Tularemia is a zoonotic infection caused by Francisella tularensis. Human cases in Germany are emerging and are usually associated with hare or tick exposure. Transmission via squirrel bites has only been reported once before in Germany. We describe a 23-year-old woman who developed tularemia 11 days after being bitten by an injured red squirrel (Sciurus vulgaris) in southern Germany. Initial symptoms included headache, chills and fatigue, followed by painful right axillary lymphadenopathy without fever. Empirical ciprofloxacin (500 mg twice daily) was initiated on day 10 post-bite. Francisella tularensis serology was negative at presentation but seroconversion was documented 19 days later, confirming the diagnosis. The patient recovered fully after a 10-day course of ciprofloxacin. This case underscores the need to consider tularemia after rodent bites in endemic areas, including squirrel bites, and highlights the favourable clinical course following early fluoroquinolone therapy.
Background: In recent years, there has been a significant increase in cases of tularemia, a rare zoonotic disease caused by Francisella tularensis, in Europe. Methods: To investigate the epidemiological, clinical, and therapeutic characteristics of tularemia patients in Germany, we performed a retrospective evaluation of tularemia cases treated between 2010 and 2025 at selected treatment centers of the Permanent Working Group of Competence and Treatment Centers for High Consequence Infectious Diseases (STAKOB) at the Robert Koch Institute. Results: A total of 65 patients (median age: 48.5 years; 66.2% male) were identified. Most common manifestation was ulceroglandular (70.7%), followed by oropharyngeal (13.8%), pulmonary (10.8%), oculoglandular (7.7%), typhoidal (4.6%), and meningitic (4.6%). Serological confirmation of the diagnosis was achieved in all patients (90.8% ELISA, 46.2% Western blot). PCR-based direct pathogen detection was successful in 26.2%. Bloodstream infection was detected in 4.6%. Median incubation period was 7 days (IQR: 4–10), with fever being the most common symptom in 96.9% and lymphadenopathy in 46.2%. Median time to recovery was 56 days (IQR: 37–80) in patients diagnosed and treated early (≤3 weeks after symptom onset), compared to 84 days (IQR: 66–182) in patients with late diagnosis (>3 weeks after symptom onset; p = 0.015). Empirical therapy with beta-lactam antibiotics was initiated in 49.2% of cases. Following suspicion of tularemia, 96.9% received recommended treatment with fluoroquinolones, tetracyclines, or aminoglycosides. Conclusions: Delayed diagnosis and inappropriate initial therapy can significantly prolong disease courses and increase morbidity. Early treatment with effective antibiotics, considering the intrinsic beta-lactam resistance of Francisella tularensis, leads to faster recovery.
Today, MALDI-ToF MS is an established technique to characterize and identify pathogenic bacteria. The technique is increasingly applied by clinical microbiological laboratories that use commercially available complete solutions, including spectra databases covering clinically relevant bacteria. Such databases are validated for clinical, or research applications, but are often less comprehensive concerning highly pathogenic bacteria (HPB). To improve MALDI-ToF MS diagnostics of HPB we initiated a program to develop protocols for reliable and MALDI-compatible microbial inactivation and to acquire mass spectra thereof many years ago. As a result of this project, databases covering HPB, closely related bacteria, and bacteria of clinical relevance have been made publicly available on platforms such as ZENODO. This publication in detail describes the most recent version of this database. The dataset contains a total of 11,055 spectra from altogether 1,601 microbial strains and 264 species and is primarily intended to improve the diagnosis of HPB. We hope that our MALDI-ToF MS data may also be a valuable resource for developing machine learning-based bacterial identification and classification methods.
