- Email: [email protected]
The importance of enterovirus surveillance in a Post-polio world
Accepted Manuscript The importance of Enterovirus surveillance in a Post-polio world Charlotte C. Holm-Hansen, Sofie Elisabeth Midgley, Susanne Schjørring, Thea K. Fischer PII:
S1198-743X(17)30098-8
DOI:
10.1016/j.cmi.2017.02.010
Reference:
CMI 858
To appear in:
Clinical Microbiology and Infection
Received Date: 10 January 2017 Revised Date:
3 February 2017
Accepted Date: 7 February 2017
Please cite this article as: Holm-Hansen CC, Midgley SE, Schjørring S, Fischer TK, The importance of Enterovirus surveillance in a Post-polio world, Clinical Microbiology and Infection (2017), doi: 10.1016/ j.cmi.2017.02.010. 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
The importance of Enterovirus surveillance in a Post-polio world
2 Charlotte C. Holm-Hansen1,2, Sofie Elisabeth Midgley1, Susanne Schjørring 1,3, and Thea K.
4
Fischer1,4#
RI PT
3
5
Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark. Department of Paediatrics, Zealand University Hospital, Roskilde, Denmark
SC
2
3
M AN U
EUPHEM Fellow: European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. 4
Center for Global Health and Department of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark. #
Corresponding author. Denmark.
Address: Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S,
TE D
Phone: 0045 3268 3443 Email: [email protected]
EP
22
1
AC C
6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
ACCEPTED MANUSCRIPT In 1988, the Global Poliovirus Eradication Initiative (GPEI) was launched, and now in 2017, we are
24
close to achieving that goal. The poliovirus type 2 component was removed from the vaccine
25
formulations, and, as of August 2016, Afghanistan and Pakistan were the only two countries in the
26
world which still reported endemic wild polio circulation; Nigeria was declared polio-free in 2015,
27
but during 2016 both circulating vaccine-derived polio (cVDPV) type 2 and wild poliovirus type 1
28
have been detected [1], (http://www.who.int/mediacentre/news/releases/2016/nigeria-
29
polio/en/). Circulating vaccine-derived polioviruses are vaccine strains which have evolved over
30
time within a vaccinated individual, accumulating mutations. Such viruses also have the potential
31
to recombine with other related enteroviruses, leading the the emergence of new pathogenic
32
strains [2]. The golden standard of polio surveillance through the GPEI is systematic screening of
33
stools from patients with either aseptic meningitis and/or acute flaccid paralysis (AFP) for
34
poliovirus. However, countries that have been declared polio-free are challenged by the AFP
35
sensitivity criteria specified by the GPEI (2 AFP cases per 100 000 children under the age of 15
36
years per year,
37
http://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/active
38
/poliomyelitis_standards/en/). Therefore, in polio-free countries, alternative surveillance systems
39
including environmental surveillance and non-polio enterovirus surveillance, are often in place
40
[3]. Of note, an absence of detection of vaccine derived or wild type viruses in environmental
41
samples does not signify a total absence of such strains in the population.
42
In the coming years, heading towards complete poliovirus eradication, there is a need to maintain
43
sensitive surveillance systems in order to detect silent circulation of residual poliovirus (wild or
44
vaccine-derived) rapidly and effectively, to avoid outbreaks of potentially devastating disease. This
45
is currently the main role of the global polio surveillance system, organised in national and
AC C
EP
TE D
M AN U
SC
RI PT
23
ACCEPTED MANUSCRIPT regional World Health Organization (WHO) poliovirus reference laboratories. In the aftermath of
47
documented poliovirus eradication, it has been suggested to replace the current comprehensive
48
case-based stool investigations of aseptic meningitis cases with environmental surveillance.
49
Environmental surveillance, the sampling and analysis of sewage or wastewater for the presence
50
of poliovirus, has already played a pivotal role in documenting the poliovirus elimination phase in
51
some countries, such as India and Egypt [4,5]. Furthermore, it acts as a supplement to AFP
52
surveillance in the few remaining endemic countries [6].
53
Since 2015 the Centers for Disease Control and Prevention and the WHO has recommended
54
enterovirus surveillance in order to 1) detect and control outbreaks, 2) perform virological
55
investigation and research, and 3) establish disease burden data for long-term public health
56
planning. Yet, routine surveillance of enteroviruses is not common practice in most countries [3].
57
Current enterovirus surveillance systems are passive, based on characterization of enteroviruses in
58
diagnostic samples, and geared towards the detection of poliovirus. To accurately detect and
59
characterize circulating enteroviruses and estimate their burden on the community, a pro-active
60
system is needed. Such a system should be based on a data-driven practice, sampling the correct
61
patient groups to enable rapid detection, which is a vital aspect of outbreak control.
62
Enteroviruses are endemic and among the most common causes of human disease globally. They
63
are associated with a variety of clinical manifestations, ranging from respiratory, gastrointestinal
64
or skin symptoms, to severe infections of the myocardia or central nervous system [3].
65
Enteroviruses are a common cause of aseptic meningitis [3], particularly in very young children.
66
The correct and timely identification of enteroviruses as the cause, rather than the more serious
67
bacterial meningitis, has at least two important implications. Not only does it lead to a reduction
68
in unnecessary long-term use of high dose antibiotic treatment, but it also helps alleviate some of
AC C
EP
TE D
M AN U
SC
RI PT
46
ACCEPTED MANUSCRIPT the psychological strain suffered by the parents of patients, as viral meningitis has a much more
70
favourable prognosis as compared to bacterial. Furthermore, new enteroviruses are emerging and
71
causing major outbreaks, with both severe respiratory and neurological complications leading to
72
fatalities.
73
Late Summer and Autumn 2014 there was an unprecedented international outbreak of
74
enterovirus D68 associated with severe respiratory infection and polio-like acute flaccid myelitis
75
(AFM), primarily affecting North America, but also several European countries (Holm-Hansen).
76
Enterovirus D68 differs somewhat from most enteroviruses, and has primarily been detected in
77
respiratory samples, and only very rarely identified in stools [7]. In 2016 there has been an
78
upsurge of enterovirus D68 cases in France, the Netherlands and Sweden associated with
79
respiratory disease and AFM [8,9,10].
80
In the last few years, several new enteroviruses belonging to species C have been identified in
81
respiratory samples from patients with respiratory illness, including enterovirus C104, C105, C109
82
and C117 [11]. Some of these new enteroviruses are not detectable in stool and/or cerebrospinal
83
fluids, but require the testing of e.g. respiratory material. It is therefore important to include
84
several types of sample material in a surveillance system, as it is not possible to predict whether
85
the next new virus will be found in stool, cerebrospinal fluid, blood or samples of respiratory
86
origin. Also, the genetic heterogeneity of enteroviruses (as illustrated in Figure 1) challenges
87
detection and characterization of the >250 enterovirus types using standard enterovirus
88
diagnostic approaches by polymerase-chain reaction (PCR).
89
Newly discovered enteroviruses are named numerically by the International Committee on
90
Taxonomy of Viruses [12], rather than being given more informative names, which likely adds to
AC C
EP
TE D
M AN U
SC
RI PT
69
ACCEPTED MANUSCRIPT the challenges of ensuring recognition of the role of these enteroviruses in specific diseases. In
92
2012 rhinovirus species A-C were re-classified as enterovirus species resulting in a total of 12
93
enterovirus species, of which enterovirus A-D and rhinovirus A-C infect humans. Figure 1 shows
94
the genetic diversity of the seven enterovirus species infecting humans. Despite the inclusion of
95
rhinoviruses in the enterovirus species, many diagnostic tests still distinguish between the two.
96
This has implications for the awareness of enteroviruses among both the public and health
97
professionals. As more and more cases of “common colds” are classified as enterovirus infections
98
there may well be a tendency towards not suspecting rare and serious disease manifestations as
99
being caused by enteroviruses, delaying diagnosis and potentially leading to inappropriate
M AN U
SC
RI PT
91
treatment with antibiotics. It should also be noted that rhinoviruses are also capable of causing
101
severe infections, particularly in immunocompromised patients [13].
