Immunity against poliomyelitis in the Netherlands, assessed in 2006 to 2007: the importance of completing a vaccination series.

Europe has been declared polio-free since 2002. Here we describe the seroprotection against poliomyelitis in the Dutch population using banked serum samples. Samples from 1,581 inhabitants of eight municipalities with low vaccination coverage (LVC) and an additional 6,386 samples from a nationwide (NS) group (clinical trial number: ISRCTN20164309; collected in 2006­07) were tested for neutralising antibodies (log² reciprocal titres (GMT); non-protection <3) against all three poliomyelitis serotypes. Demographic and epidemiological data were used for statistical regression analysis. Seroprevalence in the NS was 94.6% (type 1), 91.8% (type 2) and 84.0% (type 3). Infants (0­7 months-old) had ≥80% seroprevalence for all serotypes. The highest seroprevalence was found in children, with type 1 and type 2 in five year-olds and type 3 in nine to 10 year-olds. In the LVC group, orthodox protestants, many of whom refuse vaccination, showed seroprevalence rates of 64.9% (type 1), 61.0% (type 2) and 62.1% (type 3). In the NS group, non-Western immigrants and travellers to non-European continents had higher seroprevalences compared to Western immigrants and travellers within Europe, respectively. The Dutch National Immunisation Programme against poliomyelitis has provided good seroprotection, with high and long-lasting GMTs against all serotypes upon completion. The unvaccinated population remains at risk.

[The control of pertussis after half a century of vaccination]. / De bestrijding van kinkhoest na een halve eeuw vaccineren.

Notification of laboratory-confirmed pertussis is mandatory in the Netherlands. Thus, the public health service can see to it that timely chemoprophylaxis (within 3 weeks after the onset of symptoms in the index case) is prescribed for all members of the household, should there be a vulnerable non-vaccinated or insufficiently vaccinated newborn in the family. However, it was shown that the delay in this notification was so long that intervention by the prescription of chemoprophylaxis could take place in time to protect a newborn infant in only 10% of the cases. The effectiveness of the notification system in facilitating timely chemoprophylaxis is therefore questioned and it is concluded that other ways to achieve such intervention, independent of notification, are needed. Doctors should always ascertain the presence of a newborn infant in the household of pertussis patients and consider chemoprophylaxis immediately, even ahead of notification. Even if not in time for effective prophylaxis, mandatory notification is still of utmost importance for the evaluation of pertussis immunisation. Surveillance data obtained from notification are used in scenario analysis and contribute to the underpinning of alternative immunisation policies. After all, major improvements in pertussis control can be expected from the addition of (re)vaccination of other target groups, such as mothers of newborns, adolescents or adults, to the national immunisation programme.

Sudden deaths following influenza vaccination: can this be expected?

BACKGROUND: In November 2006, four Dutch people, aged 53, 58, 80 and 88, died unexpectedly on the day they had received their influenza vaccination. A rapid epidemiological assessment was needed to quantify the risk of a causal association. METHODS: Using routinely available data on age-stratified population size, cardiovascular mortality, and vaccination coverage, a daily rate and daily risk of sudden death per 5-year age-group was calculated. A cumulative probability that at least one person in four specific age-groups would die on the day of vaccination was calculated using a binomial distribution. No assumptions on deaths in other age groups were included. RESULTS: The overall likelihood that at least one person in each of the four age categories 50-54, 55-59, 80-84 and 85-89 would die suddenly on the day of influenza vaccination in the Netherlands was calculated to be 0.016. This was 330 times more likely than nobody dying in each of these categories, and 45 times less likely than the most probable outcome. CONCLUSION: We concluded that there was a small but real chance of the four deaths occurring without a causal link to the vaccination. Policy decisions regarding unexpected deaths following vaccination can benefit from a rapid epidemiological evaluation.

[Adverse events following influenza vaccination: reaction to specific reports and the necessity of a central registration system]. / Bijwerkingen na influenzavaccinatie: reactie op enkele incidenten en het belang van centrale registratie.

The influenza vaccine is considered safe, but information on vaccine-related adverse events is limited and a nationwide overview of adverse events is lacking. In 2006, after deaths occurred in Israel and the Netherlands following influenza vaccination, the Dutch Ministry of Health, Welfare and Sport (VWS) asked the National Institute for Public Health and the Environment (RIVM) twice for a recommendation regarding the continuation of the national vaccination campaign. After 4 deaths were reported in Israel in October 2006 following administration of Vaxigrip, the Dutch vaccination campaign was suspended for one week. One month later, 4 additional deaths were reported after influenza vaccination in the Netherlands. The newly appointed outbreak management team concluded that a causal relationship between vaccination and the deaths was highly unlikely, based on data regarding the individual cases, background mortality rates and prior reports of adverse events. Further suspension of the vaccination campaign was deemed unnecessary this time. A centralised nationwide registry of adverse events has since been established to provide further insight into the incidence of adverse events following influenza vaccination. Physicians are advised to report potential adverse events following influenza vaccination to the Netherlands Pharmacovigilance Centre Lareb (www.lareb.nl).

