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Nationwide outbreak of invasive listeriosis associated with consumption of meat products in health care facilities, Germany, 2014–2019

Published:September 23, 2020DOI:https://doi.org/10.1016/j.cmi.2020.09.020

      Abstract

      Objectives

      Invasive listeriosis is a severe foodborne infection caused by Listeria (L.) monocytogenes. The aim of this investigation was to verify and describe a molecular cluster of listeriosis patients and identify factors leading to this outbreak.

      Methods

      Whole genome sequencing and core genome multilocus sequence typing were used for subtyping L. monocytogenes isolates from listeriosis cases and food samples in Germany. Patient interviews and investigational tracing of foodstuffs offered in health-care facilities (HCF), where some of the cases occurred, were conducted.

      Results

      We identified a German-wide listeriosis outbreak with 39 genetically related cases occurring between 2014 and 2019. Three patients died as a result of listeriosis. After identification of HCF in different regions of Germany for at least 13 cases as places of exposure, investigational tracing of food supplies in six prioritized HCF revealed meat products from one company (X) as a commonality. Subsequently the outbreak strain was analysed in six isolates from ready-to-eat meat products and one isolate from the production environment of company X. No further Sigma1 cases were detected after recall of the meat products from the market and closure of company X (as of August 2020).

      Conclusions

      Interdisciplinary efforts including whole genome sequencing, epidemiological investigations in patients and investigational tracing of foods were essential to identify the source of infections, and thereby prevent further illnesses and deaths. This outbreak underlines the vulnerability of hospitalized patients for foodborne diseases, such as listeriosis. Food producers and HCF should minimize the risk of microbiological hazards when producing, selecting and preparing food for patients.

      Keywords

      Introduction

      Listeriosis is a severe, usually foodborne, infection associated with high case fatality and hospitalization rates compared with other gastrointestinal bacterial pathogens [
      • Werber D.
      • Hille K.
      • Frank C.
      • Dehnert M.
      • Altmann D.
      • Muller-Nordhorn J.
      • et al.
      Years of potential life lost for six major enteric pathogens, Germany, 2004–2008.
      ]. Invasive listeriosis mainly affects the elderly, immunocompromised patients, newborn infants and pregnant women and can lead to sepsis, meningitis, encephalitis, neonatal infections or miscarriage. Patients in hospitals and other health-care facilities (HCF), such as rehabilitation centres or homes for the elderly, are especially vulnerable [
      • Silk B.J.
      • McCoy M.H.
      • Iwamoto M.
      • Griffin P.M.
      Foodborne listeriosis acquired in hospitals.
      ]. A review of published reports on listeriosis acquired in HCF indicates that a substantial number of cases result from patients consuming food contaminated with Listeria (L.) monocytogenes during HCF visits and stays [
      • Silk B.J.
      • McCoy M.H.