102
Emerging enteroviruses, such as D68 and enteroviruses belonging to species C, have taught us that
103
even in a polio-free world there are still pathogens capable of causing devastating disease
104
including severe neurological infection, polio-like AFP, myelitis and life-threating respiratory
105
disease [8,9,10,11]. Enterovirus surveillance will be increasingly important in the post-polio
106
eradication era, as an early warning system not only for possible poliovirus re-introduction (CDC),
107
but also for the detection and response to outbreaks of other potentially severe enteroviruses,
108
exemplified by the re-emergence of enterovirus D68 in 2016 North America and some European
109
countries [8,9,10]. However, many of the existing enterovirus surveillance systems will not detect
110
D68 and other respiratory enteroviruses, unless they are enhanced to also include the routine
111
screening of respiratory samples, and subsequent characterisation of respiratory enteroviruses.
112
The picornavirus family contains other viruses of public health concern, such as parechoviruses,
AC C
EP
TE D
100
ACCEPTED MANUSCRIPT and an established robust surveillance system for enteroviruses can also be utilized/expanded to
114
include detection of other viruses.
115
It is the responsibility of the Public Health sector to detect, and react to, threats to the health of
116
the community. A robust and sensitive surveillance system is key in order to achieve this, and thus,
117
we suggest improving the capacity for detection of emerging enteroviruses globally by enhancing
118
current enterovirus surveillance systems. Numerous methodologies are available for the detection
119
as well as thecharacterization of polio and other enteroviruses, including generic protocols
120
developed and recommended, respectively, by the CDC and WHO. The focus of system
121
strengthening efforts should therefore be on the sample collection. Firstly, by including routine
122
surveillance of respiratory samples from children seen both in the primary and secondary
123
healthcare sector. Secondly, by ensuring diagnostic analyses of stool, cerebrospinal fluid, blood,
124
and respiratory samples in patients with unexplained neurological clinical presentations and/or
125
severe unexplained respiratory disease. Thirdly, by including environmental surveillance. The
126
latter system is the main methodological recommendation for enterovirus surveillance in a post-
127
polio world. Therefore, current initiatives to develop and implement environmental surveillance
128
systems should be considered constructive investments for safeguarding populations in the future.
129
The main challenge will be a shift from passive surveillance, to pro-active surveillance. These
130
measures will increase the understanding of the burden of enterovirus diseases, and enable the
131
detection of, as well as a rapid and effective response to, future outbreaks of these emerging
132
viruses. The first joint European expert meeting on the design of enhanced enterovirus
133
surveillance systems for present, as well as the future post-polio world, will take place in Oxford in
134
March 2017, with support from the European Society for Clinical Virology and the European
135
Centre for Disease Prevention and Control (ECDC), with representatives from the WHO attending
AC C
EP
TE D
M AN U
SC
RI PT
113
ACCEPTED MANUSCRIPT (http://www.escv.org/uploads/Oxford,%20workshop2017,%20Enterovirus.pdf). Here, the added
137
value of enhanced enterovirus surveillance systems, and opportunities for development of generic
138
surveillance protocols, will be discussed and the outcome of the workshop with recommendations
139
made available for public use. This workshop can be regarded as one of many first steps in the
140
global effort to strengthen enterovirus surveillance systems for a post-polio world.
RI PT
136
141
SC
142 Contributors
144
Thea, Sofie, Susanne and Charlotte conceptualized the study, Charlotte and Thea drafted the first
145
version, and all authors have contributed to the development of the manuscript and approved its
146
content.
M AN U
143
147 Conflict of interest
149
The authors declare no competing interest.
EP
150
TE D
148
Funding
152
No external funding was received for this article.
153 154 155 156 157 158 159 160 161 162
1.
2.
3.
AC C
151
Etsano A, et al., Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission — Nigeria, 2016. Morbidity and Mortality Weekly Report, 2016. 65(30). Bessaud M, et al., Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity. Science Reports 2016; 6: 38831. Centre for Disease Control and Prevention and World Health Organization, R.O.f.E., Enterovirus surveillance guidelines - Guidelines for enterovirus surveillance in support of the Polio Eradication Initiative. 2015.
ACCEPTED MANUSCRIPT
9.
10. 11.
12. 13.
