- Email: [email protected]
The contribution of the European high containment laboratories during the 2014–2015 Ebola Virus Disease emergency
Accepted Manuscript The contribution of the European high containment laboratories during the 2014-2015 Ebola Virus Disease (EVD) emergency Carla Nisii, Donatella Vincenti, Francesco M. Fusco, Jonas Schmidt-Chanasit, Caroline Carbonnelle, Hervé Raoul, Markus Eickmann, Roger Hewson, Andreas Brave, Sofia Nuncio, Mari Paz Sanchez-Seco, Bernadette Palyi, Zoltan Kis, Sabine Zange, Andreas Nitsche, Andreas Kurth, Marc Strasser, Maria R. Capobianchi, Amanda Ozin, Paolo Guglielmetti, Cinthia Menel-Lemos, Daniela Jacob, Roland Grunow, Giuseppe Ippolito, Antonino Di Caro, MD PII:
S1198-743X(16)30227-0
DOI:
10.1016/j.cmi.2016.07.003
Reference:
CMI 646
To appear in:
Clinical Microbiology and Infection
Received Date: 28 April 2016 Revised Date:
30 June 2016
Accepted Date: 2 July 2016
Please cite this article as: Nisii C, Vincenti D, Fusco FM, Schmidt-Chanasit J, Carbonnelle C, Raoul H, Eickmann M, Hewson R, Brave A, Nuncio S, Sanchez-Seco MP, Palyi B, Kis Z, Zange S, Nitsche A, Kurth A, Strasser M, Capobianchi MR, Ozin A, Guglielmetti P, Menel-Lemos C, Jacob D, Grunow R, Ippolito G, Di Caro A, The contribution of the European high containment laboratories during the 2014-2015 Ebola Virus Disease (EVD) emergency, Clinical Microbiology and Infection (2016), doi: 10.1016/j.cmi.2016.07.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Intended Category: Commentary
2
The contribution of the European high containment laboratories during the 2014-2015 Ebola
3
Virus Disease (EVD) emergency
5
RI PT
4
Running Title: European BSL-3/4 laboratories in the EVD emergency
6
Carla Nisii1, Donatella Vincenti1, Francesco M Fusco1, Jonas Schmidt-Chanasit2, Caroline
8
Carbonnelle3, Hervé Raoul3, Markus Eickmann4, Roger Hewson5, Andreas Brave6, Sofia Nuncio7,
9
Mari Paz Sanchez-Seco8, Bernadette Palyi9, Zoltan Kis9, Sabine Zange10, Andreas Nitsche11,
M AN U
SC
7
10
Andreas Kurth11, Marc Strasser12, Maria R. Capobianchi1, Amanda Ozin13 , Paolo Guglielmetti14,
11
Cinthia Menel-Lemos15 , Daniela Jacob11, Roland Grunow11, Giuseppe Ippolito1, and Antonino Di
12
Caro1*.
TE D
13 1
‘Lazzaro Spallanzani’ National Institute for Infectious Diseases-IRCCS, Rome, Italy
15
2
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
16
3
Laboratoire INSERM Jean Mérieux, Lyon, France
17
4
Institute of Virology, University of Marburg, Marburg, Germany
18
5
Public Health England, Porton Down, Salisbury, UK
19
6
SMI, Solna, Sweden
20
7
Instituto Nacional de Saude, Lisbon, Portugal
21
8
Centro Nacional de Microbiologia, ISCIII, Madrid, Spain
22
9
National Center for Epidemiology, Budapest, Hungary
23
10
Bundeswehr Institute of Microbiology, Munich, Germany
AC C
EP
14
ACCEPTED MANUSCRIPT 11
Robert Koch Institut, Berlin, Germany
25
12
Federal Office for Civil Protection, Spiez Laboratory, Switzerland
26
13
European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
27
14
European Commission - DG SANTE – Health threats Unit – Luxembourg
28
15
29
Luxembourg
RI PT
24
European Commission - Consumers, Health, Agriculture and Food Exceutive Agency (Chafea) –
SC
30
*Address for correspondence:
34
Antonino Di Caro, MD
35
Lazzaro Spallanzani National Institute for Infectious Diseases
36
292 Via Portuense, 00149 Rome (Italy)
37
Phone: +39 06 55170688
38
Fax: +39 06 55170683
39
E-mail: [email protected]
42 43 44
Word Count: 1187
TE D
AC C
41
EP
40
M AN U
31 32 33
45 46 47 48 2
ACCEPTED MANUSCRIPT Since December 2013, the world has experienced the worst-ever epidemic of Ebola virus disease
50
(EVD), which has caused thousands of deaths in several West African countries. When the
51
epidemic began, the European Union (EU) was not unprepared, thanks to the ten-year-long
52
commitment of the European Commission (EC) to fund several networks in the area of highly
53
infectious diseases. The European Network of Biosafety-Level 4 (BSL-4) laboratories (Euronet-P4,
54
later called ENP4-Lab) was one of them; it has been operating since 2004, bringing together the
55
facilities where Risk-Group 4 (RG-4) pathogens such as Ebola can be safely handled [1]. In 2010,
