccination began in communities with a high percentage of Orthodox Reformed persons not vaccinated for religious reasons. However, despite high vaccination coverage, three larger poliomyelitis outbreaks occurred in recent decades (1971, 1978, 1992–1993), with consequent exportation to polio-free countries (Canada and the United States) (9Go, 10Go). The last two outbreaks were confined to Orthodox Reformed persons who refused vaccination. The last outbreaks occurred in 1978, with 110 reported cases of disease caused by poliovirus type 1, and in 1992–1993, with 71 cases caused by poliovirus type 3 (10Go, 11Go). Between these two outbreaks, three imported cases of poliomyelitis were reported in persons who acquired the disease abroad; no cases have been reported since the 1992–1993 outbreak.

The majority of unvaccinated persons in the Netherlands have not been vaccinated for various, mostly trivial, reasons but are protected against poliomyelitis because of natural or herd immunity. However, an Orthodox Reformed minority of approximately 275,000 persons is insufficiently protected by herd immunity since they form a sociogeographically closely knit network (12Go). Vaccination is accepted to some degree among even the Orthodox Reformed groups; about a third of the Orthodox Reformed participants in our study reported that they had been vaccinated. This proportion matches the prevalence of tetanus antitoxin that we detected in the sera from this cohort (13Go).

We established a serum bank through population-based sampling in 1995–1996 to evaluate the effects of mass vaccination in the Netherlands (6Go), which offered an opportunity to study the prevalence of antibodies against polioviruses in the Dutch population and in groups refusing vaccination. The objective was to gain insight into the population's immunity. Such data could also provide insight into the possible waning of natural and vaccine-induced immunity in the absence of boosting opportunities. Furthermore, the study enabled us to detect evidence of poliovirus circulation by comparing the serologic profiles of cohorts born before and after recent outbreaks, both in the general population and in Orthodox Reformed groups.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Study population
Eight municipalities were sampled by using a probability proportional to their population sizes within each of five Dutch geographic regions with similar population sizes. An age-stratified sample (age classes <1, 1–4, 5–9, ..., 75–79 years) of 380 persons was randomly selected from each municipality. Subjects were requested to give a blood sample, fill out a questionnaire, and provide their certificates from the national immunization program, military service, and travel vaccinations. In addition, persons were similarly selected from eight municipalities with low rates of vaccine coverage (65–87 percent) so that immunity in Orthodox Reformed persons who refuse vaccination could be assessed. Samples and data were collected from October 1995 to December 1996. Participation rates were 55 percent in the nationwide sample and 52.5 percent in the low vaccine coverage sample. No separate response rate for Orthodox Reformed persons could be calculated, since information on religion was not available beforehand but only from questionnaire data after participation. Details on the study design and data collection have been published elsewhere (6Go).

Antibody assay
The sera were stored at -86°C. Neutralizing antibodies against poliovirus types 1, 2, and 3 were determined in a microneutralization assay with the Mahoney strain for poliovirus type 1, the MEF-1 strain for poliovirus type 2, and the Saukett strain for poliovirus type 3, as described previously (14Go). The sera were titrated in a twofold dilution range to 1:4096. The results were given as 2log reciprocal titers, expressed as the reciprocal of the greatest dilution showing complete neutralization of the cytopathic effect of 100-percent cell culture infection doses. A titer of 1:8 (2log titer = 3) was defined as an indication of protective immunity.

Statistical analysis
Frequencies of protective immunity and geometric mean titers in each municipality were weighted by the proportion of the age group in the population. To produce national estimates, the weighted frequencies and geometric mean titers were averaged over the 40 municipalities (15Go). For the low vaccine coverage sample, the geometric mean titers were averaged by weighting by the population size of the municipality. The effect of differential probabilities of response on both sample estimates was less than one standard error and therefore was ignored.

