Low hepatitis B immunogenicity of a hexavalent vaccine widely used in Germany: results of the German Health Survey for Children and Adolescents, 2003-2006.

The success of childhood vaccination against hepatitis B relies on persistence of immunity into adolescence and adulthood. In 2000, two hexavalent vaccines with a hepatitis B component (Hexavac, Infanrix hexa) were introduced in Germany. Hexavac was withdrawn in 2005 amidst concerns about its long-term hepatitis B protection. We compared hepatitis B surface antibody (anti-HBs) levels in children fully vaccinated with Hexavac or Infanrix hexa (n=477) in a secondary data analysis of a large cross-sectional health survey in Germany. On average 2.4 years after vaccination, 25.3% of Hexavac vaccinees had anti-HBs levels <10 mIU/ml (95% CI 19.0-32.8) compared to 4.7% of Infanrix hexa vaccinees (95% CI 2.4-8.9). These findings suggest that short-term hepatitis B immunogenicity in Hexavac vaccinees may also be weaker. Further studies are warranted to assess whether Hexavac vaccinees should be re-vaccinated or receive a booster vaccination before these birth cohorts reach adolescence.

A comparison of hepatitis B seroepidemiology in ten European countries.

To inform current and future vaccination strategies, we describe the seroepidemiology of hepatitis B virus (HBV) infection in ten representative European countries using standardized serology that allowed international comparisons. Between 1996 and 2003, national serum banks were compiled by collecting residual sera or by community sampling; sera were then tested by each country using its preferred enzyme immunoassays and testing algorithm, and assay results were standardized. Information on current and past HBV vaccination programmes in each country was also collected. Of the ten countries, six reported low levels (<3%) of antibodies against HBV core antigen (anti-HBc). Of the eight countries testing for HBV surface antigen (HBsAg), the highest prevalence was reported in Romania (5.6%) and in the remaining seven countries prevalence was <1%. Universal HBV vaccination programmes had been established in seven countries as recommended by the World Health Organization, but the seroprevalence of antibodies against HBsAg (anti-HBs) was lower than the reported vaccine coverage in three countries. Regular serological surveys to ascertain HBV status within a population, such as reported here, provide important data to assess the need for and to evaluate universal HBV vaccination programmes.

The European Sero-Epidemiology Network 2 (ESEN2): standardization of assay results for hepatitis A virus (HAV) to enable comparisons of seroprevalence data across 15 countries.

The European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0.90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe.

Seroprevalence of parvovirus B19 in the German population.

Acute parvovirus B19 infection is a risk for pregnant women. After vertical transmission the infected fetus may develop hydrops fetalis. Since B19 infection occurs mainly during childhood, children represent a main source for virus transmission. In order to determine whether certain groups in the German population show increased risks for B19 infection we analysed the seroprevalence using 6583 sera collected from adults in former Eastern and Western Germany during the German National Health Survey and 649 sera from healthy Thuringian children and adolescents. In adults the overall seroprevalence was 72.1%, rising from 20.4% in children (1-3 years) and 66.9% in adolescents (18-19 years) to 79.1% in the elderly (65-69 years). Significant differences were observed between females (73.3%) and males (70.9%) and between inhabitants of small (74.8%) and big cities (69.0%) but not between people of the former Eastern (72.8%) and Western states (72.0%) of Germany. For women during childbearing age (18-49 years) highest values were observed in those living together with two or more children (81.6%) and in women with occupational contact with children aged <6 years (88.9%). In contrast seroprevalence was significantly lower in age-matched female singles (64.8%) and in women with occupational contact with children aged >6 years and adolescents (63.8%).

Vitamin D status and health correlates among German adults.