Public health implications of using various case definitions in The Netherlands during the worldwide SARS outbreak.

This study analysed the consequences of deviation from the WHO case definition for the assessment of patients with suspected severe acute respiratory syndrome (SARS) in The Netherlands during 2003. Between 17 March and 7 July 2003, as a result of dilemmas in balancing sensitivity and specificity, five different case definitions were used. The patients referred for SARS assessment were analysed from a public health perspective. None of the patients referred had SARS, based on serological and virological criteria. Nevertheless, all 72 patients required thorough assessment and, depending on the results of the assessment, institution of appropriate prevention and control measures. Changing case definitions caused confusion in classifying cases. A centralised assessment of the reported cases by a team with clinical and public health expertise (epidemiological and geographical risk assessment) is a practical solution for addressing differences in applying case definitions. The burden of managing non-cases is an important issue when allocating public health resources, and should be taken into account during the preparation phase, rather than during an outbreak. This applies not only to SARS, but also to other public health threats, such as pandemic influenza or a bioterrorist episode.

Estimation of minimum infection rates with Legionella pneumophila in an exposed population.

The distribution of antibody levels to Legionella (L.) pneumophila (serotypes 1-7) was compared between subjects who worked near the source of a large outbreak of Legionnaires' disease (n=668) and a population sample of comparable age (n=480). In a previous analysis of these data, it was estimated that 80% of those working near the source were infected with L. pneumophila. However, the estimation procedure implicitly assumes that the probability of infection does not depend on the antibody level of a person before exposure. This is questionable, as antibodies could protect against infection. We have now estimated the minimum value consistent with the data on the number of infected persons. We observed that a minimum of 40% [95% confidence interval (CI) 32-48] of those working near the source and 13% (95% CI 8-18) of those working further away were infected with L. pneumophila. Implications of these findings for design options in future research are discussed.

The seroepidemiology of Bordetella pertussis infection in Western Europe.

High titres of pertussis toxin (PT) antibody have been shown to be predictive of recent infection with Bordetella pertussis. The seroprevalence of standardized anti-PT antibody was determined in six Western European countries between 1994 and 1998 and related to historical surveillance and vaccine programme data. Standardized anti-PT titres were calculated for a series of whole-cell and acellular pertussis vaccine trials. For the serological surveys, high-titre sera (> 125 units/ml) were distributed throughout all age groups in both high- (> 90%) and low-coverage (< 90%) countries. High-titre sera were more likely in infants in countries using high-titre-producing vaccines in their primary programme (Italy, 11.5%; Western Germany, 13.3%; France, 4.3%; Eastern Germany, 4.0%) compared to other countries (The Netherlands, 0.5%; Finland, 0%). Recent infection was significantly more likely in adolescents (10-19 years old) and adults in high-coverage countries (Finland, The Netherlands, France, East Germany), whereas infection was more likely in children (3-9 years old) than adolescents in low-coverage (< 90%; Italy, West Germany, United Kingdom) countries. The impact and role of programmatic changes introduced after these surveys aimed at protecting infants from severe disease by accelerating the primary schedule or vaccinating older children and adolescents with booster doses can be evaluated with this approach.

Population-based Toxoplasma seroprevalence study in The Netherlands.

During 1995--1996 a population-based seroprevalence study was conducted in The Netherlands. Risk factors were established for postnatally acquired toxoplasmosis. The results were compared with a study conducted during 1987-1988 in pregnant women in the Southwest of The Netherlands in order to estimate the change in seroprevalence. In total, 7521 sera were tested and the national seroprevalence was 40.5 % (95 % CI 37.5-43.4). Living in the Northwest, having professional contact with animals, living in a moderately urbanized area, being divorced or widowed, being born outside The Netherlands, frequent gardening and owning a cat were independently associated with Toxoplasma seropositivity. Risk factors like eating undercooked meat could not be studied. The seroprevalence among women aged 15-49 years was 10 % lower (35.2 %, 95 % CI 32.9-38.6) in the study of 1995-1996, compared to the Toxoplasma study of 1987--1988 (45.8 %, 95 % CI 45.2-46.3). The steepest rise in seroprevalence still occurred among the subjects aged 25-44 years.

