Acceptance and feasibility of a low-threshold and substitution services-based periodical monitoring system for blood-borne and sexually transmitted infections among people who inject drugs in Germany: a mixed-methods analysis.

BACKGROUND: To reach the global elimination goals of viral hepatitis B and C (HBC, HCV), human immunodeficiency virus (HIV) and other sexually transmitted infections as a public health threat by 2030, monitoring is needed. Staff members of drug services and opioid substitution treatment (OST) practices in Berlin and Bavaria recruited clients for a pilot study addressing the respective infections among people who injected drugs (PWID) in Germany, 2021/2022. Participants filled a questionnaire and were tested for HBV, HCV, HIV and syphilis using dried blood spots (DBS). We evaluated the study design to implement a feasible and accepted nationwide periodical monitoring among PWID and serve as an example for the implementation of similar monitoring systems in other countries. METHODS: A mixed-methods design was used, including focus group discussions with study participants and staff members and a semi-quantitative questionnaire filled by the latter. Aspects covered were the setting for recruitment, study preparation for staff members, willingness of clients to participate, the study questionnaire, blood collection and return of results. RESULTS: The majority (96%) of 668 study participants were recruited in low-threshold services, drug consumption rooms and OST-practices. Flexibility of recruiting study participants during routine work or testing weeks/days was important to the facilities. Collaborations with local AIDS services helped cope with the work load of data collection. The need to train staff for DBS collection was highlighted. Study participants welcomed the testing opportunity in familiar places. Study participants frequently needed assistance to complete the study questionnaire. Return of results was considered as ethically mandatory by staff members but referral to treatment remained challenging. CONCLUSIONS: For a successful monitoring time flexibility and adequate training are essential. Individual benefits for study participants by receiving their test results should be ensured and referral networks with infectiology practices may increase number of infected PWID receiving treatment. Overall, the evaluation confirmed that a monitoring through drug services and OST-practices is feasible and well accepted in Germany. Beyond that it shows important lessons learnt for the implementation in other countries.

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.

COVID-19 cross-border case and contact tracing activities - experiences and lessons learnt, Germany, April-December 2020.

BACKGROUND: Interruption of transmission chains has been crucial in the COVID-19 response. The Emergency Operations Centre (EOC) at the Robert Koch Institute (RKI) coordinated cross-border case and contact tracing activities at the national level by sharing data with German public health authorities (PHA) and other countries. Data on these activities were not collected in the national surveillance system, and thus were challenging to quantify. Our aim was to describe cross-border COVID-19 case and contact tracing activities including lessons learnt by PHA to adapt the procedures accordingly. METHODS: Case and contact tracing events were recorded using unique identifiers. We collected data on cases, contacts, dates of exposure and/or SARS-CoV-2 positive test results and exposure setting. We performed descriptive analyses of events from 06.04.-31.12.2020. We conducted interviews with PHA to understand experiences and lessons learnt, applying a thematic approach for qualitative analysis. RESULTS: From 06.04.-31.12.2020 data on 7,527 cross-border COVID-19 case and contact tracing activities were collected. Germany initiated communication 5,200 times, and other countries 2,327 times. Communication from other countries was most frequently initiated by Austria (n = 1,184, 50.9%), Switzerland (n = 338, 14.5%), and the Netherlands (n = 168, 7.2%). Overall, 3,719 events (49.4%) included information on 5,757 cases (median 1, range: 1-42), and 4,114 events (54.7%) included information on 13,737 contacts (median: 1, range: 1-1,872). The setting of exposure was communicated for 2,247 of the events (54.6%), and most frequently included private gatherings (35.2%), flights (24.1%) and work-related meetings (20.3%). The median time delay between exposure date and contact information receipt at RKI was five days. Delay between positive test result and case information receipt was three days. Main challenges identified through five interviews were missing data or delayed accessibility particularly from flights, and lack of clear and easy to use communication channels. More and better trained staff were mentioned as ideas for improving future pandemic response preparedness. CONCLUSION: Cross-border case and contact tracing data can supplement routine surveillance but are challenging to measure. We need improved systems for cross-border event management, by improving training and communication channels, that will help strengthen monitoring activities to better guide public health decision-making and secure a good future pandemic response.

A shift from travel-associated cases to autochthonous transmission with Berlin as epicentre of the monkeypox outbreak in Germany, May to June 2022.

By 22 June 2022, 521 cases of monkeypox were notified in Germany. The median age was 38 years (IQR: 32-44); all cases were men. In Berlin, where 69% of all cases occurred, almost all were men who have sex with men. Monkeypox virus likely circulated unrecognised in Berlin before early May. Since mid-May, we observed a shift from travel-associated infections to mainly autochthonous transmission that predominantly took place in Berlin, often in association with visits to clubs and parties.