OBJECTIVE: To analyze vitamin D status based on serum 25-hydroxyvitamin D (25OHD) measurements, its determinants and health correlates in a representative sample of German adults. SUBJECTS: A total of 1763 men and 2267 women, 18- to 79-year old, who participated in the representative German National Health Interview and Examination Survey 1998 and the integrated German Nutrition Survey. RESULTS: The median vitamin D intake from both diet and supplements did not meet the recommended level of 5 microg/day, in either men (2.8 microg/day) or women (2.3 microg/day). Altogether 80.9% of men and 88.5% of women had vitamin D intakes below this level. Moderate (12.5-25 nmol/l serum 25OHD levels) and mild (25-50 nmol/l) vitamin D deficiency was prevalent in the adult population in Germany, even in younger age groups. Overall, 57% of men and 58% of women had vitamin D levels below 50 nmol/l. Among 65- to 79-year-old women, the proportion amounted to 75%, even during the sunnier half of the year. In sex-specific multiple linear regression models, independent determinants of serum 25OHD levels consistently included season, vitamin D intake from both diet and supplements, physical activity and living in a partnership. In addition, age and current menopausal hormone use contributed to the model among women, as opposed to time of day of blood sampling and body mass index (marginally) among men. Significantly lower serum 25OHD levels were observed in women with hypertension, cardiovascular diseases and noninsulin-treated diabetes mellitus as well as in men with insulin-treated diabetes mellitus compared with nonaffected participants. CONCLUSIONS: Vitamin D deficiency is a public health issue in Germany. We identified a number of determinants with potential for primary prevention of vitamin D deficiency. Risk and benefits of preventive actions need to be examined in further studies.

[The German Health Interview and Examination Survey for Children and Adolescents (KiGGS): study management and conduct of fieldwork]. / Der Kinder- und Jugendgesundheitssurvey (KiGGS): Studienmanagement und Durchführung der Feldarbeit.

UNLABELLED: From May 2003 to May 2006, the Robert Koch Institute conducted the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Nationwide data collection in 167 cities and municipalities was carried out by 4 survey teams, each consisting of a physician, centre interviewer, examiner, medical laboratory technician, environmental interviewer. Regional and seasonal factors were excluded by systematised route planning. Invitation of the participants and appointments for examinations were handled by a survey office with subsidised service telephone. Data processing in the survey office was performed using an SQL data base system programmed in the RKI. One central and several regional members of staff performing preparatory field visits were responsible for finding suitable examination rooms and for subject recruitment respectively. To further increase the response rate, continuous public relation actions were established. The survey involved questionnaires filled in by parents and parallel questionnaires for children from the age of 11 years onwards, physical examinations and tests and a computer assisted personal interview performed by the physician. The wide range of blood and urine testing carried out at central laboratories required standardised transport logistics. To achieve a high degree of standardisation of the survey, the examination teams were initially trained and then underwent continuous further training. The concept of quality management covered action of internal and independent external quality control monitoring each data collecting and data processing step as well as the training courses. CONCLUSION: Dedicated public relations activities and the deployment of staff performing preparatory field visits increased the willingness of the subjects to participate. Intensive personnel care and continuous quality checks contribute to increased job satisfaction and data quality. By bindingly defining all laboratory diagnostic processes as well as transport logistics, high-quality laboratory test results are ensured. The conduct of the study from design via conduct to data processing and analysis by one institution guarantees complete control of all steps of the survey.

[Allergic diseases. Results from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Allergische Erkrankungen. Ergebnisse aus dem Kinder- und Jugendgesundheitssurvey (KiGGS).

In the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) from 2003-2006 information was collected on allergic diseases (asthma, atopic dermatitis, hay fever, allergic contact eczema) from a population-based sample of 17,641 0-to 17-year-olds, and blood samples were studied for specific IgE antibodies to 20 common allergens. The lifetime prevalence (LTP) of at least one atopic disease was 22.9 % (95 % CI: 22.0-23.7 %), the 12-month prevalence (12MP) was 16.1 % (15.4-16.8 %); boys (17.3; 16.3-18.2 %) were more frequently affected than girls (14.9; 14.0-15.8 %). Children with a background of migration were less often currently affected by an atopic disease, as were children from families of low social status. According to parents' accounts, the LTP of allergic contact eczema was 9.9 % (9.4-10.5 %); girls (13.8;12.9-14.8) were more frequently affected than boys (6.2; 5.6-6.9 %). Of the 3- to 17-year-olds, 40.8 % (39.6-42.0 %) were sensitised to at least one of the allergens tested; boys (45.0; 43.5-46.5 %) more frequently so than girls (36.4; 35.0-37.9 %). In the states of the former FRG, the LTP of allergic contact eczema was higher (10.2; 9.6-10.9 %) than those in the former GDR (8.4 % 7.4-9.6 %); otherwise there were no East-West differences. The KiGGS data provide the first nationally representative data on allergic diseases and sensitisation. The differences in prevalence observed correspond to a great extent with previous studies and may support the hygiene hypothesis. The prevalences in East and West Germany now seem to have equalised.

