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The importance of enterovirus surveillance in a Post-polio world

2017; Elsevier BV; Volume: 23; Issue: 6 Linguagem: Inglês

10.1016/j.cmi.2017.02.010

1469-0691

Charlotte Holm-Hansen, Sofie Midgley, Susanne Schjørring, Thea Kølsen Fischer,

Celiac Disease Research and Management

In 1988, the Global Poliovirus Eradication Initiative (GPEI) was launched, and now in 2017, we are close to achieving that goal. The poliovirus type 2 component was removed from the vaccine formulations, and, as of August 2016, Afghanistan and Pakistan were the only two countries in the world that still reported endemic wild polio circulation; Nigeria was declared polio-free in 2015, but during 2016 both circulating vaccine-derived polio type 2 and wild poliovirus type 1 have been detected [[1]Etsano A. Damisa E. Shuaib F. Nganda G.W. Enemaku O. Usman S. et al.Environmental isolation of circulating vaccine-derived poliovirus after interruption of wild poliovirus transmission—Nigeria, 2016.MMWR. 2016; 65PubMed Google Scholar], (http://www.who.int/mediacentre/news/releases/2016/nigeria-polio/en/). Circulating vaccine-derived polioviruses are vaccine strains that have evolved over time within a vaccinated individual, accumulating mutations. Such viruses also have the potential to recombine with other related enteroviruses, leading to the emergence of new pathogenic strains [[2]Bessaud M. Joffret M.L. Blondel B. Delpeyroux F. Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity.Sci Rep. 2016; 6: 38831Crossref PubMed Scopus (30) Google Scholar]. The golden standard of polio surveillance through the GPEI is systematic screening of stools from patients with either aseptic meningitis and/or acute flaccid paralysis (AFP) for poliovirus. However, countries that have been declared polio-free are challenged by the AFP sensitivity criteria specified by the GPEI (two AFP cases per 100 000 children under the age of 15 years per year, http://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/active/poliomyelitis_standards/en/). Therefore, in polio-free countries, alternative surveillance systems, including environmental surveillance and non-polio enterovirus surveillance, are often in place [[3]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. CDC, Atlanta, GA2015Google Scholar]. Of note, an absence of detection of vaccine-derived or wild-type viruses in environmental samples does not signify a total absence of such strains in the population. In the coming years, heading towards complete poliovirus eradication, there is a need to maintain sensitive surveillance systems to detect silent circulation of residual poliovirus (wild or vaccine-derived) rapidly and effectively, to avoid outbreaks of potentially devastating disease. This is currently the main role of the global polio surveillance system, organized in national and regional WHO poliovirus reference laboratories. In the aftermath of documented poliovirus eradication, it has been suggested to replace the current comprehensive case-based stool investigations of aseptic meningitis cases with environmental surveillance. Environmental surveillance, the sampling and analysis of sewage or wastewater for the presence of poliovirus, has already played a pivotal role in documenting the poliovirus elimination phase in some countries, such as India and Egypt [4Deshpande J.M. Shetty S.J. Siddiqui Z.A. Environmental surveillance system to track wild poliovirus transmission.Appl Environ Microbiol. 2003; 69: 2919-2927Crossref PubMed Scopus (73) Google Scholar, 5El Bassioni L. Barakat I. Nasr E. de Gourville E.M. Hovi T. Blomqvist S. et al.Prolonged detection of indigenous wild polioviruses in sewage from communities in Egypt.Am J Epidemiol. 2003; 158: 807-815Crossref PubMed Scopus (57) Google Scholar]. Furthermore, it acts as a supplement to AFP surveillance in the few remaining countries where polio is endemic [[6]Asghar H. Diop O.M. Weldegebriel G. Malik F. Shetty S. El Bassioni L. et al.Environmental surveillance for polioviruses in the Global Polio Eradication Initiative.J Infect Dis. 2014; 210: S294-S303Crossref PubMed Scopus (205) Google Scholar]. Since 2015 the CDC and the WHO have recommended enterovirus surveillance in order to (a) detect and control outbreaks, (b) perform virological investigation and research, and (c) establish disease burden data for long-term public health planning. Yet, routine surveillance of enteroviruses is not common practice in most countries [[3]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. CDC, Atlanta, GA2015Google Scholar]. Current enterovirus surveillance systems are passive, based on characterization of enteroviruses in diagnostic samples, and geared towards the detection of poliovirus. To accurately detect and characterize circulating enteroviruses and estimate their burden on the community, a pro-active system is needed. Such a system should be based on a data-driven practice, sampling the correct patient groups to enable rapid detection, which is a vital aspect of outbreak control. Enteroviruses are endemic and among the most common causes of human disease globally. They are associated with a variety of clinical manifestations, ranging from