Report
Teaser, summary, work performed and final results
Periodic Reporting for period 3 - DIAGORAS (Chair/bedside diagnosis of oral and respiratory tract infections, and identification of antibiotic resistances for personalised monitoring and treatment)
Teaser
What is the problem/issue being addressed?According to the WHO, antibiotic resistance already causes an estimated 700,000 deaths annually and, without effective action, is predicted to cause 10 million deaths annually by 2050. Additionally, respiratory tract infections (RTIs)...
Summary
What is the problem/issue being addressed?
According to the WHO, antibiotic resistance already causes an estimated 700,000 deaths annually and, without effective action, is predicted to cause 10 million deaths annually by 2050. Additionally, respiratory tract infections (RTIs) are among the top reasons for visiting a general practitioner, and one of the major causes associated with the unnecessary prescription of antibiotics.
Oral infections – periodontitis and caries – are the most prevalent chronic diseases with more than 5 billion cases worldwide, deteriorating people’s quality of life and heavily burdening the healthcare systems.
Detection of the correct etiological agents (bacteria, viruses) associated with the aforementioned infections is crucial for the patient’s treatment. Unfortunately, microbial diagnosis still requires centralised diagnostic laboratories and several days to complete. This delay may lead healthcare professionals to take empirical, rather than evidence-based, treatment decisions.
The project involved developing an innovative, accurate, reliable and cost effective in vitro diagnostic tool that would offer earlier disease diagnosis at the point of care, patient stratification and/or prognosis, leading to improved clinical decisions and health outcomes.
Why is it important for society:
By achieving rapid, molecular-based diagnosis of RTIs, antibiotic resistances, and oral infections, the health and social benefits of the DIAGORAS platform are potentially enormous.
In overview, the platform will:
• Increase the accuracy of the rapid diagnosis of infectious (viral and/or bacterial) diseases
• Reduce expenditure on unnecessary and non-targeted antibiotic prescribing practices
• Shorten prolonged stays in hospitals caused by infectious disease complications
• Reduce the risk of nosocomial and epidemic infections by providing an effective screening tool
• Help prevent the unchecked spread of antimicrobial resistance
• Reduce the burden and costs associated with oral diseases and severe complications caused by lack of correct treatment and patient monitoring
• Decrease the overall global burden of infectious diseases, patient morbidity and mortality.
What are the overall objectives:
• Better patient management, in case of RTIs, through rapid and accurate differentiation between bacterial and viral infections with similar clinical symptoms
• Prevention of antibiotic overuse based on antimicrobial resistance screening for targeted therapy
• Early diagnosis and determination of the disease level
• Personalised monitoring for status control during the entire period of the oral treatment.
Conclusions of the Action:
• A multi-target (syndromic instead of single-pathogen detection) approach is the suitable approach for RTIs and oral infections
• For oral infections the time-course monitoring of patients’ bacterial load and biomarker concentration has higher value rather than a single-timepoint measurement
• All questioned end-users require the result to be provided in less than 1 h, and that the diagnostic report provides guidance for treatment strategies.
Work performed
The progress described here refers to the entire project as this is the final report.
Nucleic acid assay development
• Development and validation of oral qPCR assays for 7 periodontal and 3 caries bacteria
• Development and validation of RTI qPCR assays for 9 bacteria, 10 viruses, and 3 indicative resistances
Protein assay development
• Production of antibodies and antigens for specific periodontal biomarkers
• Development of ELISA assays for 6 periodontal biomarkers
• Development of a new immunoassay method and implementation for CRP and 3 periodontal biomarkers
Integration of bioassays in the LabDisk microfluidic cartridge
• Development of two types of cartridges: one for sample-to-answer PCR and one for sample-to-answer immunoassay. Both designs are “universal†and applicable in both applications of oral and RTIs
• The disks were tested with: clinical whole saliva, reference respiratory samples, and serum
Disposable production technology and cartridge manufacturing
• Transfer of micro-thermoforming production process from prototyping to batch automated manufacturing and production of fully-packaged cartridges for testing clinical samples
Reader assembly and system integration
• Development and assembly of 7 prototypes for partners, capable of detecting both PCR- and immunoassay-disks
Analysis software and reporting user interface
• Set-up of flexible software modules to be applicable to any type of the developed disk data input
• Demonstration of the server-based system
• Creation of comprehensive oral- and RTI-output reports for end-users
Clinical validation
• Collection of whole saliva clinical samples & testing them with: benchtop qPCR; commercial iai PadoTest kit; benchtop ELISA; and LabDisk
• Testing of reference respiratory samples with routine diagnostic procedures and comparison with the LabDisk
• Demonstration to general practitioners & dentists with feedback for future improvements of the platform
Dissemination
• Participation in exhibitions and conferences with posters/oral presentations
• Publications in peer-reviewed journals
• Set up of two videos, website, interviews, press releases, flyers
• Organization of 3 workshops & webinar
Exploitation
• Set up of an exploitation plan with innovation roadmap
• Expansion of SMEs’ portfolio with new class of magnetic beads; new ELISA kits; flexible software components; and stand-alone hardware components ready for commercialization.
Final results
Healthcare impact
The project is expected to have disruptive impact on three major aspects of the healthcare practice of infectious disease diagnostics:
• Shifting the diagnostic methodology from an empirical approach (based on clinical symptoms) or traditional laboratory approach (e.g., bacterial/viral cultures) towards multiplex molecular-based analysis
• Shifting the diagnosis location from centralised laboratories and diagnostic centres towards the point-of-care at the chair/bedside
• Providing access to evidence-based results for clinical decision-making.
Sustainability of the healthcare systems
The proposed DIAGORAS platform will help to improve the sustainability of the healthcare systems by drastically reducing:
• Time to results and therefore time to treatment
• The number of incorrect antibiotic prescriptions and its additional treatment costs;
• Unnecessary hospitalisation and/or prolonged stays in hospitals due to incorrect, or withdrawal of, antibiotic treatment;
• Dental costs and frequent visits to dentists for treatment and monitoring;
• The time required to collect and report on infectious disease outbreaks in the community.
Economic impact
The large diversity of fields that the SME consortium partners cover can largely expand the European economic benefit and the SME activities in: (i) biomarker and assay development and diagnostic kit manufacturing (nucleic acid and immunoassay); (ii) biochemical components for assay integration and automation and extraction kits; (iii) microfluidic cartridge manufacturing with quality control systems; (iv) readout system combined with proper software for clinical data management. In addition, as the activities of the SMEs involved in the project are not restricted to a specific application field, the double application of DIAGORAS (oral infections and RTIs) broadens their market potential.
Website & more info
More info: http://www.diagoras.eu.