An important unmet need
Excellent care for people with suspected infections involves rapid diagnosis and treatment. For instance, administering the correct antibiotic as soon as possible to patients with blood infections dramatically improves their chances of survival. On the other hand, using antibiotics when they do not benefit patients exposes them unnecessarily to side effects and potential antibiotic resistance. Despite all the advances in medicine, we still do not have the technology available that can quickly diagnose what kind of infection a patient has and what treatment they need. Even the best of the currently available diagnostic methods are too slow to help clinicians.
The RAPP-ID project aimed to provide an integrated solution that addresses the technological challenges to enhance clinical decision-making and improve the quality of care and clinical outcomes for patients. More specifically, it aimed to develop rapid point-of-care platforms (POCTs) for the rapid detection of bacteria, tuberculosis bacteria, fungi, and viruses as well as patients’ markers of infection (less than 2 hours in hospitals, and less than 30 min in primary care).
Good outcomes in spite of challenges
Developing diagnostic tests for infectious diseases is very challenging, and due to limited time and resources, the project fell short of developing fully-fledged rapid diagnostic tests. However, some of the innovations and technologies developed within the project could speed up the development of such tests in the future. Furthermore, the project produced other resources and tools which could be useful for the future development of POCTs.
Defining user requirements
Many tests have been produced in the past that are miracles of bioengineering but have not provided clinicians with what they require for optimal care. In order to understand the requirements for these tests, the RAPP-ID team put a lot of effort into drawing up user specifications which outline what diagnostic tests for different infectious diseases should even look like. These guidelines could help anyone working on diagnostic tests for infectious diseases in the future.
Prototype of the breath sampler
After the user specifications were defined, the project team set out to develop some of the technologies needed to create rapid diagnostic tests. Perhaps the biggest and most innovative achievement of the project was the development of a prototype breath sampler for influenza. Patients exhale into the instrument, which captures tiny particles in their breath, and then uses that sample to detect the presence of pathogens. During the project, the team was able to demonstrate that the instrument is able to capture airborne pathogens, and started testing it on patients in the clinic. However, the technology is still in the relatively early stages of development, and would need more time and resources to be developed into a clinically validated test. This innovation is now part of IMI2 – Call 11 on the sustainability of IMI project results and might be developed further by one of the winning consortia.
Chips for diagnosing pneumonia
Another important project achievement was the prototype of the ventilator-associated pneumonia (VAP) test. VAP is a very serious infection in people who are in intensive care. The illness has a very high death rate and diagnostic tests that could detect these bacteria quickly are urgently needed. The RAPP-ID project developed chips which help isolate the DNA of these bacteria from aspirates of VAP patients. As the amount of DNA which can be extracted from these bacteria is very low, the DNA from these samples had to be amplified before detection. The chip was aimed to run on an instrument making it a complete diagnostic test. Although nearly there, this device-chip combination would require a further software update to run autonomously – a process which could not be fully completed within the scope of the RAPP-ID project.
In addition to the innovations mentioned above, the project developed many other resources and innovations which are now available for future research, including a technology for the acoustic manipulation of bacteria with the help of beads, and cell lines for various bacterial strains.
For the benefit of industry and academia
The academic community benefited from the project in several ways. First of all, they made big progress in developing some of their ideas for rapid diagnostic tests. Secondly, by interacting with other academic partners and industry, they were able to expand those ideas and add certain components to their technology platforms which they could not have developed on their own. The project also resulted in about 30 scientific publications, with more to come.
Thanks to RAPP-ID, both the pharmaceutical industry and academic partners learned about the challenges involved in developing diagnostic tests and bringing them to the market. As the first IMI project of this kind, RAPP-ID was in many ways a learning experience for everyone involved and could help enhance collaboration between the medicine and diagnostic worlds, shaping better EU-funded diagnostic projects in the future.
All of the partners in the project, including academia, industry and SMEs, also benefitted from the collaboration and new partnerships formed within the project. Some of these collaborations are continuing and have resulted in new spin out projects.
