Joint Action on Quality Assurance Exercises and Networking on the Detection of Highly Infectious Pathogens QUANDHIP QUANDHIP- Main results, lessons learnt, new JA Roland Grunow Giuseppe Ippolito Robert Koch Institute, Berlin National Institute for Infectious Diseases Lazzaro Spallanzani, Rome Health Security Workshop: How to benefit from European projects? 13-14 November 2014, Brussels, Belgium Disclaimer: This presentation has been produced with the support of the European Commission's Consumers, Health and Food Executive Agency (CHAFEA). Its content is the sole responsibility of Robert Koch-Institut, Centre for Biological Threats and Special Pathogens, and can in no way be taken to reflect the views of the CHAFEA or any other body of the European Union. Joint Action on Quality Assurance Exercises and Networking on the Detection of Highly Infectious Pathogens 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 Duration: 1st August 2011 – 31st January 2015 Total EU funding (50%): 3.3 million EURO http://www.quandhip.eu/ Achievements of QUANDHIP - Network The QUANDHIP Joint Action is linking the two existing EU funded networks on highly infectious bacteria and viruses - EQADeBa/ENHPB, coordinated by the Robert Koch Institute (RKI), Germany, and - ENP4Lab, coordinated by National Institute for Infectious Diseases (INMI), Italy. We are not aware that there is a comparable network of defined highly pathogenic bacteria and risk group 4 viruses with similar objectives as QUANDHIP. 17 meetings and audio-conferences (approx. half joint NIB and NIV) Website, leaflets, publications, presentations on scientific and public health conferences Linkage to other relevant networks like the European Network for Diagnostics of Imported Viral Diseases (ENIVD), European Research Infrastructure on Highly Pathogenic Agents (ERINHA), European Mobile Laboratory (EMLab), Mediterranean Living Lab for Territorial Innovation (Medlab), European Virus Archive (EVA) QUANDHIP Participants Participants: 37 Partners from 22 European countries Finland Norway Sweden Estonia Latvia Denmark Lithuania United Kingdom Poland The Netherlands Belgium France Germany Switzerland Czech Republic Austria Hungary Bulgaria Italy Portugal Spain Greece 1 Main Partner 32 Associated Partners 4 Collaborating Partners Achievements of QUANDHIP - External Quality Assurance Exercises - 3 complex EQAEs for NIB including 15-30 samples with living and inactivated high threat bacteria, transportation, speed and quality of sample analysis - 4 EQAE in NIV including a commercial test kit - Professional data analyses and evaluation, reply to laboratories - Identification of specific questions and setting up of topical working groups Antimicrobial Susceptibility Testing (AST) MALDI-TOF Rapid Test Kits Standardized Reference Material (new) - Substantial learning process and improvement by participating laboratories Time critical results Time of providing first (second) preliminary results 128 Q-3 Interpretation: normal range of providing first preliminary results was between 2.2 and 15.9 hours. 64 32 16 8 4 2 1 16 25 01 30 07 27 14 18 24 11 10 04 13 08 20 32 12 26 17 21 15 02 09 28 29 31 Partner EQAE N participants Mean Mean deviation of response time (h) response time (h) E-2 20 15.3 (29.3)* 15.4 (24.7)* E-3 20 11.5 (20.6)* 11.8 (29.3)* Q-1 28 8.4 (12.3)* 8.8 (12.8)* Q-2 28 5.7 ( 9.1)* 3.8 (7.4)* Q-3 26 (24)* 5.9 (17.7)* 2.9 (17.5)* QUANDHIP Q-2 Evaluation of test results *Second preliminary results in brackets; No correlation between response time and correct results www.quodata.de 6 Diagnostic of Native Samples - Final results EQADeBa Correct Results on Native Pathogens in % Ft ssp1 Bruc sp3 Bm Bpsm Ba Yp EQAE Negative Corr pos Corr pos Corr pos (Species level) Corr pos (Genus level) Corr pos Corr pos Corr neg E-2 90 86 73 (88) 86 (95) 86 90 91 100 96 86 (100) 89 (96) 96 96 98 96 -- -- 89 (98) -- 96 845 93 93 722 (92) 584 (94) -- 96 -- 96 92 -- 73 (88) 88 100 735 95 92 77 (93) 79 (94) 90 96 87 (n=21) E-3 (n=22) Q-1 (n=28) QUANDHIP Q-2 (n=27) Q-3 (n=26) mean 1 F.t. only correct subspecies was rated; in brackets correct on species (Ftt, Fth, Ftm) level rated F.t. ssp. mediasiatica difficult to identify 3 Brucella only correct species was rated; in brackets correct as B. melitensis-group rated 4 Three Brucella species had to be differentiated 5 F.t. ssp. novicida was quite frequently detected as target bacteria 2 Additional challenges: targets were mixed with closely related relatives or other relevant bacteria Best Approaches for the Diagnostic of Native Samples Applied methods EQADeBa E-2 participants n=21 15 samples n (%) % correct results QUANDHIP Q-2 participants n=27 10 samples n (%) % correct results Preliminary PCR (± other methods) & Confirmation by cultivation and subsequent PCR (± other methods) 15 (71) 90 20 (74) 73 PCR without cultivation 2 (10) 63 1 (4) 44 Other methods: - Staining, microscopy, electron microscopy (under discussion), metabolism Immunology MALDI-TOF for culture identification E-2 n=1, Q-2 n=12 PLEX-ID Abbott, Ligase Chain Reaction (n=2, very good results – 100% correct) Target Agents in Focus Bacteria Viruses • Bacillus anthracis • Filoviruses (Ebola Hemorrhagic Fever) • Francisella tularensis • Arenaviruses (Lassa Hemorrhagic Fever) • Yersinia pestis • Bunyaviruses (Crim Congo