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Characteristics of two zoonotic swine influenza A(H1N1) viruses isolated in Germany from diseased patients
Get PDFInterspecies transmission of influenza A viruses (IAV) from pigs to humans is a concerning event as porcine IAV represent a reservoir of potentially pandemic IAV. We conducted a comprehensive analysis of two porcine A(H1N1)v viruses isolated from human cases by evaluating their genetic, antigenic and virological characteristics. The HA genes of those human isolates belonged to clades 1C.2.1 and 1C.2.2, respectively, of the A(H1N1) Eurasian avian-like swine influenza lineage. Antigenic profiling revealed substantial cross-reactivity between the two zoonotic H1N1 viruses and human A(H1N1)pdm09 virus and some swine viruses, but did not reveal cross-reactivity to H1N2 and earlier human seasonal A(H1N1) viruses. The solid-phase direct receptor binding assay analysis of both A(H1N1)v showed a predominant binding to α2–6–sialylated glycans similar to human-adapted IAV. Investigation of the replicative potential revealed that both A(H1N1)v viruses grow in human bronchial epithelial cells to similar high titers as the human A(H1N1)pdm09 virus. Cytokine induction was studied in human alveolar epithelial cells A549 and showed that both swine viruses isolated from human cases induced higher amounts of type I and type III IFN, as well as IL6 compared to a seasonal A(H1N1) or a A(H1N1)pdm09 virus. In summary, we demonstrate a remarkable adaptation of both zoonotic viruses to propagate in human cells. Our data emphasize the needs for continuous monitoring of people and regions at increased risk of such trans-species transmissions, as well as systematic studies to quantify the frequency of these events and to identify viral molecular determinants enhancing the zoonotic potential of porcine IAV.Peer Reviewe
Author Correction: Tick-borne encephalitis vaccine effectiveness and barriers to vaccination in Germany
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Gene knock-out in Mycobacterium abscessus using Streptococcus thermophilus CRISPR/Cas
Get PDFThe CRISPRi system using dCas9Sth1 from Streptococcus thermophilus developed for Mycobacterium tuberculosis and M. smegmatis was modified to allow gene knock-out in M. abscessus. Efficacy of the knock-out system was evaluated by applying deletions and insertions to the mps1 gene. A comparative genomic analysis of mutants and wild type validated the target specificity.Peer Reviewe
Clinical and genomic features of Mycobacterium avium complex: a multi-national European study
Get PDFBackground:
The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated.
Methods:
Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort.
Results:
Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04–0.28, p < 0.001 and OR 0.11 95% CI 0.02–0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%).
Conclusions:
This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.Peer Reviewe
High-resolution modeling and projection of heat-related mortality in Germany under climate change
Get PDFBackground:
Heat has become a leading cause of preventable deaths during summer. Understanding the link between high temperatures and excess mortality is crucial for designing effective prevention and adaptation plans. Yet, data analyses are challenging due to often fragmented data archives over different agglomeration levels.
Method:
Using Germany as a case study, we develop a multi-scale machine learning model to estimate heat-related mortality with variable temporal and spatial resolution. This approach allows us to estimate heat-related mortality at different scales, such as regional heat risk during a specific heatwave, annual and nationwide heat risk, or future heat risk under climate change scenarios.
Results:
We estimate a total of 48,000 heat-related deaths in Germany during the last decade (2014–2023), and the majority of heat-related deaths occur during specific heatwave events. Aggregating our results over larger regions, we reach good agreement with previously published reports from Robert Koch Institute (RKI). In 2023, the heatwave of July 7–14 contributes approximately 1100 cases (28%) to a total of approximately 3900 heat-related deaths for the whole year. Combining our model with shared socio-economic pathways (SSPs) of future climate change provides evidence that heat-related mortality in Germany could further increase by a factor of 2.5 (SSP245) to 9 (SSP370) without adaptation to extreme heat under static sociodemographic developments assumptions.
