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Genomic surveillance of STEC/EHEC infections in Germany 2020 to 2022 permits insight into virulence gene profiles and novel O-antigen gene clusters
Shiga toxin-producing E. coli (STEC), including the subgroup of enterohemorrhagic E. coli (EHEC), are important bacterial pathogens which cause diarrhea and the severe clinical manifestation hemolytic uremic syndrome (HUS). Genomic surveillance of STEC/EHEC is a state-of-the-art tool to identify infection clusters and to extract markers of circulating clinical strains, such as their virulence and resistance profile for risk assessment and implementation of infection prevention measures. The aim of the study was characterization of the clinical STEC population in Germany for establishment of a reference data set. To that end, from 2020 to 2022 1257 STEC isolates, including 39 of known HUS association, were analyzed and lead to a classification of 30.4 % into 129 infection clusters. Major serogroups in all clinical STEC analyzed were O26, O146, O91, O157, O103, and O145; and in HUS-associated strains were O26, O145, O157, O111, and O80. stx1 was less frequently and stx2 or a combination of stx, eaeA and ehxA were more frequently found in HUS-associated strains. Predominant stx gene subtypes in all STEC strains were stx1a (24 %) and stx2a (21 %) and in HUS-associated strains were mainly stx2a (69 %) and the combination of stx1a and stx2a (12.8 %). Furthermore, two novel O-antigen gene clusters (RKI6 and RKI7) and strains of serovars O45:H2 and O80:H2 showing multidrug resistance were detected. In conclusion, the implemented surveillance tools now allow to comprehensively define the population of clinical STEC strains including those associated with the severe disease manifestation HUS reaching a new surveillance level in Germany.Peer Reviewe
The implementation of a new measles vaccine mandate in Germany: A qualitative study in local health departments
Background:
Measles is a highly contagious disease with the potential for severe complications. Despite the availability of effective vaccines, there have been recurrent measles outbreaks in Germany over the past decades. In response, a new measles vaccine mandate was introduced on March 1, 2020, aimed at closing vaccination gaps in high-risk populations. This study evaluates the mandate’s implementation, identifies operational challenges, assesses the impact of the Coronavirus disease 2019 pandemic, and investigates expert attitudes towards the new policy.
Methods:
Semi-structured expert interviews were conducted with staff members of 16 different local health departments in Germany. The interviews, carried out in April and May 2021, were electronically recorded, transcribed verbatim, and analyzed using the Framework method.
Results:
The implementation of the measles vaccine mandate in local health departments varied substantially. Challenges in implementing the mandate primarily arose from uncertainties regarding procedural specifics, such as handling fraudulent medical certificates and imposing sanctions, leading to a call from many interviewees for uniform guidelines to ensure coherent implementation. At the time the measles vaccine mandate came into force, managing the Coronavirus disease 2019 pandemic was a priority in most local health departments, often delaying the implementation of the mandate. Despite the difficulties encountered, most experts considered the mandate to be an effective step towards measles elimination.
Conclusions:
The measles vaccine mandate has imposed a new responsibility on staff in German local health departments, which is associated with implementation challenges such as procedural uncertainties and vaccine hesitancy, but also the Coronavirus disease 2019 pandemic as a contextual impediment. Significant differences in the implementation approach underscore the need for harmonization to enhance implementation efficiency and public acceptance of the mandate. Despite the mandate’s potential to increase vaccination rates, our findings advocate for a comprehensive approach, incorporating public education, accessible vaccination, and measures to address social disparities.Peer Reviewe
Evaluation of mpox contact tracing activities and data collection in EU/EEA countries during the 2022 multicountry outbreak in nonendemic countries
To control human-to-human mpox transmission during the 2022 outbreak, European Union (EU)/European Economic Area (EEA) countries conducted case investigation and contact tracing (CT). We aimed to provide an overview of CT activities, describe CT data collection practices, and identify related facilitators, barriers, and potential opportunities for improvement. Between April 03, 2023 and May 12, 2023, a survey was distributed to CT stakeholders in 30 EU/EEA countries, asking about mpox CT activities and data collection and requesting to rank enablers, barriers, and improvements for CT on a five-point Likert scale. The 139 respondents from 27 countries indicated having performed case investigations (96%, n = 133), backward CT (88%, n = 122), forward CT (87%, n = 121), and follow-up on contacts' outcomes (77%, n = 107). Sixty percent (n = 80/134) used standardized data collection forms and 73% (n = 91/124) used databases. The highest-rated enablers were clear guidelines (mean = 3.9), quick access to laboratory results (3.6), and sufficient expertise (3.6). Highly rated barriers were inability to contact contacts (3.0) or cases (2.5) and lack of staff (2.4). The most needed improvements were availability of staff (3.5), expertise on affected populations (3.4) and data reporting tools and systems (3.3). To improve CT of mpox and diseases with similar transmission patterns, EU/EEA countries should increase workforce capacity in public and sexual health, offer training on CT operations and communication with affected communities, and use common CT data collection tools and systems.Peer Reviewe
Combining RNA Interference and RIG-I Activation to Inhibit Hepatitis E Virus Replication
Hepatitis E virus (HEV) poses a significant global health threat, with an estimated 20 million infections occurring annually. Despite being a self-limiting illness, in most cases, HEV infection can lead to severe outcomes, particularly in pregnant women and individuals with pre-existing liver disease. In the absence of specific antiviral treatments, the exploration of RNAi interference (RNAi) as a targeted strategy provides valuable insights for urgently needed therapeutic interventions against Hepatitis E. We designed small interfering RNAs (siRNAs) against HEV, which target the helicase domain and the open reading frame 3 (ORF3). These target regions will reduce the risk of viral escape through mutations, as they belong to the most conserved regions in the HEV genome. The siRNAs targeting the ORF3 efficiently inhibited viral replication in A549 cells after HEV infection. Importantly, the siRNA was also highly effective at inhibiting HEV in the persistently infected A549 cell line, which provides a suitable model for chronic infection in patients. Furthermore, we showed that a 5′ triphosphate modification on the siRNA sense strand activates the RIG-I receptor, a cytoplasmic pattern recognition receptor that recognizes viral RNA. Upon activation, RIG-I triggers a signaling cascade, effectively suppressing HEV replication. This dual-action strategy, combining the activation of the adaptive immune response and the inherent RNAi pathway, inhibits HEV replication successfully and may lead to the development of new therapies.Peer Reviewe
How do national immunization technical advisory groups assess and use evidence: Findings from the SYSVAC survey
National immunization technical advisory groups (NITAGs) develop evidence-based vaccination recommendations. Systematic reviews (SRs) are important tools in that process, but conducting them is very resource-intensive. Given the considerable number of immunization-related SRs published and to minimize duplication of effort, a more practical approach for NITAGs is to use existing SRs. Among multiple initiatives and resources to strengthen NITAGs, the freely accessible SYSVAC registry supports NITAGs in identifying suitable SRs when developing vaccination recommendations. Additional SYSVAC courses provide step-by-step training on how to use SRs.
This cross-sectional survey was conducted online and involved 108 participants globally. The aim was to explore NITAGs user experience with evidence retrieval, to assess impact and use of the SYSVAC resources and training needs. Data were collected using a structured questionnaire.
Most of the respondents were > 45 years old (75.9%) and represented 50 NITAGs from all six World Health Organization (WHO) regions. In total, 13/50 NITAGs (26.0%) had ease accessing full text publications. The preferred data sources to search for evidence were peer reviewed literature via PubMed and the WHO website (Strategic Advisory Group of Experts – SAGE – on Immunization). When developing vaccination recommendations, respondents stated using SRs mostly conducted by SAGE, other institutions or NITAGs (83.2%), recommendations of other countries (79.4%) and primary studies (73.8%). Respondents from 35 NITAGs stated to use the SYSVAC registry to search for evidence, leading to ≥69 recommendations being developed by NITAGs globally with its support. Aside existing SYSVAC courses on SR use, there was great interest in training on SR use in the development of vaccination recommendations.
Our survey gathered information on evidence use and training needs. Survey results serve as a starting point to improve support of NITAGs in developing recommendations.Peer Reviewe
Effectiveness of XBB.1.5 Vaccines Against Symptomatic SARS-CoV-2 Infection in Older Adults During the JN.1 Lineage-Predominant Period, European VEBIS Primary Care Multicentre Study, 20 November 2023–1 March 2024
We estimated XBB.1.5 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection among adults aged ≥ 65 years during the 2023/2024 JN.1 lineage-predominant period in a European multi-country test-negative case–control study at primary care level. We estimated VE adjusted by study site, age, sex, chronic conditions and onset date. We included 220 cases and 1733 controls. The VE was 48% (95% CI: 12–71), 23% (95% CI: −11–48) and 5% (95% CI: −92–56) among those with symptom onset 1–5, 6–11, and ≥ 12 weeks after vaccination, respectively. XBB.1.5 vaccine provided short and moderate protection against JN.1 symptomatic infection.Peer Reviewe
Characterising HIV-Indicator conditions among two nationwide long-term cohorts of people living with HIV in Germany (1999–2023)
Background/Objective:
Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive.