In the different analyses, the following groups were distinguished:

  1. All participants in the nationwide sample (n = 7,773)
  2. Orthodox Reformed participants in the low vaccine coverage sample who frequently refuse vaccination (n = 236)
  3. The subgroup of Orthodox Reformed participants in the low vaccine coverage sample who did not report participating in the national immunization program and had no documented vaccinations against poliomyelitis (n = 167)

Linear regression analysis was used to determine the persistence of poliovirus type 1, 2, and 3 antibodies after complete participation in the national immunization program. The association between poliovirus type 1, 2, and 3 antibody titers and age was studied for persons from the nationwide sample who received the sixth documented vaccination at age 8–9 years and only for those without self-reported or documented revaccination or a military service history. Since the number of persons aged 34 years or more who met these criteria was very small, this analysis was restricted to those aged 10–34 years.

Participants more than 16 years of age were asked by questionnaire whether they had received any additional vaccination, because of military service, travel, or professional activities, for example, for diphtheria, tetanus, and polio-myelitis after their childhood vaccination. Those who reported such vaccination were considered revaccinated. Documented revaccination was defined as any documented vaccination with inactivated polio vaccine given in addition to vaccinations documented on a certificate from the national immunization program.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Protective immunity in the nationwide sample
The percentages of protective antibodies against poliovirus types 1, 2, and 3 are given for the nationwide sample in table 1. The percentage was greatest (97 percent) for poliovirus type 1; it was slightly smaller for poliovirus type 2 (93 percent) and was 90 percent for poliovirus type 3. In almost all age classes, the percentages of protective antibodies against poliovirus types 2 and 3 were smaller than for poliovirus type 1 (figure 1). For all serotypes, the percentages of protective antibodies were greatest for those persons aged 29 years or less. For poliovirus type 3, a gap in the percentage was observed for the groups aged 30–44 years. In these age groups, the percentage of protective antibodies for poliovirus type 3 ranged from 82.3 to 88.1 percent; for poliovirus types 1 and 2, it remained higher than 90 percent. In the groups aged more than 49 years, the values ranged from 90.7 to 94.8 percent for poliovirus type 1, from 80.7 to 90.0 percent for poliovirus type 2, and from 82.3 to 91.3 percent for poliovirus type 3.


View this table:
[in this window]
[in a new window]
 
TABLE 1. Percentages of protective antibodies and geometric mean titers for poliovirus types 1, 2, and 3 in persons aged <1–79 years in the nationwide sample and in Orthodox Reformed persons, the Netherlands, 1995–1996

 


View larger version (20K):
[in this window]
[in a new window]
 
FIGURE 1. Age-specific prevalence of antibodies and geometric mean titer (GMT) (with 95% confidence intervals) for poliovirus types 1, 2, and 3 in the nationwide sample of persons studied to determine immunity to poliomyelitis, the Netherlands, 1995–1996.

 
For all poliovirus types, the geometric mean titer was lower for persons aged less than 1 year than for those aged 1–4 years. For persons aged 1–14 years, it remained stable for poliovirus types 1 and 2 but increased slightly for poliovirus type 3. The geometric mean titers gradually decreased for persons aged 15–40 years for all poliovirus types (figure 1). For poliovirus types 1, 2, and 3, respectively, the geometric mean titers decreased from 10.3, 8.6, and 8.2 for persons aged 10–14 years to 7.7, 6.2, and 5.2 for those aged 35–39 years. Thereafter, they remained stable. The geometric mean titer was highest for poliovirus type 1 and lowest for poliovirus type 3 in all age groups. No differences were observed between men and women.

Persistence of poliovirus antibodies after vaccination in the nationwide sample
For persons aged 10–34 years in the nationwide sample who had received the sixth and last documented vaccination at age 9 years, without any evidence of revaccinations (n = 969), the overall percentages of protective antibodies were 99.7 (95 percent confidence interval (CI): 99.2, 100) for poliovirus type 1, 98.7 (95 percent CI: 97.7, 99.6) for poliovirus type 2, and 94.5 (95 percent CI: 90.9, 98.2) for poliovirus type 3. For those aged 10–14 years versus those aged 30–34 years, the geometric mean titers for poliovirus types 1, 2, and 3 decreased from 10.5 (95 percent CI: 10.2, 10.7) to 8.0 (95 percent CI: 7.4, 8.6), from 8.6 (95 percent CI: 8.4, 8.8) to 5.2 (95 percent CI: 4.7, 5.7), and from 8.2 (95 percent CI: 8.0, 8.5) to 4.8 (95 percent CI: 4.2, 5.3), respectively (figure 2). In the linear regression analysis of the relation between antibody titers and age (figure 2), the intercepts for poliovirus types 1, 2, and 3 were, respectively, 11.9, 10.8, and 10.1 (in 2log titer), with slopes for age (in years) of -0.12, -0.18, and -0.16.



View larger version (26K):
[in this window]
[in a new window]
 
FIGURE 2. Results of regression analysis of poliovirus types 1, 2, and 3 for persons in the nationwide sample who received their sixth poliomyelitis vaccination at age 8 or 9 years, without self-reported or documented revaccination, the Netherlands, 1995–1996. GMT, geometric mean titer; CI, confidence interval.

 
For the 39 persons who received their sixth vaccination at age 8 or 9 years and had at least one documented revaccination, the geometric mean titers averaged 10.4 (95 percent CI: 9.7, 11.1) for poliovirus type 1, 9.4 (95 percent CI: 8.6, 10.3) for poliovirus type 2, and 8.2 (95 percent CI: 7.0, 9.4) for poliovirus type 3. These geometric mean titers were similar to those for persons aged 10–14 years who received their sixth and last vaccination at age 8 or 9 years.

Protective immunity in the Orthodox Reformed groups
Orthodox Reformed persons had a smaller percentage of protective antibodies for all three poliovirus types than participants in the nationwide sample (table 1). When Orthodox Reformed persons were excluded from the low vaccine coverage sample, no differences were observed in these percentages or the geometric mean titers for poliovirus types 1, 2, and 3 between the low vaccine coverage sample and the nationwide sample.

The age-specific percentages of protective antibodies for poliovirus types 1, 2, and 3 for the Orthodox Reformed persons are compared with those for all persons in the nationwide sample in figure 3. Because of the small numbers of Orthodox Reformed persons, the age-specific percentages were less precise; therefore, the fluctuations shown could have been a result of chance. For poliovirus type 1, the percentage of protective antibodies in Orthodox Reformed persons increased from 39.1 percent for those aged 15–19 years to 88.7 percent for those aged 30–34 years. This percentage was more or less stable at approximately 90 percent for older persons. An increase in the percentage of protective antibodies for poliovirus type 2, from 54.4 to approximately 80 percent, was observed after age 25–29 years. For poliovirus type 3, the percentage increased after age 1–4 years (54.2 percent) and then fluctuated at an average of 75 percent.



View larger version (26K):
[in this window]
[in a new window]
 
FIGURE 3. Age-specific prevalence of antibodies against poliovirus types 1, 2, and 3 in the nationwide sample and in Orthodox Reformed persons, the Netherlands, 1995–1996.

 
Effects of recent outbreaks: cohortwise analysis
We performed a cohortwise analysis of the serologic profiles to study the possible effect of poliovirus circulation during recent outbreaks (i.e., 1978 and 1992–1993) among Orthodox Reformed persons. Thus, we compared the percentages of protection in various birth cohorts in the nationwide sample with those for the Orthodox Reformed persons who did not report participation in the national immunization program and had received no documented vaccinations against poliomyelitis (table 2). The following birth cohorts within these groups were distinguished: persons born after 1992 (after the poliovirus type 3 epidemic), those born between 1978 and 1992 (after the poliovirus type 1 epidemic in 1978), those born between 1945 and 1978 (those who had been offered childhood vaccination), and those born before 1945 (those who were not eligible for childhood vaccination). Table 2 summarizes the results.