      • Iwamoto M.
      • Griffin P.M.
      Foodborne listeriosis acquired in hospitals.
      ].
      Because of the relatively low number of listeriosis cases and the difficulty of obtaining reliable food histories in patient interviews, listeriosis outbreaks are often more difficult to investigate than other foodborne outbreaks. Listeriosis outbreaks may last for several years, making it almost impossible to identify affected patients without the use of whole genome sequencing (WGS) [
      • Ruppitsch W.
      • Prager R.
      • Halbedel S.
      • Hyden P.
      • Pietzka A.
      • Huhulescu S.
      • et al.
      Ongoing outbreak of invasive listeriosis, Germany, 2012 to 2015.
      ]. They are also often geographically widespread, hampering outbreak recognition by local authorities [
      • McCollum J.T.
      • Cronquist A.B.
      • Silk B.J.
      • Jackson K.A.
      • O'Connor K.A.
      • Cosgrove S.
      • et al.
      Multistate outbreak of listeriosis associated with cantaloupe.
      ,
      • Heiman K.E.
      • Garalde V.B.
      • Gronostaj M.
      • Jackson K.A.
      • Beam S.
      • Joseph L.
      • et al.
      Multistate outbreak of listeriosis caused by imported cheese and evidence of cross-contamination of other cheeses. USA, 2012.
      ,
      ECDC_EFSA
      Multi-country outbreak of Listeria monocytogenes sequence type 8 infections linked to consumption of salmon products.
      ,
      • Halbedel S.
      • Wilking H.
      • Holzer A.
      • Kleta S.
      • Fischer M.A.
      • Luth S.
      • et al.
      Large nationwide outbreak of invasive listeriosis associated with blood sausage, Germany, 2018–2019.
      ].
      Systematic collection of L. monocytogenes isolates from human listeriosis cases and their subtyping using WGS-based techniques (i.e. molecular surveillance) allows for reliable detection of outbreaks [
      • Halbedel S.
      • Prager R.
      • Fuchs S.
      • Trost E.
      • Werner G.
      • Flieger A.
      Whole-genome sequencing of recent Listeria monocytogenes isolates from Germany reveals population structure and disease clusters.
      ,
      • Kleta S.
      • Hammerl J.A.
      • Dieckmann R.
      • Malorny B.
      • Borowiak M.
      • Halbedel S.
      • et al.
      Molecular tracing to find source of protracted invasive listeriosis outbreak, southern Germany, 2012–2016.
      ,
      • Jackson B.R.
      • Tarr C.
      • Strain E.
      • Jackson K.A.
      • Conrad A.
      • Carleton H.
      • et al.
      Implementation of nationwide real-time whole-genome sequencing to enhance listeriosis outbreak detection and investigation.
      ,
      • Moura A.
      • Tourdjman M.
      • Leclercq A.
      • Hamelin E.
      • Laurent E.
      • Fredriksen N.
      • et al.
      Real-time whole-genome sequencing for surveillance of Listeria monocytogenes, France.
      ,
      • Kwong J.C.
      • Mercoulia K.
      • Tomita T.
      • Easton M.
      • Li H.Y.
      • Bulach D.M.
      • et al.
      Prospective whole-genome sequencing enhances national surveillance of Listeria monocytogenes.
      ]. We describe the investigation of a nationwide outbreak with 39 listeriosis cases occurring from 2014 to 2019 that was detected by molecular surveillance.

