Review of Public Health Microbiology Reference Laboratory Services in Scotland from 2010/11 to 2012/13

Transcription

1 Review of Public Health Microbiology Reference Laboratory Services in Scotland from 2010/11 to 2012/13

2 DOCUMENT CONTROL Document Location Document title Review of Reference Laboratory Services Scotland Document filepath J:\Corporate Office\Corporate Functions\Reference Labs\3 Year Review \Review of Reference Laboratory Services Scotland Final Report v1.1.docx Key Personnel Author: Name Role Organisation (if not HPS) Camilla Wiuff Strategic Lead Approver: Reference Laboratory Working Group Microbiology National advisory group on reference laboratory commissioning Document Kate Harley Associate Director Owner : Health Protection NHS Version History Version Date Summary of changes Changes marked V1.1 20/04/2015 P18 of 22, Section STRL, paragraph 3, line 2 added. Additional information provided by STRL. no Distribution Version Date Name Organisation (if not HPS) V1.0 01/09/2014 Reference and specialist testing laboratories, GGC, Lothian and Highland laboratory management, NSD Finance team, Reference Laboratory Working Group, Scottish Government NHS GGC, Lothian and Highland, NSD V1.1 20/04/15 As above Updated version placed on HPS website Approvals Version Date Name Approved V1.0 29/08/2014 Reference Laboratory Working Group NHS Organisation (if not HPS) References Document title Document file path

3 Table of Contents 1 Introduction Objective of the review Method of review Results Reference laboratory services provided by NHS Greater Glasgow and Clyde (GGC) Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL) Scottish Salmonella, Shigella and Clostridium difficile Reference Laboratory (SSSCDRL) Scottish MRSA Reference Laboratory (SMRSARL) Scottish Parasite Diagnostic and Reference Laboratory (SPDRL) Scottish Trace Element and Micronutrient Reference Laboratory (STEMRL) Reference laboratory services provided by NHS Lothian The Scottish E. coli O157/VTEC Reference Laboratory (SERL) Scottish Bacterial Sexually Transmitted Infection Reference Laboratory (SBSTIRL) Scottish Human Papillomavirus Reference Laboratory (SHPVRL) Scottish Mycobacteria Reference Laboratory (SMRL) Reference laboratory services provided by NHS Highland Scottish Toxoplasma Reference Laboratory (STRL) Reference laboratory services provided by NHS Lothian and NHS Greater Glasgow and Clyde Blood-Borne Virus (BBV) Specialist Testing Service Conclusions Recommendations Page 3 of 22

4 1 Introduction Public health microbiology uses an understanding of pathogens and the pathogenesis of infectious diseases with information from disease surveillance and knowledge of clinical interventions to contribute to the prevention and control of infectious diseases, including healthcare associated infections. The intelligence gathered by public health microbiology is used to develop policies and strategic approaches to improving the quality of healthcare and public health services. The provision of reference and specialist microbiology laboratory services is integral to these aims. Health Protection Scotland/National Services Division (HPS/NSD) commission services from ten reference laboratories and one joint specialist testing service. Additionally, services not provided in Scotland are purchased from Public Health England (PHE) Centre for Infections, Colindale. These laboratories provide services to NHS Scotland principally by: a) supporting diagnostic and clinical services through specialist laboratory testing and providing expertise not available in the diagnostic setting, b) underpinning public health practice and planning of interventions through surveillance and typing of key pathogens, and c) maintaining reference material (strain collections), contributing to research, quality assurance, audit and training. In addition the reference and specialist testing laboratories contribute to the following areas of public health microbiology practice: understanding the epidemiology of infectious disease including the emergence and spread of diseases horizon scanning, issuing alerts and responses to emerging issues investigating outbreaks and incidents developing and implementing new laboratory technologies quality assuring (including participation in national/international schemes) developing clinical and public health guidelines and protocols providing scientific advice undertaking translational research participating in education and training Page 4 of 22

5 2 Objective of the review To ensure reference and specialist testing laboratories commissioned by HPS/NSD contribute to the delivery of a cost effective Public Health Microbiology Service for Scotland. 3 Method of review The Reference Laboratory Working Group, which acts as an advisory group to the HPS/NSD commissioning team, reviewed information (provided in annual laboratory reports) which provides an indication of the quality of the services provided including: Activity data and expenditure information and contracted activity Financial issues Efficiency savings including those resulting from structural changes Average turn-around times of services Participation in appropriate quality assurance schemes Development of new laboratory techniques and typing schemes Examples of delivery of public health function Participation in research including publishing results in peer reviewed journals. A survey of a representative group of users of the reference services (including all members of the Scottish Microbiology and Virology Network) was undertaken. Feedback on the services provided was collected via a questionnaire. Page 5 of 22

