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Issued by the Standards Unit, Microbiology Services Division, HPA UK Protocols | P 1 | Issue no: 4| Issue date: 03.05.12 | Page: 1 of 19
Acknowledgments
UK Standards for Microbiology Investigations (SMIs) are developed under the auspices of the Health Protection Agency (HPA) working in partnership with the National Health Service (NHS), Public Health Wales and with the professional organisations whose logos are displayed below and listed on the website http://www.hpa.org.uk/SMI/Partnerships. SMIs are developed, reviewed and revised by various working groups which are overseen by a steering committee (see http://www.hpa.org.uk/SMI/WorkingGroups). The contributions of many individuals in clinical, specialist and reference laboratories who have provided information and comments during the development of this document are acknowledged. We are grateful to the Medical Editors for editing the medical content. For further information please contact us at: Standards Unit Microbiology Services Division Health Protection Agency 61 Colindale Avenue London NW9 5EQ E-mail: standards@hpa.org.uk Website: http://www.hpa.org.uk/SMI UK Standards for Microbiology Investigations are produced in association with:
Background to SMIs
SMIs comprise a collection of recommended algorithms and procedures covering all stages of the investigative process in microbiology from the pre-analytical (clinical syndrome) stage to the analytical (laboratory testing) and post analytical (result interpretation and reporting) stages. Syndromic algorithms are supported by more detailed documents containing advice on the investigation of specific diseases and infections. Guidance notes cover the clinical background, differential diagnosis, and appropriate investigation of particular clinical conditions. Quality guidance notes describe essential laboratory methodologies which underpin quality, for example assay validation, quality assurance, and understanding uncertainty of measurement. Standardisation of the diagnostic process through the application of SMIs helps to assure the equivalence of investigation strategies in different laboratories across the UK and is essential for public health interventions, surveillance, and research and development activities. SMIs align advice on testing strategies with the UK diagnostic and public health agendas.
UK Standards for Microbiology Investigations were formerly known as National Standard Methods.
Microbiology is used as a generic term to include the two GMC-recognised specialties of Medical Microbiology (which includes Bacteriology, Mycology and Parasitology) and Medical Virology.
Quality Assurance
The process for the development of SMIs is certified to ISO 9001:2008. NHS Evidence has accredited the process used by the HPA to produce SMIs. Accreditation is valid for three years from July 2011. The accreditation is applicable to all guidance produced since October 2009 using the processes described in the HPAs Standard Operating Procedure SW3026 (2009) version 6. SMIs represent a good standard of practice to which all clinical and public health microbiology laboratories in the UK are expected to work. SMIs are well referenced and represent neither minimum standards of practice nor the highest level of complex laboratory investigation possible. In using SMIs, laboratories should take account of local requirements and undertake additional investigations where appropriate. SMIs help laboratories to meet accreditation requirements by promoting high quality practices which are auditable. SMIs also provide a reference point for method development. SMIs should be used in conjunction with other SMIs. UK microbiology laboratories that do not use SMIs should be able to demonstrate at least equivalence in their testing methodologies. The performance of SMIs depends on well trained staff and the quality of reagents and equipment used. Laboratories should ensure that all commercial and in-house tests have been validated and shown to be fit for purpose. Laboratories should participate in external quality assessment schemes and undertake relevant internal quality control procedures. Whilst every care has been taken in the preparation of SMIs, the HPA, its successor organisation(s) and any supporting organisation, shall, to the greatest extent possible under any applicable law, exclude liability for all losses, costs, claims, damages or expenses arising out of or connected with the use of an SMI or any information contained therein. If alterations are made to an SMI, it must be made clear where and by whom such changes have been made. SMIs are the copyright of the HPA which should be acknowledged where appropriate. Microbial taxonomy is up to date at the time of full review.
Health Protection Agency. (2012). Surveillance of Polio in the UK. UK Standards for Microbiology Investigations. P 1 Issue 4. http://www.hpa.org.uk/SMI/pdf.
