clinician s forum Expert Views from a Roundtable on Canine Respiratory Disease

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1 Sponsored by an educational grant from Boehringer Ingelheim Vetmedica, Inc. clinician s forum Expert Views from a Roundtable on Canine Respiratory Disease Canine Infectious Respiratory Disease Complex Pathogens, Risk, & Prevention Canine infectious respiratory disease complex (CIRDC), more commonly referred to as kennel cough, continues to challenge privatepractice and shelterbased clinicians. Even with increased awareness of the multiple pathogens potentially involved, complex environmental factors present obstacles to care. In this roundtable, a panel of experts discusses their experiences in managing this challenging condition. Dr. Morris: Let s direct the first question to the practitioners in the group. Why is the term CIRDC replacing kennel cough and infectious tracheobronchitis? Dr. Neuhoff: Well, it s a much more complex disease than kennel cough or tracheobronchitis, with multiple etiologic agents. Clients are used to thinking of kennel cough as a minor nuisance disease, and they feel their pets couldn t possibly be at risk if they haven t stayed in a kennel. In reality, this disease is far more complicated. By using the term canine infectious respiratory disease complex, we can discuss it in a way that makes clients understand the importance of treating and preventing it. Dr. Ruch-Gallie: People think of Bordetella bronchiseptica as kennel cough, even though that was never really intended. I think this term allows us to reflect the complexity of those upper and lower airway diseases. THE PATHOGENS Dr. Morris: What are the pathogens actually causing this condition? Dr. Neuhoff: The organisms that are commonly found include Bordetella, Streptococcus zooepidemicus, Mycoplasma, parainfluenza, PARTICIPANTS Kate Hurley, DVM, MPVM Director of Shelter Medicine, University of California Davis Davis, California Richard Meadows, DVM, DABVP Director of Community Practice, University of Missouri Columbia, Missouri Kathleen Neuhoff, DVM, DABVP Co-Director of Magrane Pet Medical Center Mishawaka, Indiana James Roth, DVM, PhD, DACVM Professor of Veterinary Microbiology and Preventive Medicine, Iowa State University Ames, Iowa Rebecca Ruch-Gallie, DVM, MS Service Chief of Community Practice, Colorado State University Fort Collins, Colorado Moderator LeMac Morris, DVM, MPH, DACVPM Veterinary Technical Manager Pet Business, Boehringer Ingelheim Vetmedica, Inc. Saint Joseph, Missouri adenovirus type 2, canine influenza, distemper, respiratory coronavirus, and pneumovirus. In our area, we haven t seen much parainfluenza or adenovirus or distemper, but that s because we ve been protected by vaccination for decades. Dr. Ruch-Gallie: We re actually seeing pneumovirus in Colorado, particularly in some of our regional shelters. We ve also seen canine influenza in both shelter and daycare facilities here. Bordetella is probably one of the more common pathogens, as well as Mycoplasma. And I would add canine herpesvirus. Dr. Meadows: I haven t personally seen these, clinician s forum 1

2 I think it s safe to say that Bordetella bronchiseptica is a primary pathogen. It s not the only cause, but it is a major driver. Dr. Meadows Clients are used to thinking of kennel cough as a minor nuisance disease By using the term canine infectious respiratory disease complex, we can discuss it in a way that makes clients understand the importance of treating and preventing it. Dr. Neuhoff but there are published reports of reovirus, bocavirus, and the canine homolog of hepatitis C. Dr. Hurley: In shelter dogs we see the whole array, including quite a bit of Bordetella. But in outbreaks, we see less of Bordetella because vaccination keeps that in check. We see respiratory coronavirus and Mycoplasma in very high frequency. At times, we see canine distemper at a subclinical level vaccination keeps it from expressing its full virulence, but the dogs are set up to be more vulnerable to different respiratory pathogens. Dr. Morris: Is there a universal pathogen that you see? And are the others secondary pathogens, or are they primary drivers as well? Dr. Meadows: I think it s safe to say that Bordetella bronchiseptica is a primary pathogen. It s not the only cause, but it is a major driver. At the University of Missouri, Dr. Leah Cohn noticed Bordetella can facilitate disease caused by secondary pathogens, such as Mycoplasma cynos, which wouldn t normally cause significant