About Dr. Richard Harvey
Dr. Richard Harvey earned his degree from the University of Bristol School of Veterinary Science in 1978. Following his graduation, he gained experience working in both mixed and small animal practices. He furthered his education by attaining the UK Diploma and European Diploma in Veterinary Dermatology, and he successfully completed a PhD program while working in the field. Since then, he has dedicated his career exclusively to the care of small animals.
Dr. Harvey is a well-known European Specialist in Veterinary Dermatology with nearly 45 years of veterinary experience under his belt. He is currently working as head of Dermatology at Willows Referral Center in Solihull, England with his special interests being in-ear disease, bacterial skin disease, and allergy in the dog and cat.
Dr. Harvey now has 30 scientific papers in canine dermatology, including his latest 2 publications which were in collaboration with MiDOG, and co-authored textbooks on ear disease, as well as recently, a textbook on ear, nose and throat disease.
He is also a pioneer in European Veterinary Dermatology with many years of experience and much knowledge & advice to offer the veterinary community.
Needless to say, we were thrilled to have the opportunity to speak with Dr. Harvey about the benefits of Next-Gen Sequencing (NGS) as an infectious disease diagnostics tool in veterinary medicine and the future of animal diagnostics with modern technology.
Along with NGS, we also talked about his two recent publications in collaboration with MiDOG and advice veterinarians can take to solve tricky infectious disease cases.
So, without further ado, let’s explore Dr. Richard Harvey’s take on Next-Generation Sequencing.
Next-Generation Sequencing Technology as an Infectious Disease Diagnostic Tool in Veterinary Medicine
Based on your experience with using our technology, how does Next-Generation Sequencing compare to traditional culture or PCR testing methods in the field of dermatology?
“It gives you a whole lot more information very quickly.”
I think, as of yet, we’re a little unclear as to the clinical relevance of it on a day-to-day basis. For example, you can do in-house cytology and get an indication of the morphology. You can get a bacterial sensitivity on what are the cultural organisms within 7 to 10 days, and within that sort of time frame allowing for shipping from the UK, you get the MiDOG biome readout using the new generation sequencing that gives you on average 15 to 20 bacteria, most of which are not culturable and what we don’t yet know is where we’re going with those and what it actually means.
Basically, they’re part of the environment if you’re within the ear canal but whether it’s usable in many cases is another matter. So, for example, about 10% of ear cultures are negative on culture when they haven’t had antibiotic therapy. Now patiently something’s going on and that’s where this analysis is really useful.
For example, Tang pulled up something called Finegoldia major, which is a bacterium that they found in about 10 to 15% of dogs with ear disease, but in a very small number on dogs without ear disease. So, the question is, is Finegoldia a relevant organism that you’ve picked up?
I did ask one of our local labs if they could grow it for me so we could start doing some serious work on our ear swabs and they threw their hands up and said, “No way! We aren’t going to grow that. It’s too tricky. It’s not worth it.” So obviously in those situations, you’re the only man on the street.
Could you summarize the key findings and implications of your clinical studies with MiDOG which have resulted in two recently published papers?
A long time ago using cup scrubs in academic investigations, some people estimated that the number of bacteria per square centimeter on dog skin was in the order of 250. Now when you consider that in the human field, it’s about 1.5 * 10 to the five, there was obviously a big underestimate there, and then…
“… along came new-generation sequencing, and all of a sudden, we understood why there was such a big differential.”
Now, although there have been around 18 studies using new-generation technology on the biome of the dog, whether it’s a diseased dog, an affected ear, or a dog with A to B, they’ve all essentially said ‘These are the bugs that are here’, ‘These are somehow how they change from dog to dog’, but nobody has done any work on how many bugs per square centimeter. So, that was the gap in the literature I was aware of because it’s my top skin bacteriology if you will. It’s what I got my PhD in, and I realized that with a relatively simple technique, we could get a quantifiable result.
So, this is the first time that the dog biome has been analyzed and characterized on a per centimeter section of skin, and it’s about 1.5 * 10 to the four in the bacteriology and about 1.1 * 10 to the five with the fungi, so about the same order as the human skin, which is pretty similar because the skin on the ventral abdomen of the dog is very similar to human skin – there’s no hair, it’s clean, it’s pale, it’s not in the armpit, it’s not in the groin, and that’s what we’re going to do next time. We’re going to take a few more swabs because obviously if you just take it in the umbilical area, it complies with an ethical demand. You don’t clip the dogs, you don’t sedate them, you just do it, and within those constraints, it was a good place to start, and produced a nice result.
On a broader scale regarding your approach to diagnosing infectious diseases in animals, how has the adoption of NGS technology influenced that, and what benefits have you observed in your practice?
In my practice, I’ve submitted samples from a couple of ears, which gave us an indication of where we could go with treatment and that was quite successful. I’m in a very limited sphere, as I’m just focused on dermatology.
I don’t do exotics, where you’ve been doing some really interesting work, and that’s an area that’s completely different. Obviously being in a managed environment, an exotic animal is more prone to have exotic diseases where new 16 S analysis is going to be much more relevant.
“Dogs tend to live in our environment, which is a relatively clean, predictable environment so outlying diseases on the skin are going to be very uncommon. But the ear canal of course is a special environment and that’s where it may be quite useful.”
You could also think maybe the mouth or the anal sack as areas where the environment matters a lot more than on the open skin where you do get a bigger selection of bacteria as well with Gram-negatives, obviously as part of the normal flora.
As you know, the use of NGS technology allows for the simultaneous detection of multiple pathogens in a single sample. How would you say this capability has impacted your ability to diagnose complex cases and co-infections?