Contents
ACKNOWLEDGMENTS ............................................................................................................. 2 UK STANDARDS FOR MICROBIOLOGY INVESTIGATIONS: STATUS .................................................. 3 AMENDMENT TABLE ............................................................................................................... 6 SCOPE OF DOCUMENT ........................................................................................................... 7 INTRODUCTION ..................................................................................................................... 7 1 2 3 THE ROLE OF HPA AND NHS LABORATORIES ................................................................... 8 THE ROLE OF VIRUS REFERENCE DEPARTMENT, MICROBIOLOGICAL SERVICES DIVISION, COLINDALE .............................................................................................................. 10 THE ROLE OF HEALTH PROTECTION SERVICES AT HPA COLINDALE .................................. 10
APPENDIX 1 TECHNICAL INFORMATION ON THE LABORATORY DIAGNOSIS OF POLIOVIRUS INFECTION ............................................................................................................... 12 APPENDIX 2 POLIO SURVEILLANCE FORM ................................................................................ 13 APPENDIX 3. LETTER TO CLINICIANS ....................................................................................... 13 APPENDIX 4. PUBLIC HEALTH RESPONSE TO POTENTIAL WILD POLIOVIRUS INFECTION.................. 14 APPENDIX 5. CASE DEFINITIONS FOR PARALYTIC POLIOMYELITIS ................................................ 18
Amendment Table
Each SMI method has an individual record of amendments. The current amendments are listed on this page. The amendment history is available from standards@hpa.org.uk. New or revised documents should be controlled within the laboratory in accordance with the local quality management system. Amendment No/Date. Issue no. discarded. Insert Issue no. Section(s) involved. Whole document. Introduction. Appendix 2. 32/03.05.12 3.3 4 Amendment. Document presented in a new format. Contents updated Surveillance form now embedded in to the document
Amendment No/Date. Issue no. discarded. Insert Issue no. Section(s) involved. Whole document.
Scope of Document
This SMI covers the surveillance of Polio within the UK and should be used in conjunction with other SMIs.
Introduction
The World Health Organization continues its efforts to eradicate polio worldwide and believes that this goal is attainable, even in the most challenging settings in the world. Once eradication is achieved, and prior to any decision to stop mass immunisation against polio, it will be essential to demonstrate that all countries are free of wild poliovirus infections. Certification of a country or region as polio-free requires demonstration that surveillance systems are adequate to detect any endemic wild poliovirus infections. In 1997/8, the Public Health Laboratory was asked to prepare part of the UK submission to the WHO commission for the certification of eradication of polio in the European region. This aimed to demonstrate that current clinical and laboratory practice was adequate to detect cases of paralytic illness, aseptic meningitis and asymptomatic infection due to wild poliovirus. The UK submission was forwarded from the Department of Health in Spring 1998 and it was accepted by the commission that the UK is now free of wild poliovirus. Formal certification could not proceed, however, until the whole region had been free of wild polio for three years. Europe was declared polio-free in 2002. It is essential that enhanced surveillance of poliovirus continues as importation from endemic regions is still possible. Furthermore, outbreaks of poliomyelitis caused by vaccine derived recombinant strains have occurred in countries certified as polio-free and where vaccine uptake has fallen. We need to demonstrate that cases with a possible diagnosis of poliomyelitis are adequately investigated to exclude infection with wild poliovirus. Supporting evidence is also provided by the ability to identify correctly non-polio enteroviruses and vaccine strains of poliovirus. Detailed review of the clinical and laboratory data from all suspected cases of paralytic poliomyelitis (including cases of acute flaccid paralysis with persistent paralysis) should be performed by the UK Expert Panel. Cases of paralysis which are not adequately investigated should also be subjected to clinical review. In 2004, the UK changed from using live oral polio vaccine (OPV) to inactivated vaccine (IPV). All