Masern sind keine harmlose Kinderkrankheit. Häufig ist eine Infektion mit dem Masernvirus durch schwere Komplikationen begleitet, nicht zu vernachlässigen ist die äußerst hohe Infektiosität des Virus. Die Schutzimpfung gegen Masern, die vor über 30 Jahren eingeführt wurde, ist eine medizinische Notwendigkeit. Seit den 70er Jahren gehört die Impfung zu den allgemein empfohlenen Impfmaßnahmen und ist Bestandteil des Erweiterten Impfprogrammes (EPI) der WHO. Die 2-Dosen-Impfung gewährleistet einen sicheren und lang anhaltenden Schutz gegen Masern. Als Impfstoff der Wahl gilt die kombinierte MMR-Vakzine. Für Deutschland geschätzte Raten für die Erstimpfung bei Schuleintritt liegen zwischen 50 und 80%, für die Wiederimpfung bei 10 bis 20%. Masern kommen in Deutschland noch endemisch vor und führen gelegentlich zu Ausbrüchen, wobei zunehmend mehr Jugendliche und Erwachsene betroffen sind. Erst eine deutlich höhere Impfakzeptanz von über 90% bereits im Kleinkindalter kann zu einem entscheidenden Rückgang der Masern führen. Mit den Masern steht nach den Pocken und der Poliomyelitis die dritte impfpräventable Erkrankung zur Elimination bzw. Eradikation an. Bereits vorliegende Erfolge in zahlreichen Ländern unterstützen dieses Vorhaben als realisierbares Ziel für Europa in den nächsten 10 bis 15 Jahren.

The ESEN (European Sero-Epidemiology Network) project was established to harmonize the seroepidemiology of five vaccine preventable infections including measles, mumps and rubella in eight European countries. This involved achieving comparability both in the assay results from testing in different centres and also sampling methodology. Standardization of enzyme immunoassay results was achieved through the development of common panels of sera by designated reference centres. The panels were tested at the reference laboratory and then distributed to each participating laboratory for testing using their routine methods. Standardization equations were calculated by regressing the quantitative results against those of the reference laboratory. Our study found large differences in unitage between participants, despite all using an EIA method standardized against an international or local standard. Moreover, our methodology adjusted for this difference. These standardization equations will be used to convert the results of main serosurvey testing into the reference country unitage to ensure inter-country comparability.

Zusammenfassung Die Seroprävalenzstudien aus den Jahren 1990 bis 1998 spiegeln die aktuelle Rötelnsituation wider. Selektive Impfungen von jungen Mädchen und Frauen haben in der weiblichen Population ab dem 13. Lebensjahr erreicht, dass die bei der natürlichen Durchseuchung noch bestehenden Immunitätslücken im jungen Erwachsenenalter weitgehend geschlossen wurden. 1998 waren bei den 18- bis 30-jährigen Erwachsenen nur 0,8% bis 3% Frauen Röteln-seronegativ, aber 5% bis 13% der Männer. Unterschiede in der Immunitätslage zwischen alten und neuen Bundesländern, in denen die Rötelnschutzimpfung erst nach der Wiedervereinigung eingeführt wurde, lassen sich nicht mehr nachweisen. Ein Risikopotenzial für Schwangere ohne Rötelnschutz stellen vor allem die Immunitätsdefizite bei Kindern im Vorschulalter dar, die auf den verzögerten Beginn der Kleinkindimpfung, aber auch auf die geringere Akzeptanz der Kombinationsimpfung zurückzuführen sind. Im Vergleich zu Ländern wie Finnland, Schweden oder den USA, die der Elimination der konnatalen Röteln nahe sind, besteht in Deutschland noch ein erhebliches Potenzial von Empfänglichen. Die anhaltende endemische Viruszirkulation gefährdet die Hauptzielgruppe der Rötelnimmunprophylaxe, die Frauen in der Frühschwangerschaft. Erst wenn Impfraten von über 90% bei der MMR-Impfung der Kleinkinder im Laufe des zweiten Lebensjahres erreicht werden, besteht auch in Deutschland die reale Chance, nicht nur die Masern, sondern auch die konnatalen Röteln in den nächsten zehn Jahren auszurotten.

