European Journal of Epidemiology 18: 161–170, 2003. 2003 Kluwer Academic Publishers. Printed in the Netherlands.
Fully vaccinated children are rare: Immunization coverage and seroprevalence in Austrian school children Markus Ringler1,2, Georg Go¨bel3, Johannes Mo¨st1 & Kurt Weithaler1 1
School of Public Health, Department of Hygiene and Social Medicine, Innsbruck University; 2Department of Internal Medicine, Schwaz District Hospital; 3Department of Biostatistics and Documentation, Innsbruck University, Austria Accepted in revised form 13 August 2002
Abstract. Vaccination coverage for vaccine-preventable diseases in Austria as well as in many Central European countries has been reported to be too low to eradicate such diseases and prevent further outbreaks. Austria lacks an adequate surveillance system to monitor prevalence of the diseases, the vaccination coverage and seroconversion. School children aged 10–14 years (n ¼ 1077) were recruited in all four schools in the city of Schwaz, Austria, to present their vaccination documents and to give blood for serological testing (diphtheria, pertussis, measles, mumps, rubella, varicella). All participants received a report with a personal guideline for (re-) vaccination. Overall vaccination coverage was 86.4% for measles, 85.5% for mumps and 35.0% for rubella. Tetanus vaccination coverage was 98.4% for the first, 97.8%
for the second and 96.7% for the third dose, while 55.4% of the study subjects received the recommended two booster injections. For diphtheria the corresponding vaccination coverage was found to be almost identical. Pertussis coverage was lower in general (first dose: 90.9%; second dose: 89.0%; third dose: 86.5%). Oral poliomyelitis vaccination showed a coverage of 98.6, 96.5, 95.3%, with 78.7% receiving the fourth dose. Overall 38.7% were classified as fully vaccinated. Seropositivity for measles was found in 90.4%, for mumps in 61.8%, for rubella in 82.3%, for diphtheria in 65.8%, for pertussis in 35.6% and for varicella in 95.0%. In summary, fully vaccinated children are rare and intensive public health efforts will be necessary to reach higher levels of immunity and prevent further outbreaks.
Key words: Children, Diphtheria, Measles, Mumps, Pertussis, Rubella, Seroprevalence, Vaccination
Background The vaccination coverage of school children for measles, mumps, rubella (MMR), diphtheria, tetanus, pertussis (DTP), and oral poliomyelitis vaccine (OPV) in Austria as well as in many European countries has been reported to be rather low and, especially for measles, too low to achieve eradication as already done, for example, in Finland [1] and Cuba [2]. Quality control and harmonization of the various vaccination strategies are current targets in the WHO’s European region [3, 4]. Published WHO data from 1997 for Austria [5] (Table 1) show a vaccination rate of 70% for MMR and 90% for three doses of DTP and OPV. These figures were calculated mainly from administered doses, because other more reliable data could not be officially provided at that time. Although some surveys were done in western Austria at the district level from 1987 to 1997 showing improving coverage rates for measles and mumps [6–8], Austria and several countries in Europe lack an adequate surveillance system to monitor prevalence of the diseases, the vaccination coverage, seroconversion and vaccine efficacy. This is despite the fact that
systematic and active surveillance methods are being implemented in other continents [9] after starting the Expanded Programme on Immunization launched jointly by the WHO and UNICEF in 1974. No systematic studies are conducted by the public health sector in Austria, and the data available are usually provided by private or university sources using different methods. The incidence of measles in Austria is an estimated 1000 cases per year (Heinz FX, Mandl C, Insitute of Virology-Vienna, personal communication). The last major outbreak occurred in 1996 with about 15,000 cases (as compared to the 2828 confirmed cases in the whole Pan-American region in 1999 [10] and the only 89 exclusively imported cases in the USA in 1998). Outbreaks in Europe are frequent as, for example, reported 1999 in The Netherlands threatening an unvaccinated population (2300 cases, three deaths, severe complications in 20%) [11] or in France [12]. No poliomyelitis wild-virus infection was detected in Austria since 1982 and the last diphtheria case was registered in 1985. For mumps and rubella there are no recent data available. Pertussis infection seems to be more frequent than reported but no exact data have been published.
