Canine Vector-Borne Diseases

Canine Vector-Borne Diseases A Roundtable Discussion 1

Introduction A group of veterinary experts recently gathered during the 5th Annual Canine Vector- Borne Disease (CVBD) World Forum Symposium for this roundtable discussion. The purpose of the discussion was to provide practicing veterinarians with current relevant information on canine vectorborne diseases in North America and to offer advice on the identification and prevention of these diseases. Moderator Joe Hostetler, DVM Veterinary Technical Services Bayer Animal Health Shawnee, Kansas Edward Breitschwerdt, DVM, PhD, DACVIM Vector-Borne Disease Diagnostic Laboratory North Carolina State University Raleigh, North Carolina Leif Lorentzen, DVM, MBA IDEXX Laboratories Westbrook, Maine Thomas Mather, MS, PhD Tick Encounter Resource Center and Center for Vector-Borne Disease University of Rhode Island Kingston, Rhode Island 2

Prevalence of CVBDs DR. JOE HOSTETLER: The first question to address is, Are we seeing an increase or a spread in the geographic distribution of canine vector-borne diseases in the United States? Or are we just looking for these diseases in areas where we haven t historically looked? DR. THOMAS MATHER: I think we are seeing an increase. The good news is that we re seeing fewer dog tick-transmitted infections in much of the United States. That s largely because of successful use of preventive products in pets. However, the big difference we are seeing now is due to the tremendous increase in deer ticks, or black-legged ticks, in much of the Eastern United States, especially the mid-atlantic states, the upper Midwest, and New England. DR. EDWARD BREITSCHWERDT: Like most complex issues in life, the increase is multifactorial. There s clearly been an increase in the incidence of tick-borne diseases related to changes in our society. People often are now frowned upon if they hunt deer. In certain communities, deer are protected, allowed to reproduce unabated. Deer are a tremendous blood reservoir for ticks, so the tick populations have increased. Also, many more people have moved out of cities and into rural environments where their contact with ticks is much more frequent. Another factor is that we ve identified new tickborne diseases or disease-causing agents, and we ve come up with better diagnostic tests to help veterinarians confirm the presence of tick-borne diseases in their patients. DR. LEIF LORENTZEN: Testing is a big part of it. With the diagnostics practitioners have in their practices today, it s easier for them to determine what is in their practice population. We re very good now at monitoring what s in an area. Following the ebbs and flows of these diseases is more challenging. I think we will begin to see more research tracking the movement of these diseases with ticks. We published some information in Veterinary Parasitology in 2009 with Drs. Susan Little and Dwight Bowman showing that prevalence is very regional and state specific. 1 In the Northeast, you see more anaplasmosis and borreliosis. In some areas of the Northeast, we are seeing that as much as 3% to 4% of animals are serologically positive for Borrelia and Anaplasma species. Likewise in the Southeast, you can see animals that are serologically positive for Ehrlichia and Anaplasma species. DR. HOSTETLER: Are these diseases moving out of an area, or are they just moving into new areas? DR. MATHER: When I first came to Rhode Island in 1993, people were getting Lyme disease in the southern part of the state. We started surveillance across the entire state looking for deer ticks and didn t find them in almost half the state. That has changed now. If you look at our earliest years data, about 275,000 Rhode Islanders might have encountered a deer tick where they lived. By 2006, that number had increased to about 720,000 almost three-quarters of our state s population. Even in a place that s less than 40 miles north to south, we ve seen changes in the distribution of ticks. That s a big factor. Veterinary Perceptions of CVBDs DR. HOSTETLER: What changes have you seen in the way we view vector-borne diseases in the veterinary profession? DR. BREITSCHWERDT: Veterinarians have embraced canine vectorborne diseases in regard to gaining a better understanding of what is going on in their practice areas. I ve been amazed by the number of veterinarians who will attend meetings about canine vector-borne diseases. Also, there is the understanding that a dog can get a canine vectorborne organism transmitted to it in Florida and be seen by a veterinarian three years later in Oregon for disease caused by that organism. The other aspect of canine vector-borne diseases that s critically important is the increasing role of veterinarians in the public health infrastructure. That s so important because almost every one of these infections, whether it s Rocky Mountain spotted fever Lyme disease, anaplasmosis, or ehrlichiosis, can occur in both dogs and people. The vector is transmitting the organism that can make your dog sick or make you sick. Veterinarians provide an important public health service in helping their clients understand these diseases. DR. MATHER: Veterinarians are seeing these diseases on the front line and have a great opportunity to make an impact. DR. LORENTZEN: We ve made it very easy for veterinarians to accurately test for these diseases and understand whether an animal s been exposed or remains infected. 3