OBJECTIVES:Brucellosis in humans is mainly caused by Brucella melitensis and is associated with a risk of chronic infections and relapses. For appropriate patient treatment decisions and outcomes, clinical breakpoints as well as standard antimicrobial susceptibility testing (AST) procedures, are needed. In this study, a Europe-wide network of Brucella reference laboratories aimed, in close collaboration with the European Committee on Antimicrobial Susceptibility Testing (EUCAST), at establishing standardized AST methods, wild-type (WT) minimum inhibitory concentrations (MICs), and zone diameter distributions, and to set epidemiological cutoff (ECOFF) values for nine therapeutically relevant antimicrobial agents. METHODS:A total of 499 B. melitensis strains were tested at six study centres by broth microdilution (BMD) and disc diffusion (DD). MICs and inhibition zone diameters were curated according to EUCAST standard operating procedure (SOP) 10.2, and the results were submitted to EUCAST for ECOFFs and clinical breakpoint determination. RESULTS:BMD and DD data distributions revealed putative wild-type distributions for the tested antimicrobial agents. MIC ECOFFs were determined for all agents based on five to six distributions, encompassing 249 to 499 observations. Six isolates showed MIC values slightly above the ECOFFs, indicating the presence of a potential resistance mechanism to rifampicin, streptomycin, and trimethoprim-sulfamethoxazole. Zone diameter ECOFFs were established for rifampicin and ceftriaxone, whereas tentative (t)ECOFFs were determined for ciprofloxacin, levofloxacin, gentamicin, and streptomycin. DISCUSSION:Standardized BMD and DD methodologies for B. melitensis were validated, and AST results were used by EUCAST to set ECOFFs. Based on these, clinical breakpoints were released in v14.0 of the EUCAST clinical breakpoints table, enabling sensitive detection of resistance mechanisms and monitoring of resistance development. Genetic changes in isolates with slightly elevated MICs remain to be investigated.
The zoonotic and highly infectious pathogen Francisella tularensis is the etiological agent of tularemia. Tularemia in humans is mainly caused by F. tularensis subspecies tularensis and holarctica, but Francisella species like F. novicida, F. philomiragia, F. hispaniensis and others are known to cause tularemia-like infections in immunocompromised humans. In addition to these Francisella species, further genera of the family Francisellaceae have been described, such as Allofrancisella, Parafrancisella and Pseudofrancisella, but less is known about the distribution and putative virulence of these genera. The methods currently available were not made for a fast and easy detection of all these strains and genera of Francisellaceae. We developed a multiplex quantitative real-time PCR assay that can accurately detect all genera of Francisellaceae, including Francisella, Francisella-like endosymbionts, Allofrancisella, Parafrancisella and Pseudofrancisella. In addition, we developed a qPCR assay to differentiate the major clades (B.4, B.6 and B.12 [B.71 and B.72]) of F. tularensis ssp. holarctica strains. Both primer sets were shown to work on isolated DNA out of human and tick samples. Since the developed qPCRs are able to detect all genera of Francisellaceae tested, an easy and fast identification of opportunistic Francisella strains causing tularemia-like symptoms in humans or animals is possible now. The application of these qPCR assays will thus improve the capability for clinical diagnostics and molecular typing during epidemiological investigations.
Objectives: Bacillus anthracis clinical breakpoints, representing a systematic approach to guide clinicians in selecting the most appropriate antimicrobial treatments, are not part of the guidance from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). This is because defined distributions of MIC values and of epidemiological cut-off values (ECOFFs) have been lacking. In this study, a Europe-wide network of laboratories in collaboration with EUCAST, aimed at establishing standardized antimicrobial susceptibility testing methods, wild-type MIC distributions, and ECOFFs for ten therapeutically relevant antimicrobials. Methods: About 335 B. anthracis isolates were tested by broth microdilution and disc diffusion methodologies. MIC and inhibition zone diameters were curated according to EUCAST SOP 10.2 and the results were submitted to EUCAST for ECOFFs and clinical breakpoint determination. Results: Broth microdilution and disc diffusion data distributions revealed putative wild-type distributions for the tested agents. For each antimicrobial agent, ECOFFs were defined. Three highly resistant strains with MIC values of 32 mg/L benzylpenicillin were found. MIC values slightly above the defined ECOFFs were observed in a few isolates, indicating the presence of resistance mechanisms to doxycycline, tetracycline, and amoxicillin. Discussion: B. anthracis antimicrobial susceptibility testing results were used by EUCAST to determine ECOFFs for ten antimicrobial agents. The MIC distributions were used in the process of determining clinical breakpoints. The ECOFFs can be used for the sensitive detection of isolates with resistance mechanisms, and for monitoring resistance development. Genetic changes causing phenotypic shifts in isolates displaying slightly elevated MICs remain to be investigated. Flavia Dematheis, Clin Microbiol Infect 2024;30:1170 (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Global warming has caused an increase in the emergence of Vibrio species in marine and estuarine environments as well as fresh water bodies. Over the past decades, antimicrobial resistance (AMR) has evolved among Vibrio species toward various antibiotics commonly used for the treatment of Vibrio infections. In