ESCMID Online Lecture Library © by Author

The European Network of Biosafety Level-4 Laboratories

Carla Nisii National Institute for Infectious Diseases© by ‘L. authorSpallanzani’

ESCMID Post-graduate Education course ESCMID OnlineMarseille, MarchLecture 19 2012 Library

WHO Collaborating Center for clinical care, diagnosis, INMI L. Spallanzani response and training on Highly Infectious Diseases Rome

The European Network of P4 laboratories, Marseille, 19th March 2012

1. Characteristics of biosafety laboratories 2. Why we need networks 3. Euronet-P4 (2004-2007), ENP4-Lab (2007- 2010) 4. Satellite activities,© by authorpresent and future (HEIBL, ERINHA, QUANDHIP, Mobile labs..). ESCMID Online Lecture Library Infectious agents: 4 risk groups

The classification in four risk groups is based on the following criteria:

• whether the agent is pathogenic for humans or animals;

• whether the agent is a hazard to employees; © by author • whether the agent is transmissible to the community;

•ESCMID whether there Onlineis effective treatmentLecture or prophylaxisLibrary available.

WHO Laboratory Biosafety Manual, 3 Ed., 2004 Risk Groups: definitions (WHO Laboratory biosafety manual, 2004, Third edition)

(WHO Laboratory biosafety manual, 2004, Third edition)

 Procedures  Controlled access (cardkey control)  Sterilization of lab clothing, equipment, waste  Clinical assessment, baseline serum of staff  Biosafety manual

 Protective equipment  Biosafety cabinets (BSC-II)  PPE (wrap-around gown, scrub suit, shoe covers eye protection) © by author  Respiratory protection may be used

 BuildingESCMID characteristics Online Lecture Library  Anteroom (Double door)  Sealable for decontamination  Negative internal pressure  Dedicated air treatment/conditioning system, no re-circulation[HEPA (high efficiency particulate air) filters for outgoing air] Biosafety level 4

 Procedures  As BSL-3, plus:  Complete change of clothing  Shower upon exit

 Protective Equipment  As BSL-3, plus:  All procedures performed in BSC-III (GLOVE BOX type), OR:  BSC-II, wearing full body positive pressure suits (‘space suits’) (SUIT type) © by author

 Building characteristics  As BSL-3, plus: ESCMID Separate from restOnline of lab Lecture Library  Airlock entry with shower  HEPA filters sia in entrata che in uscita  Double ended, interlocked autoclave Why do we need networks of BSL-4 laboratories?

The European Network of P4 ©laboratories by author ESCMID Online Lecture Library BSL4 laboratories in Europe

Glovebox-system

BSL-3 BSL-4 BSL-4 UC/planned Needs at EU level

 Ensure a rapid and effective response to health threats deriving from natural infection by highly infectious agents or their deliberate release  Stimulate complementarity and prevent duplication

 Promote exchange of information and international cooperation © by author  Share good practice and protocols ESCMID Online Lecture Library  Cooperation agreement for training, communication, and service availability to other Countries Needs of laboratories and scientists

 Few BSL-4 labs around the world

 Diagnostic methods are home-made

 Share materials and experience (External Quality Assurance Exercises)

 Share biosafety© by practicesauthor

 Offer support to other countries, rapid ESCMIDcommunication Online Lecture Library © by author ESCMID Online Lecture Library European Network of P4 laboratories

 First funded in 2005 (Euronet-P4, 2005- 2007, DG-SANCO)

 Second funding in 2007 (ENP4-Lab 2007-2010, PHEA)

 Became part© byof Quandhipauthor (2011-2014, PHE)

ESCMID ERINHA Online Lecture Library

 Mobile laboratory initiative Euronet-P4 and ENP4-Lab: Partners

 INMI IRCCS L. Spallanzani, Italy  Health Protection Agency, London and Porton Down, UK  Philipps Universitat Marburg, Germany  Bernhardt Nocht Institute of Tropical Medicine, Hamburg, Germany  Swedish Institute for Infectious Disease Control, Solna, Sweden© by author  Inserm, Lab. P3/P4 Jean Mérieux, Lyon, France (as of ESCMID2007) Online Lecture Library Euronet-P4 and ENP4-Lab: Observers

