Prevalence of vaccine-derived hepatitis B surface antibodies in children and adolescents in Germany: results from a population-based survey, 2014-2017.

INTRODUCTION: Childhood vaccination against hepatitis B has been recommended in Germany since 1995. WHO defines a primary vaccination series as successful if the initial hepatitis B surface antibody (anti-HBs) level is ≥ 10 IU/L directly after vaccination. Anti-HBs levels vary depending on the number of doses, type of vaccine, and time interval between the last two doses. In 2021, Germany began to recommend three instead of four doses of polyvalent hepatitis-B-containing vaccines. Our aim was to estimate the proportion of vaccinated children in Germany with anti-HBs levels < 10 IU/L, 10-99 IU/L, and ≥ 100 IU/L by number and type of vaccine, and assess if number of doses and compliance with recommended time interval between the last two doses are associated with an anti-HBs level ≥ 10 IU/L when considering type of vaccine and time since last dose. METHODS: We used data from a national cross-sectional study (2014-2017) of children (3-17 years). We excluded participants with unknown vaccination dates, unreadable or incomplete vaccination cards, and hepatitis B virus (HBV)-positive participants. We defined a recommended schedule as a vaccination series with at least six months between the two last doses and having three doses or more. We calculated weighted anti-HBs sero-prevalence for three anti-HBs levels: < 10 IU/L, 10-99 IU/L and ≥ 100 IU/L. We fitted two logistic regression models to examine the relationship between number of doses and recommended schedule on anti-HBs levels (≥ 10 IU/L and ≥ 100 IU/L) considering time since last dose and type of vaccine (Infanrix, Hexavac, Monovalent). RESULTS: We included 2,489 participants. The weighted proportion of vaccinated children per anti-HBs level was < 10 IU/L: 36.3% [95%CI 34.0-38.7%], 10-99 IU/L: 35.7% [33.2-38.2%] and ≥ 100 IU/L: 28.0% [25.9-30.2%]. We did not find an association between a recommended schedule of three versus four doses and anti-HBs ≥ 10 IU/L or ≥ 100 IU/L. CONCLUSIONS: Anti-HBs levels in later childhood were about equal, whether children received three or four doses. This implies that the change in the recommendations does not affect the anti-HBs level among children in Germany. Future studies are needed on the association of anti-HBs levels and adequate sustained protection against HBV.

Prevalence of hepatitis B virus infection among general population of Armenia in 2021 and factors associated with it: a cross-sectional study.

OBJECTIVES: This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia. DESIGN: A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals. SETTING: All administrative units of Armenia including 10 provinces and capital city Yerevan. PARTICIPANTS: The study frame was the general adult population of Armenia aged ≥18 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models. RESULTS: The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93). CONCLUSION: This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.

Evaluating the hepatitis B vaccination impact in the Republic of Moldova: A nationwide representative serosurvey of children born in 2013.

Objectives: The WHO European Region set targets for the control of hepatitis B through immunization, including prevalence of hepatitis B surface antigen (HBsAg) at ≤0.5% in vaccinated cohorts. The Republic of Moldova implemented universal hepatitis B vaccination since 1995. We conducted a nationwide representative serosurvey to estimate HBsAg seroprevalence in children born in 2013 to validate hepatitis B control targets. Methods: We used probability-based sampling and a two-stage cluster design. All children born in 2013 and registered in primary healthcare facilities were eligible for participation. We tested blood samples of all participants for hepatitis B core antibody (anti-HBc), using Enzyme-Linked Immunosorbent Assay (ELISA). Anti-HBc-positive samples were tested for HBsAg and HBsAg-positive samples confirmed, using ELISA. We obtained information on hepatitis B vaccination from vaccination cards. Results: Of 3352 sampled children, 3064 (91%) participated. Most participating children were 7 years old (n = 3030, 99%), 1426 (48%) were girls. The weighted, national seroprevalence estimate was 3.1% (95% confidence interval = 2.1-4.5) for anti-HBc and 0.21% (95% confidence interval = 0.08-0.53) for HBsAg. Conclusion: The study demonstrated the impact of hepatitis B vaccination and allowed the Republic of Moldova to validate regional hepatitis B control targets. Other countries with high vaccination coverage could use hepatitis B serosurveys and apply for validation. Sustained efforts in the Republic of Moldova will be crucial on the path to hepatitis B elimination.