View this table:
[in this window]
[in a new window]
 
TABLE 2. Percentages of protection against poliovirus types 1, 2, and 3, according to birth cohort, in the nationwide sample and in a subgroup of unvaccinated Orthodox Reformed persons, the Netherlands, 1995–1996

 
In the nationwide sample, the percentage of protective antibodies was smallest for those persons born before 1945, while the largest percentages were observed for those born between 1978 and 1992. In contrast, among unvaccinated Orthodox Reformed persons, the percentages of protection for all serotypes were smallest for the cohorts born between 1978 and 1992 and after 1992. For these persons, the difference between those born before and after the two epidemics was much larger than in the nationwide sample. Less than 20 percent of Orthodox Reformed persons born between 1978 and 1992, and less than 6 percent of those born after 1992, were protected against poliovirus types 1 and 2. In contrast, 53 percent of those persons born between 1978 and 1992 had protective antibodies against poliovirus type 3, as did only 1 percent of those born after 1992. In all cohorts, whether participants were born before or after childhood vaccination was introduced (1945), the percentages of protection for poliovirus types 1, 2, and 3 were smaller for Orthodox Reformed persons than for persons in the nationwide sample.


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Our study shows that the Dutch population is generally well protected against poliomyelitis. A large neutralizing antibody prevalence (>=1:8), often exceeding 90 percent, was found in all age groups. With the methods currently available, it is not possible to determine whether these antibodies are due to exposure to live, wild virus or to vaccine virus. In general, however, it is reasonable to assume that the neutralizing antibodies are mainly attributable to natural infection in those persons born before 1945, whereas these antibodies are mainly induced by vaccination with inactivated polio vaccine in those born after childhood vaccination began (1957).

Although the prevalence of antibodies (>=1:8) against poliovirus was generally somewhat lower for type 3 than for types 1 and 2, it was still close to 90 percent. It is unclear at present whether all those persons with a low level of or no detectable antibodies are susceptible to infection; some, particularly the elderly, may be protected by memory immunity, an accelerated antibody response because the immune system has been primed previously. We are currently studying memory response in seronegative elderly persons after challenge with oral polio vaccine. Moreover, the potential for poliovirus circulation in the well-protected population vaccinated with inactivated polio vaccine is an important issue for polio eradication.

The age-specific profile of antibodies was mirrored in the age-specific geometric mean titers, as shown in figure 1. The geometric mean titers were consistently high. In the cohorts born before 1945 (i.e., in our study of those persons aged 50 years or more) with predominantly natural immunity, the geometric mean titers were stable, and there was no indication of waning immunity. A seroprevalence study that used a different sampling scheme and limited numbers was carried out in the Netherlands in 1980 and 1985 (16Go). Comparison of the present results with those from previous studies indicated no waning immunity in these naturally infected persons several decades after natural infection (16Go, 17Go). Persons naturally exposed to infection seem to retain their neutralizing antibodies, which implies that those without detectable antibodies have never been exposed to live, wild virus. In contrast, a small decrease in the geometric mean titer with age or time was observed for those persons aged 10–40 years whose antibodies were probably induced predominantly by vaccine. It appears that the decrease in geometric mean titer is due to waning immunity after vaccination. No further decline was observed in the first cohorts to whom vaccination was offered (persons aged 40–49 years). These cohorts are also likely to have been exposed to live polioviruses circulating during their childhood and therefore probably have a combination of natural and vaccine-induced immunity. It is remarkable that the differences in antibody prevalence between poliovirus type 3 and types 1 and 2 were stronger in persons aged 30–44 years. This finding might be attributable to a lower potency of the poliovirus type 3 antigens. As such, assessment of poliovirus type 3 antibodies may provide the most sensitive tool to study possible waning immunity after vaccination.

For persons aged 10–34 years who had been completely vaccinated according to the Dutch vaccination program and did not have evidence of revaccination, regression analysis showed a linear decrease in antibody levels for all types of poliovirus. Antibody levels were still high, however, even about 20 years after vaccination. We cannot completely rule out the possibility that the long persistence of high levels of vaccine-induced antibodies is partly influenced by boosting through circulating poliovirus. The explanation of these high antibody levels by the boosting phenomenon might correspond to the slightly smaller slope for poliovirus type 1 in the model, as poliovirus type 1 was most prevalent in the past. However, virus circulation probably stopped in the late 1960s or early 1970s (17GoGo–19Go). In a follow-up study of children vaccinated with inactivated polio vaccine in Sweden, Böttiger et al. showed that poliovirus neutralizing antibodies could persist for more than 18 years after vaccination (20Go). A more marked decline in antibody titer was seen in the first few years, while a very slow decrease was observed afterwards (20Go).