      Methods

      The German-Austrian Binational Consultant Laboratory for L. monocytogenes (CL) at the Austrian Agency for Health and Food Safety and the Robert Koch Institute (RKI) collects clinical L. monocytogenes isolates from human infections in Germany. Submission of clinical L. monocytogenes isolates from primary laboratories to the CL is encouraged by public health authorities, but is voluntary without legal obligation. In contrast, laboratory confirmation of L. monocytogenes from a normally sterile site is notifiable to local health departments, which transmit this information to the RKI. In 2018, for example, 701 listeriosis cases were notified and 457 isolates were sent to the CL. All the isolates were analysed by WGS. Notification of listeriosis cases and typing data of the L. monocytogenes isolates that were sent to the RKI were merged for investigation.
      Genomic DNA was isolated using the GenElute bacterial genomic DNA Kit (Sigma, St Louis, MO, USA) (clinical isolates) or the QIAamp DNA Mini Kit (Qiagen, Hilden, Germany) (non-clinical isolates) and quantified using a Qubit fluorometer (Invitrogen, Carlsbad, CA, USA). Libraries were prepared using the Nextera XT DNA or Nextera DNA Flex Library Prep Kit (Illumina, San Diego, CA, USA) and sequenced on MiSeq or HiSeq sequencers. Raw reads were assembled in Ridom SeqSphere+ (version 6.0.8; Ridom GmbH, Münster, Germany) and molecular serogroups, multilocus sequence typing (MLST) sequence types (ST) and 1701 locus core genome MLST (cgMLST) complex types were automatically extracted [
      • Ruppitsch W.
      • Pietzka A.
      • Prior K.
      • Bletz S.
      • Fernandez H.L.
      • Allerberger F.
      • et al.
      Defining and evaluating a core genome multilocus sequence typing scheme for whole-genome sequence-based typing of Listeria monocytogenes.
      ]. Minimum spanning trees were calculated in the ‘pairwise ignore missing values’ mode. Genome sequencing raw data can be found at the European Nucleotide Archive. All isolates and their accession codes are listed in the Supplementary material (Table S1).
      Mapping of sequencing reads, generation of consensus sequences, alignment calculation and single nucleotide polymorphism (SNP) filtering (exclusion distance 300) were performed using in-house pipelines [
      • Halbedel S.
      • Prager R.
      • Fuchs S.
      • Trost E.
      • Werner G.
      • Flieger A.
      Whole-genome sequencing of recent Listeria monocytogenes isolates from Germany reveals population structure and disease clusters.
      ]. The L. monocytogenes R479a genome (NZ_HG813247, serogroup IIa, ST8, CT2498) was used as reference. Clustering was performed in Geneious 9.1.3 (Biomatters Ltd, Auckland, New Zealand).
      Outbreak cases were defined as patients reported to public health authorities and transmitted to the RKI with the onset of listeriosis since 2014, with isolation of L. monocytogenes from normally sterile bodily fluids or in context of birth and belonging to a specific WGS cluster called ‘Sigma1’ (see Results). Patients were interviewed regarding their food consumption in the two weeks before the onset of listeriosis, their general eating and food purchasing behaviours, and their medical history. Based on patient interviews HCF exposure was identified as a hypothesis, and information on HCF exposure was sought for all cases through local health authorities. The incubation period of 14 days was defined according to Goulet et al. [
      • Goulet V.
      • King L.A.
      • Vaillant V.
      • de Valk H.
      What is the incubation period for listeriosis?.
      ].
      Member states of the EU and other countries have been informed about this outbreak via the Epidemic Intelligence Information System for Food and Waterborne Diseases of the ECDC (EPIS-FWD) and have been asked to provide information about genetically related cases in their countries.
      This outbreak investigation and publication was executed according to the German Infection Protection Act as part of the mandate of the local public health agencies and RKI as national public health agency.
      The Federal Office of Consumer Protection and Food Safety (BVL) together with food control services of the Federal States analysed which foods were offered in the HCF where the outbreak case had stayed during the incubation period using investigational tracing [
      • Cheung C.Y.
      • Luber P.
      Investigational tracing as a method for identification of causative foods and sources of food-borne outbreaks.
      ].
      Subtyping of the L. monocytogenes isolates from food samples was performed at the National Reference Laboratory for L. monocytogenes at the German Federal Institute for Risk Assessment (BfR) in Berlin. The CL and the National Reference Laboratory regularly compare L. monocytogenes strain identities from clinical and food isolates.

      Results

       Molecular characterization of outbreak isolates

      A molecular cluster composed of 41 serogroup IIa isolates belonging to MLST ST8 and cgMLST CT2521 was identified. For easier communication, we named the cluster ‘Sigma1’. Minimum spanning tree analysis showed that these isolates formed a joint cluster with only 0–10 (median: 1) different alleles using cgMLST (Fig. 1). Mapping all isolate genomes onto the closed genome sequence of the related L. monocytogenes strain R479a as a reference [
      • Schmitz-Esser S.
      • Gram L.
      • Wagner M.
      Complete genome sequence of the persistent Listeria monocytogenes strain R479a.
      ] and subsequent SNP calling showed that all Sigma1 isolates differed from each other in 0–11 SNPs (median: 2) only, confirming a high degree of clonal relatedness (data not shown). Of the 41 isolates sent to the CL and belonging to Sigma1, 39 could be assigned to surveillance cases reported in the mandatory notification system.
      Fig. 1
      Fig. 1Phylogeny of the Sigma1 cluster. Minimum spanning tree illustrating the clonal relatedness of clinical L. monocytogenes isolates belonging to the Sigma1 cluster and associated food isolates after cgMLST. Isolates are coloured according to their source type.