disease on their own. Dr. Hurley: In the shelter environment, we assume that Bordetella is an important driver. But the vaccine against Bordetella is used pretty consistently in most shelters, so we don t see big Bordetella outbreaks as much as we see outbreaks associated with the other pathogens for which there isn t a vaccine. Dr. Morris: So if Bordetella is the primary driver, why should veterinarians be aware of these other pathogens? Dr. Neuhoff: It clearly has some bearing on what we use for our preventative. In our area, influenza is not presently part of our routine vaccination protocol, although we are testing for it. If pets are infected with a viral pathogen for which they haven t been vaccinated, the chances of a rapid resolution are much less. The client needs to know from the beginning they re in for a long haul. We re not going to just put them on 10 days of antibiotics. Dr. Ruch-Gallie: It s also important to know what pathogens are present in our community. We ve said Indiana isn t seeing very much influenza, but we are seeing it here in Colorado. So, is there dog movement across state lines? What are they potentially bringing in? Knowing where those animals are coming from is going to be critical for us to be able to protect our population. RISK FACTORS: CLIENT OWNED & SHELTER DOGS Dr. Morris: Tell us some of the risk factors that really set up a population to be at risk for CIRDC. Risk Factors SHELTERS Lack of vaccination Moist environment Adverse flow of air into kennel Some in/some out kenneling Crowding GENERAL PRACTICE Lack of/inappropriate vaccination Contact with other dogs groomers daycare dog parks social encounters pet stores veterinary clinics 2 clinician s forum

3 Dr. Hurley: From an animal perspective, it s a lack of vaccination on intake, especially if there s distemper or canine influenza endemic in the community. From an environmental perspective, air quality is really important. When ventilation systems break down, we often see an increase in respiratory disease in dogs. Moisture is another risk factor. It s difficult to get kennels fully dried for at least a few hours every day, so we ve had people go in with towels and leaf blowers to really dry them out. A big risk factor that you see in some parts of the country is some in/some out kenneling of dogs, where there is no room to house each dog individually. Crowding is an underlying factor that can exacerbate air quality, moisture, and other problems. Thus, we often see outbreaks at times of high population density, whether in a shelter or boarding environment (eg, over a big holiday weekend). Dr. Morris: Give us some ideas of strategies you can use to help minimize these issues in a shelter population. Dr. Hurley: First, be sure that dogs are vaccinated immediately upon intake, or even before intake, as we see more shelters going toward the scheduled admission process for owner-surrender pets. From the environmental perspective, there are cost-effective things that can be done to direct the flow of air into the kennel where the dog is breathing. Make sure that kennels are dried out mechanically if necessary and make sure that kennels are in good repair. If shelters are stuck with that some in/some out housing situation, they should house by day of the week so that they can move all dogs out of a pen and completely empty them on at least a weekly basis. Dr. Morris: How do the risk factors compare in community practice? Dr. Neuhoff: In general practice, the runny nose that might be missed in a shelter is going to be a big deal to a client who has one puppy, so we see them more quickly. When they come in for their vaccine series, we can educate them on when they should call. The education of clients is really critical because we have lots of doggy daycares, lots of dog parks. The groomers don t require vaccinations for anything except rabies, so clients need to understand the importance of vaccines if they re taking their pet to a high-exposure area. Dr. Hurley: Ideally, shelters experiencing respiratory disease issues in their dogs would ask people to do a voluntary quarantine for a couple weeks after adoption where they don t have the dog around a lot of unvaccinated dogs, except maybe to go to the vet if they need to. I especially recommend people keep puppies out of pet stores, since that s often the first place people will go with a newly adopted, high-risk pet. Dr. Ruch-Gallie: With any dog-to-dog contact, especially if you aren t familiar with the other dog, there is