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis.

Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.

Additional challenges in reaching hepatitis C elimination goals in Germany due to the COVID-19 pandemic - descriptive analysis of drug prescription data from January 2018 to June 2021.

Effectively treating hepatitis C viral (HCV) infections prevents sequelae and onward transmission. In Germany, HCV drug prescriptions have declined since 2015. During the COVID-19 pandemic, lockdowns impacted the access to HCV care services and HCV treatment. We assessed if the COVID-19 pandemic further decreased treatment prescriptions in Germany. We built log-linear models with monthly HCV drug prescription data from pharmacies from January 2018 - February 2020 (pre-pandemic) to calculate expected prescriptions for March 2020-June 2021 and different pandemic phases. We calculated monthly prescription trends per pandemic phase using log-linear models. Further, we scanned all data for breakpoints. We stratified all data by geographic region and clinical settings. The number of DAA prescriptions in 2020 (n = 16,496, -21%) fell below those of 2019 (n = 20,864) and 2018 (n = 24,947), continuing the declining trend from previous years. The drop in prescriptions was stronger from 2019 to 2020 (-21%) than from 2018 to 2020 (-16%). Observed prescriptions met predictions from March 2020 to June 2021, but not during the first COVID-19 wave (March 2020-May 2020). Prescriptions increased during summer 2020 (June 2020-September 2020) and fell below the pre-pandemic numbers during the following pandemic waves (October 2020 - February 2021 and March 2021 - June 2021). Breakpoints during the first wave indicate that prescriptions plummeted overall, in all clinical settings and in four of six geographic regions. Both, outpatient clinics and private practices prescribed overall as predicted. However, outpatient hospital clinics prescribed 17-39% less than predicted during the first pandemic wave. HCV treatment prescriptions declined but stayed within the lower realms of predicted counts. The strongest decline during the first pandemic wave indicates a temporary HCV treatment gap. Later, prescriptions matched predictions despite of pronounced decreases during the second and third waves. In future pandemics, clinics and private practices need to adapt more rapidly to maintain a continuous access to care. In addition, political strategies should focus more on continuously providing essential medical care during periods of restricted access due to infectious disease outbreaks. The observed decrease in HCV treatment may challenge reaching the HCV elimination goals in Germany by 2030.

Prevalence of Chlamydia trachomatis in the general population in Germany - a triangulation of data from two population-based health surveys and a laboratory sentinel system.

BACKGROUND: Chlamydia trachomatis (chlamydia) is a common, frequently asymptomatic, sexually transmitted infection. It can result in severe sequelae, such as ectopic pregnancy and infertility. In Germany, chlamydia is not notifiable. An opportunistic screening program for women < 25 years was introduced in 2008. The aim of this research was to triangulate different data sources to describe the epidemiological situation of chlamydia in Germany and to investigate whether the current target group of the chlamydia screening program aligns with these findings. METHODS: Urine specimens from participants from population-based health examination surveys of children (2014-17) and adults (2008-11) were tested for chlamydia, using nucleic acid amplification testing. These data were used to generate weighted chlamydia prevalence estimates by age group and sex. Data from a nationwide chlamydia laboratory sentinel system (2014-16) were used to calculate the positive proportion among individuals tested for chlamydia by age, sex and test reason. RESULTS: Using data from the population-based surveys, we found a chlamydia prevalence estimate of 2.8% (95% confidence interval (CI) 1.0-7.5%) among all 15- to 17-year-old girls and of 9.6% (95% CI 0.0-23) among those reporting to be sexually active. In adult women, we found the highest prevalence among 18- to 24-year-olds (all: 2.3%; 95% CI 1.0-5.3%; sexually active: 3.1%; 95% CI 1.3-7.0%). In adult men, we found the highest prevalence among 25- to 29-year-olds (all: 3.5%; 95% CI 1.6-7.7%; sexually active: 3.3%; 95% CI 1.3-7.8%). Data from the chlamydia laboratory sentinel showed the highest positive proportion among those opportunistically screened in 19-year-old women (6.1%; 95%- CI 5.9-6.4%), among those screened due to pregnancy in 15-year-old girls (10%; 95% CI 8.5-12%), and among those tested due to symptoms or a positive partner in 19-year-old women (10%; 95% CI 9.8-11%) and 19-year-old men (24%; 95% CI 22-26%). CONCLUSIONS: Chlamydia seems to mainly affect adolescents and young adults in Germany, with similar overall prevalence in men and women, but with slightly different age distributions. Women at highest risk of chlamydia are covered by the current screening program but given the on-going discussions in high-income countries on cost-effectiveness and benefit-to-harm ratio of these programs, the program-aim needs reconsideration.