       Case description

      Thirty-nine notified listeriosis patients met the Sigma1 outbreak case definition. Outbreak cases occurred in 11 out of 16 federal states in Germany (Fig. 2). Altogether 16 other countries provided feedback via EPIS-FWD (UI-582), but no country reported genetically related cases.
      Figure thumbnail gr2
      Fig. 2Spatial and temporal distribution of outbreak cases. (A) Diagram showing the number of laboratory-confirmed Sigma1 cases in Germany per month and year. (B) Geographical distribution of laboratory-confirmed Sigma1 cases residence within Germany.
      One early case in 2014 was retrospectively detected, as well as a few cases in 2016 and 2017. Most outbreak cases occurred in 2018 (Fig. 2). The last known onset of symptoms in a Sigma1 case was on 13 July 2019.
      Twenty-one (54%) out of 39 outbreak cases were men, 18 were women. They were 31–91 years old (median 73 years); the 31-year-old patient was immunocompromised. There were no pregnancy-associated cases in this outbreak. Eighteen outbreak cases died (46%), with listeriosis reported as the primary cause of death in three cases.
      Twenty-five outbreak cases (out of 27 with available information) were hospitalized because of listeriosis. Twenty-four cases (62%) were reported with fever due to listeriosis. Two cases (5%) developed meningitis, and 16 cases (41%) developed sepsis. Most individuals who developed sepsis were women (69%) and were 57–87 years old (median 78 years); among them were the three cases who died as a result of listeriosis.
      From 39 outbreak cases, 25 were invited for an interview. The reasons why 14 cases were not invited for an interview, were: eight cases occurring before 2018 were retrospectively identified, three cases could not be contacted, and three were identified when the outbreak and the outbreak vehicle were already prominently displayed in the German media and patient recollection bias regarding foods consumed was likely.
      From the contacted 25 cases, 19 refused an interview. Data from six cases (one case interview and five interviews with relatives or care takers) were retrieved. From the six interviews there was no indication of specific food items that were commonly consumed. However, it was noted that several cases had been in HCF such as hospitals or rehabilitation centres before the onset of listeriosis for other medical reasons. Therefore, information about staying in HCF available at local health authorities was collected for all cases. In total, 13 cases had an inpatient stay in 12 different HCF in the incubation period, eight cases had no stay in an HCF and the information for six cases could not be retrieved. Twelve other patients reported a stay in a HCF before the listeriosis but it could not be verified if that was during the incubation period. Outbreak cases stayed in HCF in several federal states; in most HCF only single cases were identified, the one exception being one HCF in which two cases stayed within three months.
      Reasons for staying in an HCF before listeriosis could be ascertained for 16 outbreak cases: eight cases had cancer, three needed dialysis, three had surgical interventions, two had cardiovascular diseases and one case each had multiple sclerosis, or diabetes.

       Investigations into the source of the outbreak

      Investigations revealed that 13 cases most probably acquired infection in an HCF and another 12 cases might have acquired infection in an HCF. The proportion of inpatient stays in HCF was higher than would have been expected based on the experience of the listeriosis outbreak investigation team. Drugs and medical devices appeared unlikely as the source of infection, because the types of HCF were different and the stays were due to different medical conditions. Rather, it was suspected that the source of infection might be related to the HCF's food supply.
      WGS of L. monocytogenes isolates from food products in Germany did not reveal any relationship to Sigma1; however, not all food isolates that arrived at BfR for routine diagnostics were sequenced. In a further step, ten HCF in which Sigma1 cases stayed during the incubation period were selected for further investigation of food supplies. Information about the food supply in six out of ten HCF could be retrieved by local food safety authorities. Ready-to-eat foods that have a higher probability for L. monocytogenes contamination were prioritized and their supply to HCF was analysed to find commonalities.
      The analyses of data on food deliveries identified a single company (X) that had supplied a range of different ready-to-eat sausage products to all six investigated HCF through different suppliers. Based on this result, there were event-related inspections, including sampling of products and the production environment at company X. Two isolates from routine sampling of food products from company X were already present at BfR and were sequenced immediately. Further L. monocytogenes were isolated from sausage products from company X and sequencing showed a very close relationship between the clinical Sigma1 isolates and six isolates from the sausage products and one isolate from the production environment of company X. The isolates from the food samples only differed in 0–9 cgMLST alleles (median: 1 allele) or 0–11 SNPs (median 2 SNP) from clinical isolates of the Sigma1 cases confirming a high degree of clonal relatedness (Fig. 1).