 Institut Pasteur, Lyon, France

 Robert Koch Institute, Berlin, Germany

 Bundeswehr Institute of Microbiology, Munich, Germany

 University of Marseille, France

 Austrian Agency for Health and Food Safety, Vienna, Austria

 Spiez Laboratory- Federal Office for Civil Protection, Spiez, Switzerland

 Centre International© deby Recherches author Médicales de Franceville – Gabon

 RIVM (National Institute for Public Health and the Environment ESCMID– The Netherlands Online Lecture Library

Euronet-P4 and ENP4-Lab: Aims

Aims 2005-2007  Development of a network of the existing P4 laboratories in Europe  Improvement of diagnostic capabilities  Training, communication, service availability  Cooperation with other EC-funded networks and international activities © by author Aims 2007-2010  Harmonisation of biosafety procedures through establishment of a ‘checklist’ ESCMID Harmonisation Online of diagnostic Lecture procedures through Library External Quality Assurance exercises  Mobile laboratory feasibility study

Euronet-P4/ENP4-Lab: Results

 Web Site with public and restricted access areas (www.euronetp4.eu)  Cooperation Agreement for sharing information, procedures, diagnostic samples and personnel for training  Collection and evaluation of protocols for diagnostic procedures for risk group-4 agents  Review of biosafety procedures in P4 labs  Dissemination meeting on diagnostic and biosafety/biosecurity aspects (Rome, 21©-22 by May author2007)  Definition of minimum training requirements for staff  Checklist for Biosafety and Biosecurity aspects ESCMID Quality assurance Online exercises Lecture (Arena, Filoviruses, Library CCHF, Nipah, Hendra, Orthopoxviruses)  Feasibility study for the establishment of a Mobile lab

Present and future

HEIBL, ERINHA, QUANDHIP, Mobile laboratory© by author initiative, other ESCMID Onlineresearch Lecture projects Library Satellite activities

 HEIBL Conference (Harmonising European Initiatives on Biocontainment Laboratories), Rome, 9-10 September 2010.

 Assessment of diagnostic capability through EQA and international exercises (GHSAG-LN: Global Health Security Action Group – Laboratory Network).

 EQA on: Smallpox© (2003,by author2006, molecular, CDC Atlanta); other Poxviruses (2003, molecular); (2003, 2005 EM, Berlin); VHF (2008 - Winnipeg, 2011 – Rome, molecular) ESCMID Transportation Online exercise: LectureAriel (Smallpox sample Library to CDC, 2007)

HEIBL: Objectives

 To bring together key opinion leaders, membes or EU and international networks and institutions, representatives of member states.  To provide lessons learned in the area of Biopreparedness and Research on high-risk biological agents© by author

ESCMID To harmonise Online EU initiatives,Lecture stimulate Library future networking and capacity building

HEIBL: Participants

 European Bodies (DG SANCO, DG ENTR, EAHC, ECDC)  INMI Spallanzani (I), HPA (UK), SMI (Se), PUM Marburg (DE), BNI-TM (DE), Inserm (F), Rocky Mountain Laboratories (USA), Bundeswehr Institute of Microbiology (DE), Pasteur Institute (F), RKI (DE), Spiez Laboratory (CH), ISS (I), University Innsbruck, University Graz, Italian Army and Air Force, Stockholm International© by author Peace Research Institute (Se). ESCMID Astra Diagnostics Online Lecture Library  Public Health Institutes from: Lithuania, Latvia, Portugal, Hungary.  Networks: ENIVD, Biosafety-Europe

HEIBL: Critical issues

 Sustainability (diagnostics, training, research)

 Avoiding proliferation and duplication

 Biosafety

 Training © by author

 Mobile laboratories (sample transport, ESCMIDincrease Online diagnostic Lecture capacity, Library research)

Interoperability

 Many international initiatives

 DG SANCO, DG Research

 DG ENTR, DG Justice- DG RELEX

 ECDC

 WHO, GOARN

 GHSAG-LN (Global Health Security Action Group – Laboratory Network)© by author

 ENP4-Lab, ENIVD, EURONHID, ETIDE, QUANDHIP ESCMID(from EQADeBa Online and ENP4 Lecture-Lab), Epinorth, Library Episouth  ERINHA (FP7)