Corrigendum: Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008-2019.

[This corrects the article DOI: 10.3389/fpubh.2021.667253.].

[Epidemiology of viral hepatitis A to E in Germany]. / Epidemiologie der Virushepatitiden A bis E in Deutschland.

Viral hepatitis A to E describes various infectious inflammations of the liver parenchyma that are caused by the hepatitis viruses A to E (HAV, HBV, HCV, HDV, and HEV). Although the clinical pictures are similar, the pathogens belong to different virus families and differ in terms of pathogenesis, transmission routes, clinical course, prevention, and therapy options. In Germany, there is mandatory reporting according to the Infection Protection Act (IfSG) for direct or indirect laboratory evidence and for suspicion, illness, and death of viral hepatitis. The data are transmitted to the Robert Koch Institute.In this article, on the basis of published studies and notification data, we describe the epidemiology of hepatitis A to E as well as current challenges and prevention approaches. In particular, the latter contains the improvement of existing vaccination recommendations (hepatitis A and B); improvement of access to prevention, testing, and care including therapy with antiviral drugs (hepatitis B, C, and D) and the detection and prevention of foodborne infections and outbreaks; and improvements in the field of food safety (hepatitis A and E).

[Hepatitis B virus infection and vaccine-induced immunity: the role of sociodemographic determinants : Results of the study "German Health Interview and Examination Survey for Adults" (DEGS1, 2008-2011)]. / Hepatitis-B-Virus-Infektionen und impfinduzierte Immunität: die Rolle von soziodemografischen Determinanten : Ergebnisse der "Studie zur Gesundheit Erwachsener in Deutschland" (DEGS1, 2008­2011).

BACKGROUND AND OBJECTIVE: Even though the prevalence of hepatitis B virus (HBV) infection in Germany is low, it is important to identify vulnerable groups and targeted approaches for infection prevention. Previous analyses from the "German Health Interview and Examination Survey for Adults" (DEGS1, 2008-2011) have shown that HBV infections and vaccination are associated with sociodemographic determinants. This paper examines the results in detail. MATERIALS AND METHODS: In the DEGS1, HBV serology was available for 7046 participants aged 18-79 years. HBV infection was defined by antibodies to hepatitis B core antigen (anti-HBc), vaccine-induced immunity by antibodies to hepatitis B surface antigen (anti-HBs) in the absence of other markers. Seroprevalences of HBV infection and vaccine-induced immunity were estimated stratified by sex, and associations with age, municipality size, income, formal education, health insurance and migration generation were analysed by logistic regression. RESULTS: In both sexes, HBV infection was independently associated with age groups 34-64 and ≥ 65 years, first migrant generation and living in larger municipalities as well as low income in men and low education in women. Vaccine-induced immunity was independently associated with age groups 18-33 and 34-64 years, middle and high education and high income in both sexes, middle income and private health insurance in men and having no migration background in women. CONCLUSIONS: HBV prevention measures should take into account migration status, income and education in order to focus prevention measures.

Markedly decreasing azithromycin susceptibility of Neisseria gonorrhoeae, Germany, 2014 to 2021.