162 Table 1. Vaccination coverage (in %) in EU countries according to WHO (1997) calculated mainly from adminstered doses (5) (DT 3 = three doses of diphtheria and tetanus vaccine; P 3 = three doses of pertussis vaccine; Polio 3 = three doses of poliomyelitis vaccine) Vaccination Country (year)
DT 3 (P3) (%)
Polio 3 (%)
Measles (%)
Mumps (%)
Rubella (%)
Germany (1994) Austria (1995) Belgium (1995) Denmark (1995) Spain (1994) Finland (1995) France (1994) Greece (1995) Irland (1991) Italy (1995) Luxembourg (1992) Netherlands (1995) Portugal (1995) United Kingdom (1994) Sweden (1994)
85(45) 90(90) 94(94) 97(90) 88(88) 100(100) 97(95) 90(78) ?(65) 95(50) ?(95) 97(97) 93(93) ?(92) 99(99)
80 90 92 97 88 100 97 95 63 98 90 97 95 94 99
75 60 85 88 90 98 80 70 78 50 80 94 94 92 96
75 60 85 88
70 90 85 88
98 70
98 80 70
50
50
94 94
94 94
96
96
Vaccinations in Austria are administered by both the public and the private health care sector. Children below the age of 6 years receive the vaccines mainly from private pediatricians or general practitioners, while school children are vaccinated pre-dominantly by public health officials in school. Participation in all recommended immunizations (Tables 2 and 3) is not mandatory. At the time the study-population underwent immunization vaccines and vaccination itselve had to be payed by the parents. Since 1998 all recommended vaccinations are free of charge. Different vaccines had been used in the study population. The mainly administered vaccines were: DT-Adsorbat and DTP (Pasteur Merieux), M-MVax and M-M-R-Vax (Pasteur Merieux) containing
Table 2. Vaccination guidelines in Austria 1984 (ÔMitteilungen der o¨sterreichischen Sanita¨tsverwaltungÕ 1985/H4, pp. 79–83) Recommended age
Type of vaccination
1st week 4th and 5th month or 3rd, 4th, 5th month 4th month
BCG DT DTP OPV 1,2,3 (minimum interval 6 weeks) MM DT OPV and DT BCG, if tuberculin testing negative Rubella for girls OPV and (d)T (diphtheria vaccination optional)
14th month 18th month 7th year 7–15th year 13th year 14–15th year
Table 3. Vaccination guidelines in Austria 2000 (ÔO¨sterreichische A¨rztezeitungÕ 13/14, 7/2000) Recommended age
Type of vaccination
3rd, 4th, 5th month 3rd, 4th, 5th month 3rd, (4th), 5th, 12th–15th month 3rd, 5th, 12th–15th month 14th–18th month 15th–18th month 7th year 13th year 14th–15th year
DTaP IPV Hib Hep.B MMR 1 DTaP MMR 2, OPV and dT Hep.B OPV and dT, MMR for girls if missing MMR 2
attenuated measles virus Edmonston-strain and attenuated mumps virus Jeryl-Lynn-(B level) strain, Polio Sabin oral and Rubeaten-Berna (attenuated rubella-virus Wistar RA 27/3). Anti-vaccine movements still play an important role; they did and still do damage to the immunization coverage of many well established and safe vaccinations. The real impact is difficult to estimate or prove [13]. The present study was conducted to obtain new vaccination coverage data on all immunizations recommended in the official schedule for children (according to the 1984–1989 guidelines) (Table 2) and seroprevalence data on some of the diseases and vaccinations. An additional and important target from the public health standpoint was to inform the study population about vaccinations in general and to provide a personalized recommendation for each study participant.