56
with the aim of increasing European preparedness in the fight against highly infectious trans-border
57
threats, a new Joint Action was launched, resulting from the union of the networks that had
58
previously worked on the diagnostics of highly infectious viruses and bacteria: ENP4-Lab and
59
EQADEBA. The new Joint Action was named QUANDHIP (Quality Assurance Exercises and
60
Networking on the Detection of Highly Infectious Pathogens) and one of its aim was to harmonize
61
diagnostic procedures by first reviewing the diagnostic capabilities for highly infectious pathogens,
62
including filoviruses (Ebola and Marburg) and then running external quality assessment (EQA)
63
rounds. The results included an up-to-date compilation of methods for antibody and antigen
64
detection, electron microscopy, molecular biology assays, viral culture, and reagents available for
65
sharing. All BSL-4 laboratories in Germany, the United Kingdom, Italy, France, Hungary, Sweden
66
and Switzerland successfully took part in each of the EQA rounds. Four nationally designated BSL-
67
3 reference laboratories in Portugal, Spain, and Germany, all partners of the project, also
68
participated in the molecular biology-based EQAs on filoviruses (please see Table 1, on-line only
69
Supplement).
70
The Network has also collaborated closely with the ‘European Mobile Lab’ project
71
(www.emlab.eu), another EU-funded initiative devoted to setting up mobile units to deploy in
72
outbreak-hit areas (2)
AC C
EP
TE D
M AN U
SC
RI PT
49
73
3
ACCEPTED MANUSCRIPT The Network and the EVD crisis
75
One of the main problems with the laboratory diagnosis of filoviruses, and the main reason for
76
organizing external quality assessment schemes, has been the lack of commercially available
77
methods, owing mainly to the low commercial interest in producing such tests, in times when
78
outbreaks were sporadic and the number of cases relatively limited. Therefore the network has
79
worked closely with the industry to set up commercial kits. In Spring 2014, two molecular kits for
80
filoviruses were acquired and distributed among partners for the last planned EQA and for possible
81
real cases requiring diagnosis (The RealStar® Filovirus SCREEN and TYPE kits).
82
In August 2014, when the situation in the Ebola-hit West African countries was deteriorating
83
rapidly, members of the network were formally invited by the Health Security Committee (HSC) to
84
support the laboratory capacity of EU member states by providing contacts of reference experts. In
85
the acute epidemic phase, the QUANDHIP coordinators were involved in several meetings with the
86
HSC, providing expert advice on laboratory aspects of risk assessment and outbreak management.
87
All the BSL-4 facilities were contacted to assess their availability to accept samples from other
88
countries, and were asked to provide their emergency contact information together with sample
89
shipping instructions (detailed timeline in Figure 1). The information collected was included in a
90
document describing the laboratory response to outbreaks due to highly infectious pathogens, which
91
was shared with the HSC. A shorter version was made available through the QUANDHIP website
92
and disseminated via the European Centres for Disease Prevention and Control (ECDC) to the
93
public health competent bodies. In the following months these laboratories provided support for the
94
management of suspected EVD cases, guaranteeing a turnaround time of less than 24 hours from
95
sample receipt (often providing 24/7 availability), and for clinical monitoring of infected patients in
96
the UK, Italy, Germany and Spain. Up to September 2015 the network provided EVD diagnostic
97
tests for 692 patients in Europe (Table 1). Most laboratories also provided staff and expertise for the
98
European Mobile Laboratory (EMLab) units, which were deployed to Guinea, Nigeria, Liberia and
AC C
EP
TE D
M AN U
SC
RI PT
74
4
ACCEPTED MANUSCRIPT 99 100
Sierra Leone (2). As a whole, this experience produced an integrated model of outbreak response that should represent an added value in the future.
