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: 2.2.2.1
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!