The findings of the RAPP-ID project inspired at least two spin out projects funded by the EU. The first focused on urinary tract infections (UTIs) and developed a chip which can detect drug-resistant, UTI-causing bacteria. The chip is similar to the one developed in RAPP-ID for VAP.
The second spin out project, New diagnostics for infectious diseases (ND4ID), is a Marie Skłodowska -Curie project which will enable 15 PhD students to conduct their research at industry and academic laboratories across Europe. It will run until early 2020 and involves many of the RAPP-ID project partners.
Achievements & News
Doctors treating infectious diseases still don’t have rapid diagnostic tests which could help them identify the exact strains of pathogens ailing their patients.### The development of such tests is complex and expensive, but that may improve thanks to IMI’s RAPP-ID project, which developed some of the technologies and innovations needed to speed up the development of such tests in the future. For example, the project developed a prototype of a breath sampler for influenza – the first test which uses something as simple as breathing out to detect the presence of pathogens in patients. ‘So far in clinical practice, there are no rapid point-of-care tests for detection of infections that are based on something as non-invasive as breathing out,’ said project coordinator Jorge Villacian, in an interview with the IMI Programme Office. ‘Of course, we are aware of the fact that we’re not there yet – this is still in an early stage of the development process. But the technology itself may be useful for other fields (outside of infectious diseases) as well.’ Some of the technologies created under RAPP-ID are undergoing further development in new EU-funded projects.
Flu is a highly infectious disease, yet during an epidemic, it can be hard to identify which patients have the virus. A device under development by IMI’s RAPP-ID project could deliver a flu diagnosis faster and without the hassle of an invasive nasal swab.### Patients would simply have to breathe into a bottle-like container for a few minutes to get a near-instant result at the point of care, which could be their doctor’s surgery or even their own home. Inside the device, the first step involves using highly-charged needles to direct the micro-droplets of water in the exhaled breath that carry the virus to a droplet of liquid in the bottom of the chamber. There, the walls of the virus are broken down and the viral proteins bind to specially designed magnetic beads coated with antibodies. The beads are then flushed into an array of tens of thousands of minute wells, each smaller than a red blood cell. Finally, additional reagents are brought to the array, causing the flu proteins to glow so that they can be counted with a camera. The different components have been demonstrated to work independently, as described in three papers in PLoS ONE, Applied Materials and Interfaces, and Analytical Chemistry. Now the team is keen to continue its work on the device. Meanwhile, lead researcher Professor Wouter van der Wijgaart from the KTH Royal Institute of Technology in Sweden, explains: "This kind of test will enable doctors to treat severely threatened patients the right way, and it will be valuable for use in clinical research. It’s harder than finding a needle in a haystack, but it can be done."
IMI’s RAPP-ID project along with four other European research projects (BioMaX, DiaTools, CareMore and NextDx) will organise the first European Conference on Novel Technologies for In Vitro Diagnostics in Leuven, Belgium from 6 to 8 October 2014.### The conference will offer discussion and networking opportunities with major European players and experts in the field of in vitro diagnostics.
The goal of the meeting is to provide a forum for discussions on factors driving the development of new diagnostic tools, with particular emphasis on innovative devices and molecular technologies of medical or industrial relevance. Experts in the field will discuss exciting innovations in the sector, while keynote speakers will take an interdisciplinary approach by focusing on the technological, biological, clinical and regulatory aspects of in vitro diagnostics.
- More information on the programme and how to participate here.
The ideal point of care test (POCT) is cheap, easy to use, and delivers highly accurate results in less than half an hour, according to the results of a survey run by IMI project RAPP-ID.### POCTs are tests carried out where the patient is being cared for (e.g. at a doctor’s surgery), as opposed to in a central laboratory. Currently, doctors often have to wait days to find out what infections, if any, their patient has. RAPP-ID aims to develop POCTs that deliver more accurate and faster results. The survey also highlighted the pathogens and antibiotic resistance problems that are most relevant for clinicians. The survey results will therefore help the project team to develop a test that meets clinicians’ needs. Elsewhere in the project, the consortium has reviewed the state of the art in diagnostic tools. This, along with the results of the survey, will ensure that the results of the RAPP-ID project will be truly game-changing.