Evaluation of the national immunisation programme in the Netherlands: immunity to diphtheria, tetanus, poliomyelitis, measles, mumps, rubella and Haemophilus influenzae type b.

The immunity to vaccine-preventable diseases included in the Dutch immunisation programme in the general population and among orthodox reformed individuals who refuse vaccination was assessed. The programme induces good protection. However, a large proportion of adults lacks diphtheria and tetanus immunity. Measles, mumps and rubella seroprevalence was somewhat lower among vaccinated compared to unvaccinated cohorts. The prevalence of HibPS antibodies declined during 2.5 years after the fourth vaccination. However, protection occurs also by memory immunity. Herd immunity is sufficient among the general population, but not among orthodox reformed individuals. Immunosurveillance is an efficient way to evaluate the effects of immunisation programmes and identify risk groups for infection.

Options for improvement of the Dutch measles vaccination schedule.

We investigated which vaccination schedule gives best protection to the vaccinating population, in case of a measles epidemic in pockets of unvaccinated individuals. We explored the effect of an additional measles vaccination (at 6 or 9 months), advancing the first measles-mumps-rubella (MMR) vaccination from 14 to 11 months, and advancing the second MMR from 9 to 4 years. Measures of protection among vaccinees (percentage of susceptibles, number of reported cases, percentage of lifetime spent susceptible) were estimated with a mathematical model of the impact of antibody level on seroconversion and immunity. Advancing the age of second MMR vaccination prevents considerably more cases among vaccinees than an extra early measles vaccination or advancing the age of first MMR vaccination.

Protecting the vaccinating population in the face of a measles epidemic: assessing the impact of adjusted vaccination schedules.

We investigated which vaccination schedule gives best protection to the vaccinating population, in case there is a measles epidemic in an area with low vaccine coverage. We considered combinations of an early measles vaccination (none, at 6 months or at 9 months), a measles-mumps-rubella (MMR) vaccination around the first birthday (at either 11 or 14 months), and MMR vaccination at an older age (at either 4 or 9 years). The different estimates on measures of protection (percentage of susceptibles, number of reported cases in an epidemic year, percentage of lifetime spent susceptible) relied on a mathematical model of decline of maternal antibody levels with age, and the impact of that antibody level on seroconversion and immunity. Model parameters were estimated from a Dutch population-based serological survey on measles antibodies. Different measures of protection favoured different vaccination schedules, but dropping the age of second MMR vaccination prevents considerably more cases than an extra early measles vaccination or dropping the age of first MMR vaccination.

Poliovirus circulation among schoolchildren during the early phase of the 1992-1993 poliomyelitis outbreak in The Netherlands.

During the 1992-1993 outbreak of poliomyelitis in The Netherlands, we examined 866 childrenat 7 schools for evidence of infection with the outbreak virus, poliovirus type 3(PV3), to determine the extent of the outbreak and the protection of the herd immunity. Seventy-seven children (8.9%) showed evidence of recent wild-type PV3 infection, as determined by virus isolation and/or poliovirus type-specific IgM assay. Most infected children lived in the same area as the index case patient, attended an orthodox-reformed (OR) primary school, and had not been vaccinated. At the OR school, as many as 22% of children immunized with inactive poliovirus vaccine were found to have evidence of recent infection, which is a significantly lower rate than that among unvaccinated children (59.5%). No evidence of vaccination was seen in 25.5%-43.1% of children at OR schools. Seroprevalence of antibodies against the 3 types of poliovirus suggested that no poliovirus circulation had occurred between the 1978 and 1992-1993 outbreaks.

Measles outbreak in a community with very low vaccine coverage, the Netherlands.

A 1999-2000 measles epidemic in the Netherlands started with an outbreak in an orthodox reformed elementary school with 7% vaccine coverage. The overall attack rate was 37%: 213 clinical cases among the 255 participating pupils (response 62%) and 327 household members. The attack rate ranged from 0% for the oldest groups of pupils to 88% for the youngest, who had not been exposed in previous measles epidemics. None of 25 vaccinated pupils had clinical symptoms. Among pupils with clinical symptoms, the self-reported complication rate was 25%. These data confirm that measles infection causes severe disease and that vaccination is the most effective means of preventing the disease and its complications. The data also show that clusters of persons refraining from vaccination interfere with measles elimination even in populations with very high overall vaccine coverage (96%).

Subclinical Legionella infection in workers near the source of a large outbreak of Legionnaires disease.

