Annedore Tischer

Seroprevalence of varicella-zoster virus in the German population

The present study was conducted to generate data on the epidemiology of varicella-zoster virus (VZV) infections in Germany as a basis for health economic evaluations of varicella vaccination strategies. The survey was designed as a cross-sectional, age-stratified study of the VZV seroprevalence in the German population. The status of immunity of 4602 individuals a aged 0 to >70 years was investigated by means of an indirect enzyme immunoassay and the fluorescent antibody to membrane assay. After waning of maternal antibodies over the period of 6-9 months seropositivity rates remained low by the end of the 1st year of life. By the age of 4-5 years 62.5% (95% CI; 56.0-68.5) of the pre-school children had already been infected with VZV and at the age of 10-11 years 94.2% (95% CI; 91.0-96.0) of children were positive for anti-VZV antibodies. Among the age-group of >40 years old, only few individuals were susceptible for VZV. The median antibody levels to VZV did not significantly decline with increasing age. In comparison with figures of previous studies the age-specific seroprevalence data presented here do not provide evidence for an upward shift in the age distribution of varicella in Germany. Since the majority of VZV infections occurs during the early childhood, the best option to reduce the circulation of wild-type VZV in the population would be the immunization of young children.

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.

The sero-epidemiology of diphtheria in Western Europe

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.

European Sero-Epidemiology Network: standardisation of the assay results for pertussis

A standardisation process was developed in order to compare and harmonize serological results of pertussis toxin (PT) antibody measurements performed by laboratories using different technical procedures for detection. This involved the development of a common panel, of sera by a designed reference centre, the distribution of the panel to each participating laboratory for testing with their routine methods, the comparison of the obtained results to those of the reference centre, and the calculation of standardisation equations by regressing the quantitative results against those of the reference centre. As a cut-off indicative of protection against pertussis has not yet been defined, a particular emphasis was laid upon achieving standardisation of high titre results that would allow epidemiological evaluations based on the estimation of the incidence of recent infections rather than on the traditional approach of determining the population immunity profile. A generally good agreement was achieved between the participating laboratories, all using ELISA procedures very similar in many crucial aspects, and standardisation equations were produced useful to enable inter-country comparison during the next stages of the European Sero-Epidemiology Network (ESEN) project concerning the serological surveillance of immunity to pertussis in Europe.

Rapid replacement of endemic measles virus genotypes

Although vaccination campaigns have significantly reduced the number of measles cases worldwide, endemic transmission of measles virus (MV) continues to occur in several continents, including Europe. To obtain current information on measles incidence and molecular data on circulating MVs in Germany, a nationwide measles sentinel was established. Phylogenetic analysis based on the variable part of the N gene from 80 MVs isolated between November 1999 and October 2001 revealed the presence of at least six distinct MV genotypes: B3, C2, D4, D6, G2 and a new variant of D7. Both the incidence and the pattern of MV genotypes differed markedly between the former East and West Germany. In the eastern part, few measles cases, mainly caused by genotypes originating from other countries (B3, D4, G2), were detected. In the western and southern parts, genotypes C2, D6 and D7 were associated with endemic transmission. Surprisingly, the indigenous genotypes predominant during the 1990s - C2 and D6 - disappeared simultaneously over the period of observation coinciding with the emergence and the wide spread of D7 viruses. While the incidence of measles remained constant, all MVs isolated in 2001 were assigned to D7. We note that the haemagglutinin (H) sequence of D7 viruses shows distinct exchanges of certain amino acids in the stem and propeller domain compared to C2, D6 and the MV vaccine strains used. This raises the possibility of a selective advantage of D7 viruses transmitted in the presence of H-specific antibodies.