Methods:
Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999–2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30 days) and HIV-transmission routes were collected.
Results:
In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36 years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29–40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17–20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20–24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29–32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts < 350.
Conclusion:
This analysis characterizes HIV-ICs regarding the incidence, HIV-transmission route and patients’ immune status. The results underline the importance of HIV-IC-based screening to detect PLWH with already partially impaired immune status and in need of timely ART initiation.Peer Reviewe
Corrigendum to “Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: results from the VEBIS primary care test-negative design study, September 2023–January 2024” [Vaccine 42(19) (2024)]
Peer Reviewe
RKI-Ratgeber RSV-Infektionen
Das Respiratorische Synzytial-Virus (RSV) ist ein weltweit verbreiteter Erreger von akuten Erkrankungen der oberen und unteren Atemwege in jedem Lebensalter und einer der bedeutendsten Erreger von Atemwegsinfektionen bei Säuglingen, insbesondere Frühgeborenen, Kleinkindern sowie älteren Erwachsenen. In Saisonalität und Symptomatik ähneln RSV-Infektionen der Influenza. Ihre Verbreitung in der Allgemeinbevölkerung wurde lange Zeit unterbewertet. Die Übertragung erfolgt in erster Linie durch Tröpfcheninfektion von einer infektiösen Person auf eine Kontaktperson. Die Schleimhaut der oberen Atemwege und die Konjunktiven bilden die Eintrittspforten. Es wird angenommen, dass eine Übertragung auch indirekt über kontaminierte Hände, Gegenstände und Oberflächen auf die Schleimhäute der Atemwege möglich ist. Im RKI-Ratgeber RSV-Infektionen werden wichtige Punkte wie Infektionsweg, klinische Symptomatik, Diagnostik, Infektionsschutz- und Hygienemaßnahmen zusammengefasst
GrippeWeb-Wochenbericht KW 17
Die Aktivität akuter Atemwegserkrankungen (ARE-Inzidenz) in der Bevölkerung ist in der 17. KW 2024 im Vergleich zur Vorwoche insgesamt deutlich gestiegen und lag bei rund 7.100 ARE pro 100.000 Einw. (Vorwoche: 6.200). Der Anstieg der ARE-Aktivität in der Bevölkerung kann zum Teil auf das Ende der Osterferien nach der 16. KW in dann allen Bundesländern zurückgeführt werden (s.u., Abbildung 5). Die Inzidenz der grippeähnlichen Erkrankungen (ILI) ist im Vergleich zur Vorwoche mit rund 1.300 ILI pro 100.000 Einw. leicht gestiegen (Vorwoche: 1.200). Die Gesamt-ARE-Inzidenz befand sich deutlich über dem Wertebereich der vorpandemischen Jahre zu dieser Zeit und die Gesamt-ILI-Inzidenz im oberen Wertebereich. Die geschätzte
COVID-19-Inzidenz in der Bevölkerung basierend auf Angaben der GrippeWeb-Teilnehmenden lag in der 17. KW unter 100 COVID-19-Erkrankungen pro 100.000 Einw. In der virologischen Überwachung in der Bevölkerung (GrippeWeb-Plus) wurden seit der 14. KW 2024 hauptsächlich Rhino-/Enteroviren (Tendenz steigend) nachgewiesen sowie zu niedrigeren Anteilen auch andere Erreger. Gemäß den Daten aus der Arbeitsgemeinschaft Influenza endete die Grippewelle mit der 12. KW 2024, die RSV-Welle endete mit der 10. KW 2024.
Die für die Bevölkerung in Deutschland geschätzten Inzidenzen für die 17. KW 2024 beruhen auf den Angaben von 7.221 GrippeWeb-Teilnehmenden, von diesen meldeten 508 eine ARE und 88 eine ILI (Datenstand: 30.4.2024, 0:00 Uhr). Durch Nachmeldungen, die bis zu vier Wochen lang möglich sind, können sich noch
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