6 4 Results Reference and specialist testing services in Scotland are currently provided by laboratories in three NHS boards: NHS Greater Glasgow and Clyde (NHS GGC), NHS Lothian and NHS Highland. Previous reviews (2005/6 and 2009/10) recommended consolidation of larger reference laboratory centres and relocation with diagnostic microbiology/virology laboratories to provide economies of scale in relation to use of resources, staff, laboratory equipment and IT systems while maintaining the quality and availability of reference laboratory functions. 4.1 Reference laboratory services provided by NHS Greater Glasgow and Clyde (GGC) The reference laboratories in NHS GGC comprise: Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL) Scottish Salmonella, Shigella and Clostridium difficile reference Laboratory (SSSCDRL) Scottish MRSA Reference Laboratory (SMRSARL) Scottish Parasite Diagnostic and Reference Laboratory (SPDRL) Scottish Trace Element and Micronutrient Reference laboratory (STEMRL) The four reference laboratories in NHS GGC were streamlined into a single management structure as Scottish Microbiology Reference Laboratories, Glasgow in Preparatory work for this merger was initiated in January 2012 and relocation to the new facilities was complete in November NHS GGC has contributed to this upgrade of the facilities with a major investment. The West of Scotland Specialist Virology Centre which is part of the Scottish BBV Specialist Testing Service (see section 4.4) was relocated to the same site. The merger of the reference laboratories in NHS GGC is in line with previous recommendations from HPS, and is expected to result in major efficiency savings due to shared equipment and investments, improved resilience and flexibility due shared staff and management, and will facilitate the implementation of next generation testing platforms and technologies Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL) Established in 2009 by a merger of two reference laboratories, the Scottish Meningococcus and Pneumococcus Reference Laboratory (SMPRL) and the Scottish Legionella Reference Laboratory (SLRL), the SHLMPRL provides a national reference service for the detection and characterization of human Haemophilus, Legionella, meningococcal and pneumococcal infections and the identification and typing of associated environmental isolates, while supporting national, international and local surveillance programmes, outbreak investigations and vaccine monitoring. The services offered include serology, (urinary antigen testing for Legionella), antimicrobial susceptibility testing, culture and genomic detection from clinical material and epidemiological typing of submitted isolates. Page 6 of 22

7 The activity in 2012/13 increased compared with the previous year: Numbers of culture and PCR (of respiratory secretions) of Legionella increased, and PCR of N. meningitidis, S. pneumoniae and H. influenzae also increased. A Legionella (Knoxville) outbreak in NHS Lothian generated increased workload in 2012; however, total activity is still below the contracted level. There were no financial issues identified. During the financial year 2012/13, SHLMPRL stopped providing urinary antigen testing as a primary diagnostic test. The diagnostic laboratories are now performing these tests and/or PCR/frontline kits themselves. Urinary antigen testing is undertaken on a limited number of samples, funded by NHS GG&C, to maintain expertise. Referrals from diagnostic laboratories are indicated for provisionally positive or ambiguous results only. Previously approximately 5000 tests were contracted per year; discontinuing the provision of this test has resulted in savings. Target turnaround times were achieved in 90% of the clinically important tests. SHLMPRL participated in appropriate external audit schemes and obtained good results. The laboratory is very active in terms of research with many publications in peer reviewed journals. The laboratory is developing the use of whole genome sequencing for Legionella and Meningococcus in collaboration with colleagues from the Universities of Edinburgh and Cambridge. Staffing is stable and a limited weekend service is now available. Overall, the laboratory is providing a very good clinical service and public health function that supports national and local surveillance programmes, outbreak investigations and vaccine monitoring. User survey: further development of electronic requesting was requested Scottish Salmonella, Shigella and Clostridium difficile Reference Laboratory (SSSCDRL) The laboratory provides a national reference service for the identification, typing and antimicrobial susceptibility testing of Salmonella, Shigella and C. difficile; supporting national, international and local surveillance programmes and outbreak investigations. A broad range of techniques, including serotyping, phage typing and a range of biochemical and molecular methods, for identification and typing of these pathogenic enteric bacteria are provided. In addition, the laboratory is a source of information and advice for the NHS and other agencies in Scotland, including veterinary services. SSSCDRL monitors strains of Salmonella in animal populations and from environmental/other sources during outbreaks. The activity in 2012/13 was slightly below that of the contracted numbers. In particular, antibiotic resistance profiling reached only 50% of contracted activity. Numbers of C. difficile referred for typing have stabilised at a lower level than the previous 3-year period due to a decreasing burden of disease; however, a snapshot Page 7 of 22

