High Containment Laboratory, Public Health Agency of Sweden (The Swedish BSL4 laboratory)

2. Responsible public or private organization or company
Public Health Agency of Sweden
3. Location and postal address
Public Health Agency of Sweden, SE-17182 SOLNA, Sweden
4. Source(s) of financing of the reported activity, including indication if the activity is wholly or partly financed by the Ministry of Defence

The activities are financed through the Swedish Government (Ministry of Health and Social Affairs), and through governmental agencies such as Swedish Civil Contingencies Agency (MSB), Swedish Research Council (VR) and partly by the EU (research funds and the Innovative Medicines Initiative and funding through Joint Actions within European Health Program).

5. Number of maximum containment units5 within the research centre and/or laboratory, with an indication of their respective size (SqM):
BL 4 , 136.00 SqM
Two separate BSL4 units enclosing three laboratories
6. Scope and general description of activities, including type(s) of micro-organisms and/or toxins as appropriate

The Public Health Agency of Sweden is a national expert authority with overall responsibility for public health issues at a national level. Our mission is to promote health, prevent illness and contribute to a sustainable society. There are no projects conducted related to biological defence, more than a strive to a better biological understanding of biological agents (see publication list below). The agency develops and maintain national diagnostic preparedness for highly pathogenic agents. Research results is published in international journals.


Risk group 4 agents

In the BSL4 containment units diagnostics and research regarding the following viruses are performed: Arenavirus, Bunyavirus, Coronavirus, Filovirus, Flavivirus, Nairovirus, Orthomyxovirus, Orthopoxvirus and Paramyxovirus. Special emphasis is directed towards the Crimean-Congo haemorrhagic fever virus (CCHFV) and Ebola virus.


Methods for identification

Standard methods are used for identification of these microorganisms. Methods in use include molecular biological methods (including novel high throughput/high capacity methods), serological methods such as neutralization assays, cultivation/isolation and electron microscopy. Public Health Agency of Sweden also has capacity to culture virus in small rodents. The quality of diagnostic methods for many of the pathogens is assured through participation in quality assurance exercises and ring trials within international EC-funded networks.

The general goals are to improve laboratory diagnostics, laboratory capacity and basic knowledge of highly pathogenic agents. This includes the development of platforms for broad, efficient and reliable diagnostic methods, studies of virulence and pathogenesis and the establishment and use of animal models for use in diagnostics, treatment and vaccine development.


Public Health Agency of Sweden: publications in 2020 related to high containment laboratory activities:

Enkirch T, Werngren J, Groenheit R, Alm E, Advani R, Lind Karlberg M, Mansjö M. Systematic Review of Whole-Genome Sequencing Data To Predict Phenotypic Drug Resistance and Susceptibility in Swedish Mycobacterium tuberculosis Isolates, 2016 to 2018. Antimicrob Agents Chemother 2020 Apr 21;64(5):e02550-19. doi: 10.1128/AAC.02550-19. Print 2020 Apr 21

Davies Forsman L, Niward K, Kuhlin J, Zheng X, Zheng R, Ke R, Hong C, Werngren J, Paues J, Simonsson USH, Eliasson E, Hoffner S, Xu B, Alffenaar JW, Schön T, Hu Y, Bruchfeld J. Suboptimal moxifloxacin and levofloxacin drug exposure during treatment of patients with multidrug-resistant tuberculosis: results from a prospective study in China. Clin Microbiol Infect 2020 Oct 24:S1198-743 X (20)30650-9. doi: 10.1016/j.cmi.2020.10.019

Kuhlin J, Davies Forsman L, Mansjö M, Jonsson Nordvall M, Wijkander M, Wagrell C, Jonsson J, Groenheit R, Werngren J, Schön T, Bruchfeld J. Genotypic resistance of pyrazinamide but not MIC is associated with longer time to sputum culture conversion in patients with multidrug-resistant tuberculosis. Clin Infect Dis 2020 Oct 3; ciaa1509. doi: 10.1093/cid/ciaa1509

Schön T, Werngren J, Machado D, Borroni E, Wijkander M, Lina G, Mouton J, Matuschek E, Kahlmeter G, Giske C, Santin M, Cirillo DM, Viveiros M, Cambau E. Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on Mycobacterium tuberculosis. Clin Microbiol Infect 2020 Oct 24; S1198-743X (20)30650-9. doi: 10.1016/j.cmi.2020.10.019

Schön T, Claudio Köser CU, Werngren J, Viveiros M, Georghiou S, Kahlmeter G, Giske C, Maurer F, Lina G, Turnidge J, van Ingen J, Jankovic M, Goletti D, Cirillo DM, Santin M, Cambau E, ESGMYC. What is the role of the EUCAST reference method for MIC testing of the Mycobacterium tuberculosis complex? Clin Microbiol Infect 2020 Nov; 26 (11):1453-1455. doi: 10.1016/j.cmi.2020.07.037. Epub 2020 Aug

Wilson DJ, CRyPTIC Consortium (Werngren J). GenomegaMap: Within-Species Genome-Wide dN/dS Estimation from over 10,000 Genomes. Mol Biol Evol 2020 Aug 1; 37(8):2450-2460. doi: 10.1093/molbev/msaa069

Schön T, Werngren J, Machado D, Borroni E, Wijkander M, Lina G, Mouton J, Matuschek E, Kahlmeter G, Giske C, Santin M, Cirillo DM, Viveiros M, Cambau E. Antimicrobial susceptibility testing of Mycobacterium tuberculosis complex isolates - the EUCAST broth microdilution reference method for MIC determination. Clin Microbiol Infect 2020 Nov; 26(11):1488-1492. doi: 10.1016/j.cmi.2020.07.036. Epub 2020 Aug 1