poliovirus isolates, unless known to have come from persons recently given OPV, must now be regarded as potentially non-vaccine strains. The UK will minimise the risk of reintroduction of polio through release from facilities holding poliovirus or samples that may contain poliovirus. Substantial steps have already been made towards meeting the requirements of the initial phase of the WHO Global Action Plan, 2nd edition. (http://www.polioeradication.org/content/publications/WHO-VB-03-729.pdf). As part of the UK response to the WHO initiative the Public Health Laboratory Service compiled a National Inventory of facilities holding polio materials, starting in 2001 (see Annex 4.5). An audit of the inventory by the Health Protection Agency (the successor to Public Health Laboratory Services), completed in 2009, shows that only 26 sites now retain poliovirus, or material that potentially contains the virus. Any additional laboratory that acquires or isolates wild poliovirus or vaccine virus or stores untyped enterovirus should inform the UK polio containment co-ordinator (polio@hpa.org.uk). All laboratories are encouraged to find alternatives to the use of wild poliovirus and to destroy all unneeded material. In laboratories that continue to isolate, store or use poliovirus, the current legal requirements for work with biological agents that present a risk to human health are outlined in the Control of Substances Hazardous to Health (COSHH) 2002 regulations (http://www.hse.gov.uk/COSHH/index.htm). At present in the UK poliovirus is a hazard group 2 UK Protocols |P 1 | Issue no: 4 | Issue date: 03.05.12 | Page: 7 of 19
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Health Protection Agency
Surveillance of Polio in the UK pathogen and work involving this virus, or materials containing the virus, should be undertaken at CL2. However, the WHO recommends that containment measures go beyond those required by CL2 in Schedule 3 of COSHH. The WHO recommendations, BSL-2/polio, are not currently legally required in the UK, but laboratories that continue to work with poliovirus are advised to implement enhanced BSL-2/polio measures for safe handling of the virus. The WHO guidelines are detailed in the Global Action Plan, 2nd edition (http://www.polioeradication.org/content/publications/WHO-VB-03-729.pdf). This document sets out the HPAs role in maintaining surveillance of polio in the UK until certification is completed worldwide.
Laboratories should try to ensure that poliovirus infection is excluded in all cases of acute flaccid paralysis (including Guillain-Barr syndrome) according to the WHO criteria. This involves the submission of two stool samples for viral culture which can be performed in the Virus Reference Division, HPA Colindale if virus isolation or enterovirus PCR is not available locally. Samples should be taken 48 hours apart and within two weeks of onset (see Appendix 1). Laboratories should ensure investigation of all possible polioviruses isolated in the laboratory or detected by PCR is undertaken -- including from asymptomatic individuals. To supplement acute-flaccid paralysis surveillance, enhanced surveillance of aseptic meningitis is also recommended, particularly as poliovirus causes aseptic meningitis far more frequently than paralytic poliomyelitis and the majority of enteroviruses are detected in CSF samples. It is therefore recommended that enterovirus positive CSF samples and positive nucleic acid extracts are also submitted to the Virus Reference Department for typing. Laboratories should discuss all cases of suspected polio with Virus Reference Department or Health Protection Services, HPA Colindale at an early stage. Such cases should be reported to the local CCDC or equivalent in the devolved administrations. Laboratories should recommend the following additional investigations in cases of suspected polio (see Appendix 1): Enterovirus PCR on stool, CSF or throat swabs / NPAs. Biochemistry, microscopy and viral culture of CSF specimens. Viral culture of throat swabs / NPAs. Viral culture and/or PCR of stool from household contacts. Poliovirus-specific PCR on stool, CSF or throat swabs/ NPA. Virus culture and neutralisation tests (stool, CSF, throat swabs/NPA). Intratypic poliovirus neutralisation tests. Confirmation of poliovirus and differentiation through sequence analysis of vaccine and wild-type poliovirus strains. Acute and convalescent serum for the detection of neutralising antibody to poliovirus 1, 2 and 3 in acute and convalescent serum samples (available at Virus Reference Department). Poliovirus IgM assay (arranged through Virus Reference Department if appropriate).