163 Methods Organization and population studied The study was performed from September 1998 to May 1999 in the city of Schwaz, which is district capital with about 12,000 inhabitants in western Austria (Tyrol). A cohort of 1077 school children aged 10–14 years (born 1984–1989) was recruited in the two middle schools (n ¼ 660, 61.3%) and the two secondary schools (n ¼ 417, 38.7%) to present their vaccination documents and give blood for serological testing. There are no other schools for this agegroup in the city of Schwaz. Middle schools (german ‘Hauptschule’) are usually public and are attended by the majority of the children. The different types of secondary schools (german ‘Gymnasium’) can be private or public and in general pupils with higher level of performance are accepted. The study population consisted of children from the city of Schwaz (53.2%) and from the villages nearby attending school in Schwaz (46.8%); 9.3% of the study population were children with a mother tongue other than German. Boys made up 52.2% of the cohort, girls 47.8%. From the beginning all involved parties like politicians, school authorities, the pupils themselves and their parents were informed in several presentations, visits to all classes during school and in information hand-outs containing a detailed description of the background, objectives and benefits for all participants and the health care system. Parents were asked to give their written consent. Immigrants were especially requested to participate in the study. The information hand-out was translated into Turkish and Serbo-Croatian in order to also convince children of non-German mother tongue of the project’s benefits, and translators were present at the meetings with the parents. The working group for blood sampling consisted of medical doctors participating in a community health course and nurses from Schwaz District Hospital. Blood was taken by venipuncture during schooltime in a classroom. Incentives to all children aimed to rise the rate of participation. Furthermore, all participants were promised a report on the serological tests with an explanation of the results and a personal recommendation for (re-)vaccination. Serological assays Serum samples were stored at 20 C. Antibody concentrations were determined with the following test kits (all commercially available): for measles Enzygnost Anti-Measles Virus/IgG (enzyme immunoassay; values are expressed in mIU/ml), for mumps Enzygnost Anti-Parotitis-Virus/IgG (EIA; antibody activities expressed as titres), for varicella Enzygnost Anti-VZV/IgG (EIA; mIU/ml), all from Behring
Diagnostics, Marburg, Germany; for pertussis ELIMMUN-Pertussis G (EIA, values given in U/ ml) from Labor Dr Koch–Dr Merk, Ochsenhausen, Germany (the assay uses pertussis toxin and filamentous hemagglutinin as antigens); for diphtheria Immunozym Diphtherie (EIA) from Immuno Gmbh, Heidelberg, Germany; for rubella Rubenosticon (hemagglutination inhibition; titres) from Organon Teknika, Boxtel, The Netherlands. All tests were performed according to the manufacturer’s instructions by experienced technicians. Evaluation of results and classification as negative, borderline or positive were done as proposed by the manufacturers. A special problem was encountered with the EIA for diphtheria, which showed a very high number of borderline cases. To clarify the situation a neutralization assay (the gold standard for diphtheria antibody quantification) had to be established in the laboratory and the whole series was redone. The tissue-culture toxin-neutralization assay was performed with the VERO cell-line PH2 according to the method initially published by Miyamura et al. [14]. Only the results obtained with this approach were evaluated. Statistical analysis Parametric distributed data are presented as means (SD), whereas nonparametric data are shown as medians (25%/75% percentiles). For global comparison between groups the Kruskal–Wallis Test was used. Post-hoc comparisons were performed with the Mann–Whitney Test with Bonferroni correction. Relations between categorical data were examined by v2 testing. All statistical calculations were performed using SPSS 8.0.
Results Participation Vaccination documents were shown by 81.2% of the participants and 81.0% of the study persons could be motivated to give blood for serological testing. Girls participated more frequently than did boys in both categories: vaccination card from girls 83.9 vs. 78.8% from boys, blood sample from girls 84.9 vs. 77.4% in boys. Furthermore, response in both variables (vaccination document and serology) showed a significant difference in the four examined schools although efforts to inform the parents and the pupils had been the same at each school: secondary school 1 (S1) document from 93.6% of participants (blood sample from 87.6%), secondary school 2 (S2) 78.3% (81.5%), middle school 1 (M1) 83.7% (81.6%), middle school 2 (M2) 71.7% (75.4%).