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We ve learned so much about these infections. A lot of them were once thought to be self-clearing, but that is often not the case. Many of these infections don t clear, and if you do not intervene with treatment, they re going to remain and may eventually rear their ugly heads. What should be impressed upon the profession is that the real solution is prevention. Diagnosing CVBDs DR. HOSTETLER: What is the best way for veterinary clinicians to approach diagnosis of canine vectorborne diseases? DR. LORENTZEN: We have very accurate, cost-effective ways to test animals for these diseases. Peptide technology allows us to produce cost-effective assays with high sensitivity and specificity for the pathogens. That gives practitioners a powerful tool in the clinic. In the United States, the standard of care is regular heartworm testing. It is now easy to add tests for other vectorborne diseases as well. Screening an animal on an annual basis for exposure to these infections can direct veterinarians to recommend further workup or preventive care. Furthermore, veterinarians can determine how common an organism is in their area and how vigilant they should be about recommending their patients be on a preventive. DR. BREITSCHWERDT: The other advance that has helped us in regard to canine vector-borne diseases is the use of molecular diagnostic tests. All the major veterinary diagnostic companies have introduced these tests in recent years, so they re available to veterinarians. They allow us to identify a DNA fingerprint to confirm that an animal has not only been exposed, but is actively infected. IDEXX Laboratories has done a nice job of trying to separate out the screening tests from confirmatory diagnostic tests and helping veterinarians to understand that if a screening test comes up positive, there are a few more steps to a definitive diagnosis. Doing a blood count to ensure that the dog s not anemic, thrombocytopenic, or hyperglobulinemic is one step along the way, and molecular diagnostic testing can be another important component for confirming infection. DR. LORENTZEN: Practitioners who are routinely looking for and thinking about vector-borne diseases know what s in their area, and CVBDs are higher on their list of differentials when animals come in with clinical signs consistent with those infections. In those situations, you really need the combination of the two tests because in the early stages of an infection PCR is very sensitive and obviously very specific for infection. But as that infection matures, a lot of these organisms especially the Rickettsia organism will move out of the circulation and the sensitivity of PCR will decline. That s when you start seeing seroconversion and the antibodies are detectable in the blood. DR. BREITSCHWERDT: When veterinarians use the testing that s available, they can make a diagnosis and treat the dog with an appropriate therapy, and the dog gets better. But with cases that don t respond completely, look for another canine vector-borne disease. For example, doxycycline has been the most widely used antibiotic for the treatment of infection with many of these organisms because it s highly effective. But doxycycline is not effective in clearing Babesia organisms. If the dog is co-infected with Ehrlichia and Babesia organisms it might get better on doxycycline. But once you stop the antibiotic, the dog relapses because the Babesia organism is still present. That s also true of co-infections with Bartonella species. I ve come to the conclusion over the last couple of years that you just cannot give a dog enough doxycycline to eliminate that infection. If we are unsuccessful in treating the infection, remember that co-infections are common. If the animal fails therapy, look for another organism or another disease. DR. MATHER: To make a difference, people need to be able to identify ticks. They need to be able to tell the difference between dog ticks and deer ticks and lone star ticks because each transmits different pathogens. The very first thing to know is that all ticks come in small, medium, and large sizes, so you need to look more closely. Picking up a few basic skills can be really helpful in not only a diagnosis, but in focusing on prevention as well. DR. BREITSCHWERDT: One way to do that is to have a techncian in the practice trained in tick identification. Several companies, including Bayer, have produced tools for tick identification that can be kept in the clinic. If a tick is brought in that can t be identified, send it to an entomologist. I don t expect veterinarians to become tick experts because they don t treat ticks. But on the other hand, being able to identify ticks is important to their patients. Ticks and CVBDs DR. HOSTETLER: Ticks are vectors for many of the most common canine vector-borne diseases. What are the most important consider- 5