[Iodine intake in Germany. Results of iodine monitoring in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Jodversorgung in Deutschland. Ergebnisse des Jodmonitorings im Kinder- und Jugendgesundheitssurvey (KiGGS).

Iodine is an essential trace element which is found in too low quantities in the soil in Germany. The resulting iodine deficiency in human beings is countered by iodine prophylaxis, essentially consisting of iodised table salt and the iodisation of agricultural animal feed. In iodine monitoring during the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), the thyroid volumes of all children and adolescents from six years of age were determined using sonography. To assess iodine intake among the population, iodine excretion in the urine was also measured. The median ioduria value was 117 microg/l, putting it at the lower end of the scale of 100-200 microg/l recommended by the World Health Organisation. It can be concluded from these results that the iodine prophylaxis has been successful and that iodine intake has improved compared with the past. In accordance with the WHO recommendations there is no iodine deficiency in Germany any more; however, at the same time the population's iodine intake is at a relatively low level. The aim is at least to keep up what has been achieved, meaning that measures to improve iodine intake must not be allowed to slacken.

[Biochemical measures in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. / Biochemische Messparameter im Kinder- und Jugendgesundheitssurvey (KiGGS).

In the framework of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) a variety of biochemical parameters was determined in order to provide objective information on health status and particular health risks, in addition to parent interview data and anthropometric measurements. Overall 43 parameters covered three areas of particular public health interest: micronutrient deficiency, seroepidemiology of infectious diseases and immunization status, and risk indicators or risk factors for chronic non-communicable diseases. A review of available evidence regarding valid reference or cutoff values as well as the standardization of laboratory methods led to the categorization of these parameters into five classification categories. Here, we discuss the present first descriptive results on selected parameters representing the various categories. In order to determine the public health impact of measurement results, and perhaps even derive normative reference data relevant to health care, more detailed analyses will be required. In the first step, these will focus on cross-sectional analyses of the association between biochemical parameters and other health-related anthropometric and sociodemographic variables. Intermediate and long-term objectives will include the construction of multidimensional reference values taking into account several laborato ry data and other clinical information at the same time, and the prognostic validation of reference or cut-off values based on a follow- up of the study participants for clinical outcomes.

The European Sero-Epidemiology Network 2: standardization of assay results for hepatitis B virus.

The aim of the European Sero-Epidemiology Network 2 was to coordinate and standardize the serological surveillance of vaccine-preventable diseases in Europe. In this study, the standardization of hepatitis B virus (HBV) results is described. The 15 participating national laboratories tested a unique panel of 172 sera established by the Greek reference centre for HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs) and/or to the HBV core antigen (anti-HBc) by assay methods of their choice. Country-specific quantitative measurements for anti-HBs and anti-HBc were transformed into common units using standardization equations derived by regressing each country's panel results against the reference centre's results, thus adjusting for interassay and interlaboratory variability. For HBsAg, a qualitative analysis (positive/negative) showed at least 99% agreement with the reference laboratory for all countries. By combining these standardized and qualitative results for the markers mentioned earlier, it was possible to achieve comparable estimates of the proportion of the population susceptible to HBV, vaccinated against HBV, with a past HBV infection, and with a current infection or chronic carrier state. Standardization is a very important tool that allows for international serological comparisons to assess the current vaccination policies and the progress of HBV control in Europe.

Seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in former East and West Germany, 1997-1998.

The aim of this study was to investigate the seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in representative samples of the total former East German (FEG) and total former West German (FWG) populations. Type-specific testing with the HSV-1 (gG1) and HSV-2 (gG2) indirect ELISA was performed on an age- and sex-stratified random subsample of 3,792 sera collected during the 1997-1998 German National Health Survey. Weighted seroprevalence estimates were calculated for the total FEG and FWG populations. The overall age-standardised seroprevalence of HSV-1 was 82.6% in Germany, 85.5% (95%CI, 83.4-87.3%) in FEG and 81.8% (95%CI, 79.9-83.6%) in FWG. The overall seroprevalence of HSV-2 was 13.3% (95%CI, 11.8-14.9) in Germany, 16.5% (95%CI, 14.1-18.9) in FEG and 12.6% (95%CI, 10.7-14.5%) in FWG. The difference between FEG and FWG was largely due to the significantly higher age-adjusted seroprevalence of HSV-1 and HSV-2 in women (but not men) in FEG as compared to FWG. The HSV seroprevalence estimates in this study are consistent with results of previous less representative seroprevalence studies in Germany. Differences in HSV-2 seroprevalence between FEG and FWG suggest differences in sexual behaviour that warrant further investigation.