 BBMRI Ongoing initiatives involving BSL4 labs

• QUANDHIP (Quality Assurance Exercises and Networking on Detection of Highly Infectious Pathogens)

• ERINHA (European Research Infrastructure on Highly Pathogenic Agents) © by author • Mobile laboratory initiative (DG DevCo) ESCMID Online Lecture Library • Disease specific and other research projects in EID field (CCHF, WNV, PreDemics, Antigone)

QUANDHIP

 Coordinator: Roland Grunow/ Daniela Jacob Robert Koch-Institut Berlin, Germany

 Co-Coordinator: Giuseppe Ippolito/ Antonino Di Caro L. Spallanzani National Institute for Infectious Diseases (INMI), Rome, Italy © by author Additional staff involved: RKI – Uschi Sauer, Anna Rohleder, Anne Barduhn, Birgit Arnold, et al INMI – Maria R. Capobianchi, Ramona Iacovino, Francesco Maria ESCMIDFusco, Donatella Online Vincenti, Carla LectureNisii Library QUANDHIP: General Objectives

 To provide an integrated European laboratory infrastructure and strategy to protect European citizens against exposure to a panel of globally recognized high threat bacteria and viruses, which occur naturally and are potential bioterrorism agents.

 To link and consolidate two existing networks on highly infectious bacteria and viruses emerged from the EU funded projects EQADeBa/ENHPB, coordinated© by byauthor the Robert Koch-Institut (RKI), Germany (EAHC n° 2007 204) and the ENP4-Lab coordinated by National Institute for Infectious Diseases (INMI), Italy (EAHC n° ESCMID2006 208), Online Lecture Library

 To support a sustainable long-term programme. QUANDHIP: Specific objectives

 External Quality Assurance Exercises

 Setting up of a repository for reference materials

 Training on best diagnostic practices and biosafety/biosecurity

 Further improvement© by and author application of checklists for evaluation of Biosafety and Biosecurity laboratory ESCMIDmanagement Online Lecture Library  Support to laboratory outbreak response coordination

QUANDHIP: Focus

Diagnosis and detection of high threat bacteria and viruses:

Bacteria Viruses Bacillus anthracis Filoviruses (EBOLA, MARBURG) Francisella tularensis Arenaviruses (LASSA) Yersinia pestis Bunyaviruses (CCHF) Burkholderia mallei © by authorOrthopoxviruses Burkholderia pseudomallei Paramyxoviruses like Nipah and ESCMID Online LectureHendra viruses. Library Brucella sp. New viruses Coxiella burnetii QUANDHIP: Partners/1

ENHPB: 27 AP, 4CP; ENP4-Lab: 6 AP, 2 CP

1. Robert Koch-Institut (RKI), Berlin, GERMANY 2. Agency for Health an Food Safety (AGES), Vienna, AUSTRIA 3. Veterinary & Agro-chemical Research Institute (VAR), Brussels, BELGIUM 4. Swedish Institute for Infectious Disease Control (SMI-NIB), Stockholm, SWEDEN 5. Health protection Agency, Centre for Emergency Preparedness and Response (CEPR-HPA-NIB), Porton Down, UK 6. National Center for Epidemiology (NCE), Budapest, HUNGARY 7. Friedrich Loeffler Institute, Institute for Animal Health (FLI), Jena, GERMANY 8. Norwegian Institute of Public Health© (NIPH),by Oslo,author NORWAY 9. Istituto Superiore di Sanità (ISS), Rome, ITALY 10. NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS (NKUA), Athens, GREECE 11. Nacionaline visuomenes sveikatos prieziuros laboratorija (National Public Health Surveillance ESCMIDLaboratory) (NVSPL), Vilnius, Online LITHUANIA Lecture Library 12. National Institute for Public Health and the Environment (RIVM), Bilthoven, THE NETHERLANDS 13. National Institute for Health and Welfare (THL), Helsinki, FINLAND 14. Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata (IZSPB), Foggia, ITALY QUANDHIP: Partners/2