8 typing programme is maintained to monitor the underlying changes in the epidemiology of C. difficile. There were no financial issues identified. SSSCDRL is very active in developing new typing methodology (see below) for Salmonella, Shigella and C. difficile using up to date technology such as capillary sequencers which enable automation, potentially resulting in efficiency savings. Turnaround times for C. difficile were acceptable with target turnaround times met for 95% of isolates (mean turnaround time 5.5 days). For the PFGE analysis of Salmonella and Shigella the turnaround of PFGE-typing was affected by faulty equipment, resulting in target turnaround times being met in 82% of isolates (mean turnaround 12.6 days). The equipment issues have been resolved and turnaround times improved as a result. SSSCDRL participated in multiple external audit schemes and obtained very good results. During 2012, the laboratory developed multi locus variable number tandem repeat analysis (MLVA) typing to sub-type Salmonella Typhimurium using a capillary sequencer as the current gold standard method. PFGE is of limited value due to difficulties with distinguishing currently circulating strains. The new MLVA scheme, developed and evaluated in collaboration with other European reference laboratories, includes a European real-time database of molecular typing data, enabling rapid identification of international clusters/outbreaks of food-borne disease. Since January 2013, all isolates of S. Typhimurium have been typed in the MLVA scheme at SSSCDRL. This development has increased the discriminatory power of the Salmonella typing which allows for a greater sensitivity in the detection of outbreaks. The intention is to extend this methodology to S. Enteritidis and eventually to replace existing typing methods. SSSCDRL is very active in terms of research, development and implementation of new diagnostic technologies and participates in several national and international collaborations. This work has resulted in multiple publications in peer-reviewed, often highly ranked journals. Through external collaborations, SSSCDRL is active in developing the use of whole genome sequencing recently used to investigate a foodborne (S. Newport) outbreak and in characterising the epidemiology and evolution of C. difficile and Salmonella. Staffing is generally stable; however, there is a vacancy (0.6 WTE band 6 post) caused by the departure of a Trainee Clinical Scientist. Overall, SSSCDRL provides a very valuable reference service and public health function supporting national, international and local surveillance programmes and outbreak investigations. The laboratory is at the forefront in terms of participation in, and development of, surveillance programmes, diagnostic techniques, new technologies and research via collaborations with national and international experts. The laboratory has contributed to the development of national guidance on prevention and control of Clostridium difficile infection (CDI), and has led on the development of diagnostic guidance for CDI. User survey: Nothing substantial was raised. Further development of electronic requesting of laboratory tests was suggested. Page 8 of 22

9 4.1.3 Scottish MRSA Reference Laboratory (SMRSARL) The laboratory provides a national reference service for the confirmation of MRSA status, antimicrobial susceptibility monitoring, detection of toxin genes and epidemiological typing of strains. In addition, the laboratory is a source of information and advice on infection control issues for the NHS. SMRSARL collaborates with HPS to provide data for: the national surveillance of MRSA epidemiology in Scotland, international surveillance, and to support outbreak investigations. Activity in 2012/13 was below contracted levels for the second successive year. This is partly a consequence of a continuing decline in MRSA infections but also a result of a reduction in unnecessary referrals following revised referral criteria (agreed between SMVN and HPS). The MRSA snapshot programme has been discontinued; accordingly, a suggested modification of the contracted numbers of referrals for the coming year has been submitted by the laboratory The laboratory has undertaken new activities including typing of glycopeptide resistant enterococci (GRE/VRE) and agreed to test all MRSA and MSSA isolates for Panton Valentine Leukocidin toxin (PVL) and other markers (meca, nuc and mupa). It was noted that the overall cost of running the laboratory has increased. The target for turnaround time (six days) was achieved for 97% of tests (mean turnaround time of 4 days). All results were communicated by telephone within three days followed by a written report. SMRSARL participated in a number of internal audits (including exercises designed to meet CPA requirements), QA schemes and in external audit schemes with Dublin and Colindale laboratories, and obtained good results. The laboratory has developed spa sub-typing now routinely performed on all isolates submitted to SMRSARL. PCR ribotyping has been discontinued. Development of the spa typing of S. aureus forms part of European-wide surveillance and outbreak investigation initiative. Furthermore, the laboratory is considering the best approach for implementation of whole genome sequencing. Progress has been made with developing computerised reporting system (integrated with ECOSS), and alignment with systems in the other reference laboratories in Glasgow is ongoing. SMRSARL is active in terms of research and development and implementation of new diagnostic technologies, and participate in several national and international collaborations investigating the molecular epidemiology of MRSA in Scotland and Europe. in 2012/13 SMRSARL published ten articles in high impact peer reviewed journals. Contingency plans for staffing are in place for two senior members of staff who are retiring In conclusion, SMRSARL is a very active laboratory in terms of research and development of new methodologies, and provides a robust reference service and public health function that supports national, international and local surveillance programmes and outbreak investigations. The laboratory holds a very comprehensive strain collection. Due to decreasing numbers of MRSA the laboratory Page 9 of 22