RI PT
8.
Antona D., et al., Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016. Euro Surveill. 2016; 21(46). Dyrdak R, et al., Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016. Eurosurveillance, 2016. 21.
SC
7.
Knoester M, et al., Upsurge of Enterovirus D68, the Netherlands, 2016. Emerging Infectious Diseases, 2017. 23(1). Van Leer-Buter, C.C., et al., Newly Identified Enterovirus C Genotypes, Identified in the Netherlands through Routine Sequencing of All Enteroviruses Detected in Clinical Materials from 2008 to 2015. J Clin Microbiol, 2016. 54(9): p. 2306-14. Adams, M.J., et al., Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses. Arch Virol, 2016. 161:2921-2949. Jacobs SE, etal., Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy. J Clin Virol. 2015; 71: 51-8.
M AN U
6.
TE D
5.
Deshpande JM, et al., Environmental surveillance system to track wild poliovirus transmission. Appl Environ Microbiol. 2003; 69: 2919-27. El Bassioni L., et al., Prolonged detection of indigenous wild polioviruses in sewage from communities in Egypt. Am J Epid 2003; 158: 807-15. Asghar, H., et al., Environmental Surveillance for Polioviruses in the Global Polio Eradication Initiative. Journal of Infectious Diseases, 2014. 210(suppl 1): p. S294-S303. Holm-Hansen, C.C., S.E. Midgley, and T.K. Fischer, Global emergence of enterovirus D68: a systematic review. The Lancet Infectious Diseases, 2016. 16(5): p. e64-e75.
EP
190
4.
AC C
163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189
ACCEPTED MANUSCRIPT
EVC
Figure 1. Genetic diversity of enteroviruses infecting humans.
EVD
RI PT
RVB
EP
TE D
M AN U
SC
RVC
EVB
AC C
RVA
EVJ
0,5
Figure 1 shows a maximum likelihood phylogenetic tree of representative full genomes from all 7 species of enterovirus known to infect humans (enterovirus A to D; EVA-EVD, rhinovirus A to C; RVA-RVC). Simian enterovirus J108 has been included to root the tree. A full list of accession numbers for the sequences included is available from the authors on request.
EVA
S1198-743X(17)30098-8
DOI:
10.1016/j.cmi.2017.02.010
Reference:
CMI 858
To appear in:
Clinical Microbiology and Infection
Received Date: 10 January 2017 Revised Date:
3 February 2017
Accepted Date: 7 February 2017
Please cite this article as: Holm-Hansen CC, Midgley SE, Schjørring S, Fischer TK, The importance of Enterovirus surveillance in a Post-polio world, Clinical Microbiology and Infection (2017), doi: 10.1016/ j.cmi.2017.02.010. 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
The importance of Enterovirus surveillance in a Post-polio world
2 Charlotte C. Holm-Hansen1,2, Sofie Elisabeth Midgley1, Susanne Schjørring 1,3, and Thea K.
4
Fischer1,4#
RI PT
3
5
Department of Microbiological Diagnostics and Virology, Statens Serum Institut, Copenhagen, Denmark. Department of Paediatrics, Zealand University Hospital, Roskilde, Denmark
SC
2
3
M AN U
EUPHEM Fellow: European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. 4
Center for Global Health and Department of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark. #
Corresponding author. Denmark.