A survey was conducted of exhibitors at a 1999 floral trade show, where a whirlpool spa on display caused a large outbreak of legionnaires disease (LD). In total, 742 exhibitors without LD returned a questionnaire on their whereabouts during the fair and their health afterward and supplied blood samples for the detection of IgM and IgG antibodies against Legionella pneumophila. The exhibitors had higher average antibody levels than did the general population. The closer to the whirlpool that the exhibitors worked, the higher their antibody levels. Both high-normal and high titer levels were found more frequently among workers with more exposure, suggesting that serosurveys among potentially exposed subjects are a valuable tool for outbreak investigation. Some differences in health complaints were observed between the more and less exposed groups, as estimated by the workplace location, but few differences were found between groups with different antibody levels.

Immunity to poliomyelitis in The Netherlands.

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.

[Measles epidemic in the Netherlands, 1999-2000]. / Mazelenepidemie in Nederland, 1999-2000.

OBJECTIVE: Description of measles epidemic in the Netherlands, 1999-2000. DESIGN: Observational descriptive study. METHODS: Intensified surveillance of measles cases by means of a case register established at the 'Landelijke Coördinatiestructuur Infectieziektebestrijding (LCI)' [National Co-ordination Centre for Communicable Disease Outbreak Management]. RESULTS: There were 3,292 reported measles patients, most of whom came from areas with low vaccine coverage. Of these patients, 94% had not been vaccinated; in 85% of cases this was for religious reasons. Of the 158 (5%) vaccinated patients, 157 had not (yet) received a second dose of vaccine. The incidence of measles increased with decreasing vaccine coverage in a municipality, both for unvaccinated and vaccinated persons. Three of the reported patients died. The percentage of patients with one or more complications was 22% in the group < 15 months of age, 19% in the group 15 months-4 years, 16% in the group 5-9 years, 11% in the group 10-19 years, and 15% in the group > 19 years of age. CONCLUSION: Considering the complications observed, the epidemic described involved a serious disease. Vaccination was accompanied by effective protection against measles infection and its complications. Herd immunity outside the unvaccinated groups was sufficient to prevent an epidemic there. However, incidental spread to vaccinated children did occur; the greatest risk factor for acquiring measles for vaccinated children is a stay in an area with low vaccine coverage.

The sero-epidemiology of diphtheria in Western Europe. ESEN Project. European Sero-Epidemiology Network.

Seven countries in Western Europe collected large, representative serum banks across the entire age range and tested them for diphtheria anti-toxin (sample size ranged from 2991 to 7715). Although a variety of assays were used, the results were all standardized to those of a reference laboratory and expressed in international units. The standardization process, and the availability of similar, large data sets allowed comparative analyses to be performed in which a high degree of confidence could be ascribed to observed epidemiological differences. The results showed that there were large differences in the proportion of adults with insufficient levels of protection amongst different countries. For instance, roughly 35% of 50- to 60-year-olds were found to be seronegative (titre < or = 0.01 IU/ml) in Finland compared with 70-75% in the United Kingdom. Furthermore, the proportion of seronegative adults would be expected to increase in some countries, notably Italy and the western part of Germany. In those countries with vaccination of military recruits there was a marked sex-related difference in the proportion of seropositive individuals. All countries have high levels of infant vaccine coverage (> 90%) but the accelerated schedule in the United Kingdom appears to result in lower anti-toxin titres than elsewhere. In Sweden, booster doses are not offered until 10 years of age which results in large numbers of children with inadequate levels of protection. Although the United Kingdom and Sweden both have higher proportions of seronegative children than elsewhere the likelihood of a resurgence of diphtheria in these countries seems remote.

The prevalence of antibodies to hepatitis A virus and its determinants in The Netherlands: a population-based survey.

The prevalence of antibodies to hepatitis A virus was assessed in a Dutch nationwide sample (n = 7367). A questionnaire was used to study the association with various sociodemographic characteristics. Overall, 33.8% (95% CI 31.6-36%) of the population had hepatitis A antibodies. The seroprevalence was less than 10% in people under 35; it increased from 25% at 35 years to 85% at 79 years. For those 15-49 years of age, Turks (90.9%) and Moroccans (95.8%) had greater seroprevalence than autochthonous Dutch (20.2%) and other Western people (25%). Low or middle socio-economic status, as indicated by the highest educational level achieved, was associated with greater seroprevalence, independently of age and reported immunization (OR 2.11 and 1.45; 95% CI 1.67-2.67 and 1.11-1.89, respectively). These data suggest autochthonous Dutch and other Westerners born after World War II were exposed to hepatitis A during childhood less frequently than older birth cohorts. Thus, more susceptibility is likely in the coming decades. Since this means a greater risk of outbreaks in future years, and since morbidity and mortality are more frequent in older persons, studying the cost effectiveness of selective and general vaccination might be worthwhile.