101
Legacy
103
The EVD crisis represented the real test for European high containment laboratories. It came as a
104
confirmation of the good work done, and highlighted key issues that should be addressed:
105
Sustainability. The importance of maintaining a network of nationally designated reference
106
centres, therefore already part of the decision making process in their own countries, cannot be
107
overstated. Networks ensure effective communication channels and allow for a rapid response in
108
case of need. Funding limitations are a constant threat to the survival of high containment
109
laboratories. The recommendation to support the BSL-3/4 network as an integral part of the
110
European response to Infectious Diseases of High Impact was one of the outcomes of the
111
conference on “lessons learned” held in October 2015 [3], and this must be greeted as a positive
112
step forward. The policy makers have also agreed in the new health programme to continue to fund
113
the BSL-4 network through a follow-up joint Action called ”EMERGE” (Efficient response to
114
highly dangerous and emerging pathogens at EU level, www.emerge.rki.eu), which will run until
115
2018. It was agreed that EMERGE should have a flexible budget that allows to rapidly shift
116
activities and resources between partners when an emergency is declared, triggering a so-called
117
“crisis operation mode”. Its objective is also to reach out to a number of countries that do not have
118
BSL-4 laboratories, but are capable of performing molecular diagnosis of RG-4 viral agents in
119
highly skilled nationally designated BSL-3 facilities.
120
Field diagnostics. The EVD emergency saw the first deployment to an outbreak-hit area in Africa
121
of European coordinated laboratory teams (in the past this field outbreak response has only been
122
possible with contributions from Canada and the USA). The European Mobile Laboratory (2)
123
contributed to patient management and surveillance, and provided the expertise to support research
AC C
EP
TE D
M AN U
SC
RI PT
102
5
ACCEPTED MANUSCRIPT and development of new diagnostic tests. Thanks to this experience, partner laboratories were
125
provided with the sequences of the Ebola Zaire (EBOV) strain circulating in Africa as early as April
126
2014, before they became available in the GenBank public database. On a negative note, EMLab
127
was not recognised as an integral part of the European outbreak response model and its funding was
128
not renewed.
129
Planning policy. We would like to conclude with a message to policymakers: it is important to
130
provide for long-term sustainability starting from the planning stage. Initiatives should be designed
131
in a way that ensures their survival in the long run, also reducing competition and overlapping of
132
different projects and activities. The new EMERGE project is a good example, as it has a whole
133
Work Package dedicated to engaging other networks to promote collaborations.
M AN U
SC
RI PT
124
134
The medical and scientific communities have been criticized for failing to react promptly to the
136
EVD emergency [4-5], but the experience gained by Euronet-P4 and QUANDHIP, and the funding
137
of EMERGE, represents an investment for the future.
138
From this point on, it will be important to further improve international cooperation, keeping the
139
HSC, the ECDC, the WHO HQ and EURO region, and the other networks, engaged in the
140
protection of European citizens from high-threat communicable diseases.
142
EP
AC C
141
TE D
135
6
ACCEPTED MANUSCRIPT 143
Caption to Figure 1
145
Timeline of the involvement of the Quandhip Network in the management of the EVD crisis.
146
EVD (Ebola Virus Disease); EMLab (European Mobile Laboratory Project); WHO (World Health
147
Organization); HSC (Health Security Committee of the European Commission).
RI PT
144
AC C
EP
TE D
M AN U
SC
148 149 150 151 152 153 154 155 156 157 158 159 160
7
ACCEPTED MANUSCRIPT 161
Acknowledgments
163
The authors are grateful to the European Commission and CHAFEA for financially and technically
164
supporting the following Networks: EURONET–P4 2003214, ENP4Lab 2006208, QUANDHIP
165
2010-21-02, EMLab (European Mobile Laboratory Project). Part of this work was also supported
166
by the Italian Ministry of Health, ‘Ricerca Corrente’ grants awarded to the ‘Lazzaro Spallanzani’
167
National Institute for Infectious Diseases-IRCCS, Rome, Italy.