      Discussion

      Company X was closed down on 2 October 2019 and all products were publicly recalled from the market [
      ]. No further Sigma1 cases were detected since the closing of company X and up to 10 August 2020. Follow-up investigations at company X carried out by the responsible authorities suggested extensive hygiene breaches and widespread contamination with L. monocytogenes in the production plant [
      ]. Hence, ready-to-eat meat products from company X distributed to many HCF, but also to supermarkets and restaurants, were the likely source of this large listeriosis outbreak in Germany.
      WGS was necessary to identify Sigma1 cases that occurred over several years and regions in Germany. After the detection of the Sigma1 outbreak, investigations were conducted to discover and then eliminate the contaminated foodstuffs.
      Eventually, investigations of the HCF's food supply chains indicated a single common supplier that produced ready-to-eat meat products that were distributed nationwide and internationally [
      • RASFF
      Notification details - 2019.3464—foodborne outbreak caused by Listeria monocytogenes in chilled sausages from Germany.
      ]. The absence of Sigma1 cases outside Germany is surprising, looking at the export volume of the company's products and the long-term contamination in the production plant. The distribution of products from company X to supermarkets and restaurants could explain the outbreak cases without known links to HCF.
      As L. monocytogenes is not always detected in blood cultures, there is an under-ascertainment of L. monocytogenes in individuals with sepsis. Furthermore, a proportion of L. monocytogenes isolates are not submitted to the CL for genome sequencing, therefore, we expect the true size of this outbreak to be larger. Proportionally, more Sigma1 outbreak cases died than in other German listeriosis outbreaks [
      • Ruppitsch W.
      • Prager R.
      • Halbedel S.
      • Hyden P.
      • Pietzka A.
      • Huhulescu S.
      • et al.
      Ongoing outbreak of invasive listeriosis, Germany, 2012 to 2015.
      ,
      • Halbedel S.
      • Prager R.
      • Banerji S.
      • Kleta S.
      • Trost E.
      • Nishanth G.
      • et al.
      Listeria monocytogenes ST2 clone lacking chitinase ChiB from an outbreak of non-invasive gastroenteritis.
      ]. This is likely to be explained by the underlying medical conditions of the Sigma1 cases, which were the primary reason for admission to HCF.
      Foodborne acquisition of listeriosis in hospitals is well documented in Germany and internationally [
      • Silk B.J.
      • McCoy M.H.
      • Iwamoto M.
      • Griffin P.M.
      Foodborne listeriosis acquired in hospitals.
      ,
      • Mazengia E.
      • Kawakami V.
      • Rietberg K.
      • Kay M.
      • Wyman P.
      • Skilton C.
      • et al.
      Hospital-acquired listeriosis linked to a persistently contaminated milkshake machine.
      ,
      • Najjar Z.
      • Gupta L.
      • Sintchenko V.
      • Shadbolt C.
      • Wang Q.
      • Bansal N.
      Listeriosis cluster in Sydney linked to hospital food.
      ,
      • Jacks A.
      • Pihlajasaari A.
      • Vahe M.
      • Myntti A.
      • Kaukoranta S.S.
      • Elomaa N.
      • et al.
      Outbreak of hospital-acquired gastroenteritis and invasive infection caused by Listeria monocytogenes, Finland, 2012.
      ,
      • Little C.L.
      • Amar C.F.
      • Awofisayo A.
      • Grant L.A.
      Hospital-acquired listeriosis associated with sandwiches in the UK: a cause for concern.
      ,
      • Winter C.H.
      • Brockmann S.O.
      • Sonnentag S.R.
      • Schaupp T.
      • Prager R.
      • Hof H.
      • et al.
      Prolonged hospital and community-based listeriosis outbreak caused by ready-to-eat scalded sausages.
      ]. Despite the potential for severe outcomes of listeriosis among hospitalized patients, many hospitals have no food preparation policies or practices to minimize the risk of L. monocytogenes contamination [
      • Cokes C.
      • France A.M.
      • Reddy V.
      • Hanson H.
      • Lee L.
      • Kornstein L.
      • et al.
      Serving high-risk foods in a high-risk setting: survey of hospital food service practices after an outbreak of listeriosis in a hospital.
      ]. Therefore it is important to promote and establish policies to purchase and distribute safe food for patients. Doctors, dietitians and caterers in HCF should minimize the risk of microbiological hazards in food for patients and exclude high-risk food products from the diet of vulnerable individuals.
      In Germany, recommendations concerning the catering for vulnerable people in HCF and other institutions are published [
      Bundesinstitut für Risikobewertung
      Sicher verpflegt-Besonders empfindliche Personengruppen in Gemeinschaftseinrichtungen.
      ,
      Kommission für Krankenhaushygiene und Infektionsprävention am Robert Koch-Institut, Anforderungen an die Hygiene bei der medizinischen Versorgung von immunsupprimierten Patienten.
      ]. To ensure compliance with food hygiene, the cold chain must be maintained and food must be stored at the temperatures recommended by the manufacturer. As L. monocytogenes can also multiply during refrigeration temperatures, it is recommended in Germany that ready-to-eat food intended for distribution to sensitive consumer groups should be consumed as fresh as possible [
      • Cokes C.
      • France A.M.
      • Reddy V.
      • Hanson H.
      • Lee L.
      • Kornstein L.
      • et al.
      Serving high-risk foods in a high-risk setting: survey of hospital food service practices after an outbreak of listeriosis in a hospital.
      ]. According to the General European Food Law Regulation every food business operator (including caterers in HCF) has to ensure that the distributed food is safe, especially ready-to-eat foods [
      • European Parliament
      Regulation (EC) No 178/2002 of the European Parliament and of the council of 28 January 2002.
      ,
      • European Parliament
      Commission Regulation (EC) No 2073/2005 of 15 November 2005 on microbiological criteria for foodstuffs.
      ]. Furthermore, a Hazard Analysis Critical Control Point system has to be implemented, also considering specific characteristics of consumer groups [
      ]. The burden of HCF-acquired listeriosis could be reduced if existing recommendations for safe catering in HCF were properly implemented by the operators.