Most of the countries in western Europe have now implemented mass infant rubella immunization programmes, instead of or in addition to selective vaccination in order to achieve the elimination of congenital rubella syndrome. The European countries Denmark, England and Wales, Finland, France, Germany, Italy and the Netherlands undertook large, national serological surveys collecting several thousand serum specimens during 1994–8. Antibodies against rubella virus were detected by a variety of enzyme immuno-assays. Comparability of the assay results was achieved by a standardized methodology. The age- and sex-stratified serological results were related to the schedules, coverage of rubella vaccination and the incidence in these countries. The results show widely differing levels of immunity to rubella both in the general population and in the specific age groups of males and females. A low rate (< 5%) of susceptibles in childhood and adolescents of both sexes was obtained only in Finland and the Netherlands. Countries such as Italy with only moderate coverage for the infant immunization programme currently have both high susceptibility levels in the general population and in the at-risk population. The likelihood is of continued epidemics of rubella with cases of congenital rubella syndrome. The continued implementation of selective vaccination will help to offset the impact of this ongoing transmission and to protect women on reaching childbearing age.

Zusammenfassung Die laborgestützte Überwachung der Masern in Deutschland leistet einen Beitrag zur objektiven Einschätzung der Situation. Im Vergleich zur Vorimpfära ist die Maserninzidenz reduziert worden, wobei eine Altersverschiebung zu den ab 15-jährigen auffällt. Vom Ziel der Elimination in der Region Europa bis zum Jahr 2007 ist Deutschland noch weit entfernt. Neben der fehlenden systematischen Surveillance bilden die Immunitätslücken im Kleinkindalter eine besondere Schwachstelle. Zur erfolgreichen Masernbekämpfung sind hohe Durchimpfungsraten von mindestens 90% am Ende des zweiten Lebensjahres erforderlich. Darüber hinaus müssen Aufgaben der laborgestützten Überwachung verstärkt zur Erfolgskontrolle einbezogen werden. Schwerpunkte stellen dabei die Laborbestätigung von Masernverdachtsfällen, Seroprävalenzstudien der Populationsimmunität sowie die Kontrolle der Masernviruszirkulation dar. Die Arbeitsgemeinschaft Masern (AGM) sowie das novellierte Infektionsschutzgesetz sind wichtige Instrumentarien, um auch in Deutschland messbare Fortschritte auf dem Wege zur Elimination zu erreichen. Es wird über die Tätigkeit des Nationalen Referenzzentrums für Masern, Mumps, Röteln ab 1991 berichtet. Die Ergebnisse aus Deutschland werden mit denen ausgewählter europäischer Länder verglichen.

The humoral immune response after primary and re-vaccination confirmed the high immunogenicity of the combined vaccines used: "MMR-Vax®", "Pluserix®" and "Triviraten®". The investigation of paired serum samples of prevaccinal seronegative infants (n=365) by an enzyme immuno assay (Enzygnost®) exhibited seroconversion rates of >90–100% for all three components with the exception of the mumps component of "Triviraten®" (38%). However, by additional methods (plaque neutralisation test, immunofluorescence test) mumps antibodies could be detected in 93.4% of infants having received vaccine "Triviraten®". The mean values of antibody activities against the three components did not differ significantly after vaccination with "MMR-Vax®" and "Pluserix®". However, after vaccination with "Triviraten®" the mean antibody values were significantly lower (P<0.01) against the measles strain "Edmonston-Zagreb" and especially lower (2–20 times) against the mumps virus strain "Rubini". Revaccination of pre-vaccinal seropositive schoolchildren and adolescents (n=676) with "MMR-Vax®" and "Pluserix®" produced no different results. The rate of vaccinees responding with a booster reaction reached 68.4% for measles and mumps, but only 8.6% for rubella. A booster reaction could be observed in 100% of those vaccinees who had antibodies at a low level, also in the case of naturally acquired immunity. The low-level range for antibodies against measles was defined as 0.15<0.40 IU/ml, mumps 1:230≤1:500 and rubella 7–16 IU/ml. The rate of vaccinees with low-level antibodies against measles can become as high as 10%, for mumps 20% and for rubella 3%. The correlation between the level of antibodies and protection against the disease is discussed. The rate of individuals in a population with doubtful protection (unvaccinated, non-responder and low responder after primary vaccination) prevents to reach the herd immunity of 95% necessary for elimination. The results of our serological studies strongly recommend re-vaccination against measles, mumps and rubella.