10 is in transition and should consider using its expertise in other areas. It is positive that the laboratory has taken on typing of enterococci as part of repatriation of tests previously undertaken by PHE. User survey: Nothing substantial was raised. Further development of electronic requesting was requested Scottish Parasite Diagnostic and Reference Laboratory (SPDRL) SPDRL provides specialist testing and reference services to NHS in Scotland for parasite infections. It offers a wide range of investigations including diagnosis and identification of parasites in clinical material, typing and sub-typing and participates in national surveillance programmes. The laboratory also provides advice and support on investigation of patients for parasitic disease, outbreaks, testing, and prophylaxis and treatment. The reference service for cryptosporidium has been provided by SPDRL since April 2012 (previously this was provided by the UK reference service in Swansea). Activity levels increased in 2012/13 primarily due to the introduction of the Cryptosporidium service with a consequent increase in the number of test from 3233 to 4062 per year (~26% increase). The total number of tests (excluding Cryptosporidium) undertaken in 2012/13 was slightly above the contracted number of tests. There were no financial issues identified in the laboratory. SPDRL has developed and validated a range of rapid tests which have replaced older, more time consuming tests with resultant cost savings: for example a rapid screening assay for Cryptosporidium, to assess the suitability of samples for subtyping, has been successfully implemented and has reduced costs by approximately a third staff time from ~14 hours to less than 2 hours per test. In general, the laboratory has become more streamlined in relation to its core work. Turnaround times (1-7 days) were on target in % of tests/investigations. The laboratory has undertaken internal audits and participated in a wide range of NEQAS exercises: scores were above the UK mean. SPDRL focuses on developing new tests and streamlining the workflow. In addition to the screening (for typing) developed for Cryptosporidium, real-time molecular assays for identification of Plasmodium species have been developed and implemented, and other molecular methods for characterisation of Plasmodium, Giardia and Cryptosporidium species have been evaluated with a view to implementation. Sequencing of uncommon Cryptosporidium and Plasmodium species is now performed. During 2012/13, SPDRL supported a number of Cryptosporidium outbreaks (four in Scotland, one in the UK/Europe). In January 2013, the laboratory established national enhanced surveillance of Plasmodium in collaboration with HPS. The laboratory participates in several collaborative initiatives with external partners aiming to characterise the epidemiology and population dynamics of parasitic disease in Scotland. Page 10 of 22

11 The development of new diagnostic and typing methods has resulted in a number of publications (and submitted manuscripts) in peer reviewed journals. Several research projects and collaborative pieces of work in the areas of diagnostics, typing, epidemiology and population dynamics are being progressed. This includes whole genome sequencing of Cryptosporidium species as a diagnostic and epidemiological tool. Since the last review, SPDRL has been successful in developing and implementing new diagnostic and typing methods that have resulted in efficiency savings, improved quality and streamlining of workflow. The laboratory delivers an important service to NHS Scotland in both diagnostic and reference laboratory areas, and supports investigation of individual cases and wider outbreaks in Scotland and beyond, and participates in national surveillance and characterisation of the epidemiology of parasitic disease. User survey: Nothing of concern was raised Scottish Trace Element and Micronutrient Reference Laboratory (STEMRL) STEMRL provides specialist testing services for trace elements and micronutrients at a national level. It provides a specialist analytical and advisory service to the diagnostic biochemistry services in NHS Scotland. The principal aspects of the services include testing for trace elements, analysis of trace elements in waters from renal dialysis units and monitoring of exposure to toxic elements. The laboratory has implemented a change in activity reporting practice, now reporting on referred tests only. This has allowed more accurate estimates of activity data (historic data have been updated). In 2012/13, the overall activity in STEMRL increased 16% compared with the previous year. Due to a national alert issued by the Medical Healthcare Products regulatory Agency (MHRA) on monitoring patients with metal-on-metal implants, testing for chromium and cobalt has increased considerably. Following an agreement with the Chief Dental Officer the dental (head hair) mercury monitoring scheme has been reduced to an on demand service with a steep decline in tests for mercury. There was an increase in vitamin activity spread across all vitamins measured. There were no financial issues reported by the commissioners; however, it was noted that all laboratory equipment has been financed by local endowment funds despite this being a national service, and that the workload has increased continuously over the past four years (in-house service developments and research are also fully funded by non-nss means). No efficiency savings were reported by STEMRL. The workload has increased continuously over the past three years, resulting in increased pressure on biomedical and clinical scientist staff. It is anticipated that the implementation of new analytical platform (new type mass spectrometry) will reduce some of the workload for BMS staff. Delays relative to target turnaround times were reported in significant proportions of tests due to staffing issues. The laboratory currently operates under an interim structure, as the deputy director for STEMRL is retiring. A clinical scientist has been Page 11 of 22

12 employed in a succession planning post for two years in order to progress to deputy director by the end of the period (March 2015). STEMRL participated in a broad range of relevant external (UK and US) QA schemes for trace elements and vitamins, and performed at acceptable levels in all schemes. The laboratory has explored a number of new methods for measuring specific trace elements and vitamins (for nutritional status testing) using a spectrophotometric plate reader aiming at replacing older methods with potential improvement of the existing service and replacement of older instruments. STEMRL participates in multiple collaborative research projects (in clinical and technical areas) with external partners and has presented and published research results at several international conferences and in peer reviewed journals. As STEMRL primarily delivers a biochemical service to the in NHS Scotland it is not possible to assess the public health function of in terms of control and prevention of infection. The data generated by this laboratory are not used for any local or nationally mandated surveillance programmes. The user survey was not extended to the users of this laboratory. It was noted that STEMRL does not sit comfortably in the portfolio of microbiology and virology reference laboratories as it provides a diagnostic service. Transfer of the commissioning of STEMRL to a more appropriate body should be considered and discussed further with NHS GGC. Page 12 of 22