this study, we assessed virulence and resistance patterns of Vibrio cholerae non-O1/non-O139 strains derived from Germany and other European countries. A total of 63 clinical and 24 environmental Vibrio cholerae non-O1/non-O139 strains, collected between 2011 and 2021, were analyzed. In silico antibiotic resistances were compared with resistance phenotypes according to EUCAST breakpoints. Additionally, genetic relatedness between isolates was assessed by two cgMLST schemes (SeqSphere +, pubMLST). Both cgMLST schemes yielded similar results, indicating high genetic diversity among V. cholerae non-O1/non-O139 isolates. Some isolates were found to be genetically closely related (allelic distance < 20), which suggests an epidemiological link. Thirty-seven virulence genes (VGs) were identified among 87 V. cholerae non-O1/non-O139 isolates, which resulted in 38 virulence profiles (VPs). VPs were similar between clinical and environmental isolates, with the exception of one clinical isolate that displayed a higher abundance of VGs. Also, a cluster of 11 environmental isolates was identified to have the lowest number of VGs. Among all strains, the predominant virulence factors were quorum sensing protein (luxS), repeats-in-toxins (rtxC/rtxD), hemolysin (hlyA) and different type VI secretion systems (T6SS) genes. The genotypic profiles revealed antibiotic resistance genes (ARGs) associated with resistance to beta-lactams, quinolones, macrolides, tetracycline, antifolate, aminoglycosides, fosfomycin, phenicols and sulfonamide. Carbapenemase gene VCC-1 was detected in 10 meropenem-resistant V. cholerae non-O1/non-O139 isolates derived from surface water in Germany. The proportion of resistance among V. cholerae non-O1/non-O139 species isolates against first line treatment (3rd generation cephalosporin, tetracycline and fluoroquinolone) was low. Empirical treatment would likely have been effective for all of the clinical V. cholerae non-O1/non-O139 isolates examined. Nevertheless, carbapenem-resistant isolates have been present in fresh water in Germany and might represent a reservoir for ARGs. Monitoring antimicrobial resistance is crucial for public health authorities to minimize the risks for the human population.
Journal Article Two cases of imported cholera in Germany after short business travel to Yaoundé, Cameroon Get access Michael Nürnberg, MD, Michael Nürnberg, MD Charité - Universitätsmedizin Berlin, Charité Center for Global Health, Institute of International Health, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Gabriela Equihua Martinez, MD, Gabriela Equihua Martinez, MD Charité - Universitätsmedizin Berlin, Charité Center for Global Health, Institute of International Health, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniela Jacob, PhD, Daniela Jacob, PhD Centre for Biological Threats and Special Pathogens, Highly Pathogenic Microorganisms, Robert Koch Institute, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Susann Dupke, PhD, Susann Dupke, PhD Centre for Biological Threats and Special Pathogens, Highly Pathogenic Microorganisms, Robert Koch Institute, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara Graf, MD, Barbara Graf, MD Labor Berlin - Charité Vivantes GmbH, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Sarah Kotsias-Konopelska, MD, Sarah Kotsias-Konopelska, MD Charité - Universitätsmedizin Berlin, Charité Center for Global Health, Institute of International Health, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Beate Kampmann, PhD, Beate Kampmann, PhD Charité - Universitätsmedizin Berlin, Charité Center for Global Health, Institute of International Health, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank P Mockenhaupt, MD, Frank P Mockenhaupt, MD Charité - Universitätsmedizin Berlin, Charité Center for Global Health, Institute of International Health, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Andreas K Lindner, MD Andreas K Lindner, MD Charité - Universitätsmedizin Berlin, Charité Center for Global Health, Institute of International Health, 13353 Berlin, Germany To whom correspondence should be addressed: Tel: +49 30 450 565 733; Fax: +49 30 450 565 93; Email: andreas.lindner@charite.de https://orcid.org/0000-0001-5768-5109 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Travel Medicine, Volume 30, Issue 5, July 2023, taad098, https://doi.org/10.1093/jtm/taad098 Published: 24 July 2023 Article history Received: 08 June 2023 Revision received: 15 July 2023 Revision requested: 17 July 2023 Accepted: 17 July 2023 Published: 24 July 2023 Corrected and typeset: 11 August 2023
Brucellosis, mainly caused by Brucella (B.) melitensis, is associated with a risk of chronification and relapses. Antimicrobial susceptibility testing (AST) standards for B. melitensis are not available, and the agent is not yet listed in the EUCAST breakpoint tables. CLSI recommendations for B. melitensis exist, but they do not fulfill the requirements of the ISO 20776 standard regarding the culture medium and the incubation conditions. Under the third EU Health Programme, laboratories specializing in the diagnostics of highly pathogenic bacteria in their respective countries formed a working group within a Joint Action aiming to develop a suitable method for the AST of B. melitensis. Under the supervision of EUCAST representatives, this working group adapted the CLSI M45 document to the ISO 20776 standard after testing and validation. These adaptations included the comparison of various culture media, culture conditions and AST methods. A Standard Operation Procedure was derived and an interlaboratory validation was performed in order to evaluate the method. The results showed pros and cons for both of the two methods but also indicate that it is not necessary to abandon Mueller–Hinton without additives for the AST of B. melitensis.
