Genomics for undiagnosed infectious disease evaluation and diagnosis in northern Australia (GUIDED)

In an increasingly interconnected world, there is a significant risk for the introduction, emergence or re-emergence of infectious diseases in the northern Australia region. The early detection and diagnosis of infectious diseases currently relies on a best guess of likely causative agents with specific testing for those agents. In this changing and unpredictable setting, we need a more agnostic diagnostic approach to detect unexpected or novel pathogens to both improve our diagnostic accuracy and provide early warning for diseases with epidemic potential.

In this project, we aim to evaluate a genomics approach for the diagnosis of acute febrile illnesses of moderate to severe intensity. We will conduct a regional multicentre prospective study of patients to determine the optimum conditions for sample collection and processing for genomic analysis; and determine the most efficient, clinically relevant, analysis pipeline. The project will be conducted across two different regions of northern Australia: Cairns (Queensland) and Darwin (Northern Territory).

We will use genomics to confirm diagnosis in conditions where the microbial agent has been detected through hospital-based diagnostics. This approach will enable the validation of genomics methods and provide a ‘proof-of-principle’ that an agnostic, metagenomics approach can be used to diagnose fevers of unknown origin. Acute febrile illnesses will be investigated because the diagnostic sample is considered ‘sterile’.

In theory, properly collected blood samples should only contain host nucleic acid. Our explorative research has shown that blood may contain genetic information from bacteriophages, viruses and bacteria. As such, we need to be able to differentiate potential pathogens and better define the microbial flora of blood.

Once specimen collection, sample processing and genomics pipeline methodologies have been optimized, the logical steps beyond this project are to expand the testing to screen fevers of unknown aetiology to aid diagnosis in a clinically relevant timeframe.