13 4.2 Reference laboratory services provided by NHS Lothian In the 3-year period under review, there have been no major re-organisations of reference services within the NHS Lothian. Reference services in NHS Lothian comprise: The Scottish E. coli O157/VTEC Reference Laboratory (SERL) Scottish Bacterial Sexually Transmitted Infection Reference Laboratory (SBSTIRL) Scottish Human Papillomavirus Reference Laboratory (SHPVRL) Scottish Mycobacteria Reference Laboratory (SMRL) The Scottish E. coli O157/VTEC Reference Laboratory (SERL) SERL provides a national reference and specialist testing service for samples originating from patients with a history consistent with VTEC infection but with no organism being isolated. SERL also assists with the identification of problematic isolates and provides advice on appropriate methods for diagnostic laboratories. Typing and molecular subtyping are undertaken to support local and national surveillance programmes and outbreak investigations. SERL is providing an extensive public health service to the NHS board health protection teams and hospitals. In 2012/13, activity was below that of the previous year although there was an overall increase in the total number of samples referred to the laboratory. This is partly due to streamlining of testing of faecal samples, which became routine in December There was a 14.9% increase in faecal samples received (from 3161 to 3633) compared with the previous year, while there was a 12.5% decrease in isolates received (from 233 to 204); however, the actual number of performed tests was lower in 2012/13 (11849) than in 2011/12 (15065), and below the contracted number (14295). It is possible that the contracted numbers of tests per sample had been set too high. The total costs of the laboratory service and the cost per test increased in 2012/13, despite streamlining of the testing and decreasing activity. Further clarification regarding costs is required. Turnaround times were on target for % of tests performed at SERL. Serodiagnosis which is performed at Colindale was on target (5 days) for 70% of samples referred; revision of the target turnaround time of this test is being considered as it is possibly set too low. Following extensive evaluation and validation of a new RT-PCR test, the previous methods of IMS and endpoint PCR (using a combination of two tests) were replaced by this single and less costly test. This has reduced turnaround time and led to streamlining of the faecal testing. MLVA has replaced PFGE as the main sub-typing method in the laboratory. MLVA is considered superior to PFGE in most instances due to its high discriminatory power, robustness and fast turnaround time. SERL is providing an extensive public health service to the NHS board health protection teams and hospitals, Health Protection Scotland and Public Health England in the investigation and control of outbreaks, and has contributed to development of a national action plan for E. Coli O157/VTEC. Page 13 of 22

14 SERL is an active partner in various research collaborations with UK partners (Welcome Trust, University of Edinburgh and PHE research teams), including the development of whole genome sequencing of E. Coli O157. SERL is actively involved in relevant European/International epidemiological networks. SERL provides a valuable reference service and public health function that supports surveillance activity, investigation and control of outbreaks. In the past years it has developed and optimised identification and typing techniques which has led to a streamlining of the workflow and improvement of epidemiological data quality. User survey: Nothing of concern was raised Scottish Bacterial Sexually Transmitted Infection Reference Laboratory (SBSTIRL) SBSTIRL provides a national reference and specialist testing service, including confirmation of the identity of Neisseria gonorrhoeae, antibiotic susceptibility testing, and assistance with the identification of problematic isolates. It also provides confirmatory PCR testing for those laboratories that do not have a second molecular test available locally. The laboratory provides data to national, UK and European surveillance programmes and assists in contact tracing of sexually transmitted infections. There has been an increase in the number of cases of gonorrhoea diagnosed in Scotland with a doubling of diagnosed cases over the past 5 years. In 2012/13, the overall activity was approximately 7% above the contracted number of tests (when 504 NG-MAST typings carried over from 2011/12 were excluded). Confirmatory diagnostic testing of culture positive specimens (using NAAT) are now performed in two NHS boards, while the majority of the boards use the SBSSTIRL (NAAT) confirmatory service. The backlog of the NG-MAST typing was cleared in 2012/13. There were no financial issues identified in the laboratory despite the increased activity. SBSTIRL has developed a secure automated service for sending out reports (currently used by six referring laboratories), saving up to three days in the time needed to reach the laboratories. Efficiency savings were not calculated. Turnaround times were achieved for 96-98% of the tests, except for the sub-typing (NG-MAST) where the 90-day turnaround time was not being met in the majority of cases. In 2012/13 this back-log was cleared. A snapshot programme, typing only a representative proportion of the samples is being developed in collaboration with HPS, which should alleviate the time delays, while still providing valid epidemiological information. SBSSTIRL participated in external QA schemes from the UK and Europe, and performed at acceptable levels in all schemes. In 2012/13, SBSTIRL developed a real-time PCR for confirmatory testing replacing the Aptima GC test which is incompatible with some transport media used and requires large volumes of samples (which are not always available). The real-time PCR was validated and demonstrated good sensitivity and specificity on EQA panels. Page 14 of 22

