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Published: 17 March 2015

The role of clinical mycology reference laboratories

Sarah Kidd A , Catriona Halliday B and David Ellis C

A National Mycology Reference Centre
SA Pathology
Frome Road, Adelaide
SA 5000, Australia.
Tel: +61 8 8222 3544
Email: sarah.kidd@health.sa.gov.au

B Clinical Mycology Reference Laboratory
Centre for Infectious Diseases and Microbiology Laboratory Services
Pathology West
Level 3 ICPMR, Darcy Road
Westmead Hospital
Westmead, NSW 2145, Australia.
Tel: +61 2 9845 6255
Email: Catriona.Halliday@health.nsw.gov.au

C School of Molecular and Biomedical Sciences
University of Adelaide
Adelaide, SA 5005, Australia.
Email: dellis@adelaide.edu.au

Mycology reference laboratories fulfil a critical role in clinical microbiology. Staff with extensive training and expertise in mycology: (1) perform testing (e.g. fungal identification, susceptibility testing, fungal antigen detection, fungal DNA detection) using methodologies conforming to internationally accepted standards; (2) provide education and training in mycology; (3) provide scientific advice; (4) collaborate with regulatory bodies to deliver quality assurance programs; and (5) participate in research including monitoring emerging fungal trends and outbreaks. It is critically important that reference laboratories be resourced adequately for these functions and we believe there is scope to form an officially recognised network of mycology centres in Australia.

Importance of clinical mycology reference laboratories

The incidence and mortality of life-threatening fungal infection are on par with that of tuberculosis and malaria globally1,2, and prompt, accurate diagnosis is critical to improve patient outcomes. However, variation in patient demographic and population size around the country, budgetary limitations, and a general decline in mycology expertise, means it is neither possible nor practical for many laboratories to maintain adequate staffing and resources to perform the full range of tests required for diagnosis of fungal disease. A reference laboratory fills this gap for less resourced laboratories at a state and/or national level. Less tangible, but just as important, reference laboratories provide leadership in their respective discipline and actively encourage other laboratories to improve their skills, knowledge and service delivery. This is largely achieved by providing sound clinical and scientific advice, education, and training materials. Such expertise includes interpretation of antifungal susceptibilities, updates in taxonomy and nomenclature, and developing and validating new diagnostic tests.

Defining mycology reference laboratories

After finding considerable variation in definitions and functions of reference laboratories for communicable diseases across member states of the European Union, the European Centres for Disease Control and Prevention (ECDC) identified and clarified their role, in a technical report designed for strategic planning, strengthening and maintaining a coordinated European reference laboratory network3. Based on this report, the core functions of mycology reference laboratories include provision of reference diagnostic services such as yeast and mould identification, antifungal susceptibility testing, serological and molecular detection of fungal pathogens; creating and maintaining resources such as fungal culture collections, books, and online tools; provision of scientific advice; monitoring trends such as outbreaks, emerging pathogenic fungi and antifungal resistance; collaboration and research.

It is unclear how many mycology reference laboratories are actively operating in Australia due to a lack of formal recognition at the state or federal level. This is in contrast to the Australian Mycobacterium Reference Laboratory Network and the United Kingdom Clinical Mycology Network (UKCMN)4. The UKCMN has a steering committee and comprises a four-tiered classification of laboratory capabilities. At the base are local microbiology laboratories with the capacity to identify common yeasts and moulds; followed by specialist microbiology laboratories servicing tertiary hospitals with haematology, HIV and transplant services; to regional mycology centres which are essentially reference laboratories; capped off by a single laboratory, directly funded (in part) by Public Health England to provide a national service, investigate fungal outbreaks, curate a national collection of fungi, and set the standard for mycology laboratory quality assurance and training4.

To our knowledge two Australian laboratories currently operate at a level that would be classified as a ‘reference centre’ by the UKCMN criteria: the National Mycology Reference Centre at SA Pathology, Adelaide, and the Clinical Mycology Reference Laboratory at Westmead Hospital, Sydney. A summary of the tests and functions of each of these laboratories is provided in Table 1. However, there are no laboratories in Australia that meet the UKCMN criteria for the highest level of mycology reference laboratory, mainly due to insufficient staffing by dedicated mycologists and a lack of direct funding.

Table 1. Summary of services and functions of the two currently active Australian mycology reference laboratories.
Click to zoom

Needs of clinical mycology reference laboratories

In order to perform its functions it is critical that mycology reference laboratories are recognised at the state and national level for their services, to have a mandate to perform them, be resourced accordingly, and are continuously assessed on their capabilities to perform these functions. Necessary resources include: (1) dedicated staff with extensive and ongoing training in laboratory mycology to an international standard; (2) appropriate infra-structure, including containment facilities, and equipment suitable for handling Risk Group 3 (RG-3) fungi; and (3) suitable materials, equipment and time to perform the functions of the laboratory. Critically, reference laboratories require sufficient funding to support and guarantee continuous and qualified work. The Australian mycology reference centres currently have to function within their budget for routine (local) diagnostic work. Since the cost of most specialised testing far exceeds the Medicare Benefits Schedule, invoicing referring laboratories for reference work is necessary but may prevent or discourage the appropriate utilisation of reference laboratories.

Best use of mycology reference laboratories

Both public and private laboratories may have personnel skilled in basic identification of yeasts and moulds, but may not have the resources for molecular identification of rare or poorly/non-sporulating moulds, or the facility to handle possible RG-3 pathogens. In these situations, the reference centres should be utilised. Antifungal susceptibility testing based on the ‘gold standard’ broth microdilution method (including commercially available Sensititre YeastOne) upon which clinical breakpoints are based, may be required in some situations rather than relying on the non-standardised minimum inhibitory concentrations and interpretations generated by Vitek, eTest or disk diffusion.

Pathology stewardship is important and reference laboratories should be consulted on appropriate selection of specimens and test requests prior to referral. An experienced medical mycologist and/or specialist pathologist overseeing laboratory activities is critical in this regard. This may include assessing the need for antifungal susceptibility testing (avoiding referrals of likely contaminants); use of Aspergillus PCR versus panfungal PCR, and the value of these tests on different specimen types such as bronchoalveolar lavage, blood, or tissues.

A good relationship and communication between reference laboratories and clinicians is essential for determining the most appropriate testing and in the interpretation of results. While there is co-operation and communication between the major mycology laboratories in Australia, this is not a formally recognised network, and there is limited representation of diagnostic mycology and reference laboratories at the government level. The Australia and New Zealand Mycoses Interest Group (ANZMIG) Laboratory Working Group is well placed to promote the value and resource requirements of mycology reference laboratories.

Acknowledgement

We thank Dr Elizabeth Johnson from the Public Health England Mycology Reference Laboratory, Bristol, UK, for providing information and advice.



Biographies

Sarah Kidd is the Head of the National Mycology Reference Centre at SA Pathology, and a Lecturer at University of Adelaide and University of South Australia. She is Secretary of the Australia and New Zealand Mycoses Interest Group (ANZMIG) and Co-Chair of the ISHAM 2015 Congress Organising Committee.

Catriona Halliday is the Senior Scientist in charge of the Clinical Mycology Reference Laboratory at Westmead Hospital where she has been working for over 14 years. Her research interests have focused on the development and implementation of culture independent tests to aid in the rapid diagnosis of invasive fungal infections, in particular invasive aspergillosis.

David Ellis is an Emeritus Mycologist in the National Mycology Reference Centre at SA Pathology and an Associate Professor in the School of Molecular and Biomedical Science at the University of Adelaide.

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