Geographical differences of carbapenem non-susceptible Enterobacterales and Acinetobacter spp. in Germany from 2017 to 2019.

BACKGROUND: Since May 2016, infection and colonisation with carbapenem non-susceptible Acinetobacter spp. (CRA) and Enterobacterales (CRE) have to be notified to health authorities in Germany. The aim of our study was to assess the epidemiology of CRA and CRE from 2017 to 2019 in Germany, to identify risk groups and to determine geographical differences of CRA and CRE notifications. METHODS: Cases were notified from laboratories to local public health authorities and forwarded to state and national level. Non-susceptibility was defined as intermediate or resistant to ertapenem, imipenem, or meropenem excluding intrinsic bacterial resistance or the detection of a carbapenemase gene. We analysed CRA and CRE notifications from 2017, 2018 and 2019 per 100,000 inhabitants (notification incidence), regarding their demographic, clinical and laboratory information. The effect of regional hospital-density on CRA and CRE notification incidence was estimated using negative binomial regression. RESULTS: From 2017 to 2019, 2278 CRA and 12,282 CRE cases were notified in Germany. CRA and CRE cases did not differ regarding demographic and clinical information, e.g. proportion infected. The notification incidence of CRA declined slightly from 0.95 in 2017 to 0.86 in 2019, whereas CRE increased from 4.23 in 2017 to 5.72 in 2019. The highest CRA and CRE notification incidences were found in the age groups above 70 years. Infants below 1 year showed a high CRE notification incidence, too. Notification incidences varied between 0.10 and 2.86 for CRA and between 1.49 and 9.99 for CRE by federal state. The notification incidence of CRA and CRE cases increased with each additional hospital per district. CONCLUSION: The notification incidence of CRA and CRE varied geographically and was correlated with the number of hospitals.The results support the assumption that hospitals are the main driver for higher CRE and CRA incidence. Preventive strategies and early control measures should target older age groups and newborns and areas with a high incidence.

[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 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.

COVID-19: cross-border contact tracing in Germany, February to April 2020.

IntroductionThe Robert Koch Institute (RKI) managed the exchange of cross-border contact tracing data between public health authorities (PHA) in Germany and abroad during the early COVID-19 pandemic.AimWe describe the extent of cross-border contact tracing and its challenges.MethodsWe analysed cross-border COVID-19 contact tracing events from 3 February to 5 April 2020 using information exchanged through the European Early Warning Response System and communication with International Health Regulation national focal points. We described events by PHA, number of contacts and exposure context.ResultsThe RKI processed 467 events, initiating contact to PHA 1,099 times (median = 1; interquartile range (IQR): 1-2) and sharing data on 5,099 contact persons. Of 327 (70%) events with known exposure context, the most commonly reported exposures were aircraft (n = 64; 20%), cruise ships (n = 24; 7%) and non-transport contexts (n = 210; 64%). Cruise ship and aircraft exposures generated more contacts with authorities (median = 10; IQR: 2-16, median = 4; IQR: 2-11) and more contact persons (median = 60; IQR: 9-269, median = 2; IQR: 1-3) than non-transport exposures (median = 1; IQR: 1-6 and median = 1; IQR: 1-2). The median time spent on contact tracing was highest for cruise ships: 5 days (IQR: 3-9).ConclusionIn the COVID-19 pandemic, cross-border contact tracing is considered a critical component of the outbreak response. While only a minority of international contact tracing activities were related to exposure events in transport, they contributed substantially to the workload. The numerous communications highlight the need for fast and efficient global outbreak communication channels between PHA.

[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.

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.

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.

STI in times of PrEP: high prevalence of chlamydia, gonorrhea, and mycoplasma at different anatomic sites in men who have sex with men in Germany.