We monitored antimicrobial susceptibility developments of Neisseria gonorrhoeae in Germany from January 2014 to May 2021. The proportion of isolates with azithromycin minimum inhibitory concentrations above the epidemiological cut-off increased substantially, from 1.3% in 2014 to 12.2% in 2020. Preliminary data from 2021 showed a further rise (January to May: 20.7%). Therefore, azithromycin as part of the recommended dual therapy in Germany for non-adherent patients is challenged. Antimicrobial susceptibility testing in clinical practice is crucial and continuous susceptibility surveillance indispensable.

Hepatitis B vaccination coverage in Germany: systematic review.

BACKGROUND: Despite being considered as a low prevalence country for hepatitis B (HBV), some populations in Germany are at higher risk of infection. In the context of the World Health Organization's (WHO) viral hepatitis elimination goals, a valid epidemiological data base is needed to plan and monitor the national response. Prevention strategies include general and targeted HBV vaccination programmes. OBJECTIVE: The aim of this work was to estimate the HBV vaccination coverage (VC) in the general population (GP) and different population groups in Germany from available evidence and to identify current evidence gaps for future research. METHODS: We conducted a systematic review on HBV VC in the general population and populations at high risk of HBV exposure or severe infection in Germany. We included eligible publications (01/01/2017 to 06/06/2020) from databases Embase, Pubmed and Livivo, from a previous scoping review (including data published 01/01/2005-17/03/2017), from the national surveillance system and screened the reference lists of all publications at full text level. Risk of bias was assessed using the Hoy et al. tool. RESULTS: We included 68 publications of 67 studies and assigned them to one or more suitable population groups. Twenty-one studies contained data among children/adolescents and three among adults from the GP (VC 65.8-90.5% and 22.9-52.1%, respectively), one among travelers (VC 89.0%), 13 among immunocompromised populations (VC 7.8-89.0%), 16 among populations with occupational risk and 16 with non-occupational risk of HBV exposure (VC 63.6-96.5% and 4.4-84.5%, respectively). CONCLUSION: Comprehensive evidence at low risk of bias was identified for children/adolescents. However, 25 years after including HBV in the national immunisation schedule, VC in Germany is still below the 95%-goal defined by WHO. For people at occupational risk of HBV exposure, VC was mostly reported to be over the WHO goal of 80%, but quality of evidence was heterogenous and should be improved. For people at non-occupational risk of HBV exposure, evidence was sparse and of low quality. The low VC highlights the need for future research to plan vaccination programmes targeting these populations.

Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008-2019.

Background: Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB) patients is unknown. We aimed to determine the number of CHB patients treated with nucleos(t)ide analogs (NUCs), the treatment costs within the statutory health insurance (SHI) in Germany and per patient per month. Methods: Data on pharmacy bills of NUCs to patients with SHI between 2008 and 2019 were purchased from Insight Health™ and described. Negative binomial regression was used for trend analysis. Results: Number of patients increased between 2008 and 2019 (4.9% per year) with little changes in treatment options. Overall prescription costs were increasing (6.7% per year on average) until the introduction of tenofovir and entecavir generics in 2017 after which costs decreased by 31% in 2019. Average therapy costs peaked at 498 Euro per patient per month in 2016 and decreased to 214 Euro in 2019. Prescriptions changed from 30 to 90 pills per pack over time. HBV therapy was prescribed to 97% by three medical specialist groups, mainly specialists in internal medicine (63%), followed by hospital-based outpatient clinics (20%) and general practitioners (15%). Contrary to guideline recommendation, adefovir was still prescribed after 2011 for 1-5% of patients albeit with decreasing tendency. Prescriptions per 100,000 inhabitants were highest in Berlin and Hamburg. Conclusion: Our data shows, that the number of treated CHB patients increased steadily, while NUC therapy costs decreased. We recommend continued testing and treatment for those eligible to prevent advanced liver disease and possibly decrease further transmission of HBV.

Hepatitis A outbreak among MSM in Berlin due to low vaccination coverage: Epidemiology, management, and successful interventions.

