A TB Action Plan for Scotland

2. Laboratory Services and Diagnostic Tools

Introduction

2.1 Laboratory services and the diagnostic tools laboratories use play a key role in the assessment, management and treatment of patients with TB. Currently across Scotland, nine mainly larger laboratories provide a microscopy and culture service for mycobacteria and at least four smaller laboratories provide a microscopy service only. Seven of the larger laboratories use traditional solid media only, two use liquid only and two a combination of both solid and liquid. Current Scottish Guidance and the Health Protection Agency ( HPA) recommend use of both liquid and solid media for mycobacterial culture diagnosis. Laboratories which do not directly provide culture services often perform microscopy only for mycobacteria on clinical samples and send these to culturing labs. Microscopy and culture services are generally available in Scotland 5 days a week. HPA and the US Centre for Disease Control ( CDC) CDC recommendations are for these facilities to be available 6 days a week.

2.2 The Scottish Mycobacteria Reference Laboratory ( SMRL) is a key clinical and laboratory service, which also reviews new technological developments, helping to underpin the management of TB in Scotland. The SMRL receives specimens for direct molecular detection of Mycobacterium tuberculosis complex and the detection of drug resistance, rapid culture and cultures for identification, sensitivity testing and molecular typing (mycobacterial interspersed repetitive unit - variable number tandem repeat ( MIRU- VNTR); 'fingerprinting'). The SMRL, which also reviews new technological developments, helping to underpin the management of TB in Scotland.

2.3 Technology is advancing and a number of new diagnostic tools are available now, with more likely to become available in the near future. There is a need to consider the value of these on an ongoing basis, learning from experience elsewhere in the UK, EU and globally.

2.4 The detection of active TB is the key priority for TB services. The detection of latent TB is developing technologically, but remains a lower priority than active TB. 2.5 The Laboratory Services and Diagnostic Tools sub-group considered these issues and provided advice to the TB Action Plan Working Group.

Key Issues

Microbial culture

2.6 Currently, predominant Scottish practice is for laboratories to culture mycobacterial samples on traditional solid culture media. Newer liquid culture techniques can reduce the time to obtaining a positive result by as much as 50%, and this offers significant benefit to clinicians, patient care and public health. However it is important to note that solid culture media, while slower, can provide greater sensitivity for some strains and species of mycobacteria, allowing more comprehensive diagnosis of Mycobacterium tuberculosis complex infection as well as non tuberculosis mycobacteria. 2.7 Current Scottish Health Protection Network (March 2009) and NICE (2006) guidance, is that clinical samples should be cultured by liquid and solid methods, bearing in mind that laboratories need a certain level of throughput to maintain quality control. The Working Group considers that it is now legitimate to move to the adoption of liquid culture techniques and that at a minimum all specimens should now be cultured in liquid media as this reduces by more than half the time to result from 27 to 13 days as compared with solid culture. Precious samples (e.g. CSF, biopsies, lymph nodes) and those requiring incubation at other than 36 ⁰C such as skin biopsies and abscesses should receive solid culture in addition to liquid culture. Specimens should not be cultured on solid media alone. Beyond this, solid culture, although ideal for maximal sensitivity, is less critical, particularly in a financially constrained environment, as the cost effectiveness of using both techniques has not been demonstrated. This will be reviewed in time.

Quality assurance

2.8 In line with the Quality Strategy, TB diagnostic services in Scotland should be high quality and efficient. To ensure that this is the case robust quality assurance mechanisms - which currently exist - should be adopted as standard practice. Specifically, all laboratories carrying out mycobacterial microscopy and culture should be Clinical Pathology Accreditation ( CPA) accredited, have specific quality systems and undertake appropriate External and Internal Quality Assurance.