BACKGROUND: Men who have sex with men (MSM) are disproportionally affected by sexually transmitted infections (STI). STI are often extragenital and asymptomatic. Both can delay diagnosis and treatment. Approval of HIV pre-exposure prophylaxis (PrEP) might have influenced sexual behaviour and STI-prevalence of HIV- MSM. We estimated STI-prevalence and risk factors amongst HIV- and HIV+ MSM in Germany to plan effective interventions. METHODS: We conducted a nationwide, cross-sectional study between February and July 2018. Thirteen MSM-friendly STI-practices screened MSM for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV) using self-collected rectal and pharyngeal swabs, and urine samples. APTIMA™ STI-assays (Hologic™ Inc., San Diego, USA) were used for diagnostics, and samples were not pooled. We collected information on socio-demographics, HIV-status, clinical symptoms, sexual behaviour within the last 6 months, and PrEP use. We combined HIV status and PrEP use for defining risk groups, and used directed acyclic graphs and multivariable logistic regression to identify risk factors for STI. RESULTS: Two thousand three hundred three MSM were included: 50.5% HIV+, median age 39 [18-79] years. Median number of male sex partners within the last 6 months was five. Sex without condom was reported by 73.6%, use of party drugs by 44.6%. 80.3% had a STI history, 32.2% of STI+ MSM reported STI-related symptoms. 27.6% of HIV- MSM used PrEP. Overall STI-prevalence was 30.1, 25.0% in HIV-/PrEP- MSM (CT:7.2%; MG:14.2%; NG:7.4%; TV:0%), 40.3% in HIV-/PrEP+ MSM (CT:13.8%; MG:19.4%; NG:14.8%; TV:0.4%), and 30.8% in HIV+ MSM (CT:10.1%; MG:18.4%; NG:8.6%; TV:0.1%). Being HIV+ (OR 1.7, 95%-CI 1.3-2.2), using PrEP (OR 2.0, 95%-CI 1.5-2.7), having > 5 sex partners (OR:1.65; 95%-CI:1.32-2.01.9), having condomless sex (OR:2.11.9; 95%-CI:1.65-2.86), and using party drugs (OR:1.65; 95%-CI:1.32-2.0) were independent risk factors for being tested positive for at least one STI. CONCLUSIONS: We found a high STI-prevalence in MSM in Germany, especially in PrEP users, frequently being asymptomatic. As a relevant proportion of PrEP users will not use a condom, counselling and comprehensive STI screening is essential and should be low threshold and preferably free of cost. Counselling of PrEP users should also address use of party drugs.

Overestimation of an Outbreak of Enterobacter cloacae in a Neonatal Intensive Care Unit in Germany, 2015.

BACKGROUND: In August 2015, 17 neonates with Enterobacter cloacae (E. cloacae) colonization were identified in a neonatal intensive care unit (NICU) in Germany. Two developed severe brain abscesses. Despite temporary NICU closure in September, another infant with E. cloacae colonization was detected in October 2015. METHODS: We defined potential cases as inpatients treated in the NICU or any pediatric/maternity ward in 2015 with E. cloacae in any specimen before molecular typing. Cases were at first confirmed by arbitrarily-primed-polymerase-chain-reaction and later by XbaI-macrorestriction/pulsed-field gel electrophoresis and next-generation-sequencing. Enhanced barrier precautions and cohorting were implemented for all potential cases and microbiologic screening was extended from NICU to all pediatric/maternity wards. RESULTS: Of 41 potential cases (occurring between 08/04/2015 and 15/11/2015 in 4 wards), the isolates of 23 shared identical arbitrarily-primed-polymerase-chain-reaction patterns; 3 without plausible epidemiologic link. Pulsed-field gel electrophoresis analyses verified only 10 cases (all in the NICU); next-generation-sequencing analysis confirmed these results. In addition 6 cases without isolates available for genotyping were closely linked in place and time. CONCLUSIONS: Forty-one suspected patients were cohorted and the NICU was temporarily closed. Further analyses revealed that only 16 cases belonged to the outbreak. Only close interdisciplinary collaboration and highly discriminatory genotyping methods allowed to clearly differentiate between cases and noncases in this E. cloacae outbreak.

LINE-1 retrotransposition events affect endothelial proliferation and migration.

Long interspersed nuclear element-1 (LINE-1, L1) is a retrotransposon which affects the human genome by a variety of mechanisms. While LINE-1 expression is suppressed in the most somatic human cells, LINE-1 elements are activated in human cancer. Recently, high accumulation of LINE-1-encoded ORF1p and ORF2p in endothelial cells of mature human blood vessels was described. Here, we demonstrate that LINE-1 de novo retrotransposition events lead to a reduction of endothelial cell proliferation and migration in a porcine aortic endothelial (PAE) cell model. Cell cycle studies show a G0/G1 arrest in PAE cells harboring LINE-1 de novo retrotransposition events. Remarkably, in in situ analysis LINE-1-encoded ORF2p was not detectable in tumor blood vessels of different human organs while vascular endothelial cells of corresponding normal organs strongly expressed LINE-1 ORF2p. Quantitative RT-PCR analysis revealed that LINE-1 de novo retrotransposition influences selectively the expression of some angiogenic factors such as VEGF and Tie-2. Thus, our data suggest that LINE-1 de novo retrotransposition events might suppress angiogenesis and tumor vascularisation by reducing the angiogenic capacity of vascular endothelial cells.