Surveillance of Polio in the UK Laboratories should perform all routine investigations according to the UK Standards for Microbiology Investigations (where appropriate/when available). As part of enhanced surveillance, laboratories should refer the following to the Enteric Virus Unit, Virus Reference Department (see Appendix 2): a. b. All poliovirus isolates or clinical samples from which poliovirus has been detected by molecular or serological methods. Untypable enterovirus isolates (these can be tested in suitably trained local laboratories if preferred. If they can not type them then they should be sent to Colindale for typing). CSF samples that are enterovirus positive by PCR (these can be tested in suitably trained local laboratories if preferred. If they can not type them then they should be sent to Colindale for typing). Enterovirus isolates and PCR-positive enterovirus samples from cases with paralytic symptoms. Enterovirus isolates and PCR-positive enterovirus samples from cases with neurological conditions (include those that mention meningitis / encephalitis / meningism / irritability / headache / convulsions / apnoea and sudden death on the request form). Enterovirus isolates and PCR-positive samples from immunosuppressed persons. Enterovirus PCR-positive clinical samples and enterovirus isolates from people with myocarditis.
c.
d. e.
f. g.
NB: cDNA should only be sent if generated through reverse transcription with random priming (random hexamers). Laboratories should facilitate the Health Protection Services obtaining copies of clinical information on cases of suspected paralytic polio (see Appendix 3). Furthermore, assistance should be given to obtain further clinical information whenever a poliovirus is detected in the laboratory. This includes: Clinical history (presence of any polio-like symptoms) Immune status (immunocompromised or immunocompetent) Polio vaccination history. Travel history in case and family members.
The appropriate samples should be sent urgently to Virus Reference Department to ascertain if the virus is a vaccine or wild strain. If the former, it should be ascertained if it is a vaccinederived poliovirus (VDPV) by intratypic differentiation Laboratories should assist the Health Protection Services and the local CCDC with the public health response to suspected cases (see Appendix 4). To contribute to containment: if wild or vaccine related polio is isolated in the laboratory then all relevant sample(s) should be either: Sent to Virus Reference Department; Notified to the Poliovirus register if the samples are to be retained in local laboratory Discarded
Virus Reference Department will report routine poliovirus investigations on specimens from cases with paralytic or other neurological symptoms as outlined above within one week of receipt. Virus Reference Department will perform further investigation of cases of suspected polio according to WHO and HPA-approved SOPs. These investigations include: Neutralising antibody for poliovirus types 1, 2 and 3. Enterovirus PCR on stool, CSF or throat swab / NPA. Poliovirus PCR on stool, CSF or throat swab / NPA. Characterisation of polioviruses through sequencing of the VP1 region.
Virus Reference Department will provide advice on appropriate investigation of suspected cases. Virus Reference Department will support laboratories and the Immunisation Department in a public health response to a suspected case.
Surveillance of Polio in the UK All cases of paralysis which are investigated for poliovirus infection. For cases of paralysis where stool samples were not taken at the appropriate stage. All enterovirus identifications.
Health Protection Services will collate information on poliovirus and enterovirus isolates and identifications reported to Health Protection Services and referred to EVU, Virus Reference Department. Health Protection Services will collate data on cases of suspected poliomyelitis from any source (notified to ONS, paralysis reported to the Medicines Control Agency, referred to EVU, Virus Reference Department or reported to Health Protection Services) according to agreed case definitions (see Appendix 5).
2.2
Inoculate specimens into cell cultures following local laboratory procedures. Examine cell sheet daily for cytopathic effects. If no cytopathic effects are visible after 1 week, scrape cells into tissue culture medium, freeze and thaw and reinoculate into fresh cells.
2.3
Recommended cells
Poliovirus grows in a wide range of all cultures of human and primate origin. RD (Rhabdomyosarcoma) cells are particularly sensitive for isolation of poliovirus and enteroviruses (and can be supplied by Virus Reference Department if required). Other suitable cells include MRC5 or other human fibroblasts, primary and secondary monkey kidney, Hep2, Hep2C, HeLa and PLC/PRF5.
2.4
Virus typing
Isolates should be identified and typed eg by neutralisation, fluorescence etc. Commercial fluorescence tests are available for the identification of polioviruses and a limited range of enteroviruses.
3 POLIOVIRUS ISOLATES
Poliovirus isolates should be sent to EVU, Virus Reference Department for intratypic vaccine marker tests and genotyping, together with the completed form for Enhanced Surveillance of Polio.
3.1
PCR
PCR can be used for the detection of polioviruses and enteroviruses in faeces, throat swabs, CSF and early serum specimens.