       Limitations

      The outbreak detection and investigation were complicated by the fact that the outbreak cases were not concentrated in one HCF but occurred in many different HCF, mostly with only one case per institution. In addition, many patients or the relatives of those who had died refused to be interviewed. We can only speculate about their reasons, some may have felt too ill to be interviewed or they felt unable to provide useful information about consumed food.
      The common denominator of having stayed in an HCF in the incubation period was only recognized from the interviews of outbreak cases and by specifically asking local health authorities about previous HCF admissions. Standardized information on hospitalization history readily available in surveillance would have enabled a faster outbreak investigation. Documentation of individual patients' food consumption at the HCF were not available but would have reduced the number of potentially implicated foodstuffs.

      Conclusions

      The Sigma1 listeriosis outbreak illustrates how WGS-based pathogen surveillance combined with efficient interventions of all the involved stakeholders can stop foodborne outbreaks and thereby prevent further illnesses and deaths. Increasing the use of WGS to characterize L. monocytogenes isolates, including those from apparently sporadic HCF-based cases, will further improve the detection of infections linked to food served in HCF.
      To prevent further nosocomial listeriosis outbreaks in the future, food products that may pose a high risk for L. monocytogenes contamination should not be offered to vulnerable persons.

      Acknowledgements

      We are very grateful to Andrea Thürmer and Robin Redel for genome sequencing, to Simone Dumschat, Marett Splett and Isabel Knittel-Fischer for excellent technical assistance and to the local and federal public health and food safety authorities for their strong support in the outbreak investigation.

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

      Contribution

      RL and HW wrote the original draft. SH, MA, NB, FA, AH, IB, GF, SK, SA, KS, PL and AF reviewed and edited the article. Conceptualization was done by HW, GF and KS; investigation was done by RL, AH, IB and GF; formal analysis was performed by RL, SH, MA, SK, AH and IB; and SH, MA, AH and SK were responsible for data curation.

      Transparency declaration

      The authors report no conflict of interest. This work has received funding as part of the NOVA project under the One Health European Joint Programme a European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 773830 .