Address: Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S,
TE D
Phone: 0045 3268 3443 Email: [email protected]
EP
22
1
AC C
6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
ACCEPTED MANUSCRIPT In 1988, the Global Poliovirus Eradication Initiative (GPEI) was launched, and now in 2017, we are
24
close to achieving that goal. The poliovirus type 2 component was removed from the vaccine
25
formulations, and, as of August 2016, Afghanistan and Pakistan were the only two countries in the
26
world which still reported endemic wild polio circulation; Nigeria was declared polio-free in 2015,
27
but during 2016 both circulating vaccine-derived polio (cVDPV) type 2 and wild poliovirus type 1
28
have been detected [1], (http://www.who.int/mediacentre/news/releases/2016/nigeria-
29
polio/en/). Circulating vaccine-derived polioviruses are vaccine strains which have evolved over
30
time within a vaccinated individual, accumulating mutations. Such viruses also have the potential
31
to recombine with other related enteroviruses, leading the the emergence of new pathogenic
32
strains [2]. The golden standard of polio surveillance through the GPEI is systematic screening of
33
stools from patients with either aseptic meningitis and/or acute flaccid paralysis (AFP) for
34
poliovirus. However, countries that have been declared polio-free are challenged by the AFP
35
sensitivity criteria specified by the GPEI (2 AFP cases per 100 000 children under the age of 15
36
years per year,
37
http://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/active
38
/poliomyelitis_standards/en/). Therefore, in polio-free countries, alternative surveillance systems
39
including environmental surveillance and non-polio enterovirus surveillance, are often in place
40
[3]. Of note, an absence of detection of vaccine derived or wild type viruses in environmental
41
samples does not signify a total absence of such strains in the population.
42
In the coming years, heading towards complete poliovirus eradication, there is a need to maintain
43
sensitive surveillance systems in order to detect silent circulation of residual poliovirus (wild or
44
vaccine-derived) rapidly and effectively, to avoid outbreaks of potentially devastating disease. This
45
is currently the main role of the global polio surveillance system, organised in national and
AC C
EP
TE D
M AN U
SC
RI PT
23
ACCEPTED MANUSCRIPT regional World Health Organization (WHO) poliovirus reference laboratories. In the aftermath of
47
documented poliovirus eradication, it has been suggested to replace the current comprehensive
48
case-based stool investigations of aseptic meningitis cases with environmental surveillance.
49
Environmental surveillance, the sampling and analysis of sewage or wastewater for the presence
50
of poliovirus, has already played a pivotal role in documenting the poliovirus elimination phase in
51
some countries, such as India and Egypt [4,5]. Furthermore, it acts as a supplement to AFP
52
surveillance in the few remaining endemic countries [6].
53
Since 2015 the Centers for Disease Control and Prevention and the WHO has recommended
54
enterovirus surveillance in order to 1) detect and control outbreaks, 2) perform virological
55
investigation and research, and 3) establish disease burden data for long-term public health
56
planning. Yet, routine surveillance of enteroviruses is not common practice in most countries [3].
57
Current enterovirus surveillance systems are passive, based on characterization of enteroviruses in
58
diagnostic samples, and geared towards the detection of poliovirus. To accurately detect and
59
characterize circulating enteroviruses and estimate their burden on the community, a pro-active
60
system is needed. Such a system should be based on a data-driven practice, sampling the correct
61
patient groups to enable rapid detection, which is a vital aspect of outbreak control.
62
Enteroviruses are endemic and among the most common causes of human disease globally. They
63
are associated with a variety of clinical manifestations, ranging from respiratory, gastrointestinal
64
or skin symptoms, to severe infections of the myocardia or central nervous system [3].
65
Enteroviruses are a common cause of aseptic meningitis [3], particularly in very young children.
66
The correct and timely identification of enteroviruses as the cause, rather than the more serious
67
bacterial meningitis, has at least two important implications. Not only does it lead to a reduction
68
in unnecessary long-term use of high dose antibiotic treatment, but it also helps alleviate some of
AC C
EP
TE D
M AN U
SC
RI PT
46
ACCEPTED MANUSCRIPT the psychological strain suffered by the parents of patients, as viral meningitis has a much more
70
favourable prognosis as compared to bacterial. Furthermore, new enteroviruses are emerging and
71
causing major outbreaks, with both severe respiratory and neurological complications leading to
72
fatalities.
73
Late Summer and Autumn 2014 there was an unprecedented international outbreak of
74
enterovirus D68 associated with severe respiratory infection and polio-like acute flaccid myelitis
75
(AFM), primarily affecting North America, but also several European countries (Holm-Hansen).
76
Enterovirus D68 differs somewhat from most enteroviruses, and has primarily been detected in
77
respiratory samples, and only very rarely identified in stools [7]. In 2016 there has been an
78
upsurge of enterovirus D68 cases in France, the Netherlands and Sweden associated with
79
respiratory disease and AFM [8,9,10].