SC
RI PT
162
M AN U
168
The authors also gratefully acknowledge Dr. Marc J. Struelens of the ECDC for critically reviewing
170
the manuscript
EP AC C
171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195
TE D
169
Dr. Di Caro has nothing to discose
8
ACCEPTED MANUSCRIPT 196
References
197
1. Nisii C, Castilletti C, Raoul H, Hewson R, Brown D, Gopal R, et al. Biosafety Level-4
199
laboratories in Europe: opportunities for public health, diagnostics, and research. PLoS
200
Pathog. 2013 Jan;9(1):e1003105. doi: 10.1371/journal.ppat.1003105.
RI PT
198
201
2. Wolfel R, Stoecker K, Fleischmann E, Gramsamer B, Wagner M, Molkenthin P, Di Caro A,
203
Gunther S, Ibrahim S, Genzel GH, Ozin-Hofsass AJ, P. Formenty, Zoller L. Mobile
204
diagnostics in outbreak response, not only for Ebola: a blueprint for a modular and robust
205
field laboratory. Euro Surveill 2015;20(44).
M AN U
SC
202
3. Conference ‘Lessons learned for public health from the Ebola outbreak in West Africa –
209
how to improve preparedness and response in the EU for future outbreaks”, Mondorf les
210
Bains, Luxembourg, 12-14 October 2015. Conference Summary Report. Available from:
211
http://ec.europa.eu/health/preparedness_response/docs/ev_20151012_sr_en.pdf.
212
Accessed 28th April 2016.
215 216 217 218
EP
214
4. Martin-Moreno JM, Ricciardi W, Bjegovic-Mikanovic V, Maguire P, McKee M, on behalf
AC C
213
TE D
206 207 208
of 44 signatories. Ebola: an open letter to European governments. Lancet 2014; 384 :1259.
5. Zumla A, Heymann D, Ippolito G. Be prepared: Europe needs Ebola outbreak consortium. Nature 2015; 523:35.
219
220
9
ACCEPTED MANUSCRIPT Table 1. List of European BSL-4 and BSL-3 laboratories that were members of the QUANDHIP Network and numbers of patients tested for EBOV infection up to September 2015 BSL4 laboratories
Number of
RI PT
patients tested*
Bernhard-Nocht-Institut (BNI), Hamburg
112
Germany
Philipps-Universität Marburg (PUM), Marburg
UK
Public Health England (PHE), Porton Down, Salisbury
285
National Institute for Infectious Diseases (INMI) “L.
35
Italy Spallanzani”, Rome,
M AN U
SC
Germany
Institut National de la Santé et de la Recherche France
12
125
Médicale (INSERM), Lyon,
National Centre of Epidemiology (NCE), Budapest,
1
Sweden
Folkhalsomyndigheten (FOHM), Solna,
28
Federal Office for Civil Protection (FOCP), Spiez
1
EP
Switzerland
TE D
Hungary
Laboratory, Spiez
AC C
BSL3 laboratories**
Instituto Nacional Saúde Dr Ricardo Jorge (INSA),
Portugal
12
Lisboa
Spain
Instituto de Salud Carlos III (ISCIII), Madrid
52
Germany
Robert Koch Institute (RKI), Berlin
28
Germany
1 Bundeswehr Institute of Microbiology (BMI), Munich
ACCEPTED MANUSCRIPT
* The total number of patients tested by Network laboratories is 692. This number may include also asymptomatic patients in some countries
AC C
EP
TE D
M AN U
SC
EQAs as National Reference Centres of their countries.
RI PT
** The BSL-3 laboratories listed in this table are those that took part in molecular biology-based
ACCEPTED MANUSCRIPT
December 2013 First cases of EVD reported in Guinea
6th August 2014 Official request of assistance from the EU Commission receved by Quandhip coordinators
M AN U
SC
8th August 2014 WHO declares the EVD outbreak in West Africa a Public Health Event of International Concern (PHEIC) Quandhip Network activated by EU Commission
TE D
1st August 2014 Presentation, upon request by EU Commission, of Quandhip activities to the meeting of the EU Health Security Committee
RI PT
March / April 2014 First deployment of EM-Lab to West Africa and commercial test kit sent to Network laboratories
14th August 2014 First of a series of audioconferences with the HSC.