15. Bundeswehr Institute of Microbiology (IMBBw), Munich, GERMANY 16. Instituto Nacional Saúde Doutor Ricardo Jorge (INSA), Lisboa, PORTUGAL 17. Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna (IZSLER), Pavia, ITALY 18. National Institute for Nuclear, Chemical and Biological Protection (SUJCHBO), CZECH REPUBLIC 19. Instituto de Salud Carlos III (ISCIII), Madrid, SPAIN 20. Direction Générale de l’Armement (DGA), VERT LE PETIT, FRANCE 21. National Veterinary Research Institute (NVRI), Puławy, POLAND 22. Infectiology Center of Latvia© (LIC), by Riga, LATVIAauthor 23. National Center of Infectious and Parasitic Disease (NCIPD), Sofia, BULGARIA 24. Fundación Vasca de Innovación e Investigación Sanitarias (BIOEF), Sondika, SPAIN 25. National Institute of Public Health - National Institute of Hygiene (NIZP-PZH), Warsaw, ESCMIDPOLAND Online Lecture Library 26. National Veterinary Institute, Technical University of Denmark (DTU-VET), Copenhagen, DENMARK 27. Terviseamet (Health Board) (TA), Tallin, ESTONIA QUANDHIP: Partners/3

28. L. Spallanzani National Institute for Infectious Diseases (INMI), Rome, ITALY 29. Bernhard-Nocht-Institute for Tropical Medicine (BNI), Hamburg, GERMANY 30. Health protection Agency, Centre For emergency Preperedness and Response (CEPR-HPA-NIV), Salisbury, UK 31. Philipps Universität Marburg (PUM), Marburg, GERMANY 32. SWEDISH INSTITUTE FOR INFECTIOUS DISEASE CONTROL (SMI-NIV), Stockholm, SWEDEN 33. Institut National de la Santé et de la Recherche Médicale (INSERM), Lyon, FRANCE Collaborating partners 1. Federal Office for Civil Protection (FOCP), Spiez Laboratory, Spiez, Switzerland (Bacteria) 2. Laboratoire National de Santé (LNS), Luxembourg 3. Institut de Recherche Biomédicale© des by Armées author (CRSSA), La Tronche, France 4. Hungarian Biosafety Laboratory at National Center for Epidemiology, Budapest, Hungary 5. DG ENTR, H3, SRD BEY, Brussels, EU 6.ESCMIDFederal Office for Civil ProtectionOnline (FOCP), Spiez Lecture Laboratory, Spiez, SwitzerlandLibrary (Viruses) EFTA: Norway, Switzerland missing: Malta, Romania, Cyprus, Ireland, Slovakia, Slovenia

ERINHA: General objectives

 To build a pan-European research infrastructure aiming to reinforce European capacity for the study and surveillance of highly pathogenic agents.

 To provide access to state-of-the-art BSL-4 facilities for the European scientific community to enhance basic and finalised© researchby author and diagnostic activities.

ESCMID To strengthen Online European Lecture capacity to face:Library

 Emergence and re-emergence of highly pathogenic agents

 Occurrence of bioterrorist attacks ERINHA: Specific objectives

 Diagnosis

 Research (new diagnostic tools, therapeutic and prophylactic means, animal experimentations)

 Training

 Harmonisation ©of Biosafety by author and Biosecurity

 Management of collection and access to biological ESCMIDresources Online Lecture Library

ERINHA: Creation of a Pan- European BSL-4 laboratory

Each partner laboratory:

 Offers its capacity to build ERINHA

 Shares common procedures and practices

 Shares reagents© by author

 Facilitates Access ESCMID Online Lecture Library ERINHA: Actions

 Creation of a coordination and governance body

 Upgrading some existing labs, building new ones

 Building support infrastructures where needed

 Developing common standards and harmonising procedures © by author  Building an access programme for those that will not have BSL-4 capacity ESCMID Online Lecture Library ERINHA: Partners

 Institut National de la Santé et de la Recherche Médicale - FRANCE

 Osterreichische Agentur fur Gesundheit und Ernahrungssicherheit - AUSTRIA

 Medizinische Universitaet Graz - AUSTRIA

 Prins Leopold Institut voor Tropische Geneeskunde - BELGIUM

 Statens Serum Institute - DENMARK

 Friedrich Loeffler Institut – Bundesforschungsinstitut fur Tiegersundheit – GERMANY