Conclusions:
Our approach is a valuable tool for climate-driven public health strategies, aiding in the identification of local risks during heatwaves and long-term resilience planning.Peer Reviewe
Rapid Enzymatic Detection of Shiga-Toxin-Producing E. coli Using Fluorescence-Labeled Oligonucleotide Substrates
Get PDFShiga-toxin-producing Escherichia coli (STEC) are important human pathogens causing diarrhea, hemorrhagic colitis, and severe hemolytic uremic syndrome. Timely detection of the multifaceted STEC is of high importance but is challenging and labor-intensive. An easy-to-perform rapid test would be a tremendous advance. Here, the major STEC virulence factor Shiga toxins (Stx), RNA-N-glycosidases targeting the sarcin ricin loop (SRL) of 28S rRNA, was used for detection. We designed synthetic FRET-based ssDNA SRL substrates, which conferred a fluorescence signal after cleavage by Stx. Optimal results using bacterial culture supernatants or single colonies were achieved for substrate StxSense 4 following 30 to 60 min incubation. Stx1 and Stx2 subtypes, diverse STEC serotypes, and Shigella were detected. Within a proof-of-principle study, a total of 94 clinical strains were tested, comprising 65 STEC, 11 Shigella strains, and 18 strains of other enteropathogenic bacteria without Stx. In conclusion, the assay offers rapid and facile STEC detection based on a real-time readout for Stx activity. Therefore, it may improve STEC risk evaluation, therapy decisions, outbreak, and source detection and simplify research for antimicrobials.Peer Reviewe
Nanopore adaptive sampling effectively enriches bacterial plasmids
Get PDFBacterial plasmids play a major role in the spread of antibiotic resistance genes. However, their characterization via DNA sequencing suffers from the low abundance of plasmid DNA in those samples. Although sample preparation methods can enrich the proportion of plasmid DNA before sequencing, these methods are expensive and laborious, and they might introduce a bias by enriching only for specific plasmid DNA sequences. Nanopore adaptive sampling could overcome these issues by rejecting uninteresting DNA molecules during the sequencing process. In this study, we assess the application of adaptive sampling for the enrichment of low-abundant plasmids in known bacterial isolates using two different adaptive sampling tools. We show that a significant enrichment can be achieved even on expired flow cells. By applying adaptive sampling, we also improve the quality of de novo plasmid assemblies and reduce the sequencing time. However, our experiments also highlight issues with adaptive sampling if target and non-target sequences span similar regions.Peer Reviewe
Control of Vibrio vulnificus proliferation in the Baltic Sea through eutrophication and algal bloom management
Get PDFDue to climate change the pathogenic bacterium Vibrio vulnificus proliferates along brackish coastlines, posing risks to public health, tourism, and aquaculture. Here we investigated previously suggested regulation measures to reduce the prevalence of V. vulnificus, locally through seagrass and regionally through the reduction of eutrophication and consequential formation of algal blooms. Field samples collected in the summer of 2021 covered the salinity and eutrophication gradients of the Baltic Sea, one of the largest brackish areas worldwide. Physico-, biological- and hydrochemical parameters were measured and variables explaining V. vulnificus occurrence were identified by machine learning. The best V. vulnificus predictors were eutrophication-related features, such as particulate organic carbon and nitrogen, as well as occurrence of potential phytoplankton blooms and associated species. V. vulnificus abundance did not vary significantly between vegetated and non-vegetated areas. Thus, reducing nutrient inputs could be an effective method to control V. vulnificus populations in eutrophied brackish coasts.Peer Reviewe
A systematic review of individual, social, and societal resilience factors in response to societal challenges and crises
Get PDFSocietal challenges put public mental health at risk and result in a growing interest in resilience as trajectories of good mental health during stressor exposure. Resilience factors represent multilevel psychosocial resources that increase the likelihood of resilient responses. This preregistered systematic review aims at summarizing evidence on the predictive value of individual, social and societal resilience factors for resilient responses to societal challenges and crises. Eligible studies examined the predictive value of resilience factors in stressor-exposed populations in high-income countries by means of multinomial regression models based on growth mixture modeling. Five databases were searched until August 2, 2023. Data synthesis employed a rating scheme to assess the incremental predictive value of resilience factors beyond sociodemographic variables and other resilience factors. An adapted version of the Newcastle-Ottawa Scale was used for risk of bias assessment. Fifty studies (sample sizes: 360–65,818 participants) with moderate study quality reported on various stressors (e.g., pandemics, natural disasters, terrorist attacks). Higher income, socioeconomic status and perceived social support, better emotion regulation and psychological flexibility were related to more resilient responses. The association between resilience factors and resilient responses was stronger in samples with younger mean age and a larger proportion of women. Most studies used non-representative convenience samples and effects were smaller when accounting for sociodemographic variables and other resilience factors. For many factors, findings were mixed, supporting the importance of the fit between resilience factors and situational demands. Research into social and societal resilience factors and multilevel resilience interventions is needed. Preregistration-ID: 10.17605/OSF.IO/GWJVA. Funding source: Robert Koch Institute (ID: LIR_2023_01).Peer Reviewe
Long-acting prescriptions and therapy for HIV-1 from market launch to the present in Germany (May 2021 to December 2023)
Get PDFBackground:
In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany.
Methods:
Based on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation.
Results:
The bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation).
Conclusion:
To our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.Peer Reviewe