AC C
EP
9th August 2014 Quandhip laboratory contacts sent to HSC
May – July 2014 Cases notified in Sierra Leone and Liberia. Nigeria is also affected, but spread is successfully contained. March 22nd 2014 WHO notified by Guinean authorities about a rapidly evolving outbreak
September 2015 By September 2015, Quandhip laboratories have tested 592 suspected Ebola samples, offering support to other countries in need of assistance.
13th August 2014 Expert guidance on Ebola made available to the HSC
February 2016 Outbreak under control, only sporadic cases reported in Sierra Leone. EMLAB still operating in West Africa for epidemiologial studies and research
S1198-743X(16)30227-0
DOI:
10.1016/j.cmi.2016.07.003
Reference:
CMI 646
To appear in:
Clinical Microbiology and Infection
Received Date: 28 April 2016 Revised Date:
30 June 2016
Accepted Date: 2 July 2016
Please cite this article as: Nisii C, Vincenti D, Fusco FM, Schmidt-Chanasit J, Carbonnelle C, Raoul H, Eickmann M, Hewson R, Brave A, Nuncio S, Sanchez-Seco MP, Palyi B, Kis Z, Zange S, Nitsche A, Kurth A, Strasser M, Capobianchi MR, Ozin A, Guglielmetti P, Menel-Lemos C, Jacob D, Grunow R, Ippolito G, Di Caro A, The contribution of the European high containment laboratories during the 2014-2015 Ebola Virus Disease (EVD) emergency, Clinical Microbiology and Infection (2016), doi: 10.1016/j.cmi.2016.07.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Intended Category: Commentary
2
The contribution of the European high containment laboratories during the 2014-2015 Ebola
3
Virus Disease (EVD) emergency
5
RI PT
4
Running Title: European BSL-3/4 laboratories in the EVD emergency
6
Carla Nisii1, Donatella Vincenti1, Francesco M Fusco1, Jonas Schmidt-Chanasit2, Caroline
8
Carbonnelle3, Hervé Raoul3, Markus Eickmann4, Roger Hewson5, Andreas Brave6, Sofia Nuncio7,
9
Mari Paz Sanchez-Seco8, Bernadette Palyi9, Zoltan Kis9, Sabine Zange10, Andreas Nitsche11,
M AN U
SC
7
10
Andreas Kurth11, Marc Strasser12, Maria R. Capobianchi1, Amanda Ozin13 , Paolo Guglielmetti14,
11
Cinthia Menel-Lemos15 , Daniela Jacob11, Roland Grunow11, Giuseppe Ippolito1, and Antonino Di
12
Caro1*.
TE D
13 1
‘Lazzaro Spallanzani’ National Institute for Infectious Diseases-IRCCS, Rome, Italy
15
2
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
16
3
Laboratoire INSERM Jean Mérieux, Lyon, France
17
4
Institute of Virology, University of Marburg, Marburg, Germany
18
5
Public Health England, Porton Down, Salisbury, UK
19
6
SMI, Solna, Sweden
20
7
Instituto Nacional de Saude, Lisbon, Portugal
21
8
Centro Nacional de Microbiologia, ISCIII, Madrid, Spain
22
9
National Center for Epidemiology, Budapest, Hungary
23
10
Bundeswehr Institute of Microbiology, Munich, Germany
AC C
EP
14
ACCEPTED MANUSCRIPT 11
Robert Koch Institut, Berlin, Germany
25
12
Federal Office for Civil Protection, Spiez Laboratory, Switzerland
26
13
European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
27
14
European Commission - DG SANTE – Health threats Unit – Luxembourg
28
15
29
Luxembourg
RI PT
24
European Commission - Consumers, Health, Agriculture and Food Exceutive Agency (Chafea) –
SC
30
*Address for correspondence:
34
Antonino Di Caro, MD
35
Lazzaro Spallanzani National Institute for Infectious Diseases
36
292 Via Portuense, 00149 Rome (Italy)
37
Phone: +39 06 55170688
38
Fax: +39 06 55170683
39
E-mail: [email protected]
42 43 44
Word Count: 1187
TE D
AC C
41
EP
40
M AN U
31 32 33
45 46 47 48 2
ACCEPTED MANUSCRIPT Since December 2013, the world has experienced the worst-ever epidemic of Ebola virus disease
50
(EVD), which has caused thousands of deaths in several West African countries. When the
51
epidemic began, the European Union (EU) was not unprepared, thanks to the ten-year-long
52
commitment of the European Commission (EC) to fund several networks in the area of highly
53
infectious diseases. The European Network of Biosafety-Level 4 (BSL-4) laboratories (Euronet-P4,
54
later called ENP4-Lab) was one of them; it has been operating since 2004, bringing together the
55
facilities where Risk-Group 4 (RG-4) pathogens such as Ebola can be safely handled [1]. In 2010,
56