164 No significant difference in participation was seen for serological testing (blood sample) with regard to the variable mother tongue: children with German mother tongue 81.2 vs. 79.0% for those with nonGerman mother tongue, but only 54.0% of the children with non-German mother tongue presented a vaccination card (vs. 84.0% for those with German mother tongue). Vaccination coverage Overall measles vaccination coverage was 86.4% (mumps 85.5%), whereby 23.8% received a second dose (mumps 23.4%). Of those vaccinated against measles 22.1% were immunized at an age of more than 24 months (the recommended age for measles immunization in Austria is 14–18 months). Of the study subjects an overall of 35.0% were immunized against rubella. Of those girls entering child-bearing age 86.4% underwent the recommended rubella immunization. Tetanus vaccination coverage was 98.4% for the first, 97.8% for the second and 96.7% for the third shot. 55.4% received the recommended two tetanus boosters. For diphtheria we found that 98.3, 97.4 and 96.0%, respectively, had received the first three vaccinations, while 53.9% underwent the recommended booster doses. Pertussis coverage was lower in general (first dose: 90.9%, second dose: 89.0%, third dose: 86.5%). Oral poliomyelitis vaccine showed a coverage of 98.6, 96.5 and 95.3%, while 78.7% were given the fourth dose (Table 4). Of the study population 38.7% (n ¼ 417 out of a total of 1077) was found to be completely immunized, meaning they had received every vaccination recommended in the 1984–1989 guidelines. The remaining 61.3% (n ¼ 660) either did not or could not show a vaccination document (18.8%) or was incompletely immunized (42.5%) (Figure 1). The results were analyzed for the variables school type, sex, age group, place of residence and mother
Table 4. Overall vaccination coverage rates (%) in 875 school children aged 10–14 years (Rates were calculated exclusively from children with documented vaccinations) Dose Vaccination
First (%)
Second Third (%) (%)
Fourth Fifth (%) (%)
Measles Mumps Rubella Diphtheria Tetanus Pertussis OPV BCG
86.4 85.5 35.0 98.3 98.4 90.9 98.6 95.3
23.8 23.4 47.9a 97.4 97.8 89.0 96.5
87.8 88.7 5.1 78.7
a
88.4b 96.0 96.7 86.5 95.3
53.9 55.4 3.2
Girls; b … girls born in 1984 (girls entering child-bearing age).
tongue. Highly significant differences were observed for the variables school type and mother tongue. High coverage was found in all schools for DT and OPV for the first three doses with relatively low drop-out rates. Differences between the school types were observed for the coverage of measles (min. 80.9%; max. 93.8%, p < 0.01) and mumps (min. 80.1%; max. 93.1%, p < 0.01). In addition, significant differences between the schools were found for the fourth and fifth diphtheria and tetanus dose. Middle schools showed generally lower vaccination coverage rates and higher drop-out rates than secondary schools. Furthermore, at school S1 60.5% was found to be completely vaccinated, at S2 42.9%, at M1 34.7% and at M2 24.9% (p < 0.01) (Figure 2). Children with non-German mother tongue in general showed a high frequency of non-vaccination (for example, measles vaccination 74.1% vs. 87.2%, tetanus three doses 81.5% vs. 97.7%, OPV three doses 81.5% vs. 96.2%, all differences statistically significant, p < 0.01), higher drop-out rates and a rate of only 5.0% fully vaccinated vs. 39.8% (p < 0.01) in subjects with German mother tongue.