Burkholderia mallei is the etiological agent of glanders, a highly contagious and often fatal disease in equids. Due to the high genetic clonality of B. mallei, high-resolution typing assays are necessary to differentiate between individual strains. Here we report on the development and validation of a robust and reproducible core genome-based Multi Locus Sequence Typing Assay (cgMLST) for B. mallei, which is based on 3328 gene targets and enables high-resolution typing at the strain level. The assay was validated using a set of 120 B. mallei genomes from public databases and 23 newly sequenced outbreak strains from in-house strain collections. In this cgMLST analysis, strains from different geographic regions were clearly distinguished by at least 70 allele differences, allowing spatial clustering while closely related and epidemiologically related strains were separated by only zero to three alleles. Neither the different sequencing technologies nor the assembly strategies had an influence on the cgMLST results. The developed cgMLST is highly robust, reproducible and can be used for outbreak investigations, source tracking and molecular characterization of new B. mallei isolates.
BACKGROUND:The diagnosis of tularemia is not often considered in Germany as the disease is still rare in this country. Nonetheless, Francisella tularensis, the causative agent of tularemia, can infect numerous animal species and should, therefore, not be neglected as a dangerous pathogen. Tularemia can lead to massively swollen lymph nodes and might even be fatal without antibiotic treatment. To our knowledge, the case described here is the first report of the disease caused by a squirrel bite in Germany.CASE PRESENTATION:A 59-year-old German woman with a past medical history of hypothyroidism and cutaneous lupus erythematosus presented at the emergency room at St. Katharinen Hospital with ongoing symptoms and a swollen right elbow persisting despite antibiotic therapy with cefuroxime for 7 days after she had been bitten (right hand) by a wild squirrel (Eurasian red squirrel). After another 7 days of therapy with piperacillin/tazobactam, laboratory analysis using real-time polymerase chain reaction (PCR) confirmed the suspected diagnosis of tularemia on day 14. After starting the recommended antibiotic treatment with ciprofloxacin, the patient recovered rapidly.CONCLUSION:This is the first report of a case of tularemia caused by a squirrel bite in Germany. A naturally infected squirrel has recently been reported in Switzerland for the first time. The number of human cases of tularemia has been increasing over the last years and, therefore, tularemia should be taken into consideration as a diagnosis, especially in a patient bitten by an animal who also presents with headache, increasing pain, lymphadenitis, and fever, as well as impaired wound healing. The pathogen can easily be identified by a specific real-time PCR assay of wound swabs and/or by antibody detection, for example by enzyme-linked immunosorbent assay (ELISA), if the incident dates back longer than 2 weeks.
SummaryIn November 2018, a tularaemia outbreak occurred in Bavaria, Germany, among participants of a hare hunt and butchery employees handling the hares. We conducted an epidemiological outbreak investigation, including a retrospective cohort study among hunting participants, to identify likely transmission routes and activities associated with infection. Twelve of 41 participants were antibody‐positive for Francisella (F.) tularensis (attack rate: 29%). Cases reported influenza‐like symptoms (n = 11), lymphadenopathy (n = 1) and conjunctivitis (n = 1). Infection only occurred in those hunting participants present while hares were processed, while risk of infection was highest when directly involved (RR = 10.0; 95%CI: 2.6–392). F. tularensis was isolated from 1/4 hares. Only two individuals reported using some of the recommended personal protective equipment (PPE). Occurrence of mainly non‐specific symptoms, likely due to early treatment, was not indicative of a specific transmission route. Transmissions via direct (skin/mucosa) contact and by inhalation of contaminated aerosols seem plausible. Promoting and increasing appropriate use of PPE among people processing hares is crucial to prevent future outbreaks.