going to potentially be a risk. In my area, all of our feed stores and big box stores allow dogs to come in on-leash. And in the large university setting where we re using communal waiting rooms, people don t think about isolating their puppies from the other dogs in there that may have something. MANAGING THE PATIENT Dr. Morris: Let s talk about how you work up a suspected case of CIRDC. Give us some idea of what kind of tests you re running. Dr. Neuhoff: I don t work up every dog that comes in coughing. If it s a young dog that was recently adopted and is acting normally, doesn t have a fever, and just has a sensitive trachea on palpation, we usually start doxycycline without a workup. But if they have any systemic clinical signs or if we hear congestion on lung auscultation, we start with radiographs of the chest and trachea. Or, if we start antibiotics and they aren t doing much better in 3 days, then those dogs also get chest and tracheal x-rays. If they have systemic disease, we ll also do a complete blood count to rule out any additional problems. If they aren t responding, we do an influenza test, a transtracheal wash, and our in-house cytology. We also send out for culture and sensitivity testing. Dr. Ruch-Gallie: I won t necessarily start antibiotics unless I see systemic signs or mucoid or purulent mucoid discharge. If there s just a little cough, I ll educate clients to keep them away from other dogs and give them some tincture of time. If the dog s cough is particularly bad, then we ll throw in something with With any dog-to-dog contact, especially if you aren t familiar with the other dog, there is going to potentially be a risk. I especially recommend people keep puppies out of pet stores, since that s often the first place people will go with a newly adopted high-risk pet. Dr. Hurley RISK Dr. Ruch-Gallie clinician s forum 3

4 For Bordetella, intranasal or oral vaccination is recommended in a shelter environment because of the rapid onset of protection and the potential for nonspecific local protection. Dr. Hurley Communication is a key issue, and most clients aren t aware they can put their animals at risk. Even when they re on a walk, they don t consider those cute nose-to-nose interactions with another dog as anything other than that, a cute interaction. There is a potential pathogen transfer meet-up. Dr. Meadows hydrocodone to quiet it for the evening so that everybody can get some sleep. But I m not going to work up every dog that comes in with those signs. It s going to depend on how sick they are or what I m hearing. Dr. Meadows: I may or may not start them on antibiotics, but being in a college town, we re more likely to work up a fair number of them just because that s what our clientele wants. Dr. Hurley: For a shelter that has just a few cases of respiratory disease a year, maybe they consider any case to be cause for concern. When a shelter has a background level of 30% respiratory disease, on the other hand, they might not be concerned until they hit 50% or 60%. When diagnostic tests are going to be done at a population level, we suggest they send out at least 5 to 10 samples from affected dogs for a respiratory panel. It s also a good idea to have the veterinarian observe the vaccination process and go check the ventilation system to make sure it s turned on and working as expected, and physically observe cleaning to make sure nothing has gone wrong to contribute to an outbreak. PREVENTIVE STRATEGIES Dr. Morris: Given the risk factors, let s talk about what tools we have that can aid in prevention. Can you tell us about your vaccine strategies? Prevention in Shelters All in/all out kenneling Scheduled animal intake Mechanical environmental drying Attention to positive air flow/ventilation Quarantine Vaccination on intake Dr. Hurley: On intake, we recommend a modified live subcutaneous vaccine for distemper. For Bordetella, intranasal or oral vaccination is recommended in a shelter environment because of the rapid onset of protection and the potential for nonspecific local protection. Dr. Meadows: We like to get them good broad-spectrum protection, but I am less worried about parainfluenza, so I use either a DA 2 +PL or a DA 2 P+PL modified live vaccine to get broad-spectrum coverage for the severe pathogens. Then we use the oral Bordetella vaccine to get a quick and durable immune response. This Bordetella bronchiseptica is a very quick pathogen in terms of immunologic response, so we need that protection up front now. Dr. Ruch-Gallie: That s pretty much the same protocol we use. I want to make sure we use combinations that cover all of the pathogens that we have vaccines for. VACCINATION STRATEGIES Dr. Morris: Dr. Roth, tell us about the types of vaccines against CIRDC and the roles they play. Dr. Roth: Well, CIRDC, especially in a kennel or shelter situation, is pretty reminiscent of the bovine and porcine respiratory disease complexes. The management factors we ve already discussed are probably the most important: poor sanitation, poor ventilation, not separating sick animals from well animals. That s a very challenging environment for vaccines to be effective, so my advice is to handle these factors first. Remember, all of our vaccines are tested for safety and efficacy in healthy animals under good conditions, and we can t expect the vaccines to overcome those sorts of continues on page 6 4 clinician s forum

5 Bordetella: Mucosal Immunity Bacteria Dr. Morris: If you could, go ahead and tell us about the advantages and disadvantages of each platform. siga Dr. Roth: Okay, let s start with the Bordetella because that s perceived as a primary pathogen for CIRDC, and there s a clear choice between the live oral versus killed vaccine. The live oral vaccine has been shown to colonize the respiratory tract, so it really is a respiratory vaccine even though it is given orally it s just easier to give. And we need to separate the initial vaccine, the primary immunization, from a booster. Dendritic cell MHC2 TCR TCR T H The live oral vaccine has been shown to colonize the respiratory tract, so it really is a respiratory vaccine even though it is given orally. Dr. Roth Let s talk about primary immunization of a naïve animal first. It s very clear that the respiratory or oral administration gives outstanding protection to challenge with Bordetella, and there are some good immunologic reasons for that. The immune mechanisms for protection from Bordetella are not very well defined through research, but we expect a live vaccine that s colonizing the respiratory tract to do a better job of inducing mucosal immunity. That would include mucosal IgA in the mucus, which helps to reduce colonization, neutralize toxins, and reduce bacterial load. But there s also the common mucosal lymphocyte system where lymphocytes induced at a mucosal surface tend to home back to that mucosal surface. They re induced in the lymphoid tissues, drain in lymphatics from the mucosal surface, and then recirculate back to the mucosal surface. These are the common mucosal T helper cells, T cytotoxic cells (especially for the viruses), and the gamma delta T cells. We really know very little about the exact role of those lymphocytes at the mucosal surface, other than that they re probably quite important and that immunization with a live pathogen has generally been shown to do a better job of inducing all of those. There s evidence that the oral or respiratory Bordetella does produce IgA in the respiratory tract. CD4 T H B B IgA secreting plasma cell IgA Naive CD4 T cell T H MHC2 Activated T helper cell Mesenteric LN T and B cells drain to mesenteric lymph nodes Thoracic Duct ROUTE OF ADMINISTRATION & AGE Effector and memory T and B cells home back to lamia propria Blood Circulation Dr. Morris: Is everyone using the oral Bordetella vaccine because of its mucosal immunity aspect? Dr. Neuhoff: We now use the oral mucosal vaccine. Before we used the intranasal. I m sure the protection was wonderful, but it was always a challenge to give. We now use the oral mucosal vaccine. Before we used the intranasal. I m sure the protection was wonderful, but it was always a challenge to give. Dr. Neuhoff Dr. Roth: Another consideration between live replicating vaccine and killed bacterium is that the live vaccine has a much broader array of antigens to present. Bacterial pathogens have in vivo gene expression, only turning on some of the virulence genes when they are in the host infecting their desired tissue of replication. But when Bordetella colonizes the upper respiratory tract, you get immune response to the toxins it produces. That s important for protection it s a more natural type of immunity. Challenge studies have shown protection after a single dose. B clinician s forum 5