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe.

OBJECTIVES: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. METHODS: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. RESULTS: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). CONCLUSIONS: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and HSV-2.

Alcohol consumption and its relation to cardiovascular risk factors in Germany.

OBJECTIVE: To analyse the association of alcohol consumption and blood lipids, haemostatic factors, and homocysteine in German adults by gender and age groups. DESIGN: Cross-sectional population-based survey. SETTING: Data from the German National Health Interview and Examination Survey 1998, representative for age, gender, community size, and federal state. SUBJECTS: From a sample of 7124 Germans between 18 and 79 y old, 2420 women and 2365 men were selected. Only individuals who were not currently receiving medical treatment or did not have disorders related to cardiovascular disease were selected for this study. RESULTS: Using analyses of variance, mean blood levels of total cholesterol, HDL cholesterol, HDL/total cholesterol ratio, total glycerides, fibrinogen, antithrombin III, and homocysteine adjusted for age, socioeconomic status, East/West Germany residence, body mass index, tobacco use, sports activity, and coffee consumption, if appropriate are presented by alcohol consumption groups (0, >0-10, >10-20, >20-30 and >30 g/day). The HDL/total cholesterol ratio increased with higher alcohol groups up to 10-20 g/day (+15%) for women and >30 g/day (+18%) for men, showing the strongest rise among men aged 55-79 y. Fibrinogen decreased with higher alcohol groups up to 10-20 g/day for women and 20-30 g/day for men. Among women, homocysteine levels showed a U-shaped curve with a minimum of 8.49 mmol/l at 10-20 g alcohol/day (-8%, reference: nondrinking), whereas an inverse association was observed for men. CONCLUSIONS: Moderate alcohol consumption is associated with favourable levels of several cardiovascular risk factors. The most favourable cardiovascular risk factor profile among women was observed among those drinking 10-20 g alcohol/day. Beneficial effects seem to be more pronounced among older men.

[Laboratory tests in The Child and Adolescent Health Survey]. / Laboruntersuchungen im Kinder- und Jugendgesundheitssurvey.

Laboratory tests will be performed as part of the National Health Survey for Children and Adolescents to identify health risks and to determine the seroprevalence of disease markers. The parameters were selected from haematology, clinical chemistry, allergology, endocrinology and serology of infectious diseases as indicators of individual health risks, to validate information collected by means of the questionnaires and to identify age specific immunity gaps of vaccine-preventable diseases.

[Monitoring of iodine in The Child and Adolescent Health Survey]. / Jodmonitoring im Rahmen des Kinder- und Jugendgesundheitssurveys.

In the first quarter of 2003 a National Health Survey for Children and Adolescents will be started and carried out over a period of three years. In 11,300 children and adolescents between 6 and 18 years a comprehensive iodine monitoring will be realised. The volume of the thyroid gland will be determined sonographically, thyroid hormones and the urinary iodine excretion will be measured. Apart from the nutritional intake of iodine and the use of supplements, socio-demographic and other variables relevant to health will be recorded in a self-administered questionnaire. In the pilot study of the Health Survey for Children and Adolescents from March 2001 to March 2002 the method was tested on 426 children and adolescents and has proved feasible. The sample for the pretest was not representative for the population of children and adolescents in Germany but may already be an indication for the iodine supply. A low goitre prevalence of 4.2% was found. The total thyroid volume correlated significantly with height and weight. There was no significant difference between boys and girls or between a rural and an urban sample point.

Prevalence of markers for hepatitis A, B and C in the German population. Results of the German National Health Interview and Examination Survey 1998.