4 SEROLOGY
Antibody tests for polio infection are available at EVU, Virus Reference Department (minimum volume required is 300 uL). Sera should be sent together with the Polio Surveillance form. Polio serology may be requested for reasons other than investigation of neurological illness eg immune status for travellers, patients who are immunocompromised and for Occupational UK Protocols |P 1 | Issue no: 4 | Issue date: 03.05.12 | Page: 12 of 19
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Health Protection Agency
Surveillance of Polio in the UK Health purposes. These will be treated as referred tests. Serum samples should be submitted with the Polio Surveillance form.
5 FURTHER INFORMATION
For further information contact EVU, Virus Reference Department 020 8327 6225 Main switchboard and out of hours 020 8200 4400
As you may know, the World Health Organization aims to eradicate wild poliovirus. Before any decision to stop vaccination can be made, however, it will be important to demonstrate that wild poliovirus is absent in every country. This requires a process of certification, where the surveillance data from each country is presented to the WHO regional commission for critical review. The UK has been certified as polio-free. To maintain this status, the UK needs to demonstrate that it has appropriate surveillance systems in place to rapidly detect and investigate suspect polio cases. The criteria that will be used will be extremely stringent and, in particular, evidence that wild poliovirus infection was excluded in each case of paralysis is required. The WHO has established a gold standard that all suspected cases of acute flaccid paralysis should be investigated by the submission of stool samples for virology. In the UK, however, where the diagnosis of paralytic polio is considered extremely unlikely, many such cases are excluded by clinical or other criteria. It will therefore be necessary for us to document the clinical findings and investigations in all suspected cases and to submit these for expert review. I am therefore writing to the clinicians of all cases which have been reported as acute flaccid paralysis, including those where the diagnosis of poliomyelitis has since been rejected, to obtain further details for this review. I would therefore be very grateful if you could send to me a copy of the discharge summary and/or outpatient letters (or the notes if you prefer) from the above case which was reported in (enter year). In particular we are interested in history of vaccination or travel, in laboratory investigations (eg. specimens sent for virology, examination of cells in the CSF), in the clinical presentation (eg. presence of sensory or upper motor neurone symptoms) and in the outcome (residual paralysis at least 60 days after onset). If you could please forward any information that we may not already have as soon as possible I would be very grateful. With many thanks for your help with this important initiative. Consultant Epidemiologist Immunisation Department Health Protection Agency, Colindale
Surveillance of Polio in the UK Level two: possible single case of wild poliovirus infection Defined as: Poliovirus isolate from a person with paralytic symptoms who has no history of recent vaccination or contact with a vaccinee. Poliovirus isolate from a person returning from a possible endemic area (any country outside Western Europe, North America, or Australasia). Poliovirus isolate from a child in an itinerant family. Poliovirus isolate from a child in a community which may refuse vaccination (eg Steiner communities). 1. Initiate appropriate investigations (see Appendix 1) of case and contacts immediately. Report immediately to Health Protection Services and / or Virus Reference Department. Contact Department of Health to obtain supply of OPV. 2. Ensure all close family contacts are vaccinated with OPV immediately, regardless of vaccination status. 3. Immediately investigate vaccination coverage in population at risk (eg school, residential community, locality). If vaccine coverage in local child population is suspected to be below 85% consider a mop up campaign involving: A single dose of OPV to persons of all ages if case occurs in a well defined community (regardless of vaccine history) or A single dose of OPV in all children of pre-school and school-age in locality (regardless of vaccine history) and Encourage opportunistic IPV vaccination (completion of vaccine course in all unvaccinated and partially vaccinated persons in locality). 4. If the target population (defined in 3) refuses vaccine Consider giving a single dose of vaccine to persons in adjacent communities. Institute active surveillance for paralytic and non-paralytic polio infection in locality. Level three: confirmed single case of wild poliovirus Defined as: Poliovirus isolate confirmed as wild by intratypic differentiation or sequencing at Virus Reference Department 1. Collect stool samples from household contacts. Consider collection of stool samples from wider population. 2. Report immediately to HPS. Department of Health and WHO will be informed. 3. Institute active surveillance for paralytic and non-paralytic infection in locality. Advise local laboratories and clinicians. Encourage stool samples in all acute neurological illnesses. Consider stool survey in healthy contacts.