15 On rare occasions when strains lack the PCR targets (pora and pgi1) the Aptima GC test is useful and therefore still maintained. SBSTIRL supports the diagnostic laboratories by confirming the identity of Neisseria gonorrhoeae (including the identification of problematic isolates) and performing detailed antimicrobial susceptibility testing. Subtyping of N. gonorrhoeae forms part of public health function through supporting contact tracing (and partner notification), outbreak investigation and national surveillance. Chlamydia trachomatis (LGV) diagnostic testing are also provided to support national surveillance. SBSTIRL is participating in two epidemiological studies on N. gonnorhoeae and syphilis, in collaboration with colleagues in the Chalmers Sexual Health Centre and the Royal Infirmary Edinburgh. Laboratory staff have given oral presentations and presented posters at UK conferences. SBSTIRL provides a valuable reference service and public health function that supports national, UK and European surveillance activity and contact tracing of sexually transmitted infections. Based on previous HPS recommendations a snapshot (NG-MAST) typing programme is being developed to reduce the workload and align the funding with other Scottish reference laboratories. As result of this review it is recommended that the funding for the confirmatory diagnostic NAAT testing of N. gonorrhoeae should be reviewed with a view to transferring the majority of this work to the diagnostic laboratories. User survey: No comments received Scottish Human Papillomavirus Reference Laboratory (SHPVRL) SHPVRL was established to monitor the epidemiology of circulating types of human papillomavirus (HPV) and assess the impact of new vaccination programmes. The laboratory delivers a national service, which includes national surveillance of HPV (cervical biopsies), clinical work (identifying HPV associated with head and neck cancers on request), quality assurance, research and development. The main users of SHPVRL are pathology and cancer services. Work undertaken by SHPVRL is supporting national decisions on screening programmes and prevention of cervical cancer. The overall activity (calculated as samples tested for surveillance purposes) was lower in 2012/13 (1703 tests) than in the previous year (2807 tests); however, the previous year s figure was inflated due to a major validation exercise. The number of individual clinical requested tests (including gynaecological and non-gynaecological requests) received by the laboratory was within the contracted level of 200, and in line with previous year s number of requests. As a consequence of the national rollout of test of cure for HPV, the laboratory is now receiving samples from all NHS boards and received more than 4000 samples in 2012/13 (this activity is funded separately by NSD via the Scottish Cervical Screening Programme). An audit of the gynaecological clinical requests against submission criteria was undertaken to determine the number of potentially unnecessary clinical requests. The results of this audit were fed back to the Scottish Colposcopy Quality Assurance Group to inform further development of the request form. This could potentially lead to (minor) efficiency savings. Page 15 of 22

16 No financial issues were reported this year. An application for expanding the service to include molecular HPV testing of all persons diagnosed with oropharyngeal cancer was submitted to HPS in October Turnaround times (10 days for HPV screening, 15 days for HPV genotyping) were on target for % of clinical requests. Results of surveillance testing are anonymised and not reported back on individual basis and therefore not associated with a turnaround time (there was no back-log of untested samples from 2012/13). SHPVRL participated in UK NEQAS scheme for molecular testing of HPV and QC exercises of the English Cervical Screening Programme. Full concordance was obtained in all exercises. SHPVRL is active in assessing laboratory assays and typing techniques. In 2012/13, the laboratory undertook technical evaluations of various assays (HPV testing platforms) to inform the choice of assay for the test of cure monitoring. The impact of glacial acetic acid used in liquid cytology samples was investigated to determine if HPV detection would be hindered by its use. A new genotyping technique was evaluated with regards to performance and sensitivity for detection of rare HPV types. The public health function of SHPVRL includes collection of surveillance data to monitor the epidemiology of HPV, and to inform and assess the impact of national vaccination programmes. Work delivered by SHPVRL has been instrumental in organising the Scottish Cervical Cancer Screening programme and in the choice of laboratory methodology used. A recent clinical and technical assessment of the use of HPV testing among oropharyngeal cancer patients (including a pilot study) has resulted in a service development application to HPS (funding was awarded in 2014). SHPVRL is active in investigating HPV pathology in various cancers to explore the benefits of testing/screening in order to detect preventable disease. This year this work has led to an application for expanding the service to include testing for HPV in oropharyngeal cancers. Collaborations with external UK partners on developments in the fields of genital and oral cancers have been funded. Three papers have been accepted in peer reviewed journals and a large number of posters/talks have been presented at international conferences. The user survey was not extended to users of SHPVRL. SHPVRL delivers a service of great value to NHS pathology services and cancer networks through national surveillance of HPV cervical cancer, which underpins the national efforts to prevent this infection. The laboratory that ensures the testing methodology is optimal and informs national screening and vaccine programme. The research and development undertaken by SHPVRL is aimed at the prevention of other HPV related cancers Scottish Mycobacteria Reference Laboratory (SMRL) SMRL provides specialist testing service and reference laboratory service to support the management of patients and identification of clusters to guide interventions implemented by Health Protection Teams. The laboratory also evaluates new methods and supports the implementation of the Scottish Government TB Action Plan. Page 16 of 22