Laboratory service availability

2.9 Most mycobacterial diagnostic services in Scotland are currently provided 5 days a week. Health Protection Agency and CDC recommendations are for these facilities to be available 6 days a week. It is our view that 5 days per week is an adequate minimum. Current guidance is that the acute clinical and public health management should not be delayed by awaiting laboratory confirmation e.g. microscopy results. The Scottish Government will support a 5 day minimum service, pending more evidence becoming available about potential implications of service increase to six days in terms of cost and quality. This will be reviewed in time.

Optimisation of laboratory services

2.10 In line with the above comments about service provision, it is legitimate to consider the number of laboratories across Scotland that currently provide TB bacteriological diagnosis. The Quality Strategy has set us the ambition of reducing unnecessary duplication and improving efficiency while at the same time ensuring best quality services.

2.11 The Laboratory Services Subgroup researched evidence on optimal 'size' of laboratories for primary specimen processing but found that the only available guidance on numbers of specimens processed comes from the USA. The CDC National Plan recommendations (2005) indicates that culturing less than around 1500 specimens per annum in a low incidence area raises concerns about staff proficiency and that these concerns are addressed when more than 2340 specimens annually were examined. The American Thoracic Society and CDC recommendations are that for microscopy alone numbers of more than 20/week (1040 per annum) should be performed. (discussed in: Murray PR et al Editors, Manual of Clinical Microbiology 9 ^th Edition 2007 Vol 1 Ch 36 P361. American Society of Microbiology Press, 2007 Washington).

2.12 Clearly there is a relationship between numbers of specimens and staff competency. Adequate specimen throughput for microscopy and culture is important and this too can strengthen the case that the centralisation of services into a smaller number of higher throughput laboratories would promote best quality practice and performance.

2.13 In line with the Quality Strategy and the commitment to reducing unnecessary duplication, the Scottish Government will support work through the Scottish Microbiology Forum to consider the centralisation of Scottish mycobacterial diagnostic services into a smaller number of laboratories with higher throughput and defined quality standards in laboratories in Scotland.

Future Developments

2.14 There are a range of new developments around diagnostic tools. Importantly the Interferon Gamma Release Assays ( IGRAs) are currently under review by NICE. IGRAs are whole-blood tests that can aid in the diagnosis of Mycobacterium tuberculosis infection, measuring a person's immune reactivity to the bacterium. The value of the IGRA tests are that they are not confounded (i.e. are more specific than skin testing) by previous BCG vaccination and have a role in diagnosis of latent TB infection They can however be very misleading if used in the diagnosis of active TB infection and in their current format should not be used for this purpose. They may sometimes be more sensitive than skin testing, but longitudinal data is lacking at present. IGRAs may have significant benefits for the diagnosis of latent TB infection, improving the clinical care and contact tracing exercises. New IGRA guidance is being released by NICE and this work should be considered by the Scottish Health Protection Network when available to inform guidelines on use of IGRA in Scotland.

2.15 The Working Group also notes that while IGRAs may in time to be shown to be more sensitive and specific than skin tests (which generally require more than one clinic visit by the patient) in the diagnosis of latent TB infection, these tests are expensive and their introduction should be managed in the most cost effective way.

2.16 More generally molecular and other diagnostic tools are evolving and there needs to be ongoing review of these new technologies. As with IGRA the Scottish Government should ensure a mechanism exists for the appropriate Scottish body to assess these developments on an ongoing basis to ensure the best quality and most efficient diagnostic tools are available in Scotland. This may be best achieved though a Scottish Health Technology assessment.

2.17 The SMRL provides a valuable reference service as well as being a source of clinical and laboratory advice for mycobacterial issues. In addition it provides the national fingerprinting service ( MIRU- VNTR, see 2.2 above). Fingerprinting can enable clusters of infection to be identified earlier than would be possible through traditional means, through a strain typing database, facilitating more effective control. This requires close collaboration with Consultants in Public Health Medicine (also known as Consultants in Health Protection), Health Protection Scotland, and other parts of the UK, through the Health Protection Agency. The Working Group recommends that Health Protection Scotland and SMRL should establish a group to develop a clear strategy for the systematic use of molecular typing of M. tuberculosis complex in Scotland.