Epidemiologic data from the recent polio outbreaks in the Netherlands confirm the high level of protective immunity to poliomyelitis in the general population. In both the 1978 and 1992–1993 outbreaks, cases occurred among only unvaccinated persons, nearly all of whom belonged to Orthodox Reformed groups. Our results, however, show that despite a general vaccination coverage rate of 97 percent, the potential for outbreaks in these Orthodox Reformed groups is still high; only 65, 59, and 69 percent of these persons had protective antibodies for poliovirus types 1, 2, and 3, respectively. We found that the percentages of persons aged 1–19 years with protective antibodies were 48 percent for type 1, 47 percent for type 2, and 68 percent for type 3. As expected, persons without protective antibodies were found predominantly in the cohorts born after vaccination was introduced. Actually, this occurrence seems to be a paradoxical effect of mass vaccination, although these unvaccinated groups benefit from the interruption of virus circulation that results from widespread vaccination. The Ministry of Health, advised by the Health Council, has decided against making vaccination mandatory in the Netherlands. Therefore, mandatory vaccination is not considered socially and politically feasible; thus, poliomyelitis can ultimately be prevented only through global eradication of the causative agents, the polioviruses (21Go).

The effect of virus circulation during the 1978 (type 1) and 1992–1993 (type 3) outbreaks among Orthodox Reformed persons with no evidence of vaccination becomes evident when the serologic profiles of the cohorts born before and after the outbreaks are compared. For poliovirus type 1, the seroprevalence for those persons born between 1978 and 1992, that is, after the 1978 type 1 epidemic, was only 12 percent, but it was 64 percent for those born between 1945 and 1978; for type 3, the seroprevalence for those born after 1992, the year of the type 3 outbreak, was only 1 percent in contrast to 53 percent for those persons born between 1978 and 1992. This finding indicates that as many as half of the persons in these unvaccinated groups were infected during the epidemic.

Remarkably, the pattern of cohortwise estimates of seroprevalence for poliovirus type 2 is similar to that for type 1, although there have been no signs of wild poliovirus type 2 circulation in the Netherlands for decades. We cannot explain this finding satisfactorily. However, the numbers of Orthodox Reformed persons were small, particularly when stratified by cohort. The last polio patient with a poliovirus type 2 infection in the Netherlands was reported in 1966. A wild poliovirus type 2 occasionally has been isolated from adopted children and, once, from river water in the early 1980s (17Go). Since then, only a few vaccine-derived poliovirus type 2 strains have been isolated (17Go). The apparently elevated poliovirus type 2 seroprevalence in those born after 1978 cannot be ascribed to circulation of oral-polio-vaccine–derived poliovirus type 2 after the 1978 outbreak, as only monovalent type 1 oral polio vaccine was used then to control the outbreak. In the 1992–1993 outbreak, however, trivalent oral polio vaccine was applied, which may have resulted in poliovirus type 2 circulation (22Go). There is some cross-reactivity between poliovirus serotypes 1 and 2, but it is improbable that this cross-reactivity can satisfactorily explain the comparable levels for serotypes 1 and 2 (23Go). Using seroepidemiologic data from a study of gypsies, Aylward et al. concluded that wild virus circulation could have influenced the prevalence, although the possibility could not be ruled out that the high prevalence was caused by the spread of vaccine virus (24Go). In our study, the differences in the prevalence of poliovirus type 3 antibodies in cohorts born before and after the 1992–1993 outbreak must be ascribed mainly to wild virus circulation.

In the nationwide sample and in the low vaccine coverage sample in which Orthodox Reformed persons were excluded, we found no differences in type 1 seroprevalence in the cohorts born before and after the 1978 outbreak, and only a small difference occurred in type 3 seroprevalence in cohorts born before and after the 1992–1993 outbreak. This finding supports the assumption that little or no virus has spread outside the Orthodox Reformed groups, either in the general population or among other inhabitants of the municipalities in which these groups live.