4. If the infection appears to be imported. Immediately investigate vaccination coverage in population at risk (eg school, residential community, locality). If vaccine coverage in local childhood population is suspected to be below 85% consider a mop up campaign involving:
Surveillance of Polio in the UK A single dose of IPV/OPV to persons of all ages if case occurs in a well defined community (regardless of vaccine history) or A single dose of IPV/OPV in all children of pre-school and school-age in locality (regardless of vaccine history) and Opportunistic IPV vaccination (encourage completion of vaccine course in all unvaccinated and partially vaccinated persons in the locality). Contact local laboratories to obtain any recent enterovirus isolates. Perform stool survey in health persons at risk. A single dose of IPV/OPV to persons of all ages if case occurs in a well defined community (regardless of vaccine history) or A single dose of IPV/OPV in all children of pre-school and school-age in locality (regardless of vaccine history) and Opportunistic IPV vaccination (encourage completion of vaccine course in all unvaccinated and partially vaccinated persons in the locality). Consider giving a single dose of vaccine to person in adjacent communities.
7. If the target population (defined in 4 or 6) refuses vaccine 8. Consider a mop-up campaign in other age groups / populations depending on the epidemiological circumstances Level 3: confirmed single circulating vaccine-derived poliovirus (c-VDPV*) case Defined as: Poliovirus isolate confirmed as cVDPV drifted variant on sequencing at Virus Reference Department from a person with or without paralytic symptoms
Surveillance of Polio in the UK 3. Institute active surveillance and retrospective case-finding for paralytic and nonparalytic infection in locality. Advise local laboratories and clinicians. Encourage stool samples in all acute neurological illnesses. Perform stool survey in healthy contacts. Contact local laboratories to obtain any recent enterovirus isolates. A single dose of OPV to persons of all ages if case occurs in a well defined community (regardless of vaccine history) or A single dose of OPV in all children of pre-school and school-age in locality (regardless of vaccine history) and Opportunistic vaccination (completion of all unvaccinated persons in locality)
5. Consider a mop-up campaign in other age groups / populations depending on the epidemiological circumstances. Level 4: Epidemiologically linked cases of c-VDPV Defined as: Two or more poliovirus isolates from persons in the same locality presenting with paralytic/non-paralytic/or no symptoms and confirmed as cVDPV on sequencing at Virus Reference Department
# vaccinated abroad or in a patients with underlying immunodeficiency previously vaccinated with OPV * confirmation by isolation of vaccine virus for immunocompromised individuals these periods can be considerably longer
* confirmation by isolation of vaccine virus for immunocompromised individuals these periods can be considerably longer
3. Wild indigenous
Clinical features compatible with paralytic poliomyelitis, and Wild-type virus isolation, and No travel to and no contact with anyone who has travelled to or resided in, a area where wild poliovirus is known to circulate within 30 days before symptom onset.
4. Wild imported
Clinical features compatible with paralytic poliomyelitis, and Wild-type virus isolation, and Travel to or residence in a country where wild poliovirus is known to circulate within 30 days before symptom onset (see 5 below).
5. Other categories
5.1 Wild virus - import related Clinical features compatible with paralytic poliomyelitis, and Wild-type virus isolation, and Contact with anyone who has travelled to or resided in a country where wild poliovirus is known to circulate within 30 days before symptom onset, or contact with anyone who has acute poliomyelitis thought to have travelled to or resided in a country where wild poliovirus is known to circulate within 30 days before symptom onset Clinical features compatible with paralytic poliomyelitis, and Vaccine virus isolation but no known direct contact with a vaccinee and no history of the patient receiving oral polio vaccine Clinical features compatible with paralytic poliomyelitis, and No poliovirus isolation from clinical specimens, and With or without serological evidence of recent poliovirus infection, and No evidence for infection with other neurotropic viruses
5.2
5.3
Compatible case*
*These cases are referred for expert review and subsequent categorisation