Ruth Zimmermann

Die Seroepidemiologie der Hepatitis A, B und C in Deutschland

Ten years after seroepidemiological data were obtained in the German National Health Interview and Examination Survey 1998 (GNHIES98), German Health Interview and Examination Survey (DEGS1) data contribute to a population-based, representative surveillance of hepatitis A and B immunity and of the serological markers for hepatitis C in Germany. The prevalence of antibodies against the hepatitis A virus is 48.6 %. In comparison to the situation 10 years ago, seroprevalence is significantly higher among 18- to 39-year-old adults and is significantly lower in those aged 50-79 years. The association between age and seroprevalence has changed, indicating a decrease in naturally acquired hepatitis A immunity. Individual and population immunity has to be achieved through vaccination. Prevalence of hepatitis B antibodies indicates that 5.1 % of adults have been exposed to the virus, significantly fewer than 10 years ago (7.9 %). Prevalence of hepatitis B surface antibodies indicates that 22.9 % of adults have been vaccinated against hepatitis B. Vaccination coverage has increased in all age groups and is highest in the younger age groups. These positive trends can be attributed to the general recommendation since 1995 to vaccinate against hepatitis B. For hepatitis C, the prevalence of antibodies in the general population is 0.3 %. Germany thus remains a low-HCV-endemic country. An English full-text version of this article is available at SpringerLink as supplemental.

[Epidemiology of hepatitis A, B, and C among adults in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].

Ten years after seroepidemiological data were obtained in the German National Health Interview and Examination Survey 1998 (GNHIES98), German Health Interview and Examination Survey (DEGS1) data contribute to a population-based, representative surveillance of hepatitis A and B immunity and of the serological markers for hepatitis C in Germany. The prevalence of antibodies against the hepatitis A virus is 48.6 %. In comparison to the situation 10 years ago, seroprevalence is significantly higher among 18- to 39-year-old adults and is significantly lower in those aged 50-79 years. The association between age and seroprevalence has changed, indicating a decrease in naturally acquired hepatitis A immunity. Individual and population immunity has to be achieved through vaccination. Prevalence of hepatitis B antibodies indicates that 5.1 % of adults have been exposed to the virus, significantly fewer than 10 years ago (7.9 %). Prevalence of hepatitis B surface antibodies indicates that 22.9 % of adults have been vaccinated against hepatitis B. Vaccination coverage has increased in all age groups and is highest in the younger age groups. These positive trends can be attributed to the general recommendation since 1995 to vaccinate against hepatitis B. For hepatitis C, the prevalence of antibodies in the general population is 0.3 %. Germany thus remains a low-HCV-endemic country. An English full-text version of this article is available at SpringerLink as supplemental.

Improved testing of recent HIV-1 infections with the BioRad avidity assay compared to the limiting antigen avidity assay and BED Capture enzyme immunoassay: evaluation using reference sample panels from the German Seroconverter Cohort.

Background The variety and limitations of current laboratory methods for estimating HIV-incidence has driven attempts to improve and standardize the performance of serological ‘Tests for Recent HIV-Infections’ (TRI). Primary and follow-up HIV-1 positive plasma samples from individuals with well-defined dates of infection collected as part of the German Seroconverter Cohort provided specimens highly suitable for use in comparing the performance of three TRIs: the AWARE™ BED™ EIA HIV-1 Incidence test (BED-CEIA), Genetic systems HIV-1/HIV-2 Plus O EIA antibody avidity-based assay (BioRad Avidity) and Sedia™ HIV-1 LAg Avidity EIA (LAg Avidity). Methods The evaluation panel included 180 specimens: 44 from antiretroviral (ARV)-naïve individuals with recently acquired HIV-infection (≤130 days; 25 B and 19 non-B subtypes) and 136 from long-term (>12 months) infected individuals [101 ARV-naïve subtype B, 16 non-B subtypes, 14 ARV-treated individuals, 5 slow progressors (SLP)]. Results For long-term infected, ARV-naïve individuals the false recent rates (FRR) of both the BioRad and LAg Avidity assays were 2% (2/101 for subtype B) and 6% (1/16 for subtype ‘non-B’), while the FRR of the BED-CEIA was 7% (7/101 for subtype B) and 25% (4/16 for subtype ‘non-B’) (all p>0.05). Misclassification of ARV-treated individuals and SLP was rare by LAg (1/14, 0/5) and BioRad Avidity assays (2/14, 1/5) but more frequent by BED-CEIA (5/14, 3/5). Among recently-infected individuals (subtype B), 60% (15/25) were correctly classified by BED-CEIA, 88% (22/25) by BioRad Avidity and significantly fewer by LAg (48%, 12/25) compared to BioRad Avidity (p = 0.005) with a higher true-recency rate among non-B infections for all assays. Conclusions This study using well-characterized specimens demonstrated lower FRRs for both avidity methods than with the BED-CEIA. For recently infected individuals the BioRad Avidity assay was shown to give the most accurate results.