This trial confirmed the immunogenicity of a standard dose of measles vaccine Edmonston-Zagreb strain administered at the age of 6 months as evaluated serologically at 12 months of age in 94 healthy children in Saudi Arabia. The residual seropositivity rate for measles was 53.4 and 80.6% as measured by enzyme immunoassay (EIA) and plaque neutralization, respectively, and could be increased to virtually 100% seroprotection after immunization with 1 of 2 measles-mumps-rubella (MMR) vaccines (Triviraten Berna or MMR II MSD) at 12 months of age. In both groups, more than 90% of infants showed an immune response to the mumps and rubella vaccine strains at 14 months of age. There was a difference in the geometric mean titres of mumps antibodies in favour of MMR II (P < 0.001). The seroconversion rates for mumps antibodies differed between the 2 vaccines because of the different test systems and/or the different cut-off levels used. The study reconfirmed that for the assessment of Rubini mumps vaccine-induced antibodies the indirect immunofluorescence test is superior to the EIA. The systemic tolerability of both vaccines was excellent. Triviraten Berna is exclusively propagated on human diploid cell cultures and hence free of avian proteins.

Sequence analysis of 285 nucleotides located on the variable part of the N gene was undertaken on measles virus (MV) samples collected from acutely infected patients in Germany, the Czech Republic, Denmark, Poland, and Russia. Two distinct genotypes (C2 and D6) have circulated in Germany between 1993 and 1996. Isolates of genotype C2 were related to strains reported in Germany before 1993. This genotype was also found in the Czech Republic in 1992 and in Denmark in 1997. The occurrence of genotype D6 in Germany is described below for the first time. In 1998, this genotype was identified in Poland. Genotypes C2 and D6 were also reported in Spain and in the United Kingdom between 1992 and 1996. Therefore, it is concluded that these genotypes are widely distributed over Europe. The analysis of the isolates from Russia revealed that genotype A was present in 1988 in the European part of the country and in 1996 in Siberia. An isolate identified in 1997 in Siberia belonged to genotype D6, which had never been found previously in Russia. We also analysed MV obtained from a case of subacute sclerosing panencephalitis (SSPE) in 1995 in Turkey. A comparison of this sequence with published sequences implied that this SSPE case was associated with a new genetic lineage of MV. (C) 1999 Wiley-Liss, Inc.

We performed a randomized trial to compare the safety and immunogenicity of two combined measles, mumps and rubella vaccines in healthy children 14-24 months of age. Triviraten Berna Vaccine (Swiss Serum and Vaccine Institute), contains the Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and the Wistar RA 27/3 rubella strain while MMR-Vax (Merck, Sharp & Dohme, West Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl Lynn mumps strain and the Wistar RA 27/3 rubella strain. Immunization with Triviraten Berna was associated with a significantly lower incidence of swelling and redness at the injection site in addition to a reduced rate of fever compared with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components were comparable in all tests used. However, seroconversion for the mumps vaccine component was test-dependent. Using an ELISA, the seroconversion rate following immunization with MMR-Vax was significantly (P < 0.01) higher than for Triviraten Berna. In contrast, nearly identical rates were obtained using an indirect immunofluorescence test. Both vaccines were equally effective at engendering antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA antibody titers against measles and mumps virus were higher following immunization with MMR-Vax while that for rubella was higher after immunization with Triviraten Berna. A small number (N = 13) of adolescents immunized either with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and various humoral and cellular response parameters to the measles and mumps vaccine components analyzed. While few subjects mounted a humoral antibody response to measles, most likely due to elevated baseline titers, there was a marked lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher both at baseline and after reimmunization in subjects who received MMR-Vax for primary immunization. However, there was no difference in either neutralizing titer or proliferative response in subjects primed with MMR-Vax or Triviraten Berna either before or after reimmunization.