The prevalence of serological parameters indicative of infection with hepatitis A, B and C was determined using sera collected from representative population samples in the former East German (new) federal states and the West German (old) federal states during the German National Health and Examination Survey in 1998. Sera were tested for antibodies to hepatitis A virus (HAV), to hepatitis B core antigen (HBc) and to hepatitis B surface antigen (HBsAg), hepatitis C Virus (HCV), as well as for the presence of HBsAg and HCV-RNA. The mean weighted prevalence of anti-HAV was 46.5% (95% CI: 45.3-47.7) and increased markedly with age. The mean weighted prevalence of past infection with hepatitis B was 7.7% (95% CI: 7.0-8.4) in the old federal states and 4.3% (95% CI: 3.2-5.3) in the new federal states, corresponding to an overall prevalence of 7.0% (95% CI: 6.4-7.6). The mean weighted prevalence of HBsAg carriage was 0.6% (95% CI: 0.4-0.8), while the prevalence of HCV antibodies was 0.4% (95% CI: 0.2-0.5).

[Helicobacter pylori--prevalence in the German population]. / Helicobacter pylori--Prävalenz in der deutschen Bevölkerung.

Within the framework of the German National Health interview and Examination Survey determinations of IgG-antibodies against the bacterium Helicobacter pylori in serum samples of study participants were conducted. The prevalence for the total population of Germany was 40%. No differences could be found between sexes. The comparison between study participants from the old and those from the new (territory of the former GDR) federal states of Germany did show that the prevalence rates were significantly higher in all age-groups of the eastern part (former GDR) of Germany. Possible causes and factors of influence are discussed.

[German Health survey 1997/98: immune status against poliomyelitis]. / Bundesgesundheitssurvey 1997/98: Immunitätslage gegen Poliomyelitis.

BACKGROUND: One of the goals of the WHO is the worldwide eradication of poliomyelitis in the next years. A high level of population immunity protects against imported wild viruses from endemic areas. PATIENTS AND METHODS: The first German Health Survey, a representative study of the health status of the population (aged between 17 and 79 years) in unified Germany, was started in 1997. In order to study the serological status against poliomyelitis, a representative serum panel was investigated (n = 2564). Furthermore, 881 sera from persons aged less than 18 years were included in the study. The microneutralization test was used to demonstrate antibodies against the three poliovirus types. For the first time, the results were expressed in International Units. The threshold values 0.075 IU, 0.180 IU, 0.080 IU were calculated for Polio 1, 2, 3 respectively. RESULTS: Overall, neutralizing antibodies against poliovirus type 1, 2 and 3 were detected in 96.2%; 96.8% and 89.6% of samples, respectively. 85% of test persons had antibodies against all three virus types. CONCLUSIONS: The seroprevalence of antibodies against all three types of polioviruses indicates a very high population immunity. It must be kept after the switch of immunization strategy from attenuated to inactivated vaccine in Germany (OPV to IPV).

[Prevalence of antibodies to hepatitis A, hepatitis B and hepatitis C viruses in the German population]. / Die Prävalenz von Antikörpern gegen Hepatitis-A-, Hepatitis-B- und Hepatitis-C-Viren in der deutschen Bevölkerung.

Representative random samples were tested for hepatitis A, hepatitis B and hepatitis C infections within the framework of the German National Health Interview and Examination Survey. The laboratory parameters included determination of anti-HAV, anti-HBc, anti-HBs, HbsAg, anti-HCV and hepatitis C virus RNA. The prevalence rate for anti-HAV was 46.5% with a definite age-dependence. The infection rates for hepatitis B of 7.7% in former West Germany and of 4.3% in former East Germany were obtained. This is equivalent to a total of 7% prevalence rate. The HbsAg carrier rate was 0.6%. Hepatitis C virus antibodies showed a prevalence rate of 0.4%.

[Folic acid intake of women in childbearing age]. / Folsäureversorgung von Frauen im gebärfähigen Alter.

An optimal maternal folate status reduces the risk of neural tube defects in the offspring. In the German National Health Interview and Examination Survey, red cell folate and serum folate levels have been measured in 1,266 women aged between 18 and 40 years. Applying the dietary assessment software DISHES 98 made it possible to estimate the individual folate intake. A high proportion of the participants showed sub-optimal red cell folate levels as well as folate intakes below the recommendations.