with the aim of increasing European preparedness in the fight against highly infectious trans-border
57
threats, a new Joint Action was launched, resulting from the union of the networks that had
58
previously worked on the diagnostics of highly infectious viruses and bacteria: ENP4-Lab and
59
EQADEBA. The new Joint Action was named QUANDHIP (Quality Assurance Exercises and
60
Networking on the Detection of Highly Infectious Pathogens) and one of its aim was to harmonize
61
diagnostic procedures by first reviewing the diagnostic capabilities for highly infectious pathogens,
62
including filoviruses (Ebola and Marburg) and then running external quality assessment (EQA)
63
rounds. The results included an up-to-date compilation of methods for antibody and antigen
64
detection, electron microscopy, molecular biology assays, viral culture, and reagents available for
65
sharing. All BSL-4 laboratories in Germany, the United Kingdom, Italy, France, Hungary, Sweden
66
and Switzerland successfully took part in each of the EQA rounds. Four nationally designated BSL-
67
3 reference laboratories in Portugal, Spain, and Germany, all partners of the project, also
68
participated in the molecular biology-based EQAs on filoviruses (please see Table 1, on-line only
69
Supplement).
70
The Network has also collaborated closely with the ‘European Mobile Lab’ project
71
(www.emlab.eu), another EU-funded initiative devoted to setting up mobile units to deploy in
72
outbreak-hit areas (2)
AC C
EP
TE D
M AN U
SC
RI PT
49
73
3
ACCEPTED MANUSCRIPT The Network and the EVD crisis
75
One of the main problems with the laboratory diagnosis of filoviruses, and the main reason for
76
organizing external quality assessment schemes, has been the lack of commercially available
77
methods, owing mainly to the low commercial interest in producing such tests, in times when
78
outbreaks were sporadic and the number of cases relatively limited. Therefore the network has
79
worked closely with the industry to set up commercial kits. In Spring 2014, two molecular kits for
80
filoviruses were acquired and distributed among partners for the last planned EQA and for possible
81
real cases requiring diagnosis (The RealStar® Filovirus SCREEN and TYPE kits).
82
In August 2014, when the situation in the Ebola-hit West African countries was deteriorating
83
rapidly, members of the network were formally invited by the Health Security Committee (HSC) to
84
support the laboratory capacity of EU member states by providing contacts of reference experts. In
85
the acute epidemic phase, the QUANDHIP coordinators were involved in several meetings with the
86
HSC, providing expert advice on laboratory aspects of risk assessment and outbreak management.
87
All the BSL-4 facilities were contacted to assess their availability to accept samples from other
88
countries, and were asked to provide their emergency contact information together with sample
89
shipping instructions (detailed timeline in Figure 1). The information collected was included in a
90
document describing the laboratory response to outbreaks due to highly infectious pathogens, which
91
was shared with the HSC. A shorter version was made available through the QUANDHIP website
92
and disseminated via the European Centres for Disease Prevention and Control (ECDC) to the
93
public health competent bodies. In the following months these laboratories provided support for the
94
management of suspected EVD cases, guaranteeing a turnaround time of less than 24 hours from
95
sample receipt (often providing 24/7 availability), and for clinical monitoring of infected patients in
96
the UK, Italy, Germany and Spain. Up to September 2015 the network provided EVD diagnostic
97
tests for 692 patients in Europe (Table 1). Most laboratories also provided staff and expertise for the
98
European Mobile Laboratory (EMLab) units, which were deployed to Guinea, Nigeria, Liberia and
AC C
EP
TE D
M AN U
SC
RI PT
74
4
ACCEPTED MANUSCRIPT 99 100
Sierra Leone (2). As a whole, this experience produced an integrated model of outbreak response that should represent an added value in the future.