As we have discussed in this paper, there are no signs of waning immunity in cohorts that supposedly have predominantly natural immunity. The seroprevalence for none of the three types of poliovirus reached 100 percent in the oldest cohorts, indicating that the endemic virus in the prevaccination era never fully depleted the pool of susceptible persons. This conclusion agrees with the threshold value for the percentage of protected persons required to prevent poliovirus transmission, estimated as 82–87 percent given the condition of homogeneous mixing (25Go). The 1978 and 1992–1993 outbreaks also seem not to have infected all susceptible persons in the Orthodox Reformed groups; only 64 percent of those born between 1945 and 1978 were found to have type 1 antibodies, and 53 percent of those born between 1978 and 1992–1993 had type 3 antibodies. The large percentage of children without protective antibodies clearly shows a potential for another polio outbreak in the Netherlands that will exist as long as polioviruses have not been eradicated worldwide.

In conclusion, routine childhood vaccination with inactivated polio vaccine has provided excellent protection against poliomyelitis in the general population of the Netherlands. Antibodies persist for very long periods of time, not only in naturally infected persons but also in those with vaccine-induced immunity. Our study, conducted in the era of polio eradication, provides additional evidence of the absence of poliovirus circulation in the general population during the outbreaks among Orthodox Reformed persons who refused vaccination in 1978 and 1992–1993. Since mandatory vaccination is politically and socially unacceptable in the Netherlands, pockets of susceptibility will remain because persons object to vaccination for religious reasons. Therefore, global eradication is the only means of protecting these persons against poliomyelitis.


    ACKNOWLEDGMENTS
 
The authors acknowledge the Public Health Services, the Pienter Project Team, and D. R. Jut and T. A. M. Antonioli for their very useful contributions.


    NOTES
 
Reprint requests to Dr. Marina A. E. Conyn-van Spaendonck, Department of Infectious Diseases Epidemiology, National Institute of Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, the Netherlands (e-mail: mae.conyn{at}rivm.nl).