6 I think the oral vaccine is probably nicer for everybody in the room, and the dogs seem to appreciate it as well. Dr. Ruch-Gallie Practical Considerations From a practitioner s standpoint, can you give me your reasons for using a mucosal vaccine? Dr. Neuhoff: In a clinical setting, it s not at all unusual to have a client who comes in desperate because they re going to be boarding their pet and just found out they have to be protected. Of course, the boarding kennel doesn t care if you gave it 2 months in advance or the day before, but at least they have a chance of having some protection. Dr. Roth: Full immunity is expected to be achieved after a single administration of a mucosal vaccine. conditions. It s also typically harder to get good solid immunity to bacterial respiratory infections than to most respiratory viruses. Of course, we have injectable, modified-live vaccines for the virals, and for some diseases, we have killed vaccines that are injectable. For Bordetella bronchiseptica, there are intranasal live and oral live vaccines and killed injectable vaccines. All of those stimulate different parts of the immune system more or less robustly. Dr. Morris: Can you use a mucosal vaccine in puppies? Dr. Roth: Earlier I was talking about primary immunization of a dog that has not been exposed before, so typically a puppy. There are fewer data addressing booster vaccination with the currently available live oral or intranasal versus killed vaccines. Killed vaccines with an adjuvant given by injection typically will do a pretty good job of boosting an IgG response. IgGs can be important, especially in the lower respiratory tract and somewhat up in the bronchi and trachea perhaps. Again, you won t have the wide array of antigens in a killed vaccine that a replicating live vaccine would be expected to induce. Dr. Morris: Does a mucosal vaccine maintain its effectiveness as the only vaccine? Dr. Roth: I would expect a modified-live intranasal or oral booster to work as well as a primary dose if the animal has reduced immunity that allows the live vaccine to colonize and replicate. I ve heard some concern that dogs receiving the booster have enough immunity to the Bordetella that it isn t able to colonize and stimulate a strong booster response. I don t know of any data on that, but if they have enough immunity to prevent the live booster from boosting, they probably have pretty good immunity already for a virulent exposure. My bias would again be to use the live intranasal or oral as the booster, but we could use more data to back that up. SAFETY: LIVE VACCINE Dr. Morris: If you re using a live vaccine, are you concerned about shedding? Dr. Meadows: I don t think there is any realistic concern about that. These are avirulent modified live-type organisms, and I m not aware of any evidence to suggest that they are a danger. Dr. Neuhoff: We had been using the intranasal vaccine clinically for many years before the oral was available. First of all, they do truly appear to be avirulent, because we ve seen far fewer reactions to that vaccine than to any of the others we ve used. And secondly, if shedding were to occur and the organism spread to another pet, it would, in fact, vaccinate that pet to some extent. So I can t see any negatives to it and potentially some positives. Dr. Hurley: In a shelter environment, we see the same thing. One study showed a pretty good overall reduction in CIRDC, even in dogs that had been vaccinated with a placebo, when some of the dogs in the population were vaccinated with an actual vaccine. Of course, it might have just controlled shedding and spread in the overall population, reducing disease levels. Dr. Roth: I d agree that the vaccine strain has been made avirulent, or at least very, very reduced virulence. The vaccine companies have to do a reversion to virulence study on every live vaccine, with back passage of the organism. Companies have to show the strain is 6 clinician s forum

7 stable and does not revert to virulence if it passes from dog to dog. I don t really see that as a problem. Dr. Neuhoff: We ve been using the mucosal for a long, long time and haven t had any difficulties with it. The oral mucosal vaccine is much easier to apply. The dogs actually like the oral. I was envisioning this struggle to get this bitter medication down, and they seem to handle it quite well. We re using the oral for all of our vaccinations except for some aggressive dogs. We do maintain a few doses of the subcutaneous vaccine for them. Dr. Meadows: Since I m in the teaching environment with inexperienced students, sometimes we muzzle the dog and put it in the mouth. Dr. Ruch-Gallie: Basket muzzles work well for us, so we can continue to do the oral that way. We don t carry any injectable here at all, but