Point-of-Impact Testing in the Emergency Department: Rapid Diagnostics for Respiratory Viral Infections

Christina Lingham:
Hi everyone. I'm Christina Lingham from the Molecular Diagnostics Europe event. I'm really pleased to have the opportunity to speak with Hubert Niesters, Director of the Laboratory of Clinical Virology at the University Medical Center in Groningen in the Netherlands.

He'll be talking with us about point of impact testing in the emergency department, rapid diagnostics for respiratory viral infections. He'll be giving a talk at the Point of Care Diagnostics Track this 12th, 13th of April in Lisbon, Portugal.

Bert, thank you for joining us.

Hubert Niesters:
Thank you for having me.

Christina Lingham:
We want to ask you a few questions about your talk this April in Lisbon at the Point of Care Diagnostics conference. You study point of care interactions for highly infectious patients. What have you seen in terms of improvement in both care delivered in the spread of infection, and how does your method differ from standard practice?

Hubert Niesters:
I think the biggest advantage we have achieved the last few years, and we're still improving into this, is the ability to give a very rapid result to the clinician, as well as to the patient, while the patient is still at the emergency room. Like now, in early January of this year we have a huge impact of respiratory viruses, not only influenza RSV, but also broad scale of viruses like parainfluenza and coronaviruses, which gives a lot of problems with patients being at the emergency room of a university hospital because that are the patients who, for instance, have had the lung transplantation, who are transplant patients, oncology patients. Really, patients who need good care.

One of the challenges is how can you improve diagnostics and patient care by giving results rapidly? We have used what I call a point of impact syndromic panel, in this case, BioFire Firmarray system. It gives the results within 90 minutes while the patient is still at the emergency room. On average, we know, the patient is for a period of four hours at the emergency room. Then there are a number of challenges.

Does the patient has an infectious disease? A respiratory virus, or not? The patient has influenza virus, for instance, does he need medication or not? Can he just go home? How is he doing? If the patient has to be admitted to the hospital, we can always say, "If you have influenza virus type, it's circulating, we can put you on a single room but we can also if we don't have enough single isolation rooms, we can put you in a room with two beds or three bed with patients having the same virus because you cannot infect yourself twice."

For through-put and flow in a hospital, this is really excellent. Everybody is really happy. The patient is happy because the patients knows I have a problem or I don't have a problem and the best care is being taken for me. The physician is also very happy because the physician knows exactly within the period of this 90 minutes what he has to do, what he doesn't have to do, because once the patient is out of this emergency room, his care is taken over by somebody else and then out of the vision of the initial clinician. It think that's the biggest advantage so far.

Christina Lingham:
How does it impact the cost of care? In the long run, are you saving money by delivering more appropriate care or is it costing more?

Hubert Niesters:
It's always a big discussion about is it expensive or not. We have looked into that and it depends, of course, on which model you are choosing. At the end, you're saving money for the hospital as a whole business. Although these essays are more expensive than, for instance, in house essays, which you do batch-wise, at the end it's about logistics.

We decided to introduce a new concept, which we call the YouHour, the same as calculating a kilowatt hour for electricity, in which you combine the use that the cost of the system and multiply this with the time. Is you have an expensive essay, which for instance would cost 200 Euros, but you have the results within one hour, the total cost is only 200 Euros. If you calculate batch-wise analysis, which might be for instance cheaper, say 50 Euros, but it takes your 24 hours to get the result to the clinician, then the result is even close to ... well it actually is 1200 Euros, so it's more expensive.

At the end, you save money. You save money because you can decide what to do with the patient, you don't have to transfer the patient to a different hospital if you don't have enough isolation beds. You save money because if you calculate the cost of the physician, or nurse, who has to take care of the patient getting him or her to another hospital, which is also very expensive. You avoid also nosocomial infections because we know during the respiratory season or in general, about 12-15% of hospital acquired infections are due to the fact that you have patients in house which have an underdiagnosed infection. If you only focus, for instance, on influenza or RSV and you know that in university hospital where they have to take care of really critically ill patients, all these other viruses can really kill you.

A lung transplant patient can die from para-influenza virus or lose a lot of breathing capacity because you're getting screened for the right targets. You have to take all these components into account. It turned out that it is for the hospital, cheaper. We calculate for every Euro we invest, we save the hospital about three Euros. If you would have 100,000 Euros you need to invest during the respiratory season, you save a few hundred thousand Euros. Money-wise, it is also a very good activity.

Christina Lingham:
What are some of the limitations of the technology? What would you like to see improve?