Kontsevaya I, Werngren J, Holicka Y, Klaos K, Tran A, Nikolayevskyy V. Non-commercial phenotypic assays for the detection of Mycobacterium tuberculosis drug resistance: a systematic review. Eur J Clin Microbiol Infect Dis. 2020 Mar; 39 (3):415-426.  doi: 10.1007/s10096-019-03723-8. Epub 2019 Oct 30

Battaglia S, Spitaleri A, Cabibbe AM, Meehan CJ, Utpatel C, Ismail N, Tahseen S, Skrahina A, Alikhanova N, Mostofa Kamal SM, Barbova A, Niemann S, Groenheit R, Dean AS, Zignol M, Rigouts L, Cirillo DM. Characterization of Genomic Variants Associated with Resistance to Bedaquiline and Delamanid in Naive Mycobacterium tuberculosis Clinical Strains. J Clin Microbiol 2020 Oct 21; 58(11):e01304-20


Hua Y, Bai X, Zhang J, Jernberg C, Chromek M, Hansson S, Frykman A, Yang X, Xiong Y, Wan C, Matussek A. Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden. Emerg Microbes Infect 2020 Dec; 9(1):2562-2570. doi: 10.1080/22221751.2020.1850182

Karatuna O, Dance DAB, Matuschek E, Åhman J, Turner P, Hopkins J, Amornchai P, Wuthiekanun V, Cusack TP, Baird R, Hennessy J, Norton R, Armstrong M, Zange S, Zoeller L, Wahab T, Jacob D, Grunow R, Kahlmeter G. Burkholderia pseudomallei multi-centre study to establish EUCAST MIC and zone diameter distributions and epidemiological cut-off values. Clin Microbiol Infect 2020 Jul 9; S1198-743X(20)30384-0. doi: 10.1016/j.cmi.2020.07.001

Hawman DW, Ahlén G, Appelberg KS, Meade-White K, Hanley PW, Scott D, Monteil V, Devignot S, Okumura A, Weber F, Feldmann H, Sällberg M, Mirazimi A. A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model. Nat Microbiol 2020 Nov 30. doi: 10.1038/s41564-020-00815-6

Appelberg S, Gupta S, Svensson Akusjärvi S, Ambikan AT, Mikaeloff F, Saccon E, Végvári Á, Benfeitas R, Sperk M, Ståhlberg M, Krishnan S, Singh K, Penninger JM, Mirazimi A, Neogi U. Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-Transcriptomics of SARS-CoV-2 infected cells. Emerg Microbes Infect 2020 Dec; 9(1):1748-1760. doi: 10.1080/22221751.2020.1799723

Monteil M, Salata C, Appelberg S, Mirazimi A. Hazara virus and Crimean-Congo Hemorrhagic fever Virus show a different pattern of entry in fully-polarized Caco-2 cell line. PLoS Negl Trop Dis 2020 Nov 24; 14(11):e0008863. doi: 10.1371/journal.pntd.0008863

Devignot S, Kromer T, Mirazimi A, Weber F. ISG15 overexpression compensates the defect of Crimean-Congo hemorrhagic fever virus polymerase bearing a protease-inactive ovarian tumor domain. PLoS Negl Trop Dis 2020 Sep 15; 14(9):e0008610. doi: 10.1371/journal.pntd.0008610

Ahlén G, Frelin L, Nekoyan N, Weber F, Höglund U, Larsson O, Westman M, Tuvesson O, Gidlund EK, Cadossi M, Appelberg S, Mirazimi A, Sällberg M. The SARS-1 CoV-2 N protein is a good component in a vaccine. J Virol 2020 Aug 31;94(18):e01279-20. doi: 10.1128/JVI.01279-20

Jääskeläinen AJ, Sironen T, Kaloinen M, Kakkola L, Julkunen I, Hewson R, Weidmann MW, Mirazimi A, Watson R, Vapalahti O. Comparison of Zaire ebolavirus realtime RT-PCRs targeting the nucleoprotein gene. J Virol Methods 2020 Oct; 284:113941. doi: 10.1016/j.jviromet.2020.113941. Epub 2020 Jul 22

Mertens P, De Vos N, Martiny D, Jassoy C, Mirazimi A, Cuypers L, Van den Wijngaert S, Monteil V, Melin P, Stoffels K, Yin N, Mileto D, Delaunoy S, Magein H, Lagrou K, Bouzet J, Serrano G, Wautier  M, Leclipteux T, Van Ranst M, Vandenberg O. Development and Potential Usefulness of the COVID-19 Ag Respi-Strip Diagnostic Assay in a Pandemic Context. Front Med (Lausanne) 2020 May 8; 7:225. doi: 10.3389/fmed.2020.00225. eCollection 2020 

Zheng Z, Monteil VM, Maurer-Stroh S, Yew CW, Leong C, Mohd-Ismail NK, Arularasu SC, Chow VTK, Lin RTP, Mirazimi A, Hong W, Tan YJ. Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2. Euro Surveill 2020 Jul; 25(28):2000291. doi: 10.2807/1560-7917.ES.2020.25.28.2000291

(4) For facilities with maximum containment units participating in the national biological defence research and development programme, please fill in name of facility and mark "Declared in accordance with Form A, part 2 (iii)".

(5) In accordance with the latest edition of the WHO Laboratory Biosafety Manual, or equivalent.