101
Legacy
103
The EVD crisis represented the real test for European high containment laboratories. It came as a
104
confirmation of the good work done, and highlighted key issues that should be addressed:
105
Sustainability. The importance of maintaining a network of nationally designated reference
106
centres, therefore already part of the decision making process in their own countries, cannot be
107
overstated. Networks ensure effective communication channels and allow for a rapid response in
108
case of need. Funding limitations are a constant threat to the survival of high containment
109
laboratories. The recommendation to support the BSL-3/4 network as an integral part of the
110
European response to Infectious Diseases of High Impact was one of the outcomes of the
111
conference on “lessons learned” held in October 2015 [3], and this must be greeted as a positive
112
step forward. The policy makers have also agreed in the new health programme to continue to fund
113
the BSL-4 network through a follow-up joint Action called ”EMERGE” (Efficient response to
114
highly dangerous and emerging pathogens at EU level, www.emerge.rki.eu), which will run until
115
2018. It was agreed that EMERGE should have a flexible budget that allows to rapidly shift
116
activities and resources between partners when an emergency is declared, triggering a so-called
117
“crisis operation mode”. Its objective is also to reach out to a number of countries that do not have
118
BSL-4 laboratories, but are capable of performing molecular diagnosis of RG-4 viral agents in
119
highly skilled nationally designated BSL-3 facilities.
120
Field diagnostics. The EVD emergency saw the first deployment to an outbreak-hit area in Africa
121
of European coordinated laboratory teams (in the past this field outbreak response has only been
122
possible with contributions from Canada and the USA). The European Mobile Laboratory (2)
123
contributed to patient management and surveillance, and provided the expertise to support research
AC C
EP
TE D
M AN U
SC
RI PT
102
5
ACCEPTED MANUSCRIPT and development of new diagnostic tests. Thanks to this experience, partner laboratories were
125
provided with the sequences of the Ebola Zaire (EBOV) strain circulating in Africa as early as April
126
2014, before they became available in the GenBank public database. On a negative note, EMLab
127
was not recognised as an integral part of the European outbreak response model and its funding was
128
not renewed.
129
Planning policy. We would like to conclude with a message to policymakers: it is important to
130
provide for long-term sustainability starting from the planning stage. Initiatives should be designed
131
in a way that ensures their survival in the long run, also reducing competition and overlapping of
132
different projects and activities. The new EMERGE project is a good example, as it has a whole
133
Work Package dedicated to engaging other networks to promote collaborations.
M AN U
SC
RI PT
124
134
The medical and scientific communities have been criticized for failing to react promptly to the
136
EVD emergency [4-5], but the experience gained by Euronet-P4 and QUANDHIP, and the funding
137
of EMERGE, represents an investment for the future.
138
From this point on, it will be important to further improve international cooperation, keeping the
139
HSC, the ECDC, the WHO HQ and EURO region, and the other networks, engaged in the
140
protection of European citizens from high-threat communicable diseases.
142
EP
AC C
141
TE D
135
6
ACCEPTED MANUSCRIPT 143
Caption to Figure 1
145
Timeline of the involvement of the Quandhip Network in the management of the EVD crisis.
146
EVD (Ebola Virus Disease); EMLab (European Mobile Laboratory Project); WHO (World Health
147
Organization); HSC (Health Security Committee of the European Commission).
RI PT
144
AC C
EP
TE D
M AN U
SC
148 149 150 151 152 153 154 155 156 157 158 159 160
7
ACCEPTED MANUSCRIPT 161
Acknowledgments
163
The authors are grateful to the European Commission and CHAFEA for financially and technically
164
supporting the following Networks: EURONET–P4 2003214, ENP4Lab 2006208, QUANDHIP
165
2010-21-02, EMLab (European Mobile Laboratory Project). Part of this work was also supported
166
by the Italian Ministry of Health, ‘Ricerca Corrente’ grants awarded to the ‘Lazzaro Spallanzani’
167
National Institute for Infectious Diseases-IRCCS, Rome, Italy.
SC
RI PT
162
M AN U
168
The authors also gratefully acknowledge Dr. Marc J. Struelens of the ECDC for critically reviewing
170
the manuscript
EP AC C
171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195
TE D
169
Dr. Di Caro has nothing to discose
8
ACCEPTED MANUSCRIPT 196
References
197
1. Nisii C, Castilletti C, Raoul H, Hewson R, Brown D, Gopal R, et al. Biosafety Level-4
199
laboratories in Europe: opportunities for public health, diagnostics, and research. PLoS
200
Pathog. 2013 Jan;9(1):e1003105. doi: 10.1371/journal.ppat.1003105.