Hemorrhagic Fever) • Burkholderia mallei • Orthopoxviruses • Burkholderia pseudomallei • Paramyxoviruses like Nipah and Hendra viruses. • Brucella sp. • New viruses • Coxiella burnetii Achievements of QUANDHIP - Repositories, training, biosafety Repository of reference material • Almost 150 strains of highly pathogenic bacteria – centralized at RKI • Viral DNA from almost 24 strains – stored at different laboratories Training • Partners offered practical laboratory based one-week training for other participants according to best practices and needs: appropriate diagnostic algorithm, syndromic approach, differential diagnosis, biosafety and biosecurity. • Conducted training course: 12 in NIB on topical issues and several in NIV focused on BSL-4 working practice, security measures, staff prerequisites, risk assessment and emergency scenario planning. Biosafety and Biosecurity • Checklists for self-evaluation of BSL-3 and BSL-4 laboratories based on own experiences and other documents like CWA 15793:2008/16393: 2012 Laboratory biorisk management-Guidelines. • Experience on shipment and sample sharing of Category A agents Achievements of QUANDHIP - Laboratory Response (WP8) Recommendations for support to coordination of operational response to health threats events due to highly infectious pathogens (BSL 3/4) developed by a specific Working Group. - A Working Group (WG) under the lead of INMI was established - Questionnaires to evaluate the capacities, capabilities, and collaboration procedures of participating laboratories have been developed. - Guideline “QUANDHIP laboratories response to outbreaks due to Highly Infectious Pathogens” Adopted to the current outbreak of Ebola-fever: Brief instructions for handling and transport of samples from suspected cases and exposed contacts, including referral for diagnostic confirmation Antonino Di Caro Main priority areas and gaps on lab health security preparedness 1. The collaboration between the bacterial and viral components of the network is required including the management of diagnostics of unknown infectious pathogens requiring the collaboration of BSL3and BSL4-laboratories. 2. The collaboration with other EU networks (ENIVD, ERINHA) and projects was initiated but need to become effective. 3. EQAE on highly pathogenic agents has a clear European dimension. Many MS do not have the power to conduct such proficiency tests, which on the other hand are required for assessing the quality of diagnostics and finally for accreditation purposes. Main priority areas and gaps on lab health security preparedness 4. The centralized repository of bacterial isolates is a useful tool to generate quality assured reference material of highly pathogenic bacteria. The risk group 4 viruses repository is decentralised due to security issues. 5. Training courses on diagnostic approaches and biorisk management of the laboratories are effective and appropriate tools to improve the performance of the laboratories and to set up new approaches. The training courses have been an important element to establish cooperation and mutual support between laboratories. 6. The check-list on biosafety and biosecurity appeared in a first evaluation as a helpful tool and should become an applicable document. 7. An effective and coordinated laboratory response to health threats is required. Main priority areas and gaps on lab health security preparedness 8. The viral network should be extended including also non-BSL4 laboratories that are national referral centres for viral haemorrhagic fever and other risk group 4 agents in MS. 9. A more flexible use of available funds must be implemented in order to support outbreak response in case of need. Ideas on how to ensure sustainability • Appropriate laboratory response to health threats is required on long term. • Quality assurance of diagnostics is a permanent task. • Due to the rare occurrence of highly pathogenic infectious agents, this has a clear European dimension requiring networks of nominated laboratories. • Because of the European dimension, basic activities require European funding. • Identified long term tasks should be funded on a long term basis using alternative mechanisms in comparison to projects and Joint Actions. Main future actions for strengthening the laboratory preparedness WP 2014 - Rapid and coordinated responses to emerging threats (Decision 1082/2013) objective: ensure efficient response to events through reinforcing the existing EU network of Risk Group 3 and Risk Group 4 laboratories • enable an efficient and coherent EU level response and support for MS in implementing IHR • fully linked to existing structures in place in other sectors (FP7 networks, initiatives developed by ECDC, WHO Reference Laboratory Networks) • build on previous work of QUANDHIP consortium and further integrate activities of the two different networks ENHPB and EuronetP4 Health Programme - Work Programme for 2014: 22.214.171.124 Specific services: (a) rapid identification of pathogens causing serious cross-border threats to health (bacterial and viral); (b)rapid mechanisms for sample sharing in case of an event to be managed under Decision No 1082/2013/EU; (c) confirmation of laboratory diagnosis; (d)quality assurances for detection of highly pathogenic bacteria of potential bioterrorism risk; (e) training, capacity building in the infection control area and in the biosafety/biosecurity quality management; (f) consolidation of bio-diverse repository of reference materials; and (g)promotion of interoperability with other relevant EU and international research and public health networks/projects/organizations in the field of emerging infection. Main future actions for strengthening the laboratory preparedness The new Joint Action should function in a normal mode and in an outbreak response mode. 1. Network of networks should be improved and consolidated. Based on previously made agreements a coordinated and effective response in outbreak situations. 