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

BACKGROUND & AIMS Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Real-world treatment for chronic hepatitis C infection in Germany: Analyses from drug prescription data, 2010–2015

BACKGROUND & AIMS Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have strongly improved treatment options since 2014, but it is unclear if treatment numbers have increased. We aimed to estimate the number of treatment regimens per month from 2010-2015 and the number of patients treated and cured with DAAs since 2014, as well as the associated costs. METHODS Drug prescription data of hepatitis C virus (HCV) antivirals for patients with statutory health insurance in Germany (∼85% of population) from January 2010-December 2015 were evaluated. Standard 28-day prescriptions of pegylated interferon (PegIFN) and 1st/2nd generation DAAs were combined according to treatment guidelines and analysed. Drug costs were calculated from pharmacy sales prices. Mean treatment durations/regimen from real-world data were used to calculate drug costs/regimen and numbers of DAA-treated persons in 2014/15. RESULTS From January 2010-December 2015 PegIFN/ribavirin-treatments/month decreased from ∼6500 to ∼650. Monthly HCV-prescriptions rose with the approval of 1st generation DAAs (2011), and decreased at the end of 2013. With the approval of 2nd generation DAAs, prescriptions/month increased (peak: ∼6600; March 2015), and subsequently decreased (∼4000; December 2015). In 2014, ∼7000 patients were treated with DAAs, and ∼20,100 in 2015. Treatment costs/month were stable at 12 million EUR (2010-2011), increased to ∼38 million EUR (March 2012), and peaked to 150 million EUR (March 2015). DAA-drug costs/year added up to ∼664million EUR (2014) and ∼1.3billion EUR (2015). CONCLUSIONS Despite an increase in DAA prescriptions, in December 2015 less persons/month were under treatment compared to January 2010, even though access to DAAs is not limited. However, yearly treatment numbers increased from 2014-2015. Under observed conditions, ∼18,000 patients/year can be cured, making substantial reduction of the estimated 160,000 diagnosed patients realizable. Political commitment to achieve further reduce DAA-prices and increase treatment numbers is recommended. LAY SUMMARY New treatment options with all-oral second generation direct-acting antivirals (DAAs) have resulted in the potential to cure chronic hepatitis C infection, but at high costs. Analyses from HCV drug prescription data of patients with statutory health insurance in Germany from 2010-2015, showed that DAAs replaced treatments with pegylated interferon and ribavirin, but accompanied by a disproportionate rise in costs. Although the monthly number of patients under treatment did not increase over time, the total number of patients yearly treated with DAAs increased from ∼7000 patients in 2014 to ∼20,100 in 2015, with a trend to shorter treatment regimens. Under observed conditions ∼18,000 patients can be cured yearly, making a substantial reduction of the estimated 160,000 diagnosed patients in Germany achievable.

