Elsevier

Vaccine

Volume 29, Issue 45, 19 October 2011, Pages 7949-7959
Vaccine

Sero-epidemiology of measles-specific IgG antibodies and predictive factors for low or missing titres in a German population-based cross-sectional study in children and adolescents (KiGGS)

https://doi.org/10.1016/j.vaccine.2011.08.081Get rights and content

Abstract

Background and objective

In the European Region, measles elimination is now targeted to 2015. To measure progress towards elimination age-group specific susceptibility targets have been defined. Age-specific measles susceptibility in children and adolescents was evaluated in Germany. Taking into account a broad range of socio-demographic, health- and vaccination status related variables, populations for vaccination campaigns were identified.

Method

We analysed data from children aged 1–17 years in the representative German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Measles immunoglobulin G antibodies were measured in 13,977 participants by enzyme immunoassay (ELISA). Bivariate and multivariate logistic regression analyses were used to determine parental and infant related factors associated with measles susceptibility.

Results

The overall prevalence of seronegativity in children tested for measles IgG aged 1–17 years was 10.0% (95% CI 9.4–10.7). The prevalence of seronegativity in the German population was below the WHO targets for measles elimination in children aged 2–9 year-olds but exceeded the target for 10–17 year-olds. Age differences in the level of seronegativity were found to be mainly due to differences in vaccination coverage. A higher level of susceptibility was observed if parents did not comply with the request to present the child's vaccination card. In vaccinated children, immigration, male gender, very young age at first vaccination and a longer time period since last vaccination were associated with a higher level of susceptibility.

Conclusion

Further increase of the two-dose vaccination coverage is necessary in order to achieve the WHO targets. Catch up vaccination campaigns should focus on adolescents and immigrants.

Highlights

► German Health Survey for Children provides representative data on measles antibodies. ► Prevalence of seronegativity in children aged 1–17 years was 10.0%. ► Age differences mainly due to differences in vaccination coverage. ► Waning and very young age at first dose associated with higher level of seronegativity. ► Immigrant children more often seronegative even if vaccination documented.

Introduction

Despite worldwide vaccination activities, measles is still a major cause of death especially in young children. The WHO called into action a program that led to successful elimination in the Americas and a reduction in disease burden in Africa and Asia. Although Europe had targeted measles for elimination by the year 2010, this goal was not met and a new target date for eliminating measles has been set to 2015. Successful elimination will be accredited to the European Region when the following criteria have been met: vaccine coverage of more than 95%, continued disease surveillance with incidence rates below 1 per million population as well as a rate 80% laboratory confirmed suspected cases. In addition the WHO European Region targets for measles elimination define that the proportion of seronegative children in the whole population should not exceed 15% in children aged 2–4 years, <10% in 5–9-year-olds and <5% in older age groups [1].

In Germany, indigenous measles virus (MV) circulation has been interrupted [2], but importation of MV from other countries is common [3]. Pockets of susceptible individuals often associated with anthroposophic communities or the catchment area of a naturopathist have experienced MV transmission leading to small and middle-sized outbreaks [4], [5], [6].

In Germany, a two-dose regime is recommended for measles mumps rubella (MMR) vaccination by the Standing Committee of Vaccination (STIKO). The first dose should be given at months 11–14, the second dose not less than 4 weeks later. MMR immunisation should be completed at the age of 2. Vaccination coverage in Germany has been described in our previous study [7]. Besides several smaller outbreaks, a large measles outbreak occurred in North-Rhine Westphalia, Germany in 2006. Analysis of the age distribution revealed that the majority of cases were aged >9 years [8], [9] and that also a high number of infants was affected. Investigation of a school outbreak in the city of Duisburg displayed major immunisation gaps in older children and young adults. These results indicate a need for further studies in German children, adolescents and young adults to assess the demand on supplementary immunisation activities.

The German Health Interview and Examination Survey for Children and Adolescents (KiGGS) was conducted in a representative sample of children 0–17 years of age. Health related and socio-demographic data plus the vaccination status were recorded. A blood sample was obtained from children aged >1. This set-up enabled us for the first time to study the seroprevalence of measles-specific IgG antibodies in a well-defined cohort representative for all children in Germany. Moreover, titres could be correlated to the time point of vaccination and the number of doses administered. Analysing these data, we investigated presence of gaps in seroprevalence in certain age groups and identified factors predicting low measles IgG titre seroprevalence in vaccinated children.

Section snippets

Survey design and study population

The KiGGS methodology has been described elsewhere [10], [11]. In brief, the KiGGS survey is based on a nationally representative sample of children and adolescents 0–17 years of age with main residence in Germany. A total of 17,641 children and adolescents were surveyed—8985 boys and 8656 girls. Study participants were enrolled from May 2003 to May 2006. Children and adolescents from families with a non-German nationality were oversampled, as a higher proportion of undeliverable contacts and

Seronegativity and WHO target

Fig. 1 shows the percentages of children who displayed a negative or equivocal measles IgG antibody titre by age. This analysis included 13,977 children aged 1–17 year regardless of the presence of a vaccination card.

The overall prevalence of seronegativity in children tested for measles IgG aged 1–17 years was 10.0% (95% CI 9.4–10.7). In addition, 2.3% (95% CI 2.0–2.7) of children displayed an equivocal titre. In 2–4 year old children, the prevalence of seronegativity was, on average, 10.0%

Main results

The prevalence of seronegativity found in our study was below the WHO European Region targets (1) for measles elimination of <15% in children aged 2–4 years and <10% in 5–9 year-olds. However, the prevalence of seronegativity in 10–17 year-olds seen in our study, exceeded the WHO European Region target of <5%. The proportion of seronegative children was particularly high in the youngest children (one year of age), indicating a relevant delay of the first measles vaccination which is scheduled

Conclusions

The prevalence of seronegativity in the German population was below the WHO targets for measles elimination in children aged 2–9 year-olds but exceeded the target for 10–17 year-olds. Age differences in the level of seronegativity were found to be mainly due to differences in vaccination coverage. However, immigrant children were more often seronegative even if vaccination(s) had been documented. Further increase of the two-dose vaccination coverage is necessary in order to achieve the WHO

Acknowledgements

We thank Ms. Melanie Tobler and Ms. Ingrid Deitemeier for excellent technical support. We are grateful to Ms. Petra Kurzendörfer for her valuable assistance in handling more than 13,000 samples.

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