OBJECTIVES: To describe the characteristics of a large hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) in Berlin and to assess the impact of measures implemented. METHODS: Cases of laboratory-confirmed, symptomatic HAV infection notified in Berlin, Germany between August 2016 and February 2018 were analysed using routine and enhanced surveillance data including genotyping results. Several studies involving different groups of participants were conducted to further investigate the outbreak, including surveys on knowledge and practices of HAV vaccination among physicians and vaccination coverage and determinants of vaccination status among MSM. The measures implemented were categorized by target group in a Gantt chart. To assess their impact, health insurance data on HAV vaccination uptake were analysed, comparing Berlin and other federal states. RESULTS: During the outbreak period, a total of 222 cases were reported (of which 91 were sequence-confirmed), with a peak in case numbers in January 2017. Physicians were aware of the existing vaccination recommendations, but vaccination coverage among 756 MSM was low, with 32.7% being completely vaccinated and 17.3% being incompletely vaccinated before 2017. HAV vaccination before 2017 was associated with being born in Germany (odds ratio 2.36) and HIV-positive (odds ratio 1.80). HAV monovalent vaccination uptake increased by 164% from 2016 to 2017 among males in Berlin, compared to 7% in other federal states. CONCLUSIONS: Multiple measures targeting the MSM community, physicians, and public health to increase HAV vaccination uptake were successfully implemented. To prevent future HAV outbreaks, we recommend monitoring vaccination coverage among MSM, promoting awareness of existing recommendations among physicians, and ensuring access for foreign-born and young MSM.

[How to assess the elimination of viral hepatitis B, C, and D in Germany? Outcomes of an interdisciplinary workshop]. / Wie lässt sich die Eliminierung von Hepatitis B, C und D in Deutschland messen? Ergebnisse eines interdisziplinären Arbeitstreffens.

BACKGROUND: In 2016, the World Health Organization (WHO) released a strategy to eliminate hepatitis B, C, and D and defined indicators to monitor the progress. The Robert Koch Institute organized an interdisciplinary working meeting in 2019 to identify data sources and gaps. OBJECTIVES: The objectives were to network, to create an overview of the data sources available in Germany on hepatitis B and C, and to discuss how to construct indicators. MATERIALS AND METHODS: We extracted the WHO indicators relevant for Germany and determined how they can be constructed on the basis of available data. Stakeholders from public health services, clinics, laboratories, health insurance companies, research institutes, data holders, and registries attended a workshop and discussed methods of constructing the indicators for which data are lacking. Data sources and data were evaluated and prioritized with regard to their quality and completeness. RESULTS: Indicators on prevalence, incidence, prevention, testing and diagnosis, treatment, cure, burden of sequelae, and mortality for the general population can be constructed using secondary data such as diagnosis, health service, and registry data, data from laboratories and hospitals as well as population-based studies. Data sources for vulnerable groups are limited to studies among drug users, men who have sex with men, and about HIV coinfected patients. Data for migrants, prisoners, and sex workers are largely lacking as well as data on burden of disease from chronic viral hepatitis in the general population. CONCLUSIONS: We identified data sources, their limitations, and methods for construction for all selected indicators. The next step is to convert the ideas developed into concrete projects with individual stakeholders.

Molecular epidemiological typing of Neisseria gonorrhoeae isolates identifies a novel association between genogroup G10557 (G7072) and decreased susceptibility to cefixime, Germany, 2014 to 2017.

BackgroundEmerging antimicrobial resistance (AMR) challenges gonorrhoea treatment and requires surveillance.AimThis observational study describes the genetic diversity of Neisseria gonorrhoeae isolates in Germany from 2014 to 2017 and identifies N. gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroups associated with AMR or some patient demographics.Methods1,220 gonococcal isolates underwent AMR testing and NG-MAST. Associations between genogroups and AMR or sex/age of patients were statistically assessed.ResultsPatients' median age was 32 years (interquartile range: 25-44); 1,078 isolates (88.4%) originated from men. In total, 432 NG-MAST sequence types including 156 novel ones were identified, resulting in 17 major genogroups covering 59.1% (721/1,220) of all isolates. Genogroups G1407 and G10557 (G7072) were significantly associated with decreased susceptibility to cefixime (Kruskal-Wallis chi-squared: 549.3442, df: 16, p < 0.001). Their prevalences appeared to decline during the study period from 14.2% (15/106) to 6.2% (30/481) and from 6.6% (7/106) to 3.1% (15/481) respectively. Meanwhile, several cefixime susceptible genogroups' prevalence seemed to increase. Proportions of isolates from men differed among genogroups (Fisher's exact test, p < 0.001), being e.g. lower for G25 (G51) and G387, and higher for G5441 and G2992. Some genogroups differed relative to each other in affected patients' median age (Kruskal-Wallis chi-squared: 47.5358, df: 16, p < 0.001), with e.g. G25 (G51) and G387 more frequent among ≤ 30 year olds and G359 and G17420 among ≥ 40 year olds.ConclusionAMR monitoring with molecular typing is important. Dual therapy (ceftriaxone plus azithromycin) recommended in 2014 in Germany, or only the ceftriaxone dose of this therapy, might have contributed to cefixime-resistant genogroups decreasing.