Hubert Niesters:
That's not an easy question, there's always room for improvement. You want to know more about qualitation of virotargets and see my qualification, so we have an impression that virus present or not. We need to have more information about the primers and probes or the essay, which are often protected by the companies, because we need to be sure that the essays we are using do recognize the viruses that are circulating.

Every laboratory in Europe as well as in United States is more critical to comply with regulations, whether it's FDA or with ISO guidelines and you need to have this information. I have to admit, it's sometimes really a challenge to get the information from companies.

Christina Lingham:
What are you hoping to improve in your own system and what are you working towards?

Hubert Niesters:
At this moment we have improved our IT system, so we have something what we called improved the flow in our hospital, flow-withholding in or we call it Flow G. That improved in such a way that clinician or the nurse at emergency room gets already in the patient registration system, the time point when they have the results so they know is there a delay or not. They don't have to call us all the time. Is the sample already there? When can we get the results?

They can see this all online and they know if they have taken the sample, send it to the laboratory. It just take two minutes to get it into laboratory. They already get the information when they will have the results. That's really unique.

Everything is paperless, everything is done electronically and all the automation, confirmation, validation, interpretation is linked into our flow system. Also, a good improvement is the connection with infection control because infection control is, of course, always important in the hospital and it's all the Netherlands has low incidence of nosocomial infections and we want to keep it like that.

Linked to our results, automatically, all the information about infection control, the infection control technicians and nurses are also informed when the patient is admitted into the hospital with a respiratory infection, for instance.

Christina Lingham:
What are you looking forward to and hoping to learn in April at the Molecular Diagnostics Event?

Hubert Niesters:
At the end, I would like to have more information about the technological advances also outside of the emergency room. Is it possible in the near future? Is there hope in the next two to five years to be able to get proper results, actually done in clinical chemistry. Random access molecular diagnostics in infectious diseases, rapid turnaround time, easier IT systems, because that's actually something we really need.

Everybody's talking about the possibilities of molecular diagnostics, but we also have to admit that is not always linked to easy to use IT system. Every company has it's own system and it would be great if we would have more connectivity which is universal.

Christina Lingham:
Bert, thank you for your time and insights today. That was Hubert Niesters, director of the Laboratory of Clinical Virology at the University Medical Center in Groningen. He'll be speaking at the Point of Care Diagnostics Track at the upcoming Molecular Diagnostics Europe Event this April in Lisbon. If you'd like to hear him in person, go to www.modeculardxeurope.com for registration information and enter the key code 'podcast'. I'm Christina Lingham, thank you for listening.

Tom Cahoon:
Welcome to this podcast from Cambridge Innovation Institute about the upcoming Molecular Diagnostics Europe event running from April 10th through the 13th, 2017 in Lisbon, Portugal. I'm Tom Cahoon, market research analyst and administrative assistant. I'm pleased to have the opportunity to speak with Kfir Oved, co-founder and CTO of MeMed to speak with us about his upcoming talk A Set of Solutions for Antibiotics Misuse Using Host Response Based Diagnostics. He will be giving a talk at the Advanced Diagnostics for Infectious Disease track running from April 11th through 12th at the Molecular Diagnostic events. Kfir, thank you for joining us.

Kfir Oved:
I'm privileged. Thank you for inviting me.

Tom Cahoon:
Can you outline what you consider to be some of the greatest obstacles to controlling antibiotic misuse?

Kfir Oved:
What I can try to describe is basically what we have identified as the biggest hurdles in antibiotics misuse. There are three pillars for this problem. The first one is the issue of time. There are a lot of available solutions out there today, but many of them still takes hours and even days, including, for example, cultures, but also, the PCRs and the multiplex PCRs still take some time for the vast majority of settings. The problem is an acute infectious disease is a disease that usually is a very acute setting type of disease and decisions are being made within minutes, so there is one gap over there.

The second one is the issue of pathogen inaccessibility. I think it's pretty known to everyone that if you have a sore throat, you can just go to the CVS and buy a rapid strep test, test yourself and get the result within five to ten minutes, but that's only possible because the pathogen is accessible. Cases like, for example, pneumonia, sinusitis, otitis media, fever without source and other types of infections do not enable us to effectively sample the pathogen and therefor about one third to one fourth of the patients actually can not be served by the currently available solutions at all and are a major source, especially otitis media, for antibiotics they overuse.

The third element, which is also something that is extensively explored in the last decade is the issue of colonization and natural flora. The more sensitive the tools we develop, the more false positive and false negative results we get. Just as an example, the mere fact that you have identified streptococcus pneumonia in the nasal pharynx of a child with fever does not necessarily mean this is the disease causing agent. Those false positives are also a major source for both confusion, overuse and underuse of antibiotics in the acute infected patient.

Tom Cahoon:
Can you describe your product?