80
In the last few years, several new enteroviruses belonging to species C have been identified in
81
respiratory samples from patients with respiratory illness, including enterovirus C104, C105, C109
82
and C117 [11]. Some of these new enteroviruses are not detectable in stool and/or cerebrospinal
83
fluids, but require the testing of e.g. respiratory material. It is therefore important to include
84
several types of sample material in a surveillance system, as it is not possible to predict whether
85
the next new virus will be found in stool, cerebrospinal fluid, blood or samples of respiratory
86
origin. Also, the genetic heterogeneity of enteroviruses (as illustrated in Figure 1) challenges
87
detection and characterization of the >250 enterovirus types using standard enterovirus
88
diagnostic approaches by polymerase-chain reaction (PCR).
89
Newly discovered enteroviruses are named numerically by the International Committee on
90
Taxonomy of Viruses [12], rather than being given more informative names, which likely adds to
AC C
EP
TE D
M AN U
SC
RI PT
69
ACCEPTED MANUSCRIPT the challenges of ensuring recognition of the role of these enteroviruses in specific diseases. In
92
2012 rhinovirus species A-C were re-classified as enterovirus species resulting in a total of 12
93
enterovirus species, of which enterovirus A-D and rhinovirus A-C infect humans. Figure 1 shows
94
the genetic diversity of the seven enterovirus species infecting humans. Despite the inclusion of
95
rhinoviruses in the enterovirus species, many diagnostic tests still distinguish between the two.
96
This has implications for the awareness of enteroviruses among both the public and health
97
professionals. As more and more cases of “common colds” are classified as enterovirus infections
98
there may well be a tendency towards not suspecting rare and serious disease manifestations as
99
being caused by enteroviruses, delaying diagnosis and potentially leading to inappropriate
M AN U
SC
RI PT
91
treatment with antibiotics. It should also be noted that rhinoviruses are also capable of causing
101
severe infections, particularly in immunocompromised patients [13].
102
Emerging enteroviruses, such as D68 and enteroviruses belonging to species C, have taught us that
103
even in a polio-free world there are still pathogens capable of causing devastating disease
104
including severe neurological infection, polio-like AFP, myelitis and life-threating respiratory
105
disease [8,9,10,11]. Enterovirus surveillance will be increasingly important in the post-polio
106
eradication era, as an early warning system not only for possible poliovirus re-introduction (CDC),
107
but also for the detection and response to outbreaks of other potentially severe enteroviruses,
108
exemplified by the re-emergence of enterovirus D68 in 2016 North America and some European
109
countries [8,9,10]. However, many of the existing enterovirus surveillance systems will not detect
110
D68 and other respiratory enteroviruses, unless they are enhanced to also include the routine
111
screening of respiratory samples, and subsequent characterisation of respiratory enteroviruses.
112
The picornavirus family contains other viruses of public health concern, such as parechoviruses,
AC C
EP
TE D
100
ACCEPTED MANUSCRIPT and an established robust surveillance system for enteroviruses can also be utilized/expanded to
114
include detection of other viruses.
115
It is the responsibility of the Public Health sector to detect, and react to, threats to the health of
116
the community. A robust and sensitive surveillance system is key in order to achieve this, and thus,
117
we suggest improving the capacity for detection of emerging enteroviruses globally by enhancing
118
current enterovirus surveillance systems. Numerous methodologies are available for the detection
119
as well as thecharacterization of polio and other enteroviruses, including generic protocols
120
developed and recommended, respectively, by the CDC and WHO. The focus of system
121
strengthening efforts should therefore be on the sample collection. Firstly, by including routine
122
surveillance of respiratory samples from children seen both in the primary and secondary
123
healthcare sector. Secondly, by ensuring diagnostic analyses of stool, cerebrospinal fluid, blood,
124
and respiratory samples in patients with unexplained neurological clinical presentations and/or
125
severe unexplained respiratory disease. Thirdly, by including environmental surveillance. The
126
latter system is the main methodological recommendation for enterovirus surveillance in a post-
127
polio world. Therefore, current initiatives to develop and implement environmental surveillance
128
systems should be considered constructive investments for safeguarding populations in the future.