      References

        • Werber D.
        • Hille K.
        • Frank C.
        • Dehnert M.
        • Altmann D.
        • Muller-Nordhorn J.
        • et al.
        Years of potential life lost for six major enteric pathogens, Germany, 2004–2008.
        Epidemiol Infect. 2013; 141: 961-968
        • Silk B.J.
        • McCoy M.H.
        • Iwamoto M.
        • Griffin P.M.
        Foodborne listeriosis acquired in hospitals.
        Clin Infect Dis. 2014; 59: 532-540
        • Ruppitsch W.
        • Prager R.
        • Halbedel S.
        • Hyden P.
        • Pietzka A.
        • Huhulescu S.
        • et al.
        Ongoing outbreak of invasive listeriosis, Germany, 2012 to 2015.
        Euro Surveill. 2015; 20
        • McCollum J.T.
        • Cronquist A.B.
        • Silk B.J.
        • Jackson K.A.
        • O'Connor K.A.
        • Cosgrove S.
        • et al.
        Multistate outbreak of listeriosis associated with cantaloupe.
        N Engl J Med. 2013; 369: 944-953
        • Heiman K.E.
        • Garalde V.B.
        • Gronostaj M.
        • Jackson K.A.
        • Beam S.
        • Joseph L.
        • et al.
        Multistate outbreak of listeriosis caused by imported cheese and evidence of cross-contamination of other cheeses. USA, 2012.
        Epidemiol Infect. 2016; 144: 2698-2708
        • ECDC_EFSA
        Multi-country outbreak of Listeria monocytogenes sequence type 8 infections linked to consumption of salmon products.
        ECDC_EFSA, Solna2018
        • Halbedel S.
        • Wilking H.
        • Holzer A.
        • Kleta S.
        • Fischer M.A.
        • Luth S.
        • et al.
        Large nationwide outbreak of invasive listeriosis associated with blood sausage, Germany, 2018–2019.
        Emerg Infect Dis. 2020; 26: 1456-1464
        • Halbedel S.
        • Prager R.
        • Fuchs S.
        • Trost E.
        • Werner G.
        • Flieger A.
        Whole-genome sequencing of recent Listeria monocytogenes isolates from Germany reveals population structure and disease clusters.
        J Clin Microbiol. 2018; 56 (e00119-18)
        • Kleta S.
        • Hammerl J.A.
        • Dieckmann R.
        • Malorny B.
        • Borowiak M.
        • Halbedel S.
        • et al.
        Molecular tracing to find source of protracted invasive listeriosis outbreak, southern Germany, 2012–2016.
        Emerg Infect Dis. 2017; 23: 1680-1683
        • Jackson B.R.
        • Tarr C.
        • Strain E.
        • Jackson K.A.
        • Conrad A.
        • Carleton H.
        • et al.
        Implementation of nationwide real-time whole-genome sequencing to enhance listeriosis outbreak detection and investigation.
        Clin Infect Dis. 2016; 63: 380-386
        • Moura A.
        • Tourdjman M.
        • Leclercq A.
        • Hamelin E.
        • Laurent E.
        • Fredriksen N.
        • et al.
        Real-time whole-genome sequencing for surveillance of Listeria monocytogenes, France.
        Emerg Infect Dis. 2017; 23: 1462-1470
        • Kwong J.C.
        • Mercoulia K.
        • Tomita T.
        • Easton M.
        • Li H.Y.
        • Bulach D.M.
        • et al.
        Prospective whole-genome sequencing enhances national surveillance of Listeria monocytogenes.
        J Clin Microbiol. 2016; 54: 333-342
        • Ruppitsch W.
        • Pietzka A.
        • Prior K.
        • Bletz S.
        • Fernandez H.L.
        • Allerberger F.
        • et al.
        Defining and evaluating a core genome multilocus sequence typing scheme for whole-genome sequence-based typing of Listeria monocytogenes.
        J Clin Microbiol. 2015; 53: 2869-2876
        • Halbedel S.
        • Prager R.
        • Fuchs S.
        • Trost E.
        • Werner G.
        • Flieger A.
        Whole-genome sequencing of recent Listeria monocytogenes isolates from Germany reveals population structure and disease clusters.
