Infectious and inflammatory diseases are amongst the most common conditions for which patients consult medical care in the community and hospitals. A large proportion of patients attending medical care with fever or inflammation have self-resolving viral or other conditions. However, amongst them are a small proportion with serious life-threatening bacterial infections or serious inflammatory diseases. The major problem facing clinicians is how to rapidly identify and distinguish the serious conditions that require specific treatments.
The current approach to infectious and inflammatory diseases relies first on exclusion of severe bacterial infection using microbiological approaches including bacterial cultures. Bacterial culture results may not be available for 24-48 hours, and patients with suspected significant infection are first treated with broad-spectrum antibiotics, pending the microbiological results, which in many cases fail to confidently identify the cause. Thus, many patients undergo unnecessary investigation and treatment with broad-spectrum antibiotics. A small proportion of patients with fever and inflammation do not have infections but have serious and persistent inflammatory disorders that require specific treatments. These are often only diagnosed after a lengthy process of first excluding infection and then stepwise exclusion of other conditions.
DIAMONDS aims to revolutionise the diagnostic process for infectious and inflammatory diseases by demonstrating and bringing into clinical use diagnostic approaches based on host molecular signatures. The underlying hypothesis in DIAMONDS is that individual infectious and inflammatory conditions are associated with unique patterns of genes that are activated or repressed in the patient’s blood in response to the individual disease. These unique molecular patterns can be discovered through genome-wide RNA sequencing (RNA-Seq) and can be used as a “molecular signature” or “fingerprint” specific for each disease process. DIAMONDS builds on our previous EU-funded EUCLIDS and PERFORM studies which recruited over 10,000 patients with fever and inflammation at multiple hospitals in Europe, Africa, and Asia. We have established proof of principle that individual diseases, such as tuberculosis, bacterial infections, viral infections, or inflammatory diseases like Kawasaki disease and rheumatoid arthritis, are characterised by unique RNA signatures. DIAMONDS will move the concept of diagnosis of infection and inflammatory disease by RNA molecular signatures a step closer to clinical introduction by first expanding the range of infectious and inflammatory diseases for which we have gene expression data, to cover a wide range of infectious and inflammatory diseases. Using samples from carefully phenotyped patients, DIAMONDS has undertaken RNA-Seq and bioinformatic analyses to identify the RNA profile of common infectious and inflammatory diseases. DIAMONDS is establishing a European Diagnostic Transcriptomic Library which will be available to researchers and clinicians worldwide as a resource for understanding infectious and inflammatory diseases.
Using bioinformatic methods we have selected the smallest number of genes that enable individual infectious and inflammatory diseases to be distinguished – an approach called Personalised Molecular Signature Diagnosis (PMSD). We are developing diagnostic devices to rapidly detect the genes required to distinguish common diseases, and are testing these prospectively. By the end of the study, we aim to have validated the concept of diagnosis of infectious and inflammatory diseases using PMSD, established the accuracy of a PMSD detection device, and provided evidence on cost-effectiveness and clinical value of PMSD.