129
The main challenge will be a shift from passive surveillance, to pro-active surveillance. These
130
measures will increase the understanding of the burden of enterovirus diseases, and enable the
131
detection of, as well as a rapid and effective response to, future outbreaks of these emerging
132
viruses. The first joint European expert meeting on the design of enhanced enterovirus
133
surveillance systems for present, as well as the future post-polio world, will take place in Oxford in
134
March 2017, with support from the European Society for Clinical Virology and the European
135
Centre for Disease Prevention and Control (ECDC), with representatives from the WHO attending
AC C
EP
TE D
M AN U
SC
RI PT
113
ACCEPTED MANUSCRIPT (http://www.escv.org/uploads/Oxford,%20workshop2017,%20Enterovirus.pdf). Here, the added
137
value of enhanced enterovirus surveillance systems, and opportunities for development of generic
138
surveillance protocols, will be discussed and the outcome of the workshop with recommendations
139
made available for public use. This workshop can be regarded as one of many first steps in the
140
global effort to strengthen enterovirus surveillance systems for a post-polio world.
RI PT
136
141
SC
142 Contributors
144
Thea, Sofie, Susanne and Charlotte conceptualized the study, Charlotte and Thea drafted the first
145
version, and all authors have contributed to the development of the manuscript and approved its
146
content.
M AN U
143
147 Conflict of interest
149
The authors declare no competing interest.
EP
150
TE D
148
Funding
152
No external funding was received for this article.
153 154 155 156 157 158 159 160 161 162
1.
2.
3.
AC C
151
Etsano A, et al., Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission — Nigeria, 2016. Morbidity and Mortality Weekly Report, 2016. 65(30). Bessaud M, et al., Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity. Science Reports 2016; 6: 38831. Centre for Disease Control and Prevention and World Health Organization, R.O.f.E., Enterovirus surveillance guidelines - Guidelines for enterovirus surveillance in support of the Polio Eradication Initiative. 2015.
ACCEPTED MANUSCRIPT
9.
10. 11.
12. 13.
RI PT
8.
Antona D., et al., Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016. Euro Surveill. 2016; 21(46). Dyrdak R, et al., Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016. Eurosurveillance, 2016. 21.
SC
7.
Knoester M, et al., Upsurge of Enterovirus D68, the Netherlands, 2016. Emerging Infectious Diseases, 2017. 23(1). Van Leer-Buter, C.C., et al., Newly Identified Enterovirus C Genotypes, Identified in the Netherlands through Routine Sequencing of All Enteroviruses Detected in Clinical Materials from 2008 to 2015. J Clin Microbiol, 2016. 54(9): p. 2306-14. Adams, M.J., et al., Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses. Arch Virol, 2016. 161:2921-2949. Jacobs SE, etal., Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy. J Clin Virol. 2015; 71: 51-8.
M AN U
6.
TE D
5.
Deshpande JM, et al., Environmental surveillance system to track wild poliovirus transmission. Appl Environ Microbiol. 2003; 69: 2919-27. El Bassioni L., et al., Prolonged detection of indigenous wild polioviruses in sewage from communities in Egypt. Am J Epid 2003; 158: 807-15. Asghar, H., et al., Environmental Surveillance for Polioviruses in the Global Polio Eradication Initiative. Journal of Infectious Diseases, 2014. 210(suppl 1): p. S294-S303. Holm-Hansen, C.C., S.E. Midgley, and T.K. Fischer, Global emergence of enterovirus D68: a systematic review. The Lancet Infectious Diseases, 2016. 16(5): p. e64-e75.
EP
190
4.
AC C
163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189
ACCEPTED MANUSCRIPT
EVC
Figure 1. Genetic diversity of enteroviruses infecting humans.
EVD
RI PT
RVB
EP
TE D
M AN U
SC
RVC
EVB
AC C
RVA
EVJ
0,5
Figure 1 shows a maximum likelihood phylogenetic tree of representative full genomes from all 7 species of enterovirus known to infect humans (enterovirus A to D; EVA-EVD, rhinovirus A to C; RVA-RVC). Simian enterovirus J108 has been included to root the tree. A full list of accession numbers for the sequences included is available from the authors on request.
EVA