17 In 2012/13, identification of mycobacteria by culture and susceptibility testing increased 30% due to increasing number of cases of TB. This increase in activity has been offset by the decline in samples sent for rapid isolation/molecular detection as most NHS boards now have their own rapid isolation facilities. A total of 296 isolates from the Mycobacterium tuberculosis complex (MTBC) were typed by 24-loci MIRU- VNTR (mycobacterial interspersed repetitive units variable number tandem repeats). No financial issues were reported for 2012/13; however, implementation of newer susceptibility testing methods may have financial implications in the longer term. The prices of consumables have increased. The implementation of rapid isolation of mycobacteria in diagnostic laboratories in ten NHS boards has resulted in quicker diagnosis and a reduction of referrals. Automated electronic reporting via has been initiated in five laboratories. No efficiency savings were mentioned in the annual report. It was not possible to assess the timeliness of the turnaround times in SMRL. This may be due to the complex nature of the identification and characterisation laboratory procedures, which can vary due to the species of Mycobacterium and contamination of the culture. On-target rates were not calculated and tables were not comparable with those in the SLA. The laboratory reported that turnaround times have improved overall in part due to introduction of chromatographic immunoassay detection of MTBC isolates. SMRL participated in UK and international quality assurance exercises (PHE, NEQAS and WHO) on culture, microscopy, molecular detection, susceptibility testing and obtained high scores in all (>95%). A new typing method, 24-loci VNTR, has been implemented for MTBC isolates, which allows identification of clusters across the UK (using an analytical on-line tool provided by PHE). Various methods and new antimicrobial agents are being validated continuously as new evidence and technologies become available. Commercial (Hain MTBDR version 2.0) kits, which are more sensitive and quicker, have been implemented for susceptibility testing of key antimicrobials. Interferon gamma release assays for the diagnosis of latent TB was audited in SMRL over a 12-months period in support of the national TB action plan. MALDITOF is also being assessed for future identification of cultured mycobacteria. SMRL provides data for national epidemiology surveillance programmes and supports various aspects of the Scottish TB Action Plan. This includes evaluation of new diagnostic tools (molecular tests for diagnosing TB and monitoring resistance) and interferon gamma assay to detect latent tuberculosis. It participates in multidisciplinary TB case management teams and contributes to the development of national guidance. SMRL currently collaborates with UK colleagues on sequencing of M. abscessus and MTBC isolates. A UK-wide collaborative group on mycobacteria strain typing has been established to coordinate developments in this area. The laboratory has given several oral and poster presentations at UK conferences and has published in peer reviewed journals in the past three years. Page 17 of 22

18 SMRL provides a valuable specialist testing and reference service that supports health protection team in case management, national surveillance activity and evaluation of new technologies, some of which underpins the national TB Action Plan. Molecular typing (using 24-loci MIRU-VNTR) has been implemented for epidemiological investigations of MTBC with a potential for further public health utility. User survey: Positive feedback was received. 4.3 Reference laboratory services provided by NHS Highland In the 3-year period under review, there have been no major re-organisations of the single reference service within the NHS Highland. The Scottish Toxoplasma Reference Service has expressed an interest in developing a Lyme s disease reference service Scottish Toxoplasma Reference Laboratory (STRL) STRL provides a specialist testing service, which supports the diagnosis and management of toxoplasmosis throughout Scotland, and to a smaller extent Northern Ireland on a paid basis). The numbers of cases tested and identified within each NHS board are too small to justify diagnostic services within each board. The laboratory participates in epidemiological studies to improve our understanding of toxoplasmosis and its management. In 2012/13, a total of 1055 samples were referred to STRL for testing (91% originated from Scottish NHS boards). In the previous years, 1715 samples were referred; however, the number of samples from Northern Ireland has declined (from around 800 to 100) since cross charging was introduced. The number of tests (5979) undertaken in 2012/13 was 5% above that of the contracted number (5693), in part due to the testing of 2634 samples from a study on antenatal women in NHS Highland. In total 20 cases of toxoplasmosis were identified in Scotland and nine in Northern Ireland in 2012/13; however, this may represent less than 20% of the burden of disease due to under-diagnosis. In 2012/13, there was an overspend on salaries of 16,184 (13%) partially caused by a reduction in income from Northern Ireland compared with 2011/12. This reduction in testing, and so income was due to discussions at a visit by Drs Watson and Chatterton to the Northern Ireland lab staff about how to improve their referral procedures and make testing more patient centred. There has been no up-lift in nonpay costs, and the laboratory remains within budget for these. STRL is planning savings of 15-20% through restructuring of staffing. In order to save staffing time used on validation of in-house BAM ELISA, following an audit this method was discontinued and replaced with the CE-marked Abbot AxSym test for determining the timing of the infection. Turnaround times for serological, confirmatory and specialised tests were on target for 99.6% of tests. STRL participated in external audit schemes for serology and confirmatory tests including UK NEQAS and other UK schemes and obtained success rates of %. Page 18 of 22