RI PT
198
201
2. Wolfel R, Stoecker K, Fleischmann E, Gramsamer B, Wagner M, Molkenthin P, Di Caro A,
203
Gunther S, Ibrahim S, Genzel GH, Ozin-Hofsass AJ, P. Formenty, Zoller L. Mobile
204
diagnostics in outbreak response, not only for Ebola: a blueprint for a modular and robust
205
field laboratory. Euro Surveill 2015;20(44).
M AN U
SC
202
3. Conference ‘Lessons learned for public health from the Ebola outbreak in West Africa –
209
how to improve preparedness and response in the EU for future outbreaks”, Mondorf les
210
Bains, Luxembourg, 12-14 October 2015. Conference Summary Report. Available from:
211
http://ec.europa.eu/health/preparedness_response/docs/ev_20151012_sr_en.pdf.
212
Accessed 28th April 2016.
215 216 217 218
EP
214
4. Martin-Moreno JM, Ricciardi W, Bjegovic-Mikanovic V, Maguire P, McKee M, on behalf
AC C
213
TE D
206 207 208
of 44 signatories. Ebola: an open letter to European governments. Lancet 2014; 384 :1259.
5. Zumla A, Heymann D, Ippolito G. Be prepared: Europe needs Ebola outbreak consortium. Nature 2015; 523:35.
219
220
9
ACCEPTED MANUSCRIPT Table 1. List of European BSL-4 and BSL-3 laboratories that were members of the QUANDHIP Network and numbers of patients tested for EBOV infection up to September 2015 BSL4 laboratories
Number of
RI PT
patients tested*
Bernhard-Nocht-Institut (BNI), Hamburg
112
Germany
Philipps-Universität Marburg (PUM), Marburg
UK
Public Health England (PHE), Porton Down, Salisbury
285
National Institute for Infectious Diseases (INMI) “L.
35
Italy Spallanzani”, Rome,
M AN U
SC
Germany
Institut National de la Santé et de la Recherche France
12
125
Médicale (INSERM), Lyon,
National Centre of Epidemiology (NCE), Budapest,
1
Sweden
Folkhalsomyndigheten (FOHM), Solna,
28
Federal Office for Civil Protection (FOCP), Spiez
1
EP
Switzerland
TE D
Hungary
Laboratory, Spiez
AC C
BSL3 laboratories**
Instituto Nacional Saúde Dr Ricardo Jorge (INSA),
Portugal
12
Lisboa
Spain
Instituto de Salud Carlos III (ISCIII), Madrid
52
Germany
Robert Koch Institute (RKI), Berlin
28
Germany
1 Bundeswehr Institute of Microbiology (BMI), Munich
ACCEPTED MANUSCRIPT
* The total number of patients tested by Network laboratories is 692. This number may include also asymptomatic patients in some countries
AC C
EP
TE D
M AN U
SC
EQAs as National Reference Centres of their countries.
RI PT
** The BSL-3 laboratories listed in this table are those that took part in molecular biology-based
ACCEPTED MANUSCRIPT
December 2013 First cases of EVD reported in Guinea
6th August 2014 Official request of assistance from the EU Commission receved by Quandhip coordinators
M AN U
SC
8th August 2014 WHO declares the EVD outbreak in West Africa a Public Health Event of International Concern (PHEIC) Quandhip Network activated by EU Commission
TE D
1st August 2014 Presentation, upon request by EU Commission, of Quandhip activities to the meeting of the EU Health Security Committee
RI PT
March / April 2014 First deployment of EM-Lab to West Africa and commercial test kit sent to Network laboratories
14th August 2014 First of a series of audioconferences with the HSC.
AC C
EP
9th August 2014 Quandhip laboratory contacts sent to HSC
May – July 2014 Cases notified in Sierra Leone and Liberia. Nigeria is also affected, but spread is successfully contained. March 22nd 2014 WHO notified by Guinean authorities about a rapidly evolving outbreak
September 2015 By September 2015, Quandhip laboratories have tested 592 suspected Ebola samples, offering support to other countries in need of assistance.
13th August 2014 Expert guidance on Ebola made available to the HSC
February 2016 Outbreak under control, only sporadic cases reported in Sierra Leone. EMLAB still operating in West Africa for epidemiologial studies and research