we keep some of the intranasal product available to use with dogs that have very painful mouths. The challenge of intranasal is many dogs sneeze after administration. I think the oral vaccine is probably nicer for everybody in the room, and the dogs seem to appreciate it as well. Dr. Meadows: I think a lot of dogs perceive that they are getting a treat. HUMAN SAFETY Dr. Morris: There has been some concern about zoonotic risk for CIRDC from shedding of the vaccinal organism from affected dogs, especially for Bordetella. Do you find that to be an issue? Dr. Meadows: There are very sparse case reports in highly immunocompromised people of zoonotic risk from Bordetella bronchiseptica, the field strain. From the vaccine strain, I m not aware of any reports of that, period. Anyone with a semblance of an immune system would not seem to be at much risk at all. Dr. Neuhoff: I suspect practically every employee in a veterinary hospital using intranasal has been vaccinated, and there are not tons of reports. In fact, I ve also looked and didn t find any reports of zoonosis. Dr. Hurley: When doing a Bordetella study, we had an incident with a lab worker who was culturing a wild-type bacteria and became infected. We were sure it was the same strain that was in the shelter dogs, but obviously that was potentially a pretty high dose exposure. Dr. Roth: You know there is shedding from the vaccinated dog, which would be pretty low titer, versus having the dog sneeze the vaccine back in your face, which is pretty high titer. Getting away from the intranasal to the oral should reduce those exposures. VACCINATION FREQUENCY Dr. Morris: Are there any other factors that we may have overlooked? Dr. Meadows: The only other issue for me is that if/when you re doing boosters every 3 years for the core antigens, the bacterial vaccines simply aren t going to last that long. In my mind, that s a very valid reason to get that animal in for an annual checkup. That s my opportunity to interact with the client and do a physical examination on that animal, to bring up my concerns, and to see what their concerns are in addition to giving those bacterial vaccine boosters. Dr. Neuhoff: We are certainly doing that annually as well even twice annually if it s what we consider highly exposed. We re using the vaccination guidelines for every 3 years as far as distemper, parvovirus, and rabies go. Dr. Ruch-Gallie: I haven t seen the data on parainfluenza, but part of our challenge is that some weren t using parainfluenza because it s no longer included as a core vaccine. The number of parainfluenza cases we see in our area is pretty minimal, as far as a pathogen in CIRDC. Dr. Meadows: The same is true in Missouri; we don t diagnose parainfluenza here very often at all. It s rarely isolated. Dr. Morris: Is that another reason that good Bordetella protection plays a role in minimizing these respiratory diseases? Dr. Meadows: I believe so, personally. Dr. Neuhoff: Bordetella is also not listed as a core vaccine, but it s certainly considered to be in our practice. With a mucosal vaccine, at least you re in the race. There are data that show that perhaps within 3 days you have good immunity, whereas the incubation period may be 6 days; so you ve got a better chance of winning that race. Dr. Meadows clinician s forum 7

8 Just 1 ml of Bronchi-Shield ORAL squirted into the buccal cavity provides protection. No more hassles of intranasal administration. 83% of veterinarians believe mucosal vaccination is the best route for respiratory disease in dogs. 1 Efficacy in dogs challenged with B. bronchiseptica after oral mucosal vaccination 2 : 93% AAHA Canine Vaccination Guidelines recommend mucosal CIRDC vaccines for high-risk dogs. The only way a significant IgA response can be triggered is to use live vaccines where vaccine organisms can temporarily invade mucous membranes. 3 Dr. Ian Tizard Mucosal vaccines protect from B. bronchiseptica with a single dose annual booster recommended. 4, Data on file, veterinarian survey, Boehringer Ingelheim Vetmedica, Inc., Evaluation of efficacy of oral administration of Bordetella bronchiseptica intranasal vaccine when used to protect puppies from tracheobronchitis due to B. bronchiseptica infection. Hess TJ, Parker DS, Hassall AJ, et al. Int J Appl Res Vet Med 9: , Veterinary Immunology 8th Ed. Tizard IR. St. Louis, 2009, pp Bronchishield ORAL Product Insert. 5. Bronchi-Shield III Product Insert. Copyright 2015 Educational Concepts LLC, dba Brief Media 8 clinician s forum CAN