 Philipps Universitat Marburg – GERMANY

 Bernhard Nocht Institut fur Tropenmedizin – GERMANY

 Robert Koch Institut – GERMANY

 Hellenic Pasteur Institut – GREECE

 Istituto Nazionale Malattie Infettive L. Spallanzani – ITALY

 Dr Victor Babes Foundation – ROMANIA  Dr Victor Babes Clinical Hospital© of byInfectious author and Tropical Diseases – ROMANIA  Slovak Medical University – SLOVAKIA

 Smittskyddinstitutet – SWEDEN

 Health Protection Agency – UK ESCMID Instituto Nacional deOnline Saude Dr Ricardo Jorge Lecture – PORTUGAL Library  Hacettepe University – TURKEY

 Marmara University – TURKEY

 Inserm Transfert SA – FRANCE

 Instituto de Salud Carlos III – SPAIN

 National Center for Epidemiology - HUNGARY ERINHA: Associated Partners

 Austrian Federal Ministry of Science and Research – AUSTRIA

 Flemish Government, Department Science, Technology and Innovation – BELGIUM

 National Ministry of Higher Education and Research – FRANCE

 General Secretariat for Research and Technology, Ministry of Development – GREECE

 Ministry of Labour, Health and Social Policies – Health Sector – ITALY

 Health Research Board – IRELAND

 Instituto de Higiene e Medicina Tropical – PORTUGAL

 Romanian Academy – Stefan S. Nicolau Institute of Virology – ROMANIA

 Swedish Research Council – SWEDEN

 Karolinska Institute – SWEDEN ESCMID Ministry of Health Online of the Slovak Republic Lecture – SLOVAKIA Library  St. George’s Hospital - UK Mobile laboratory Initiative

 Instrument for Stability (DG-DevCo, EC)

 Establishment of Mobile laboratories for pathogens up to Risk Group 4  All sub-Saharan© byAfrican author countries  South-Eastern Europe

 End users: African and South Eastern European ESCMIDInstitutions Online Lecture Library Mobile BSL-3/4 laboratories

 CDC (USA), Public Health Agency Canada

 Rapid deployment via public transport systems (small units)

 Able to process large numbers of samples

ESCMID Bring BSL Online-3/4 capacity Lecture in areas Library where it is limited or non-existent Mobile labs: examples

 Towner JS, et al. Rapid diagnosis of Ebola haemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol. 2004;78:4330-41.

 Grolla A, et al. Laboratory diagnosis of Ebola and Marburg haemorrhagic fever. Bull soc Pathol Exot. 2005;98:205-9.

 Towner JS, et al. Marburgvirus genomics and association with a large haemorrhagic fever outbreak in Angola. J Virol. 2006;80:6497-516.

 Onyango CO, Opoka ML, et© al. Laboratory by author diagnosis of Ebola haermorrhagic Fever during an outbreak in Yambio, Sudan, 2004. J Infect Dis. 2007;196:S193-8.

 Towner JS, et al. High-throughput molecular detection of haemorrhagic fever virus threats ESCMIDwith applications for Online outbreak settings. JLecture Infec Dis. 2007;196:S205 Library-12.

 Grolla A, et al. The use of a mobile laboratory unit in support of patient management and epidemiological surveillance during the 2005 Marburg Outbreak in Angola. PLoS Negl Trop Dis. 2011;5:1183. Epub 2011 May 24.

Mobile lab initiative: objectives

 To set up a collaborative network involving European and African Institutions

 Post-crisis management of samples, ESCMIDstrains, Onlineintellectual Lecture property. Library

 One Unit in Europe, 2 Units in Africa WHO ENIVD GOARN-Global outbreak/alert response CDSR-Communicable Disease Surveillance and Response RiViGene European Commission Research DG

Public Health DG (SANCO, EAHC)

EURONET DevCo DG

ESCMID Online Lecture LibraryNetworks with developing countries Laboratory Network RESEARCH COORDINATION INTERNATIONAL (FP6 – FP7) DG-SANCO COOPERATION DG-DevCo (EuropeAid)

VHF – Variola (2004-2006) Euronet-P4 (2005-2007)

ENP4-Lab (2007-2010)

Mobile laboratory initiative (2012-?) ERINHAESCMID (2010-2016) Online Lecture Library