Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands.

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed.

Hepatitis B/C in the countries of the EU/EEA: a systematic review of the prevalence among at-risk groups.

BACKGROUND: In 2016, the World Health Organisation set a goal to eliminate viral hepatitis by 2030. Robust epidemiological information underpins all efforts to achieve elimination and this systematic review provides estimates of HBsAg and anti-HCV prevalence in the European Union/European Economic Area (EU/EEA) among three at-risk populations: people in prison, men who have sex with men (MSM), and people who inject drugs (PWID). METHODS: Estimates of the prevalence among the three risk groups included in our study were derived from multiple sources. A systematic search of literature published during 2005-2015 was conducted without linguistic restrictions to identify studies among people in prison and HIV negative/HIV sero-status unknown MSM. National surveillance focal points were contacted to validate the search results. Studies were assessed for risk of bias and high quality estimates were pooled at country level. PWID data were extracted from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) repository. RESULTS: Despite gaps, we report 68 single study/pooled HBsAg/anti-HCV prevalence estimates covering 23/31 EU/EEA countries, 42 of which were of intermediate/high prevalence using the WHO endemicity threshold (of ≥2%). This includes 20 of the 23 estimates among PWID, 20 of the 28 high quality estimates among people in prison, and four of the 17 estimates among MSM. In general terms, the highest HBsAg prevalence was found among people in prison (range of 0.3% - 25.2%) followed by PWID (0.5% - 6.1%) and MSM (0.0% - 1.4%). The highest prevalence of anti-HCV was also found among people in prison (4.3% - 86.3%) and PWID (13.8% - 84.3%) followed by MSM (0.0% - 4.7%). CONCLUSIONS: Our results suggest prioritisation of PWID and the prison population as the key populations for HBV/HCV screening and treatment given their dynamic interaction and high prevalence. The findings of this study do not seem to strongly support the continued classification of MSM as a high risk group for chronic hepatitis B infection. However, we still consider MSM a key population for targeted action given the emerging evidence of viral hepatitis transmission within this risk group together with the complex interaction of HBV/HCV and HIV.

Trends and determinants of antimicrobial susceptibility of Neisseria gonorrhoeae in the Netherlands, 2007 to 2015.

BackgroundNeisseria gonorrhoeae antibiotic resistance surveillance is important to maintain adequate treatment. We analysed 2007-15 data from the Gonococcal Resistance to Antimicrobials Surveillance (GRAS), which currently includes 19 of 25 sexually transmitted infection (STI) centres in the Netherlands. Methods: From each patient with a gonorrhoea culture, the minimum inhibitory concentration (MIC) for several antibiotics was determined. Time trends were assessed by geometric means and linear regression of logarithmic MIC. Determinants for decreased susceptibility to ceftriaxone (MIC > 0.032 mg/L) and resistance to cefotaxime (MIC > 0.125 mg/L) and azithromycin (MIC > 0.5 mg/L) were assessed using stratified logistic regression. Results: 11,768 isolates were analysed. No ceftriaxone resistance was found. In 2015, 27 of 1,425 isolates (1.9%) were resistant to cefotaxime and 176 of 1,623 (10.9%) to azithromycin. Ceftriaxone susceptibility showed no trend (p = 0.96) during the study period, but cefotaxime MIC decreased (p < 0.0001) and azithromycin MIC increased (p < 0.0001) significantly. Concerning ceftriaxone, isolates of men who have sex with men (MSM) from 2013 (p = 0.0005) and 2014 (p = 0.0004) were significantly associated with decreased susceptibility. Significant determinants for cefotaxime resistance were having ≥ 6 partners for women (p = 0.0006). For azithromycin,isolates from MSM collected in 2012 (p = 0.0035), 2013 (p = 0.012), and 2014 (p = 0.013), or from non-Dutch (p < 0.0001) or older (≥ 35 years; p = 0.01) MSM were significantly associated with susceptibility. Resistance in heterosexual men was significantly associated with being ≥ 25 years-old (p = 0.0049) or having 3-5 partners (p = 0.01). Conclusions: No ceftriaxone resistance was found, but azithromycin MIC increased in 2007-15. Resistance determinants could help with focused intervention strategies.

Education pathways and key tasks for research nurses in Europe, results from a VACCELERATE online survey.

AIM: This article aims to provide a comprehensive overview of the educational pathways and responsibilities of research nurses in Europe, particularly focusing on their essential role in conducting research in clinical settings, including clinical trials, while adhering to ethical and regulatory standards. BACKGROUND: Research nurses play a crucial role in clinical research settings, especially in clinical trials, ensuring adherence to ethical and regulatory standards. Understanding their educational pathways and responsibilities is essential for promoting consistency and quality in research practices across Europe. DESIGN: Between October and November 2022, relevant European nursing education authorities, including those focused on research nursing, were contacted to participate in an online cross-sectional survey. The survey aimed to gather information about research nurse education and training in their respective countries. METHODS: The study followed a cross-sectional design. Contacts were made with European nursing education authorities based on recommendations from the VACCELERATE National Coordinators and the VACCELERATE Site Network. Participating organizations were invited to complete an online survey regarding research nurse education in their countries. RESULTS: Responses were obtained from 37 European countries, a response rate of 74%. The most common terms used to refer to nurses involved in clinical trials and epidemiological studies were "study nurse" (62%) and "clinical research nurse" and "research nurse" (43% each). The requirements to become a research nurse varied across countries, with a nursing degree necessary in 87% of countries and Good Clinical Practice (GCP) courses mandatory in 81%. Local providers of research nurse courses existed in 84% of countries, coordinated by online organisations (51%) or universities/hospitals (46%). The most common tasks assigned to research nurses were the administration of investigational medicinal products (from 78% in observational studies to 89% in phase IV trials) and blood sample processing (84% in phase II and IV trials). CONCLUSIONS: This study provides valuable insights into research nurse education and tasks in European countries. It highlights the need for standardisation to enhance consistency and quality of training across Europe.

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe.

BACKGROUND: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. METHODS: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. RESULTS: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. CONCLUSIONS: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit.

BACKGROUND: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials.