TM-REST
- Framework programme:
- 7
- Project number:
- 202145
- EC contribution:
- 2,900,000 €
- Duration:
- 36 months
- Instrument:
- Focused Research Project
- Starting date:
- 01/01/2008
- Project Web site:
- http://www.tm-rest.org/
Keywords: MDR-TB, XDR-TB, fast molecular diagnosis, biochips
Background
Drug-resistant Mycobacterium tuberculosis strains are a threat to tuberculosis (TB) control worldwide as strains resistant to available anti-TB drugs have emerged. Drug-resistant (DR) TB and multidrug resistant (MDR) TB are manmade problems related to poor case management and quality of drugs. They require expensive chemotherapy and have an increased fatality rate.
The increasing threat of infections due to M. tuberculosis, including MDR-TB and extensively drug-resistant (XDR) infections, poses important questions that call for development of integrated tools for rapid diagnosis. In the specific case of TB, an integrated rapid diagnostic approach should be able to permit species identification, drug susceptibility testing and molecular typing.
Malaria, caused by the protozoan parasite Plasmodium falciparum, kills between 1.5 million and 3 million people each year. Deaths from malaria are increasing, especially in Africa, largely because of antimalarial drug resistance. A rapid diagnostic tool for drug resistance would be affordable within European healthcare systems and advantageous in countries where patients are treated in walk-in clinics with no follow-up. Diagnosis of drug susceptibility of the infecting patients at the same time as diagnosis of infection would allow selection of the most efficacious drug.
Aims and expected results
For TB, the project aims to test and validate an affordable, high-tech platform for rapid molecular diagnosis and monitoring of TB and its drug-resistant variants, as well as to other infectious and poverty-related diseases. It will develop and validate a silicon-based open platform for molecular biology testing consisting of a single disposable device (biochip) and on associated specific instruments (reader). The main advance over existing technology (i.e. real-time polymerase chain reaction or PCR) consists in the possibility of performing PCR and hybridisation in a single device at competitive costs, using a higher number of genic probes by integrating multiple PCR chambers and medium density array (between 50 and 200 probes), with faster and more stable amplification and hybridisation reactions through optimised and controlled thermal ramps and profile. Special focus will be placed on the feasibility and cost-effectiveness of such a novel tool for application in countries with high TB and MDR-TB incidence. In parallel to the diagnostic platform for TB, a feasibility study on its applicability to other poverty-related diseases such as malaria will be carried out.
The project will also provide information regarding the feasibility, impact, and cost of a novel molecular identification methods in low- to middle-income, high-MDR-TB European countries. If the In-check(TM) method is validated in these settings, and the improved time-to-detection and economic benefits outweigh the overall costs associated with this diagnostic product, then the laboratories involved may consider performing the tests routinely across Europe. Rapid diagnosis of DR-TB will have several benefits. These include earlier treatment of patients and reduction of time spent on inappropriate and ineffective treatment. Early identification of MDR-TB will allow much faster investigation of whether a patient has XDR-TB, speeding up the time to diagnose MDR-TB patients who should then be fast-tracked for XDR-TB laboratory tests.
For malaria, a rapid diagnostic test would provide significant benefits for patients and could contribute to reduced hospital time, and hopefully reduced patient mortality. This project will assess the feasibility of developing chip-based assays for the detection of drug-resistant malaria. If successful, the technology could be more widely adopted, especially in malaria-endemic countries where it could have significant impact on malaria morbidity and mortality.
Potential applications:
The project will provide improved molecular diagnosis and monitoring of TB and its drug-resistant variants, and improved support and guidance of therapeutic interventions. It will also apply same platform technology and methodology adapted for the detection of specific markers of drug-resistant variants of malaria.
Installed lab-on-chip-based platform (In-checkTM).
Coordinator:
Dr Daniela M Cirillo
HSR - Fondazione Centro San Raffaele del Monte Tabor
Milan
Italy
E-mail: cirillo.daniela@hsr.it
Partners:
| Nº | Principal Scientific Participants |
Official Address | Other Information |
| 1 | Stefan Niemann | Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften Borstel Germany |
Email: sniemann@fz-borstel.de |
| 2 | Marco Rinaldo Oggioni | Università degli Studi di Siena Siena Italy |
Email: oggioni@unisi.it |
| 3 | Elizabeta Bachiyska | National Centre for Infectious and Parasitic Diseases Sofia Bulgaria |
Email: elizabetbatchiiska@abv.bg |
| 4 | Toby G. Barbuzzi | STMicroelectronics s.r.l. Catania Italy |
Email: tony.barbuzzi@st.com |
| 5 | Silva Tafaj | University Hospital of Lung Diseases Tirana Albania |
Email: stafaj@hotmail.com |
| 6 | Lisa C. Ranford-Cartwright | University of Glasgow, Biomedical Research Centre Glasgow UK |
Email: L.C.Ranford-Cartwright@bio.gla.ac.uk |
| 7 | Mark Perkins | Foundation for Innovative New Diagnostics Geneva Switzerland |
Email: giorgio.roscigno@finddiagnostics.org |
| 8 | Francis Drobniewski | Queen Mary and Westfield College, University of London London UK |
Email: f.drobniewski@qmul.ac.uk |