Hepatitis B immune status in adolescents vaccinated during infancy: A retrospective cohort study from a pediatric practice in Germany

abstract In Germany, vaccination of infants against hepatitis B is recommended since 1995. However, data on long-term immunity is sparse and the necessity of a booster dose remains uncertain. Aims of this study were to assess the long-term persistence of antibodies to the hepatitis B surface antigen (anti-HBs) after immunization during infancy and the effect of a subsequent hepatitis B booster vaccination during adolescence on anti-HBs levels. Patients from a private pediatric practice who had received a full vaccination course of hepatitis B as infants and who were quantitatively tested for anti-HBs during adolescence (pre-booster levels) were included. In those participants who received a hepatitis B booster, post-booster anti-HBs levels were measured. Univariate analyses were conducted to determine factors associated with pre- and post-booster anti-HBs levels, respectively. 106 participants (53% male) were included in the study. At an average of 13.7 y after primary vaccination, 14% of participants had an anti-HBs level of ≥100 IU/l, while 46% were at 10–99 IU/l and 40% had anti-HBs levels of <10 IU/l. In total, 34 received a booster vaccination. Of those, 97% (33/34) had post-booster anti-HBs levels ≥ 100 IU/l, which were independent from pre-booster levels. No other patient characteristics were associated with pre-booster or post-booster anti-HBs≥ 100 IU/l. Although almost half of study participants showed low anti-HBs levels at follow-up, robust responses to booster vaccination suggest that adolescents who received the full vaccination course during infancy are still protected against hepatitis B infection.

Epidemiology of hepatitis A, B and C among adults in Germany

Ten years after seroepidemiological data were obtained in the German National Health Interview and Examination Survey 1998 (GNHIES98), German Health Interview and Examination Survey (DEGS1) data contribute to a population-based, representative surveillance of hepatitis A and B immunity and of the serological markers for hepatitis C in Germany. The prevalence of antibodies against the hepatitis A virus is 48.6 %. In comparison to the situation 10 years ago, seroprevalence is significantly higher among 18- to 39-year-old adults and is significantly lower in those aged 50-79 years. The association between age and seroprevalence has changed, indicating a decrease in naturally acquired hepatitis A immunity. Individual and population immunity has to be achieved through vaccination. Prevalence of hepatitis B antibodies indicates that 5.1 % of adults have been exposed to the virus, significantly fewer than 10 years ago (7.9 %). Prevalence of hepatitis B surface antibodies indicates that 22.9 % of adults have been vaccinated against hepatitis B. Vaccination coverage has increased in all age groups and is highest in the younger age groups. These positive trends can be attributed to the general recommendation since 1995 to vaccinate against hepatitis B. For hepatitis C, the prevalence of antibodies in the general population is 0.3 %. Germany thus remains a low-HCV-endemic country. An English full-text version of this article is available at SpringerLink as supplemental.

High variability of TB, HIV, hepatitis C treatment and opioid substitution therapy among prisoners in Germany

BackgroundIn Germany, medical care of prisoners is completely separated from extramural health care. The extent and quality of medical care among prisoners in Germany are therefore largely unknown. We performed a secondary data analysis of pharmacy sales data for tuberculosis (TB), HIV, hepatitis C (HCV) and opioid substitution treatment (OST) delivered to prisons in 11 federal states (FS) in Germany between 01/2012 and 03/2013. The aims of this study were to assess (i) the treatment availability for the selected diseases and OST in German prisons, (ii) the proportion of prisoners treated per FS and overall for TB, HIV, HCV and OST during the study period.MethodsSubstances unique to or typically used for the treatment of each disease were defined as marker substances with defined daily doses (DDD).For each marker substance we assessed the cumulative number of DDD, the average daily number of DDD (DDDd) and average treatment prevalence per day in percent (adTP). Accordingly, the DDDd represents one person treated per day and the adTP means the proportion of prisoners treated per day. We compared the adTP of the diseases with previously measured prevalences.ResultsWe obtained data from pharmacies supplying prisons in 11 of 16 German FS. Of the included prisons, 41% were supplied with medicines for TB, 71% for HIV and 58% for HCV and OST. Twice as many delivered marker substances for TB were indicated for the continuation phase and chemoprevention than the intensive phase. The HIV adTP ranged from 0.06% to 0.94%, HCV adTP ranged from 0.03% to 0.59% and OST adTP ranged from 0% to 7.90%. The overall adTP for the respective treatment was 0.39% for HIV, 0.12% for HCV and 2.18% for OST.ConclusionsAccording to our findings treatment rates for TB were consistent with the expected TB prevalence, at least in Berlin. HIV treatment seems to be offered to an adequate proportion of estimated infected prisoners. In contrast, the HCV treatment prevalence was low. High variation among FS in provision of all treatments, particularly of OST, point to inconsistent treatment practices, although nationwide extramural treatment guidelines for Germany exist.