Seroprevalence Descriptive analysis of the seroprevalence data concerning the whole study population, the vaccinated children and those unvaccinated are shown in Tables 5–7. The dataset was screened for significant quantitative differences of antibody titres. The median titre for measles in vaccinated children (1500 mIU/ml; 810–2700) (n ¼ 701) was significantly lower than in the non-vaccinated (and therefore naturally infected) group (5400 mIU/ml; 0–8900) (p < 0.01), which was much smaller (n ¼ 105). For mumps a significant difference was also shown, but with higher titres in the vaccinated group (non-vaccinated: n ¼ 113; median ¼ 0.0 mIU/ml; 0.0–0.0) (vaccinated: n ¼ 693; median ¼ 830 mIU/ml; 380–1430). No significant differences in antibody levels of measles in once- or twice-vaccinated children were observed (once vaccinated: median 810 mIU/ml; 1600–2650) (twice vaccinated: median 790 mIU/ml; 1400–2700). Antibody levels of mumps showed a significantly higher median titre for the group twice vaccinated (once vaccinated: median 320 mIU/ml; 750–1350) (twice vaccinated: median 613 mIU/ml; 1000–1800) (p < 0.05). Girls more frequently showed positive rubella titres than did boys (92.7% vs. 85.2%) (p < 0.01). None of the girls born in 1984 (girls >12 years) had negative rubella titres (positive 91.3%, borderline 8.7%). For diphtheria a correlation between the age groups and the altitude of the titres was detected. The children born in 1988 showed significantly higher titres than did those born in 1984 (p < 0.01).
165
Figure 1. Immunization status of 1077 school children aged 10–14 years. Due to the Austrian vaccination guidelines for the years 1984–1989 children were quoted as completely vaccinated if they received the following doses: measles and mumps vaccine once, DT four times or DPT five times, four courses of OPV, a BCG shot and rubella in girls older than 12 years.
Figure 2. Cross-calculation of fully vaccinated children and school types. Significant differences in the four schools investigated (S1 = secondary school 1; S2 = secondary school 2; M1 = middle school 1; M2 = middle school 2). Table 5. Seroprevalence (titer categories positive, borderline and negative) in all 872 pupils, who were serologically tested (High rates of negatives for mumps and pertussis) Titer category Vaccination/ disease Positive (%) Borderline (%) Negative (%) Measles Mumps Rubella Diphtheria Pertussis Varicella
90.4 61.8 82.3 65.8 35.6 95.0
4.9 16.1 6.7 24.9 0.0 1.1
4.7 22.1 11.0 9.3 64.4 3.9
Discussion Participation and representativity The overall response rate was high as compared to similar studies in Europe [15–19]. High participation in most of these studies was generally linked to institutionalized investigations performed by the public health services, for example in Germany when starting first grade. By conducting an information campaign for the study population, providing strong
personal contacts and guaranteeing a personal benefit for each participant we, too, were able to motivate a large number of people. The reliability and representativity of the results appear to be as adequate as those of other studies. In the same area, District Schwaz, a study was performed by Hladik et al. in September 1997 using a systematic sampling technique (unpublished data, master’s thesis, London School of Hygiene and Tropical Medicine). In the comparable age group significant differences in vaccination coverage, but similar trends in general and the same low percentage of children not being fully vaccinated were observed. Vaccination rates in our study were calculated only from those pupils who showed their vaccination cards (81.2% of the entire study population, n=875). The question whether the rest of the pupils had the same, a higher or lower rate was discussed in a similar study and the possible causes of non-participation demonstrated [16, 20]. To estimate the vaccination rate in those pupils who did not show a vaccination card we performed the following calculation: We selected the children without vaccination card (n=202 or 18.8% of the entire study population) and filtered out those who gave a blood sample (n=66, 7.6%). Since we know that a positive or borderline titre of diphtheria can be