2. Further improving the capabilities for rapid diagnosis, including sample sharing. Offering appropriate support to all MS in outbreak situations. 3. Maintaining the quality assurances for detection of highly pathogenic agents, maintenance of repositories of reference material. Solving topical diagnostic issues. Agent directed quality assurance and provision of reference material in outbreak situations. 4. Training of new participants and on special issues. Agent directed training in outbreak situations. Ebola outbreak response activities • Support to HSC • Support to diagnostic activities in Europe • Support to diagnostic activities in West Africa Network activation for EBOLA outbreak HSC invited the coordinator of QUANDHIP-NIV to contact all NIV partners to evaluate their capabilities and to give information on: the availability to accept samples from other countries; the laboratory capacity and the methods which they are able to perform; the list of names and contact; details of persons available to be contacted by the NIV coordinator in case of need; (landline phone, mobile, e-mail, days and times of 24/7 availability); the procedures for shipment of samples, including exact address and contact person for delivery. Network activation for EBOLA outbreak The network has supported the activities of the European Mobile Laboratory project in the field (3 labs and more than 60 highly specialized European lab workers deployed in Africa starting from the very beginning of the international outbreak response at the end of march 2014). Strong collaboration between partners for management of samples in Europe and for the exchange of referral and diagnostics material and viral sequences. Distribution of diagnostic kits to partners’ laboratories. European Laboratories available for Ebola diagnostics in framework of QUANDHIP List of BSL-4 laboratories BNI, Hamburg, Germany Contact information PHE, Porton Down, Salisbury, UK Contact information INMI, Rome, Italy Contact information INSERM, Lyon, France NCE, Budapest, Hungary Contact information Contact information PUM, Marburg, Germany FOHM, Solna, Sweden Contact information Contact information FOCP, Spiez, Switzerland Contact information Additional skilled diagnostic capabilities for Viral Hemorrhagic Fevers Instituto Nacional Saúde Dr Ricardo Jorge, Lisboa, Portugal Robert Koch Institute, Berlin, Germany Contact information Bundeswehr Institute of Microbiology, Munich, Germany Instituto de Salud Carlos III (ISCIII), Madrid, Spain Contact information Contact information Contact information The European mobile lab project: Partners Partners The European mobile lab project: Partners This project is funded by: The European Commission, EuropAid - DG Developement and Cooperation (DEVCO)(EC) Implementing partner: Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany (BNITM) Partners in sub-Saharan Africa: Institute for Lassa Fever Research and Control (ILFRC), Irrua Specialist Teaching Hospital, Irrua, Nigeria (ISTH) National Institute for Medical Research, Dar es Salaam, Tanzania (NIMR) Partners in Europe: Institute of Microbiology of the German Armed Forces, Munich, Germany (InstMikroBioBw) Istituto Nazionale per le Malattie Infettive "L. Spallanzani", Rome, Italy (INMI) Institute for Virology, Philipps-University Marburg, Marburg, Germany (PUM) Laboratoire P4 Inserm Jean Merieux, Lyon, France (INSERM) Spiez Laboratory, Spiez, Switzerland (Labor-Spiez) Public Health England, Microbiology Services Division-Colindale, London, UK, and Microbiology Services-research (Porton), Salisbury, UK (PHE) Associated Partners: National Centre for Epidemiology, Budapest, Hungary (NCE) Robert Koch Institut, Berlin, Germany (RKI) Institute of Microbiology and Immunology, University of Ljubljana, Ljubljana, Slovenia (IMI) Further organizations relevant to the project: The World Health Organization (WHO) Global Outbreak Alert & Response Network (GOARN) European Centre for Disease Prevention and Control (ECDC) Other networks for infectious diseases research and diagnostics: European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) European Network of P4 Laboratories (ENP4Lab) European Research Infrastructure on Highly Pathogenic Agents (ERINHA) European Virus Archive (EVA) Quality Assurance Exercises and Networking on the Detection of Highly Infectious Pathogens (QUANDHIP) Joint Action „QUANDHIP“ Thanks to all partners of the project. Thanks to decision makers of the EU Commission supporting our Joint Action. Thanks to the CHAFEA for helpful advice and support. Thanks to the ECDC, WHO and others for participating in the Scientific Advisory Board. Thank you for your attention!