Background Vibrio spp. are aquatic bacteria that prefer warm seawater with moderate salinity. In humans, they can cause gastroenteritis, wound infections, and ear infections. During the summers of 2018 and 2019, unprecedented high sea surface temperatures were recorded in the German Baltic Sea. Aim We aimed to describe the clinical course and microbiological characteristics of Vibrio infections in Germany in 2018 and 2019. Methods We performed an observational retrospective multi-centre cohort study of patients diagnosed with domestically-acquired Vibrio infections in Germany in 2018 and 2019. Demographic, clinical, and microbiological data were assessed, and isolates were subjected to whole genome sequencing and antimicrobial susceptibility testing. Results Of the 63 patients with Vibrio infections, most contracted the virus between June and September, primarily in the Baltic Sea: 44 (70%) were male and the median age was 65 years (range: 2–93 years). Thirty-eight patients presented with wound infections, 16 with ear infections, six with gastroenteritis, two with pneumonia (after seawater aspiration) and one with primary septicaemia. The majority of infections were attributed to V. cholerae (non–O1/non-O139) (n = 30; 48%) or V. vulnificus (n = 22; 38%). Phylogenetic analyses of 12 available isolates showed clusters of three identical strains of V. vulnificus, which caused wound infections, suggesting that some clonal lines can spread across the Baltic Sea. Conclusions During the summers of 2018 and 2019, severe heatwaves facilitated increased numbers of Vibrio infections in Germany. Since climate change is likely to favour the proliferation of these bacteria, a further increase in Vibrio-associated diseases is expected.
In November 2018, an outbreak of tularemia occurred among hare hunters in Bavaria, Germany. At least one infected hare was confirmed as the source of infection. A number of hunting dogs showed elevated antibody titers to Francisella tularensis, but the absence of titer increases in subsequent samples did not point to acute infections in dogs. Altogether, 12 persons associated with this hare hunt could be diagnosed with acute tularemia by detection of specific antibodies. In nine patients, the antibody and cytokine responses could be monitored over time. Eight out of these nine patients had developed detectable antibodies three weeks after exposure; in one individual the antibody response was delayed. All patients showed an increase in various cytokines and chemokines with a peak for most mediators in the first week after exposure. Cytokine levels showed individual variations, with high and low responders. The kinetics of seroconversion has implications on serological diagnoses of tularemia.
Objectives: Melioidosis, caused by Burkholderia pseudomallei, requires intensive antimicrobial treatment. However, standardized antimicrobial susceptibility testing (AST) methodology based on modern principles for determining breakpoints and ascertaining performance of methods are lacking for B. pseudomallei. This study aimed to establish MIC and zone diameter distributions on which to set epidemiological cut-off (ECOFF) values for B. pseudomallei using standard EUCAST methodology for non-fastidious organisms. Methods: Non-consecutive, non-duplicate clinical B. pseudomallei isolates (9-70 per centre) were tested at eight study centres against eight antimicrobials by broth microdilution (BMD) and the EUCAST disc diffusion method. Isolates without and with suspected resistance mechanisms were deliberately selected. The EUCAST Development Laboratory ensured the quality of study materials, and provided guidance on performance of the tests and interpretation of results. Aggregated results were analysed according to EUCAST recommendations to determine ECOFFs. Results: MIC and zone diameter distributions were generated using BMD and disc diffusion results obtained for 361 B. pseudomallei isolates. MIC and zone diameter ECOFFs (mg/L; mm) were determined for amoxicillin-clavulanic acid (8; 22), ceftazidime (8; 22), imipenem (2; 29), meropenem (2; 26), doxycycline (2; none), tetracycline (8; 23), chloramphenicol (8; 22) and trimethoprim-sulfamethoxazole (4; 28). Conclusions: We have validated the use of standard BMD and disc diffusion methodology for AST of B. pseudomallei. The MIC and zone diameter distributions generated in this study allowed us to establish MIC and zone diameter ECOFFs for the antimicrobials studied. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
Here, we report the complete genome sequence of Francisella tularensis subsp. holarctica strain A271_1, isolated from a Eurasian beaver (Castor fiber) in 2012 in the Berlin/Brandenburg region, Germany.