166 Table 6. Seroprevalence (titer categories positive, borderline and negative) in the vaccinated cluster (vaccination document and serology in 806 cases) (Seronegativity in high percentage of the vaccinated children for mumps and pertussis) Titer category Vaccination
Subjects (N)
Measles (1 dose) 701 Measles (2 doses) 196 Mumps (1 dose) 693 Mumps (2 doses) 193 Rubella (1 dose, girls only) 198 Diphtheria (3 doses) 774 Diphtheria (5 doses) 436 Pertussis (3 doses) 702
Positive (%)
Borderlline (%)
Negative (%)
93.9 94.4 69.3 82.4 90.4 68.2 76.1 35.6
5.0 5.1 17.9 13.0 9.1 24.7 21.3 0.0
1.1 0.5 12.8 4.7 0.5 7.1 2.5 64.4
Table 7. Seroprevalence (titer categories positive, borderline and negative) in the unvaccinated cluster (High frequency of positive titers for measles and rubella) Titer category Disease
Subjects Positive Border Negative (N) (%) line(%) (%)
Measles 105 Mumps 113 Rubella (girls only) 206 Diphtheria 12 Pertussis 69
70.5 20.4 81.1 41.7 24.6
2.9 1.8 5.8 16.7 0.0
26.7 77.9 13.1 41.7 75.4
due only to vaccination (no infections in Austria since 1985), we checked this subgroup for diphtheria titres and found that 56.1% were positive, 24.2% borderline and 19.7% negative, while of those with vaccination cards (n=806, 92.4%) 66.6% were found to be positive, 24.9% borderline and 8.4% negative. Although the difference between these figures is statistically significant, one would anticipate it to be even greater and to find exclusively negative titres. Moreover, out of 12 pupils with a vaccination card but without documented diphtheria vaccination seven presented positive or borderline titres (58.3%). According to these facts we can estimate the general vaccination rate in those pupils not presenting a vaccination card to be lower than in the documented cluster. This would represent a true positive selection of the documented cluster, as proved in other studies using similar methodology and giving evidence that such design can overestimate coverage [21]. Furthermore, a deficit not only in vaccination itself but also in documentation can be observed, especially among children of non-German mother tongue, of whom only a very small percentage were able to present a vaccination card. Vaccination coverage The vaccination rate for measles and mumps was found to be higher than in the WHO data, but overall
the result is far from the goal of reaching a rate which can eradicate measles and interrupt wild virus circulation. This seems to be a persistent problem in EU countries as we know that many countries have even lower rates (for example, Italy below 56% in 1998 [22]). Only a rate of 95% or higher is sufficient to eradicate measles. The high percentage of vaccinations administered after 24 months (22.1%) leaves too many children unprotected for an unnecessarily long period of time. Similar studies performed in the same area in the late 1980s and early 1990s done by the School of Public Health in Innsbruck showed late vaccination in 11–29% of children. Possible reasons for the relatively low rate are the cost of the vaccine, which was higher for MM vaccines than for others like DT/DTP at that time or parental attitude to the disease, namely that it is a common childrenÕs infection without major complications. A major change could evolve in future because all recommended vaccinations for children up to the age of 15 have been free of charge since 1998. The low overall rate of rubella vaccination is linked to Austria’s 1984–1989 immunization guideline, which recommended immunization only for girls entering child-bearing age (this was before introduction of the triple vaccine MMR). The vaccination rates for the first three doses of diphtheria and tetanus (and OPV) were acceptably high with a relatively low drop-out rate. This shows that it should be and is possible to reach high rates. But here we meet another problem in immunization in general: the revaccination or booster. The drop-out rates from the third to the fifth dose were extremely high although these three vaccinations are in fact the most accepted ones. Awareness for diphtheria infection in general is low, which reflects the fact that there were no recent infections in Austria and the disease is mostly unknown in the general population. The outbreaks of diphtheria in the former USSR (115,000 cases and 3000 deaths from 1990 to 1997) [23, 24] and other countries like India underscore the need for immunization and booster doses to provide persistent protection.