respiratory, gastrointestinal or skin symptoms, to severe infections of the myocardia or central nervous system [[3]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. CDC, Atlanta, GA2015Google Scholar]. Enteroviruses are a common cause of aseptic meningitis [[3]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. CDC, Atlanta, GA2015Google Scholar], particularly in very young children. The correct and timely identification of enteroviruses as the cause, rather than the more serious bacterial meningitis, has at least two important implications. Not only does it lead to a reduction in unnecessary long-term use of high-dose antibiotic treatment, but it also helps to alleviate some of the psychological strain suffered by the parents of patients, as viral meningitis has a much more favourable prognosis compared with bacterial meningitis. Furthermore, new enteroviruses are emerging and causing major outbreaks, with both severe respiratory and neurological complications leading to fatalities. Late summer and autumn 2014 there was an unprecedented international outbreak of enterovirus D68 associated with severe respiratory infection and polio-like acute flaccid myelitis, primarily affecting North America, but also several European countries [[7]Holm-Hansen C.C. Midgley S.E. Fischer T.K. Global emergence of enterovirus D68: a systematic review.Lancet Infect Dis. 2016; 16: e64-e75Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar]. Enterovirus D68 differs somewhat from most enteroviruses, and has primarily been detected in respiratory samples, and only very rarely identified in stools [[7]Holm-Hansen C.C. Midgley S.E. Fischer T.K. Global emergence of enterovirus D68: a systematic review.Lancet Infect Dis. 2016; 16: e64-e75Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar]. In 2016 there has been an upsurge of enterovirus D68 cases in France, the Netherlands and Sweden associated with respiratory disease and acute flaccid myelitis [8Antona D. Kossorotoff M. Schuffenecker I. Mirand A. Leruez-Ville M. Bassi C. et al.Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016.Euro Surveill. 2016; 21Crossref Scopus (60) Google Scholar, 9Dyrdak R. Grabbe M. Hammas B. Ekwall J. Hansson K.E. Luthander J. et al.Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016.Eurosurveillance. 2016; 21Crossref Scopus (67) Google Scholar, 10Knoester M. Schölvinck E.H. Poelman R. Smit S. Vermont C.L. Niesters H.G. et al.Upsurge of enterovirus D68, the Netherlands, 2016.Emerg Infect Dis. 2017; 23Crossref PubMed Scopus (72) Google Scholar]. In the last few years, several new enteroviruses belonging to species C have been identified in respiratory samples from patients with respiratory illness, including enteroviruses C104, C105, C109 and C117 [[11]Van Leer-Buter C.C. Poelman R. Borger R. Niesters H.G. 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: 2306-2314Crossref PubMed Scopus (29) Google Scholar]. Some of these new enteroviruses are not detectable in stool and/or cerebrospinal fluids, but require the testing of, for example, respiratory material. It is therefore important to include several types of sample material in a surveillance system, as it is not possible to predict whether the next new virus will be found in stool, cerebrospinal fluid, blood or samples of respiratory origin. Also, the genetic heterogeneity of enteroviruses (as illustrated in Fig. 1) challenges detection and characterization of the >250 enterovirus types using standard enterovirus diagnostic approaches by PCR. Newly discovered enteroviruses are named numerically by the International Committee on Taxonomy of Viruses [[12]Adams M.J. Lefkowitz E.J. King A.M. Harrach B. Harrison R.L. Knowles N.J. et al.Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses.Arch Virol. 2016; 161: 2921-2949Crossref PubMed Scopus (221) Google Scholar], rather than being given more informative names, which probably adds to the challenges of ensuring recognition of the role of these enteroviruses in specific diseases. In 2012 rhinovirus species A–C were re-classified as enterovirus species resulting in a total of 12 enterovirus species, of which enteroviruses A–D and rhinoviruses A–C infect humans. Fig. 1 shows the genetic diversity of the seven enterovirus species infecting humans. Despite the inclusion of rhinoviruses in the enterovirus species, many diagnostic tests still distinguish between the two. This has implications for the awareness of enteroviruses among both the public and health professionals. As more and more cases of 'common colds' are classified as enterovirus infections there may well be a tendency towards not suspecting rare and serious disease manifestations as being caused by enteroviruses, delaying diagnosis and potentially leading to inappropriate treatment with antibiotics. It should also be noted that rhinoviruses are also capable of causing severe infections, particularly in immunocompromised patients [[13]Jacobs S.E. Lamson D.M. Soave R. Guzman B.H. Shore T.B. Ritchie E.K. et al.Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy.J Clin Virol. 