I think you would say that it’s not so much the number of putative pathogens you’re pulling up, it’s your predictor on their bacterial sensitivity that’s most important because at the end of the day if you’ve got a multi-bacterial infection you’ve got to pick an antibiotic that’s likely to have the best effect on the vast majority unless you want to mix and match.
In the UK you have to adhere to the cascade, I.E. use a licensed product for that condition in that animal first, if there isn’t one, then a licensed product for that condition in another animal, then a compounded product.
“So, it’s helpful because it tells you the spectrum of bacterium, but it also gives the bacteria that are predicted antibacterial sensitivity and that’s particularly useful.”
From your experience collaborating with MiDOG, what aspects of our infectious disease diagnostics service do you find particularly unique and valuable for the veterinary world?
“The comprehensive report and the rapidity of the turnaround.”
Would you mind sharing any specific patient cases or success stories from your studies that demonstrate the practical applications and positive outcomes of using our NGS-based diagnostics service?
Well, as I alluded to, I’ve had two cases of chronic unilateral ear disease. Now unilateral is much more difficult to deal with than bilateral because bilateral has usually got an underlying allergic course. You deal with the allergy or identify it; you’ve got a predictable sequence of events. In the unilateral ear, there can be all sorts of things. You might have had a grass seed years ago; it might have got a punctured tympanic membrane and you’ve got an otitis media. So, it’s much more difficult to manage, and in those situations. So, it’s much more difficult to manage, and in those situations, …
“… it’s helpful to have an NGS spectrum because it gives you a broader insight of what’s happening in that ear and what might be going wrong.”
Regarding your strong interest in bacterial skin disease and allergy management, how has our diagnostic service assisted you in addressing these specific areas of focus in your research and practice?
Looking at the relevance of the study we’ve done, you are now in a position to say, ‘I want to trial a new antimicrobial shampoo.’ How am I going to assess its effect?
Well, the answer is you get a quantified bacteriology. You know how many bacteria per square centimeter. You can have an assessment of what bacteria your product is affecting, how it’s affecting the density, and how it’s shifting the spectrum of bacteria on the skin. So, you get a better answer as to what your product might do.
You could also apply it to a systemic antibiotic, but more likely it’s going to be a topical or maybe an ear medication where again you can do a quantified bacteriology. You might have to think of a way of doing it, but you could certainly get a quantifiable result and then you could assess the response to a topical ear treatment. For example, we know that in about 10% of otitis cases that are treated, you’ve still got viable bacteria in there. So, what’s happening? What are you doing? Why are you not cleaning the environment completely?
“You’re affecting it, but you might not be eliminating it. And NGS technology can help you try and understand what’s happening in that situation.”
What role do you see NGS playing in the future of veterinary medicine and its potential impact on improving animal health globally?
“It’s got the potential to have a huge impact.”
If you can get into factory farming, where a small change in management can make a huge difference in productivity, …
“… then understanding what’s happening in the gut on the skin at the sort of NGS level, you can make really important decisions.”
But the other extreme is on a single animal, a bit of a pet or goldfish.
“You’ve got the potential to help those animals on an individual basis where you’ve got an unidentifiable infection that you can’t get your head around, you can’t identify.”
So, yes, on an individual level and a macro level, it has the potential to be very important.
As an expert in the field, what recommendations would you give to veterinarians who are considering utilizing NGS technology for infectious disease diagnostics in their practice?
Well, I think we’ve covered the two big examples, a discharging sinus, a chronic otitis, something that is normally somewhat refractory to first-line medicine where you would then want to know a little bit more about what’s going on inside that particular environment.
At MiDOG, we really value collaboration between industry and veterinary experts and believe it is crucial for advancing animal health on a larger scale. So, for you, especially after collaborating with MiDOG, I’m curious as to how you view our company’s commitment to partnering with professionals like yourself to enhance the quality of diagnostics available to veterinarians.
“Double A+, Triple Star!”
I can’t fault it, it’s been perfect! You’ve helped me with my projects and studies. We’re going to do another one. I know of all the other work you’ve done. Obviously, pure science comes at a cost. Though appliable science can be a justified expense and what we’re hoped to be doing is appliable science.
Now, looking ahead, are there any specific areas in veterinary dermatology where you believe Next-Generation Sequencing technology could bring significant advancements or breakthroughs?
Yes, I think we don’t yet understand dysbiosis. So, in dogs’ atopic dermatitis, several of the NGS studies have demonstrated a dysbiosis, but it’s one thing to recognize the dysbiosis. It’s another thing to understand what’s happening on the quantifiable level, what’s happening to the bacteria per square centimeter. That’s what you need to understand because the shift in balance is what’s occurring because of the disease.
So, any disease that has a dysbiosis – superficial skin infection, discharging sinuses, chronic otitis, anal succulitis, allergic skin disease, chronic conjunctivitis, chronic stomatitis in the mouth; Anything chronic with an -itis on the end.
Considering your extensive experience and expertise in veterinary dermatology, how do you envision the role of diagnostics evolving in the broader context of animal healthcare in the coming years?
I suppose one of the aims would be an immediate reading which you can’t get. In point of diagnosis testing, you do a skin scrape, you do a cytology. There’s nothing out there yet that can give you an answer in 24 hours, except some very early slide technique which will give you a genus reading but not a species reading, and it won’t give you an antibiogram. So that’s the immediate one we can see. The technology is changing.
If you look at human medicine, they’ve got point of diagnostic urinary tests that can give you in 12 hours, a bacteriology and a sensitivity. But obviously, cystitis in people is a whole lot more important than otitis in dogs in terms of human health and human expense and diagnostics.
Categories: Next-Gen DNA Sequencing Technology, Veterinarian Guides, Veterinary Best Practices