167 The lower rate of pertussis vaccination is also linked to the vaccination guidelines during the years 1984–1989 where it is considered to be less important than the others. The vaccination rate is below the WHO-recommended goal of 90%. Eradication of poliomyelitis in Europe and many regions of the world is already a reality [25] and OPV coverage in our study was acceptably high for the first three doses. Polio outbreaks are therefore not very likely. The percentage of fully vaccinated children as documented by a vaccination card in our study population (n ¼ 1077) was very low at 38.7%, which suggests that those who showed no vaccination card are not fully vaccinated. If we suppose that all children without vaccination card are fully vaccinated (which is not realistic), the percentage increases to 57.5%. Calculation only in the cluster with vaccination card (n ¼ 875) gave 47.7% fully vaccinated cases. All three figures show the range of actual acceptance of the official recommendations and should prompt new strategies in public health interventional work and health education. Similar results were reported for other EU countries like Spain [26]. In the two middle schools (M1 and M2) the vaccination rates in general were significantly lower than those in the secondary schools (S1 and S2). In an additional subclassification performed to identify a correlation between school performance and the variable ‘fully vaccinated’, those classes with the poorest school performance were shown to be those with the lowest immunization coverage. This might be related to the pupils social situation, since correlations between vaccination coverage and social variables were observed in other studies [8, 27]. In our study children with non-German mother tongue presented a vaccination card in a small percentage and showed average participation in serological testing. In those children overall vaccination rates were found to be highly significant lower and drop-out rates for DTP and OPV vaccination to be extremely high. Although this situation was to be expected, parental attitudes and the possible reasons are unknown. As in other fields, children with nonGerman mother tongue seem to profit less than those with German mother tongue from information campaigns. Providing adequate information for this subgroup is time-consuming and expensive but worthwhile and possible, as we demonstrated for participation in serological testing (no significant difference to the other cluster). In fact, children with non-German mother tongue as well as the other groups with significantly lower vaccination rates represent the reservoir for possible infections and continuous circulation of wild viruses or agents. Public health interventions in the field of health education like information campaigns rarely reach such people.
Seroprevalence In general no differentiation between antibodies generated by natural infection or by vaccination is possible with serological methods. Furthermore, the importance or impact of contact with a wild virus or agent like a natural booster is not yet definitely known [28]. This shows the importance of well-documented vaccinations in order to provide a person with information on his vaccination status. In the case of measles, mumps and rubella we know that natural infection provides lifelong protection. For vaccination the same is expected, but protection could also be limited [29]. The impact of a second dose (two-dose regimen) on the interruption of wild virus circulation in measles has already been proved by several surveys [28–30], but seems not to be linked to the level of antibody titres, because we found no significant difference in titres between persons vaccinated once or twice. On the contrary, another study showed better protection with and the importance of a two-dose regimen [31]. Protection is not exclusively correlated to the level of antibody titres, because antibody measurement is only one part of evaluating protection. Waning immunity also for measles immunization will possibly become more important as boostering by contact between vaccinated children and wild virus becomes less frequent [28, 29]. The results of serological testing for mumps revealed a detail which needs to be further investigated. A total of 12.8% of those vaccinated (one dose) showed negative titres and the percentage of borderline cases (17.8%) was also high. To interrupt circulation of mumps virus a vaccination coverage of at least 70% is favorable [32]. The level of protection in our cohort after immunization is insufficient, and the rate of only 61.8% seropositives in the whole cohort investigated (n ¼ 872) will lead to further wild-virus circulation and shift infection to an older population with a higher complication rate. At the moment it is not known whether these results reflect primary vaccine failure, non-responding or waning immunity. Other studies have recently reported the same problem in Southeast Asia [33], the USA [34], Switzerland [35] and Italy [36] and there is an on going discussion about low immunogenicity of Rubini strain vaccines [33, 37]. In our study population mainly vaccines containing Jeryl Lynn strain had been administered. Twice-vaccinated children showed a significantly higher conversion rate (only 4.7% negative) and mean titres. For rubella in one of the secondary schools (S1) significantly higher titres were observed. Moreover, girls showed significantly more positive rubella titres than did boys (92.7% vs. 85.2%). There is no apparent explanation for these results. None of the girls born in 1984 (girls over 12 years) had negative titres, but instead positive (91.3%) or borderline (8.7%) titres to provide protection.