Prevalence of Hepatitis B, C, and D in Germany: Results From a Scoping Review.

Background: One of the five strategic directions in the World Health Organization global health sector strategy on viral hepatitis 2016-2021 is to generate strong strategic information for focused action to understand the viral hepatitis epidemic and focus the response. Knowledge of national prevalence is a cornerstone of strategic information. Germany is considered to be a low prevalence country for viral hepatitis B, C, and D, however the prevalence is likely to be higher among at-risk groups. Methods: The aim of this work was to give a detailed overview of the prevalence of viral hepatitis B (HBsAg, anti-HBc), C (anti-HCV, HCV RNA), and D (anti-HDV, HDV RNA) in different population groups in Germany. Therefore, we analyzed the results of a comprehensive literature search on various aspects of the epidemiological situation of hepatitis B, C, and D in Germany. Eligible publications including information on hepatitis B, C, and D prevalence were extracted from the overall spreadsheet table and summarized and analyzed based on virus and different population groups. A quality appraisal was performed using a checklist developed by Hoy et al. to assess risk of bias in prevalence studies. Results: Overall, 51 publications were identified through the literature search. The overall prevalence of HBsAg in the general (and proxy) population ranged from 0.3 to 1.6%. Among at-risk groups, including clinical populations and health care workers, the HBsAg prevalence ranged from 0.2% (among rheumatic patients) to 4.5% among HIV positive patients. The overall prevalence of anti-HCV in the general (and proxy) population ranged from 0.2 to 1.9%. Among at-risk groups, including clinical populations and health care workers, the anti-HCV prevalence ranged from 0.04% (among health care workers) to 68.0% among people who inject drugs. Conclusions: The hepatitis B and C prevalence in the general population in Germany is low. Prevalence is high to very high among at-risk populations, however for some groups evidence was incomplete or missing completely. To reach the elimination goals in Germany and implement a targeted response, more research among at-risk groups is needed.

[How well is the screening of pregnant women for HIV, syphilis, and hepatitis B implemented in Germany? An analysis based on routine data]. / Gelingt das Screening von Schwangeren auf HIV, Syphilis und Hepatitis B in Deutschland? Eine Analyse auf Basis von Routinedaten.

BACKGROUND: Infections during pregnancy are one of the leading causes of increased morbidity and mortality in mothers and their newborns worldwide. In Germany, there has been standardized healthcare for pregnancy for more than 50 years. The maternity guidelines of the Joint Federal Committee form the legal framework for this and include the screening of pregnant women for HIV, syphilis, and hepatitis B, among other things. AIM OF THE WORK: The aim of this work is to determine the extent to which screening is covered by the German population. MATERIAL AND METHODS: With the help of anonymized routine data of legally insured persons available to the Institut für angewandte Gesundheitsforschung Berlin GmbH (InGef) from 2011 to 2015, a definition of pregnancy was developed with the use of various ICD-10 and EBM codes and the first evaluation of the use of tests for infectious agents in pregnancy was carried out. RESULTS: The high proportion of women who are tested for syphilis (95.3%) and hepatitis B (91.6%) during pregnancy indicates very good accessibility and use of prenatal screening services. For HIV, the proportion of women tested is significantly lower (84.9%). DISCUSSION: Whether pregnant women refuse an HIV test, the test was performed elsewhere, or not recommended by the medical staff cannot be clarified on the basis of the available data. In view of the highly effective medical intervention options for syphilis, HIV, and hepatitis B, the aim should be to test pregnant women in Germany as completely as possible. The reasons for the lack of screening must be further investigated and starting points for increasing the use must be identified.

External quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in primary laboratories in Germany.

BACKGROUND: Worldwide, an increase in antimicrobial resistance (AMR) of Neisseria gonorrhoeae has been observed. Until now, no protocol for an external quality assessment (EQA) has been available for Germany. The German gonococcal resistance network (GORENET) performed an EQA of primary laboratories in Germany in order to assess quality of antibiotic susceptibility testing, to gain information about laboratory procedures and to assess the impact of these procedures on test results. METHODS: Laboratories assessed drug susceptibility to cefixime, ceftriaxone, azithromycin, penicillin and ciprofloxacin for five N. gonorrhoeae strains, using their standard laboratory protocols. Minimal inhibitory concentrations (MICs) were compared to World Health Organisation (WHO) consensus results (or, if not available, reference laboratory results), while deviation by +/- one doubling dilution was accepted. Data on laboratory procedures were collected via a standardised questionnaire. Generalized linear models and conditional inference trees (CTREE) were used to assess relationships between laboratory procedures and testing outcomes. RESULTS: Twenty-one primary laboratories participated in the EQA in June 2018. 96% of ciprofloxacin MICs were reported within accepted deviations, as well as 88% for cefixime, 85% for ceftriaxone, 79% for penicillin and 70% for azithromycin. The use of interpretation standards and general laboratory procedures like agar base, incubation settings or the use of control strains strongly differed between laboratories. In statistical analysis, incubation time of cultures < 24 h was associated with correct measurements. Additionally, a 5% CO2 concentration was associated with correct results regarding azithromycin compared to 3%. CTREE analysis showed that incubation time, humidity and CO2 concentration had the greatest influence on the average deviation from consensus results. CONCLUSIONS: In conclusion, we report the development of a protocol for N. gonorrhoeae antimicrobial susceptibility testing in Germany. While testing results were in accordance with the expected consensus results in 70-96%, depending on the antibiotic agent, laboratory methodology was heterogeneous and may significantly affect the testing quality. We therefore recommend the development of a standard operating procedure (SOP) for N. gonorrhoeae susceptibility testing in Germany.

The epidemiology of Hepatitis B, C and D in Germany: A scoping review.

BACKGROUND: Germany is considered to be a low prevalence country for viral Hepatitis B, C and D (HBV, HCV, HDV). However, the burden of disease can be high among subpopulations. To meet the world Health Organization (WHO) viral hepatitis (VH) elimination goals, a national strategy was developed by the German government in 2016. We performed a scoping review to understand the baseline epidemiological situation in Germany regarding burden of disease, sequelae and care of HBV, HCV and HDV as a reference to monitor the progress of the national VH elimination and to identify further knowledge gaps and research needs. METHODS: The protocol of the systematic review was prepared following the PRISMA statement guidelines for scoping reviews. Relevant search terms were used to identify eligible studies according to the research questions. We searched six online databases for original work published between January 2005 and March 2017. Based on the identified references, a matrix was developed presenting the eligible literature by targeted population group and outcome category. RESULTS: 104 publications were eligible for extraction covering 299 outcome results. The population groups targeted in the identified studies included the general population and proxy populations, a range of clinical populations, people who inject drugs, men who have sex with men, healthcare workers, people in prisons and different migrant/mobile populations. Other vulnerable populations (e.g. sex workers) were not targeted. Overall, good evidence was found for HBV and HCV prevalence and HBV vaccination coverage in the GP and proxy populations. Evidence for these outcomes was weaker in populations at risk for VH. For HBV and HCV incidence and mortality, we identified large evidence gaps in all population groups. Outcomes on VH sequelae and care were mainly covered by studies in clinical populations of people living with viral hepatitis. For HDV the overall evidence available was scarce. CONCLUSIONS: We created a comprehensive evidence-based overview on the current epidemiological situation of viral hepatitis in Germany. We identified knowledge gaps for further research and established a baseline for future monitoring of viral hepatitis elimination goals in Germany.