Editor's note: An invited commentary on this paper appears on page 215, and the authors' response is on page 217.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. World Health Organization. Global eradication of poliomyelitis by the year 2000. In: Forty-first World Health Assembly: resolutions and decisions, WHA41/1988/REC/1, resolution WHA41.28. Geneva, Switzerland: World Health Organization, 1988:26–8.
  2. Tangermann RH, Aylward B, Birmingham M, et al. Current status of the global eradication of poliomyelitis. World Health Stat Q 1997;50:188–94.[Medline]
  3. Progress toward global poliomyelitis eradication—1997–1998. MMWR Morb Mortal Wkly Rep 1999;48:416–21.[Medline]
  4. van Loon AM, Rümke HC, Conyn-van Spaendonck MAE. Polio eradication in the Netherlands: a proposal for surveillance. Bilthoven, the Netherlands: National Institute of Public Health and the Environment, 1998. (RijksInstituut voor Volksgezondheid en Milieu (RIVM) report no. 242500003).
  5. Mensi C, Pregliasco F. Poliomyelitis: present epidemiological situation and vaccination problems. Clin Diagn Lab Immunol 1998;5:278–80.[Free Full Text]
  6. de Melker HE, Conyn-van Spaendonck MAE. Immunosur-veillance and the evaluation of national immunisation programmes: a population-based approach. Epidemiol Infect 1998;121:637–43.[ISI][Medline]
  7. Bijkerk H. Surveillance and control of poliomyelitis in the Netherlands. Rev Infect Dis 1984;6:S451–6.[ISI][Medline]
  8. Verbrugge HP. The national immunization program of the Netherlands. Pediatrics 1990;86:S1060–3.
  9. Isolation of wild poliovirus type 3 among members of a religious community objecting to vaccination—Alberta, Canada, 1993. MMWR Morb Mortal Wkly Rep 1993;42:337–9.[Medline]
  10. Schaap GJP, Bijkerk H, Coutinho RA, et al. The spread of wild poliovirus in the well-vaccinated Netherlands in connection with the 1978 epidemic. Prog Med Virol 1984;29:124–40.[ISI][Medline]
  11. Oostvogel PM, van Wijngaarden JK, van der Avoort HGAM, et al. Poliomyelitis outbreak in an unvaccinated community in the Netherlands, 1992–93. Lancet 1994;344:665–70.[ISI][Medline]
  12. Geubbels ELPE, Conyn-van Spaendonck MAE, van Loon AM. Poliomyelitis vaccinatie in Nederland. In: Gunning-Schepers LJ, Jansen J, eds. Volksgezondheid toekomst verkenning 1997. IV. Effecten van preventie. (In Dutch). Maarssen, the Netherlands: Elsevier/De Tijdstroom, 1997:79–87.
  13. de Melker HE, van den Hof SH, Berbers GAM, et al. A population-based study on tetanus immunity in the Netherlands. Vaccine 1999;18:100–8.[ISI][Medline]
  14. Albrecht P, van Steenis G, van Wezel AL, et al. Standard-ization of poliovirus neutralising antibody tests. Rev Infect Dis 1984;6:S540–6.[ISI][Medline]
  15. Cochran WG. Sampling techniques. 3rd ed. New York, NY: John Wiley & Sons, Inc, 1977.
  16. Conyn-van Spaendonck MAE, Hannik CA, Bijkerk H, et al. Immune status for poliomyelitis, rubella and morbilli in the Dutch population of 10 years and older in 1980: a serological survey. Ned Tijdschr Geneeskd 1984;128:1884–7.[Medline]
  17. Rümke HC, Oostvogel PM, van Steenis G, et al. Poliomyelitis in the Netherlands: a review of population immunity and exposure between the epidemics in 1978 and 1992. Epidemiol Infect 1995;115:289–98.[ISI][Medline]
  18. Conyn-van Spaendonck MAE, Oostvogel PM, van Loon AM, et al. Circulation of poliovirus during the poliomyelitis outbreak in the Netherlands in 1992–1993. Am J Epidemiol 1996;143:929–35.[Abstract]
  19. van Loon AM. Circulation of polioviruses in the Netherlands. Geneva, Switzerland: World Health Organization, 1998. (Publication no. WHO/EPI/POLIO/SIM.98/WP3.4).
  20. Böttiger M. Polio immunity to killed vaccine: an 18-year follow-up. Vaccine 1990;8:443–5.[ISI][Medline]
  21. Health Council of the Netherlands. Committee Poliomyelitis. Poliomyelitis. The Hague, the Netherlands: Health Council of the Netherlands, 1995. (Publication no. 1995/19).
  22. van der Avoort HG, Reimerink JH, Ras A, et al. Isolation of epidemic poliovirus from sewage during the 1992–1993 type 3 outbreak in the Netherlands. Epidemiol Infect 1995;114:481–91.[ISI][Medline]
  23. Danes L, Sladká E, Hancil J, et al. Cross reactivity among human enterovirus serotypes as revealed by microneutralization assay technique. J Hyg Epidemiol Microbiol Immunol 1988;32:233–8.[Medline]
  24. Aylward RB, Porta D, Fiore L, et al. Unimmunized gypsy populations and implications for the eradication of poliomyelitis in Europe. J Infect Dis 1997;175(suppl 1):S86–8.
  25. Anderson RM, May RM. Infectious diseases of humans: dynamics and control. 2nd ed. New York, NY: Oxford University Press, 1991.
Received for publication July 7, 1999. Accepted for publication May 26, 2000.


Related articles in Am. J. Epidemiol.:

Invited Commentary: Stopping Polio Immunization
Harry F. Hull, R. Bruce Aylward, and Julie Milstien
Am. J. Epidemiol. 2001 153: 215-216. [Extract] [FREE Full Text]  

The Authors Respond to Hull et al.
Tjeerd G. Kimman, Hester E. de Melker, Frithjofna Abbink, Nazrin Elzinga-Gholizadea, Ton van Loon, and Marina A. E. Conyn-van Spaendonck
Am. J. Epidemiol. 2001 153: 217-218. [Extract] [FREE Full Text]