Lower respiratory tract infection (LRTI), primarily pneumonia and bronchitis, is the third leading cause of death worldwide. The incidence of LRTIs in Europe is 30 million, greater than diabetes mellitus (2 million) and malignant neoplasms (2.4 million) combined leading to 230,000 deaths, and over 1 million hospitalizations. The attendant economic burden of LRTI in Europe is estimated at €46 billion annually (direct and indirect costs). LRTI presents a diagnostic challenge due to the difficulty in pathogen sampling and the often indistinguishable clinical symptoms of bacterial and viral etiologies. This uncertainty leads to antibiotic misuse, both overuse (typically for bronchitis) and underuse (often for community-acquired pneumonia, CAP). Overuse of antibiotics may expose the patient to unnecessary adverse side effects and contributes to emergence of antimicrobial resistance, currently a major global health threat. Underuse may cause the patient to suffer prolonged disease and increases the likelihood of hospitalization and mortality, with attendant health and economic costs. In the case of CAP, late treatment with antibiotics has been shown to directly impact mortality.
Older adults are at risk for LRTIs due to immunosenescence and co-morbidities, as reflected by increasing incidence with age. In view of the aging European population, the human and economic burden of LRTI is predicted to increase in the coming years. Since most adult LRTIs are managed on an outpatient basis, innovative approaches are warranted that will provide the clinician with actionable information at the point-of-need (community clinic and emergency department [ED]) – to treat or not to treat with antimicrobial therapy – with the goal of promoting 'healthy aging'.Today, LRTI patient management at the point-of-need is guided mainly by clinical symptoms, and in some cases, by the circulating levels of biomarkers. However, the diagnostic performance of each biomarker alone is often restricted. Furthermore, as all these biomarkers are predominantly bacterially-induced, their combination leads to limited diagnostic improvement.
To address this, MeMed has previously identified a three host-biomarker signature that comprises a novel viral induced protein called TRAIL, which at that time was not in clinical use. Based on this proprietary biomarker signature, MeMed developed and received EU regulatory approval (CE-IVD) for a diagnostic test called ImmunoXpert™. This test uses microplates to measure serum levels of the three proteins (TRAIL, IP-10 and CRP) and applies proprietary software to integrate their values and generate viral and bacterial likelihood scores. In a prospective clinical study with over 1000 patients MeMed demonstrated that ImmunoXpert™ accurately distinguished viral versus bacterial acute infections across different group ages, physiological systems (e.g. upper respiratory, urinal and gastrointestinal) and a broad range of pathogens (56 strains), significantly outperforming traditional tests.
Two main objectives were pursued as part of this project with the aim of facilitating wide adoption of the ImmunoXpert™ test for managing LRTI adult patients at the point-of-need:
Objective (1): To clinically validate the biomarker signature for accurate diagnosis of viral versus bacterial LRTI, in a multi-center, prospective pan-European study enrolling adults in EDs and clinics.
Objective (2): To develop, validate and prepare for EU regulatory clearance for a new point-of-need device, that will allow rapid measurements (15 minutes) of the signature and is compatible with serum and whole blood samples.