Die Seroepidemiologie der Hepatitis A, B und C in Deutschland@@@Epidemiology of hepatitis A, B, and C among adults in Germany: Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1)@@@Results of the German health interview and examination survey for Adults (DEGS1)

Ten years after seroepidemiological data were obtained in the German National Health Interview and Examination Survey 1998 (GNHIES98), German Health Interview and Examination Survey (DEGS1) data contribute to a population-based, representative surveillance of hepatitis A and B immunity and of the serological markers for hepatitis C in Germany. The prevalence of antibodies against the hepatitis A virus is 48.6 %. In comparison to the situation 10 years ago, seroprevalence is significantly higher among 18- to 39-year-old adults and is significantly lower in those aged 50-79 years. The association between age and seroprevalence has changed, indicating a decrease in naturally acquired hepatitis A immunity. Individual and population immunity has to be achieved through vaccination. Prevalence of hepatitis B antibodies indicates that 5.1 % of adults have been exposed to the virus, significantly fewer than 10 years ago (7.9 %). Prevalence of hepatitis B surface antibodies indicates that 22.9 % of adults have been vaccinated against hepatitis B. Vaccination coverage has increased in all age groups and is highest in the younger age groups. These positive trends can be attributed to the general recommendation since 1995 to vaccinate against hepatitis B. For hepatitis C, the prevalence of antibodies in the general population is 0.3 %. Germany thus remains a low-HCV-endemic country. An English full-text version of this article is available at SpringerLink as supplemental.

Piloting second generation HIV surveillance in Berlin, Germany, 2005 - 2007

Men having sex with men (MSM) are by far the transmission-risk-category most affected by HIV in Berlin and were investigated in this pilot-study with the aim to identify detailed riskand prevention-behaviours in recently infected persons. From November, 2005 February, 2007, venous blood samples were taken from patients in Berlin aged 18 years within 3 months after diagnosis of HIV-infection and tested with BED IgGcapture-ELISA (BED-CEIA) to differentiate between longstanding and recent HIV-infections dating back no longer than 140 days from blood sampling. Data on knowledge, attitudes, behaviour and practices (“KABPsurvey”) relating to HIV/AIDS, were collected anonymously by structured patients’ questionnaires, accomplished by demographic data via additional questionnaires filled by the physicians. SPSS 15.0 was used for data analysis. This sub-analysis includes 37 MSM with confirmed recently acquired HIV infection. Mean age was 34 years (20 53). Good knowledge on HIV/AIDS in Germany and transmission risks was present in most cases; nevertheless unprotected sexual contacts were indicated by 90% of recently HIVinfected MSM (independent from type of intercourse and partners’ sero -status) with 64% reporting unprotected anal intercourse. Unprotected anal intercourse with a person they knew to be infected with HIV was stated by 19% of cases. In 5% drugs/alcohol and in 48% (n = 18/37) uncertain HIV-related knowledge, hope and beliefs about transmission risks were stated as reasons for unprotected sex. Almost half of recently infected MSM in this pilot -study were infected because hope and beliefs on HIVtransmission-risks had guided their personal decisions on HIV-prevention efforts. Limitations due to a small study population, lack of HIV-negative-tested controls and selection bias should be optimised in future studies; however, the findings have strong implications for amending prevention messages in Germany addressing MSM.