Developing Rapid Diagnostics for Infectious Disease Agents

Research led by Dr Alan McNally has driven the development of rapid diagnostic protocols and devices for infectious diseases, principally influenza, salmonella and campylobacter.

The research began by working on the validation of a standardised real-time PCR test for H5N1 avian influenza which is now used in European reference laboratories. Follow-on funding led to the development of fully-automated diagnostic devices for companies who have taken their products to market and attracted substantial investment from world-leading pharmaceutical companies.

Point-of-care diagnostics for influenza

Dr McNally transferred crucial background intellectual property to industry and academia and created and validated reference laboratory-quality diagnostic and detection assays. Demonstrating the impact of his work, the following companies all adopted assay design practices based on Dr McNally's scientific input: Genewave, Gaiker,Ikerlan, and Whatman GE Healthcare. Additionally, the validation of testing procedures and devices during the project was designed by Dr McNally, allowing the final product to be tested to OIE reference laboratory standards.

The impact of rapid diagnosis of human cases of H5N1 infection was quantified in a 2008 Lancet study which concluded that rapid point-of-care diagnosis of cases in humans would allow more effective infection control measures and quicker delivery of the antiviral oseltamivir to patients.

This research also created multiple opportunities for public outreach to educate the public on influenza and the benefits of rapid diagnostic research. These included editorials in the Lancet, and expert opinion pieces in national and international media such as BBC Radio 5 live, BBC Radio 4, and Naturenews.com.

Rapid PCR-based detection system for salmonella and campylobacter

In a project with industry NTU developed a sample preparation protocol for a diagnostic device which was incorporated into the marketed product. The sample preparation technique is absolutely integral to the ability of the ML diagnostic device to be used on any sample type, from faecal samples to respiratory samples. This ensures the ML is able to detect any infectious agent from any clinical sample type and is a truly multi-functional platform.

During the project, substantial investment was put into developing their device for use in influenza diagnostics. Since then GSK has further invested in a collaboration to commercialise the ML device and assay development.

Dr McNally began diagnostics development research as a post-doctoral scientist. Working on a Department of Environment, Food and Rural Affairs (Defra) funded project from 2004-2006, he validated the newly developed real-time PCR assay planned for use in future European H5N1 outbreaks. The work was presented to an emergency European Union meeting to discuss implementation of molecular detection in reference laboratories. The validation led to the test being approved for use in all avian influenza reference laboratories, and the protocols provided for testing.

Dr McNally took this work forward in 2007 as part of a consortium which secured €3 million for the PortFastFlu project to develop rapid, point-of-care diagnostics for influenza. This involved creating new improved assays to detect all influenza subtypes in veterinary and clinical samples by a combination of a PCR amplification and microarray hybridisation. The entire test was to be run in a single self-contained device, providing a simple "inject and forget" diagnostic machine for influenza.

Dr McNally was the sole member of the consortium with experience of designing and validating reference laboratory standard detection tests, and was directly involved in assay design, assay validation, and device validation. As a result of McNally's experience, there was transfer of knowledge from NTU to industrial partners (Genewave, Gaiker, Ikerlan, and GE Whatmann) and academic partners at VIB (Flanders Institute of Biotechnology) and the Centre for Agricultural Research and Development, France. The project ended in January 2011 with the lead SME Genewave launching their hardware device to market.

The success of the EU project led to Dr McNally being Principal Investigator on a Technology Strategy Board (TSB) funded project developing a portable, rapid, automated DNA analysis (PRADA) molecular point-of-care test system for intestinal infectious disease from October 2008 to October 2010.

The project involved creating assays for the detection of salmonella and campylobacter in faecal samples, and crucially a sample preparation technique to allow direct fully automated PCR detection of pathogens from faecal samples; thus a wider application for healthcare associated infections. The project was in collaboration with industry who developed the hardware and technology. Dr Georgina Manning at NTU was a co-investigator, and Dr Jennifer Ince was a post-doctoral research associate.

• European Community's Seventh Framework Programme [FP7/2007-2013] under grant agreement 201914. PortFastFlu – final report. The report contains full details of the role of each partner, and provides details on the outcomes of the project including consortium patents and stage of product to commercialisation.
• Kandun, I.N., et al. 2008. Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series. The Lancet 372. 744-49. A full analysis of the potential benefits of rapid detection of Influenza during an Influenza epidemic.
• Bird flu hits UK newspapers. An example of the positive press surrounding the Influenza diagnostics project.
• Case notes – swine flu. BBC coverage of the PortFastFlu project and its potential benefits to the UK. (From 4:26 min onwards.)

• OIE, FAO approved diagnostic algorithm from molecular testing of H5N1 (first posted 18/09/2007 – present day)
• Slomka, M.J., Pavlidis, T., Banks, J., Shell, W., McNally, A., Essen, S. C., & Brown, I. H., 2007. Validated H5 Eurasian RealTime PCR and its application in H5N1 outbreaks in 2005-06. (http://wok.mimas.ac.uk on 18 October 2013).
• Aldous, E. W, Seekings, J. M., McNally, A., Nili, H., Irvine, R. M., Alexander, D. J. and Brown, I. H. (2010). Infection dynamics of highly pathogenic avian influenza and virulent avian paramyxovirus type 1 viruses in chickens, turkeys and ducks. Avian Pathol. 39: 265-273. DOI: 10.1080/03079457.2010.492825. Impact Factor 1.729, citations 10 (http://wok.mimas.ac.uk on 18 October 2013).

• Alan McNally Co-Investigator on PortFastFlu: European Community's Seventh Framework Programme ([FP7/2007-2013] under grant agreement 201914. Grant awarded 3 Million Euro. (01/01/2008 – 31/12/2010)
• Alan McNally Principal Investigator on Portable Rapid Automated Detection and Analysis (PRADA). TSB project– AG182K. Grant awarded £1.8 Million (01/11/2008 – 31/10/2011).