168 Pertussis is different because protection is limited in the case of infection and vaccination [38]. Furthermore, the correlate for protection has not been clearly defined. Pertussis seroprevalence showed a high number of seronegatives after vaccination. Of the 702 participants who received the recommended full course of three doses only 35.6% had detectable antibodies; the remaining 64.4% were unprotected more or less 10 years after immunization. The low protection rate may in part be linked to the absence of a fourth dose, which was not recommended at that time. In the meantime a fourth dose has been included into the vaccination schedule at the age of 15– 18 month and revaccination is recommended every 10 years in the guidelines of 2002. In general, a pertussis booster vaccination for adults is discussed controversially, and a real benefit for infants has not yet been scientifically proved [39, 40]. The rapid loss of protective titres (waning immunity) is known from other studies as, for example, in The Netherlands [41]. In contrast to mumps, very young children (as well the elderly population [42]) are at risk of being infected by adults and at high risk of incurring severe complications like pertussis-pneumonia. Pertussis infection is common, underestimated and widely spread [43]. Diphtheria antibodies in our study population stem from vaccination, because there were no infections in Austria in the last 15 years. A negative immune status in vaccinated children must be linked to primary vaccine failure, non-responding or waning immunity. In the unvaccinated cluster it is extremely unlikely that 41.7% underwent diphtheria infection. These are most likely vaccinated children without adequate documentation. We were able to demonstrate a correlation between the age groups and the level of diphtheria mean titres. The children born in 1988 had highly significant higher titres than those born in 1984. An even lower protection rate must be expected for adults [44, 45]. Waning immunity against diphtheria is a well-known phenomenon [46], which includes the risk of outbreaks such as those that recently threatened the former USSR with high case fatality rates [23, 24]. Seroprevalence of varicella antibodies in the study population showed high seropositivity due to natural infection, because vaccination is not done routinely in Austria, not even in seronegative employees in the health sector. Vaccination can be cost-effective for the whole community, as was recently demonstrated in other European regions [47].
Conclusion Vaccination coverage for measles and mumps in Austria is significantly higher as compared to relevant WHO data, although eradication is not possible at the prevailing rates. The new data show that the
MMR vaccination rate continues to be far below those for DTP and OPV (recently changed to IPV in Austria). Measles coverage rates of 80–90% are too low to eradicate the disease [48]. A similar low or even lower coverage rate is found in different European countries (France, Switzerland, Germany, Italy, Greece). The target of eliminating measles by the year 2007 in the European region [49] appears to be unreachable. A two-dose regimen for measles vaccination results in higher coverage [31] but not in higher antibody levels. The large number of seronegatives to mumps seen in vaccinated children supports the former suspicion that the vaccines used have low immunogenicity [37]. The high vaccination coverage achieved for the first three doses of DTP and OPV is followed by high drop-out rates. High coverage rates for DTP and OPV were reported in Austria over the last 20 years [50]. Maintaining participation in the vaccination programs and thus preventing high drop-out rates should be one of the future targets of immunization policy. Children with non-German mother tongue and persons of lower socioeconomic or educational status show significantly lower vaccination rates [51, 52], lacking documentation and are at risk of being unprotected. High coverage rates can be reached only by implementing special motivation strategies in this part of the population. Fully vaccinated children are rare in Austria and maybe also in other comparable regions of Central Europe [53]. To date Austria lacks a sufficient surveillance system that would monitor prevalence of childhood diseases, vaccination coverage and seroconversion. Furthermore, it does not participate in the European Sero-Epidemiology Network [3] and shows provider-based misguiding [54]. Changing vaccination guidelines alone (especially to polyvalent vaccines), as has happened over the past 15 years, could have a substantial impact on acceptance and coverage levels, but will maybe not be effective enough. The situation justifies future intensive efforts in public health education and promotion in Austria to prevent further outbreaks.
Acknowledgements We are grateful to participants, parents, teachers, school authorities and local politicans for their interest in the project, the Tyrol State Government for financial support, the participants of the university course for community health in Innsbruck 1997/1998 and the nurses from Schwaz district hospital for drawing blood, Dr Vera Worm and the technicians of the serology unit of the Department of Hygiene in Innsbruck (head: Prof Dr M. Dierich) for performing the serological testing, Dr Michael Bro¨ker (Marburg,
169 Germany) for help with the protocol and reagents for the diphtheria neutralization assay, Dr Ingrid Rapp (Ochsenhausen, Germany) for providing the pertussis test kits.
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Address for correspondence: Markus Ringler, Department of Internal Medicine, Schwaz District Hospital, Swarovskistr. 1–3, A-6130 Schwaz, Austria Phone: +43-5242-600 E-mail:
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