Kfir Oved:
Sure. I think that's a natural continuation to the previous question. Eight years ago when we went out to try to find a solution, a rapid solution that would enable physicians to make better antibiotics decision making, we envisioned those three problems as time, a pathogen inaccessibility and sensitivity to the natural flora. We decided to go on a slightly different route than others and try to gather the forces of our immune system, an amazingly effective protection system that is built within each and every one of us. What we actually do is listen to the immune response of a patient and by doing that, measure its immune response, integrate using that algorithms and translate that into actual diagnostics.

We went through a process of screening over 600 different proteins is a quantitative measure. This is arguably the largest quantitative host response prodromic study every to be conducted in infectious diseases. We were able to identify the set of three soluble proteins that we can quantitatively measure in a standard blood sample using standard immuno assay. It takes us around 10 to 15 minutes to do this measurement. We integrate them using a proprietary algorithm and gets a score ranging from zero to 100. The lower third of this scale, zero to 35 indicates a viral infection. 35 to 65 is an indeterminate area. 65 to 100 is a bacterial infection. Now we were able to show that using this scale we can basically classify viral and bacterial infections from multiple sources, children and adults, respiratory tract infections, fever without source and many, many other types of infection with sensitivity and specificity of over 90% as was validated in multiple clinical studies.

Tom Cahoon:
What is unique about your approach?

Kfir Oved:
There is no silver bullet for this problem. This approach can assist a lot to physicians in their current decision making. I do not think that there is a single answer to this problem and this is definitely going to be a, we see if as a kind of triage test that can be performed to the vast majority of acute infectious patients. They make better antibiotics decision making. It will need to be integrated together with other potential tests, especially in the more critically ill and severely ill type of patients.

Tom Cahoon:
What advice do you have for people introducing new products in the clinical setting?

Kfir Oved:
To be really honest, to develop a tool for clinical setting or for clinical practice was, and still is, a humbling experience but if I need to narrow that down into two major points, that would be clinical utility and health economics. If someone wants to introduce a new technology or a new product to the clinic, it needs to show A, accuracy. That's a prerequisite. Accuracy is not good enough. Today you also need to show that you can change the physician's behavior. You can really impact the physician in the decision making process and you can basically show that you improve the patient management. That would be one [anvil 00:05:24] and the way over there is just creating a lot of data. High quality, massive amount of clinical validation, both using clinical studies, randomized control trials and others that would be one pillar for this answer.

The second point would be health economics. We are living today in a budget constrained environment in the healthcare system and there are a lot of cool technologies out there. One of the biggest challenges for a new technology is basically to show that you can not only improve the management of the patient but also not increase the cost of treating this patient. Especially in the acute infectious disease arena where the number of patients are hundreds of millions and sometimes billions, it really depends on how you count, annually, worldwide. The potential impact of high cost diagnostics, for example, can be tremendously high on the system. There is a challenge on how to balance between the value you can bring from a health economics perspective and how much you can bill for such a technology.

Tom Cahoon:
What are some of the most exciting new developments emerging for AMR?

Kfir Oved:
Maybe I'm a bit subjective here, but I would say that one of the most thrilling things that happens these days in AMR is actually using the host response. I think that the host response, there is huge potential for us as humanity, not only to solve the issue of antibiotics misuse but also other clinical problems. I think that over there, we are at the end of the first decade of host response based diagnostics and host response tools and the future looks really, really bright for this topic.

Other advancements that have been shown the last few years were to use [inaudible 00:07:03] genomics and sequencing for exploring antibiotics resistance for being able to identify a potential targets and for being able to basically dissect or identify the flow of antibiotics resistance worldwide.

Tom Cahoon:
What are you hoping to learn at this conference?

Kfir Oved:
I'm really hoping to come and to listen to smart people coming with A, new ideas and new technologies, new perspectives. To be able to have some dialog with some of those different views. Also, maybe to join an integrative approach where more than one attitude can be joined together to a policy or into a strategy that can assist us fighting antibiotics resistance, which is basically one of the biggest healthcare challenges of our days and maybe one of those problems that we really, really need to solve to leave our children a better place to live in.

Tom Cahoon:
Kfir, thank you for your time and insights today.

Kfir Oved:
It was my pleasure. Thank you very much for the opportunity.

Tom Cahoon:
That was Kfir Oved, PhD. Co-founder and CTO at MeMed. He'll be speaking in the Advanced Diagnostics for Infectious Disease Track at the upcoming Molecular Diagnostics Europe event, running from April 10th through the 13th in Lisbon, Portugal. If you'd like to hear him in person, go to www.moleculardxeurope.com for registration information and enter the key code podcast.

I'm Tom Cahoon. Thank you for listening.