Milestones

Since its inception in 2006 when 50 individuals met together in a room during International Society for Human and Animal Mycoses (ISHAM) in Paris, the EAPCRI continues to gain momentum. The foundation links 86 participants in 69 centres in 29 countries and has expanded to include centres in North America, Australia and South America. EAPCRI is a cohesive force bringing together Infectious Diseases specialists, medical Microbiologists, Haematologists, Clinical Scientists Epidemiologists, Statisticians and industrial partners working symbiotically together.Systematic research through a series of specimen panels sent out between 2007 and 2012 to 24 participating laboratories across Europe and Australia, followed by meticulous analysis of results and methodologies has produced optimized standardised methodology.

Milestones
– The EAPCRI has achieved its aim of developing standards for Aspergillus PCR and published protocols for a variety of specimen types: Whole blood:White PL, Bretagne S, Klingspor L, Melchers WJD, McCulloch E, Schulz B, Finnstrom, Mengoli C, Barnes RA, Donnelly JP, Loeffler J on behalf of the European Aspergillus PCR Initiative. Aspergillus PCR: one step closer towards standardisation. Journal of Clinical Microbiology. 2010; 48: 1231-40 Serum: White PL, Mengoli C, Bretagne S, Cuenca-Estrella M, Finnstrom N, Klingspor L, Melchers, W. J. G.; McCulloch, E; Barnes, R A.; Donnelly, J. Peter; Loeffler, J. Evaluation of Aspergillus PCR Protocols for Testing Serum Specimens. Journal of Clinical Microbiology 2012; 49(11): 3842-3848 Plasma (work in progress)

– Importantly, the EAPCRI has assessed the critical stages Aspergillus DNA extraction and published a protocol ensuring optimal performance across laboratories. White PL, Perry MD, Loeffler J, Melchers W, Klingspor L, Bretagne S, McCulloch E, Cuenca-Estrella M, Finnstrom N, Donnelly JP, Barnes RA, on behalf of the EAPCRI The critical stages of extracting DNA from Aspergillus fumigatus in whole blood specimens. J. Clin. Microbiol.2010 . 48: 3753-3755 doi:10.1128/JCM.01466-10.

– A WHO International standard has been agreed provide the opportunity to develop and participate in an External Quality Control programme to enable all laboratories to evaluate performance in using PCR to detect Aspergillus.
– A systematic review of Aspergillus PCR was undertaken and published in 2009. Mengoli C, Cruciani M, Barnes RA, Loeffler J Donnelly P. Performance of Polymerase Chain Reaction for diagnosing invasive aspergillosis: Systematic Review and Meta-analysis. The Lancet Infectious Diseases. 2009; 9: 89-96.

– The EAPCRI is currently repeating the process and attempting to assess the impact of the standardized Aspergillus PCR protocols on diagnostic utility.

Milestones (Pending)
– An ongoing European Organization for Research and Treatment of Cancer (EORTC) clinical trial incorporates a translational arm to more closely assess the diagnostic utility of fungal biomarkers in a randomised controlled trial. The clinical trial is recruiting and due to complete in 2013.

– The EAPCRI has provided Aspergillus PCR testing centres that underpin the current AmBiguard prophylactic study undertaken by Gilead Sciences. The trial is nearing completion and has achieved its anticipated numbers of Invasive Fungal Disease and it is anticipated that this will enable clinical evaluation of PCR to be undertaken.

– A specific collaboration with The University of Texas Health Science Center at San Antonio and the Invasive Aspergillosis Animal Models (IAAM) evaluated the proposed standard in rodents and a publication is anticipated in 2013.

– The EAPCRI has formed a Cochrane Review Diagnostic test accuracy (CRDTA) working group for a systematic review of Polymerase Chain Reaction for diagnosing invasive aspergillosis (review no N010). Publication on this is planned for 2013 and will strengthen the evidence base and validate our standards.

– The EAPCRI is working closely with Quality Control for Molecular Diagnostics (QCMD). The QCMD is a non-profit organisation dedicated to advancing the quality of molecular diagnostics through External Quality Assessment (EQA), Proficiency Testing (PT) and other quality initiatives (http://www.qcmd.org). EAPCRI is helping develop and externally validate quality control panels for Aspergillus PCR sent out by QCMD.

– The ongoing cooperation of all EAPCRI participant has been fundamental is enabling all these outputs to be achieved. The ultimate aim to incorporate a standard for Aspergillus PCR methodology into future consensus definitions for diagnosing IFD is within our grasp.