19 Development of QA testing of existing methodology was undertaken by STRL in collaboration with UK NEQAS and the National Institute of Biological Standards to set new standards for combined IgG/IgM serology, IgG avidity and PCR testing. As mentioned above (under efficiency savings) the BAM ELISA was replaced with a commercial test to monitor timing of infection. STRL continues to maintain Toxoplasma gondii tachyzoits in cell culture. Although STRL collects national data on the occurrence of toxoplasmosis by patient group and NHS board, and obtains clinical detail on 40% of current cases of toxoplasmosis, these data are not used in national surveillance programmes and do not underpin any health protection activity, such as establishing epidemiological links, controlling outbreaks or interventions to prevent spread. The main function of the laboratory is specialist (diagnostic) testing to support the management of cases. STRL is participating in a study on seroprevalence and susceptibility among antenatal women in NHS Highland. It is also involved in collaborative study with US colleagues on the source of infection in food involving a panel of Scottish patients. None of this work has been published. The primary function of STRL is specialist diagnostics and support of the management of cases. The delivery of the diagnostic function centrally is justified and provides equitable provision of testing to all NHS boards; however, the very low number of cases identified on a yearly basis (<50 infections per year) since 2008, with only 20 infected cases in 2012/13, raise questions of sustainability of this service currently staffed with 3.3 WTE. From financial, staffing, training, management, laboratory equipment and infrastructure perspectives the Toxoplasma service would conceivably be more cost effective and resilient if embedded in one of the larger reference laboratories in Scotland. Although, STRL is collecting limited epidemiological and clinical data on cases in Scotland, this information is currently not used for surveillance or health protection purposes. A consultation report issued by FSA in highlighted the importance of toxoplasmosis in vulnerable groups including immunocompromised persons and pregnant women, and cautioned that there is a lack of current knowledge of the sources of Toxoplasma and, in particular, its role in food borne infection. To date, however, there has been a lack of suitable funding opportunities arisen following the publication of the FSA report. Toxoplasmosis has not yet been identified as a public health priority in Scotland. User survey: No issues were raised. Page 19 of 22

20 4.4 Reference laboratory services provided by NHS Lothian and NHS Greater Glasgow and Clyde Blood-Borne Virus (BBV) Specialist Testing Service The BBV services, located in Glasgow and Edinburgh, jointly provide a national specialist testing service which supports the management of patients infected with blood-borne viruses (mainly HIV and hepatitis C) and investigation and control of outbreaks in the NHS boards, and lead on diagnostic developments while supporting the local virology diagnostic services. They provide epidemiological data for national surveillance programmes, including viral reference data, and support the implementation of national action plans for sexual health, and conduct research studies. Total HIV testing activity has declined continuously in the past five years: within the three-year period of this review, HIV testing activity decreased 11% (from 2406 to 2134 total tests per year). Numbers of tests undertaken in 2012/13 were below the contracted numbers for all types of HIV tests. Many of the confirmatory tests previously performed at the BBV laboratories; including confirmatory ELISA, immunoblots (to confirm status of HIV) and confirmatory HIV RNA testing (in babies) are now undertaken in local diagnostic laboratories. HIV pro-viral DNA testing has declined significantly due to protocol changes. There were no issues with the reference testing for HIV (including molecular typing and susceptibility testing). The total activity for hepatitis C testing has declined over the past five years, mainly due to a decrease in confirmatory hepatitis C ELISA testing, which many of the diagnostic laboratories now undertake, whereas the frequency of genotyping has remained stable. The number of genotyping tests (1982 tests) was above the contracted level (1750 tests), while the number of confirmatory ELISA tests (576 tests) was only about half of the contacted level (1000 tests). It is expected that hepatitis C confirmatory ELISA testing will be discontinued as a service provided by BBV in These changes in provision of activity, caused by decreasing number of cases and by local testing, should be considered in the next SLA with BBV and reflected in funding arrangements. Financial reports were not included in the annual report; however, there was an underspend in the Edinburgh BBV service in 2012/13 due to streamlining of the confirmatory algorithms. The duplication of services provided by the Edinburgh and Glasgow BBV Specialist Testing Services raises the question of financial sustainability in the current fiscal climate. It is recommended that the BBV services are reviewed to rationalise the service arrangements due to the changes in epidemiology, provision of diagnostic BBV services locally and technological developments. The BBV laboratories are planning to phase out confirmatory hepatitis C testing in As mentioned above, efficiency saving have been obtained in the Edinburgh service due to streamlining of the confirmatory algorithms. Turnaround times for confirmatory HIV testing were on target (within 14 days) for 100% of tests in both laboratories; however, confirmatory PCR testing in Edinburgh Page 20 of 22