        J Clin Microbiol. 2018; 56e00119-18
        • Goulet V.
        • King L.A.
        • Vaillant V.
        • de Valk H.
        What is the incubation period for listeriosis?.
        BMC Infect Dis. 2013; 13: 11
        • Cheung C.Y.
        • Luber P.
        Investigational tracing as a method for identification of causative foods and sources of food-borne outbreaks.
        J Verbrauch Lebensmitt. 2016; 11: 241-248
        • Schmitz-Esser S.
        • Gram L.
        • Wagner M.
        Complete genome sequence of the persistent Listeria monocytogenes strain R479a.
        Genome Announc. 2015; 3e00150-15
      1. Regierungspräsidium Darmstadt, Bericht der Task-Force Lebensmittelsicherheit. Regierungspräsidium, Darmstadt2019
        • RASFF
        Notification details - 2019.3464—foodborne outbreak caused by Listeria monocytogenes in chilled sausages from Germany.
        RASFF, 2019
        • Halbedel S.
        • Prager R.
        • Banerji S.
        • Kleta S.
        • Trost E.
        • Nishanth G.
        • et al.
        Listeria monocytogenes ST2 clone lacking chitinase ChiB from an outbreak of non-invasive gastroenteritis.
        Emerg Microbe. Infections. 2019; 8: 17-28
        • Mazengia E.
        • Kawakami V.
        • Rietberg K.
        • Kay M.
        • Wyman P.
        • Skilton C.
        • et al.
        Hospital-acquired listeriosis linked to a persistently contaminated milkshake machine.
        Epidemiol Infect. 2017; 145: 857-863
        • Najjar Z.
        • Gupta L.
        • Sintchenko V.
        • Shadbolt C.
        • Wang Q.
        • Bansal N.
        Listeriosis cluster in Sydney linked to hospital food.
        Med JAust. 2015; 202: 448-449
        • Jacks A.
        • Pihlajasaari A.
        • Vahe M.
        • Myntti A.
        • Kaukoranta S.S.
        • Elomaa N.
        • et al.
        Outbreak of hospital-acquired gastroenteritis and invasive infection caused by Listeria monocytogenes, Finland, 2012.
        Epidemiol Infect. 2016; 144: 2732-2742
        • Little C.L.
        • Amar C.F.
        • Awofisayo A.
        • Grant L.A.
        Hospital-acquired listeriosis associated with sandwiches in the UK: a cause for concern.
        J Hosp Infect. 2012; 82: 13-18
        • Winter C.H.
        • Brockmann S.O.
        • Sonnentag S.R.
        • Schaupp T.
        • Prager R.
        • Hof H.
        • et al.
        Prolonged hospital and community-based listeriosis outbreak caused by ready-to-eat scalded sausages.
        J Hosp Infect. 2009; 73: 121-128
        • Cokes C.
        • France A.M.
        • Reddy V.
        • Hanson H.
        • Lee L.
        • Kornstein L.
        • et al.
        Serving high-risk foods in a high-risk setting: survey of hospital food service practices after an outbreak of listeriosis in a hospital.
        Infect Control Hosp Epidemiol. 2011; 32: 380-386
        • Bundesinstitut für Risikobewertung
        Sicher verpflegt-Besonders empfindliche Personengruppen in Gemeinschaftseinrichtungen.
        Bundesinstitut für Risikobewertung, 2017
      2. Kommission für Krankenhaushygiene und Infektionsprävention am Robert Koch-Institut, Anforderungen an die Hygiene bei der medizinischen Versorgung von immunsupprimierten Patienten.
        Bundesgesundheitsblatt. 2010; 53: 357-388
        • European Parliament
        Regulation (EC) No 178/2002 of the European Parliament and of the council of 28 January 2002.
        Official Journal L 031, 2002
        • European Parliament
        Commission Regulation (EC) No 2073/2005 of 15 November 2005 on microbiological criteria for foodstuffs.
        Official Journal of the European Union, 2005
      3. Regulation (EC) No 852/2004 of the European Parliament and of the council of 29 April 2004 on the hygiene of foodstuffs. 2004