The IMI project RAPP-ID has launched a web-based survey to find out how clinicians currently manage certain infections and what they need for a diagnostic Point Of Care Test (POCT) to be useful in the clinic.### POCTs refer to tests that are carried out where the patient is being cared for, such as a doctor’s office, as opposed to in a central laboratory. Today, doctors and patients often have to wait for days for the results of tests to identify what infection, if any, a patient has. RAPP-ID is working to develop POCTs that will provide information in less than two hours on the cause of infection and, in the case of bacterial infections, whether the bacteria are resistant to certain drugs. This will allow doctors to administer the right medicines sooner. The survey will help the project partners focus the development of POCT platforms and ensure that they are clinically relevant and meet clinicians’ needs. All clinicians are welcome to complete the survey; the deadline for submitting responses is the end of this year. The results will be released early next year.
ND4BB – the story so far, in Nature Reviews Microbiology
IMI’s antimicrobial resistance (AMR) programme New Drugs for Bad Bugs (ND4BB) is the focus of a recent comment piece in Nature Reviews Microbiology by John Rex of AstraZeneca, who is involved in ND4BB. The article explains how ###IMI and other projects around the world are tackling the biggest challenges in antibiotic research and development. For example, TRANSLOCATION is investigating how to transport antibiotics into bacteria, while COMBACTE focuses on the design and implementation of more efficient clinical trials. ENABLE, IMI’s newest AMR project, is creating a drug discovery platform to fast-track the development of promising molecules. The article also highlights IMI project RAPP-ID, which is working on point-of-care tests, as well as a number of US-based initiatives. Looking to the future, the article notes that IMI has a project in development which will investigate new business models and economic strategies to incentivise the development of new antibiotics.
The article concludes: ‘Although the [AMR] crisis is far from resolved, the leadership of the European Commission are to be commended for their far-sighted approach to creating ND4BB and its projects, all of which provide hope that the global community will have access to an adequate pipeline of novel antimicrobial agents with which to address the challenge of AMR.’
ParticipantsShow participants on map
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Glaxosmithkline Vaccines SRL, Siena, Italy
- Janssen Pharmaceutica Nv, Beerse, Belgium
- Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
Universities, research organisations, public bodies, non-profit groups
- Cardiff University, Cardiff, United Kingdom
- Interuniversitair Micro-Electronica Centrum, Leuven, Belgium
- Katholieke Universiteit Leuven, Leuven, Belgium
- Kungliga Tekniska Hoegskolan, Stockholm, Sweden
- Stockholms Universitet, Stockholm, Sweden
- Universite De Geneve, Genève 4, Switzerland
- Universiteit Antwerpen, Antwerp, Belgium
- Universiteit Gent, Gent, Belgium
- Universiteit Twente, Enschede, Netherlands
- University of Cambridge, Cambridge, United Kingdom
Small and medium-sized enterprises (SMEs)
- Lionex GMBH, Braunschweig, Germany
- Microfluidic Chipshop GMBH, Jena, Germany
- Q-Linea AB, Uppsala, Sweden
- Universitair Ziekenhuis Antwerpen, Edegem, Belgium
|Name||IHI funding in €|
|Cardiff University||75 379|
|Interuniversitair Micro-Electronica Centrum||229 726|
|Katholieke Universiteit Leuven||366 540|
|Kungliga Tekniska Hoegskolan||1 327 277|
|Lionex GMBH||476 900|
|Microfluidic Chipshop GMBH||467 400|
|Mobidiag Oy (left the project)||174 455|
|Q-Linea AB||491 845|
|Stockholms Universitet||537 377|
|Universite De Geneve||60 500|
|Universiteit Antwerpen||1 238 424|
|Universiteit Gent||458 075|
|Universiteit Twente||364 003|
|University of Cambridge||489 154|
|Uppsala Universitet (left the project)||37 123|
|Name||Funding in €|
|Universitair Ziekenhuis Antwerpen||34 260|
|Total Cost||6 828 438|