Comparison of rubella seroepidemiology in 17 countries: progress towards international disease control targets

OBJECTIVE To standardize serological surveillance to compare rubella susceptibility in Australia and 16 European countries, and measure progress towards international disease-control targets. METHODS Between 1996 and 2004, representative serum banks were established in 17 countries by collecting residual sera or community sampling. Serum banks were tested in each country and assay results were standardized. With a questionnaire, we collected information on current and past rubella vaccination programmes in each country. The percentage of seronegative (< 4 IU/ml) children (2-14 years of age) was used to evaluate rubella susceptibility, and countries were classified by seronegativity as group I (< 5%), group II (5-10%) or group III (> 10%). The proportion of women of childbearing age without rubella protection (< or = 10 IU/ml) was calculated and compared with WHO targets of < 5%. FINDINGS Only Romania had no rubella immunization programme at the time of the survey; the remaining countries had a two-dose childhood schedule using the measles, mumps and rubella (MMR) vaccine. The percentage of susceptible children defined five countries as group I, seven as group II and four as group III. Women of childbearing age without rubella protection were < 5% in only five countries. CONCLUSION Despite the low reported incidence in many countries, strengthening the coverage of the routine two-dose of MMR vaccine among children is needed, especially in group III countries. Catch-up campaigns in older age groups and selective targeting of older females are needed in many countries to ensure necessary levels of protective immunity among women of childbearing age.

The European Sero-Epidemiology Network: standardizing the enzyme immunoassay results for measles, mumps and rubella.

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.

The seroepidemiology of rubella in western Europe

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.

The seroepidemiology of measles in Western Europe

The European Regional Office of WHO has targeted measles for elimination from the region in 2007. Large national, age and sex stratified serological surveys of measles antibody were conducted in seven Western European countries from 1994-8 as part of the European Seroepidemiology Network. Three patterns were observed in the country-specific measles seroprofiles, ranging from (very) low susceptibility (four countries) to high susceptibility (one country). Susceptibility levels amongst 2-4-year-olds ranged from 2.9 to 29.8%, in 5-9-year-olds from 2.5 to 25% and 10-19-year-olds from 2.1% to 13.9%. A countrys susceptibility profile was highly associated with vaccine coverage for the first dose. First dose coverage ranged from 91 to 97.5% for low susceptibility countries, 75 to 85% for intermediate susceptibility countries and 55% for the high susceptibility country. Only the high susceptibility country still reports epidemic measles. In low susceptibility countries, which have achieved or are very close to measles elimination, the priority will be to maintain high MMR vaccine coverage in all geopolitical units for both vaccine doses. In moderate susceptibility countries there is still some endemic transmission, but also risk of outbreaks as pools of susceptibles accumulate. In the high susceptibility country the priority will be to increase infant vaccine coverage and reduce regional variation in coverage levels.

Towards elimination : measles susceptibility in Australia and 17 European countries

OBJECTIVE To evaluate age-specific measles susceptibility in Australia and 17 European countries. METHODS As part of the European Sero-Epidemiology Network 2 (ESEN2), 18 countries collected large national serum banks between 1996 and 2004. These banks were tested for measles IgG and the results converted to a common unitage to enable valid intercountry comparisons. Historical vaccination and disease incidence data were also collected. Age-stratified population susceptibility levels were compared to WHO European Region targets for measles elimination of < 15% in those aged 2-4 years, < 10% in 5-9-year-olds and < 5% in older age groups. FINDINGS Seven countries (Czech Republic, Hungary, Luxembourg, Spain, Slovakia, Slovenia and Sweden) met or came very close to the elimination targets. Four countries (Australia, Israel, Lithuania and Malta) had susceptibility levels above WHO targets in some older age groups indicating possible gaps in protection. Seven countries (Belgium, Bulgaria, Cyprus, England and Wales, Ireland, Latvia and Romania) were deemed to be at risk of epidemics as a result of high susceptibility in children and also, in some cases, adults. CONCLUSION Although all countries now implement a two-dose measles vaccination schedule, if the WHO European Region target of measles elimination by 2010 is to be achieved higher routine coverage as well as vaccination campaigns in some older age cohorts are needed in some countries. Without these improvements, continued measles transmission and outbreaks are expected in Europe.