The sequence of the 300 nucleotides region of the measles virus genome was determined that includes a part of the 3'-untranslated region of the matrix (M) gene, the intergenic region and a part of the 5'-untranslated region of the fusion (F) gene [M-F region] for vaccine strain Leningrad-16 and 14 wild-type isolates. The data obtained demonstrate the variability of this long non-coding M-F region. No mutations in this region of the genome were found which seem to be specific for vaccine strains of measles virus (MV).

Antibodies reacting with porcine circovirus (PCV) were found in sera of humans, mice, and cattle by means of an indirect immunofluorescence assay (IFA) and an ELISA. In man, the highest seroprevalence (23.9% in IFA and 30.2% in ELISA) was found among hospitalized patients with fever of partially unclear etiology. Non-hospitalized “healthy” persons of the former German Democratic Republic showed a significantly higher number of positive sera (IFA=20%) than blood donors from Berlin-West (IFA=8.6%). Murine sera reacted positive with PCV in IFA between 12 to 69% in different breeding groups and about 35% of cattle sera were found reactive with PCV in IFA. Double-staining IFAs, immuno-electron microscopy and immunoblotting showed that non-porcine antibodies reacted with PCV structural antigen. Mathematical analysis releaved that in ELISA, non-porcine antibodies reacted specifically with PCV. Loss of binding specificity of non-porcine antibodies in ELISA after storage of sera and lower maximal optical densities obtained at equal titers in ELISA with non-porcine than with porcine sera suggest that antibodies in man, mice and cattle are caused by related species specific viruses sharing antigenic epitopes with PCV.

Considerable immunity gaps in respect of mumps and rubella (German measles) of up to 30% among pupils of the prepuberty age are the requisite arguments in favour of the need for vaccination measures. Combined protective vaccination with live attenuated measles-mumps-rubella vaccine without preceding laboratory tests is recommended for practical reasons and economy. No side effects have been seen on renewed protective vaccination with live attenuated measles vaccine in case of already existent natural immunity. A booster effect can be demonstrated in vaccinated persons with low or borderline antibody levels. Revaccination from the 6th year of life onwards is recommended and advocated to close existing vaccination and immunity gaps.

Serum samples were tested for antibodies against polio virus and measles virus from two serum banks after having been stored under different conditions for several years. The results are compared with those ones obtained immediately after sampling. Despite of small increases of antibody-negative samples and of small decreases of the titres the suitability of the samples stored could be shown. Special attention should be given to the establishment, e.g. in the framework of Expanded Programme on Immunization of the World Health Organization and in order to study new pathogens unknown to date, and the technical preconditions for that should be planed.

Studies into occurrence of parvovirus B 19 in East Germany have shown widespread presence of the pathogen and have also indicated that acute infections must be expected far beyond childhood. About 50 percent of all adults up to the age of 30 years should be rated susceptible to B 19. In other words, potential danger cannot be ruled out, when it comes to primary infection during pregnancy. The importance of parvovirus B 19 should not be underestimated as a pathogen to cause atypical exanthematous diseases. The use of DNA hybridisation has been recomendid for diagnosis together with immunoglobulin-specific ELISA.

Evaluating the current stage and future trends of WHO's Expanded Programme on Immunization (EPI), conclusions for national immunization strategies have been considered. The global eradication of poliomyelitis is an important target. In 1988, an Immunization Advisory Group of the Ministry of Health has been founded. Recommendations regarding the update of immunization schedule have been elaborated. Changes are foreseen for BCG (deletion of revaccination), rubella (implementation of immunization for all girls aged 11/12 years), diphtheria (diphtheria/tetanus booster for adults), and measles (2-shot-strategy for young children and schoolchildren.