Tularemia is a zoonotic disease caused byFrancisella tularensisa small, pleomorphic, facultative intracellular bacterium. In Europe, infections in animals and humans are caused mainly byFrancisella tularensissubspeciesholarctica. Humans can be exposed to the pathogen directly and indirectly through contact with sick animals, carcasses, mosquitoes and ticks, environmental sources such as contaminated water or soil, and food. So far,F. tularensissubsp.holarcticais the onlyFrancisellaspecies known to cause tularemia in Germany. On the basis of surveillance data, outbreak investigations, and literature, we review herein the epidemiological situation-noteworthy clinical cases next to genetic diversity ofF. tularensissubsp.holarcticastrains isolated from patients. In the last 15 years, the yearly number of notified cases of tularemia has increased steadily in Germany, suggesting that the disease is re-emerging. By sequencingF. tularensissubsp.holarcticagenomes, knowledge has been added to recent findings, completing the picture of genotypic diversity and geographical segregation ofFrancisellaclades in Germany. Here, we also shortly summarize the current knowledge about a newFrancisellaspecies (Francisellasp. strain W12-1067) that has been recently identified in Germany. This species is the secondFrancisellaspecies discovered in Germany.
Europe-wide activities to improve biosafety and biosecurity performed within the frameworks of the European Union (EU)-funded Joint Actions EMERGE and QUANDHIP led to the development of an Integrated European Checklist for Laboratory Biorisk Management (ECL).To better understand different approaches shaping biorisk management (BRM) systems on an operational level in high containment laboratories, the ECL was used to map the implementation of BRM in 32 high containment laboratories in 18 countries in Europe. The results suggest that the BRM elements referring to standard microbiological working practices and the handling of infectious material were fulfilled particularly well. The elements safety exercises involving internal and external emergency responders, and appropriate decommissioning plans were not fulfilled particularly well. BRM in Biosafety Level (BSL) 4 laboratories handling Risk Group (RG) 4 viruses appear to vary among each other less than BSL3 laboratories handling RG 3 bacteria. It is important to agree on comparable regulations in Europe as high containment laboratories are indispensable for a safe, quick and effective response to public health threats. As high containment laboratories may also present a public health risk it is crucial to have robust BRM on organisational and operational levels.
Abstract Although the preparedness to health emergencies of biological, chemical, environmental and unknown origin across the Europe is at high level, gaps do exist across the EU Member States and European countries. The previous coronavirus epidemic, SARS in 2002, showed that countries responded largely individually to this emerging threat. EU wide, joint responses were not taken. SARS epidemic showed that strengthening of the common EU efforts was needed. Many actions were taken, and since 2013 the European Commission Decision 1082/2013/EU on serious cross-border threats to health has provided a framework to improve preparedness and to strengthen the response capacities in Europe to health threats. SHARP Joint Action is a 3-year collaborative action of 26 countries and 61 partners, co-funded by the EC and coordinated by the Finnish Institute for Health and Welfare, Finland, and co-coordinated by Robert Koch Institute, Germany and National Institute of Infectious Diseases Lazzaro Spallanzani, Italy. SHARP started it's actions in June 2019, and it aims to strengthen implementation of the International Health Regulations (IHR) and the Decision 1082/2013/EU. SHARP consists of ten work packages covering core public health capacities, including: IHR core capacity strengthening and assessment, preparedness and response planning, training, laboratory preparedness and responsiveness, chemical safety and threats, and case management, infection prevention and control preparedness. Through this cross-sectoral approach, SHARP supports the Member States and partner countries in strengthening their capacities. In response to the COVID-19 outbreak, SHARP has also supported the EC and the Member States, and especially work packages for laboratory preparedness and responsiveness (WP7) and for case management and infection prevention and control preparedness (WP10) were activated. The activities regarding laboratory preparedness and response have been coordinated with the ECDC. Key messages SHARP Joint Action strengthens the implementation of Decision 1082/2013/EU on serious cross-border threats to health and the implementation of International Health Regulations in the EU. SHARP improves preparedness and response to serious cross-border threats to health, and resilience of the health systems at national, EU and regional level.