2015; 71: 51-58Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar]. Emerging enteroviruses, such as D68 and enteroviruses belonging to species C, have taught us that even in a polio-free world there are still pathogens capable of causing devastating disease including severe neurological infection, polio-like AFP, myelitis and life-threatening respiratory disease [8Antona D. Kossorotoff M. Schuffenecker I. Mirand A. Leruez-Ville M. Bassi C. et al.Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016.Euro Surveill. 2016; 21Crossref Scopus (60) Google Scholar, 9Dyrdak R. Grabbe M. Hammas B. Ekwall J. Hansson K.E. Luthander J. et al.Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016.Eurosurveillance. 2016; 21Crossref Scopus (67) Google Scholar, 10Knoester M. Schölvinck E.H. Poelman R. Smit S. Vermont C.L. Niesters H.G. et al.Upsurge of enterovirus D68, the Netherlands, 2016.Emerg Infect Dis. 2017; 23Crossref PubMed Scopus (72) Google Scholar, 11Van Leer-Buter C.C. Poelman R. Borger R. Niesters H.G. 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: 2306-2314Crossref PubMed Scopus (29) Google Scholar]. Enterovirus surveillance will be increasingly important in the post-polio eradication era, as an early warning system not only for possible poliovirus re-introduction [[3]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. CDC, Atlanta, GA2015Google Scholar], but also for the detection and response to outbreaks of other potentially severe enteroviruses, exemplified by the re-emergence of enterovirus D68 in 2016 in North America and some European countries [8Antona D. Kossorotoff M. Schuffenecker I. Mirand A. Leruez-Ville M. Bassi C. et al.Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016.Euro Surveill. 2016; 21Crossref Scopus (60) Google Scholar, 9Dyrdak R. Grabbe M. Hammas B. Ekwall J. Hansson K.E. Luthander J. et al.Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016.Eurosurveillance. 2016; 21Crossref Scopus (67) Google Scholar, 10Knoester M. Schölvinck E.H. Poelman R. Smit S. Vermont C.L. Niesters H.G. et al.Upsurge of enterovirus D68, the Netherlands, 2016.Emerg Infect Dis. 2017; 23Crossref PubMed Scopus (72) Google Scholar]. However, many of the existing enterovirus surveillance systems will not detect D68 and other respiratory enteroviruses, unless they are enhanced to also include the routine screening of respiratory samples, and subsequent characterization of respiratory enteroviruses. The picornavirus family contains other viruses of public health concern, such as parechoviruses, and an established robust surveillance system for enteroviruses can also be used/expanded to include detection of other viruses. It is the responsibility of the Public Health sector to detect, and react to, threats to the health of the community. A robust and sensitive surveillance system is key to achieving this, and so we suggest improving the capacity for detection of emerging enteroviruses globally by enhancing current enterovirus surveillance systems. Numerous methodologies are available for the detection as well as the characterization of poliovirus and other enteroviruses, including generic protocols developed and recommended, respectively, by the CDC and WHO. The focus of system strengthening efforts should therefore be on the sample collection. First, by including routine surveillance of respiratory samples from children seen both in the primary and secondary healthcare sector. Second, by ensuring diagnostic analyses of stool, cerebrospinal fluid, blood and respiratory samples in patients with unexplained neurological clinical presentations and/or severe unexplained respiratory disease. Third, by including environmental surveillance. The latter system is the main methodological recommendation for enterovirus surveillance in a post-polio world. Therefore, current initiatives to develop and implement environmental surveillance systems should be considered constructive investments for safeguarding populations in the future. The main challenge will be a shift from passive surveillance, to pro-active surveillance. These measures will increase the understanding of the burden of enterovirus diseases, and enable the detection of, as well as a rapid and effective response to, future outbreaks of these emerging viruses. The first joint European expert meeting on the design of enhanced enterovirus surveillance systems for the present, as well as the future post-polio world, will take place in Oxford in March 2017, with support from the European Society for Clinical Virology and the European Centre for Disease Prevention and Control, with representatives from the WHO attending (http://www.escv.org/uploads/Oxford,%20workshop2017,%20Enterovirus.pdf). Here, the added value of enhanced enterovirus surveillance systems, and opportunities for the development of generic surveillance protocols, will be discussed and the outcome of the workshop with recommendations will be made available for public use. This workshop can be regarded as one of many first steps in the global effort to strengthen enterovirus surveillance systems for a post-polio world. TKF, SEM, SS and CCH-H conceptualized the study, CCH-H and TKF drafted the first version, and all authors have contributed to the development of the manuscript and approved its content. The authors declare no competing interest. No external funding was received for this article.