ations for veterinarians in clinical practice with regard to ticks? DR. BREITSCHWERDT: In some instances, a single tick can transmit more than one organism to a dog, resulting in two diseases, or co-infection. More commonly, we see dogs that have three or four different tick species on them at one time, or at different times, which can result in chronic infections with multiple organisms. That s where it becomes difficult for the veterinarian in practice. Ten or 15 years ago, we had one pathogen, one disease. Frequently, when an animal presents with clinical signs of a tick-borne disease it s because the dog already had infection with one or two organisms that it was fighting immunologically. The third organism comes along, and the dog can no longer deal with it. DR. LORENTZEN: In a recent study, animals were twice as likely to have clinical signs when they were exposed to both Anaplasma and Borrelia organisms. 2 The same was true in the paper presented here at the symposium looking at Anaplasma and Ehrlichia co-infections. 3 When you have two infectious agents on board, it s more complicating, more confounding. DR. BREITSCHWERDT: The study we published in the Journal of Clinical Microbiology several years ago is a good example. 4 We were able to demonstrate that 99% of dogs in a North Carolina kennel were infected with multiple pathogens. From an individual EDTA sample, we were able to identify six different organisms from four different genera. Dogs really are welladapted to not show overt clinical disease when they re infected with these organisms. But we were asked to come to this kennel because dogs were dying. Many dogs don t clear these organisms and can carry them around for months or years before the animals demonstrate clinical signs. They can be infected with one organism and do pretty well until they get another tick that transmits another organism. Fleas and CVBDs DR. BREITSCHWERDT: We know that fleas carry several Bartonella species, and Wolbachia species has been amplified and sequenced out of fleas and dog blood. Fleas carry Bartonella species known to cause endocarditis in dogs and also in people, as well as other problems. So flea biology relative to the role of fleas in transmitting infectious agents is clearly more important than once thought only a few years ago. DR. HOSTETLER: What is really going on out there related to Bartonella species infections in people and dogs? DR. BREITSCHWERDT: In North America, Bartonella species infection was discovered as a cause of disease in people because of the HIV epidemic. From that very early association it became more obvious that Bartonella species was the cause of cat-scratch disease. If you read the older literature, about 10% of all people with catscratch disease had osteomyelitis, thrombocytopenia, and pleural and pericardial effusions, which were considered atypical manifestations of the disease. Those atypical manifestations are not so atypical and are due to persistent intravascular or intralymphatic infections with Bartonella species. There are a large number of papers finding Bartonella organisms in transplant patients and describing granulomatous hepatitis, granulomatous splenitis, and granulomatous lymphadenitis in children. In our laboratory, we ve developed a new way of growing Bartonella species out of the blood of dogs and people. Both can maintain a persistent Bartonella bacteremia for months to years. In a manuscript that was just accepted by the Journal of Clinical Microbiology, we present data suggesting that a mother transmitted this organism to two of her children; one is still infected 10 years later, the other died nine days after birth. 5 DR. MATHER: Does the high incidence of immune suppression factor into that? DR. BREITSCHWERDT: Yes, it s an important factor of Bartonella infection that s been demonstrated both in veterinary and human medicine. The very first Bartonella organism isolated from a dog would have never occurred if it were not for the fact that the veterinarian was immunosuppressing the dog and treating it for lupus. We ve seen subsequent examples of veterinarians treating immunemediated thrombocytopenia, immune-mediated polyarthritis, or immune-mediated meningoencephalitis in which we were able to detect Bartonella species in blood samples by using PCR, but still couldn t grow it without completely changing our approach. Endocarditis is probably the best example. Immunosuppression likely raises the level of bacteremia and allows the organism to localize to the heart valve. Mosquitoes and CVBDs DR. LORENTZEN: Veterinarians think about heartworm. There is 6

great testing and great prevention available. Even though we ve got about one-third of dogs being tested and a little over half on heartworm preventives, heartworm disease is diagnosed in about a quarter of a million dogs each year. We re not vigilant enough as a profession. Dogs shouldn t be getting heartworm or tick-borne disease. DR. MATHER: Easy to use, wellpackaged diagnostics are one of the strongest decision support tools for a client. To encourage veterinarians and clients in this area, broad-spectrum diagnostics and preventives for canine vector-borne diseases are the way to go. Preventing CVBDs DR. HOSTETLER: What preventive measures would you recommend veterinarians take for themselves as well as for their patients? DR. MATHER: Anything you can apply to the dog topically is headed in the right direction. We are good proponents of products that have a quick knockdown for ticks. We know that pets are likely to be exposed to many more ticks than people are because they wander farther away from the center of the trail and ticks get into their fur. So it s really important to have products with quick knockdown properties so that ticks fall off and potentially die before they ve started to bite. That s potentially effective at protecting people from tick-borne diseases as well. Advice for veterinarians and their clients on diagnosing and preventing CVBDs Michael Lappin, DVM, PhD, DACVIM Department of Clinical Sciences College of Veterinary Medicine & Biomedical Sciences Colorado State University Fort Collins, Colorado In my opinion, the most important thing veterinarians should remember about canine vectorborne diseases is to include them on their list of differential diagnoses for the appropriate problems that might be induced by these agents. By missing the diagnosis in some of these diseases, the long-term manifestations can be much more severe and difficult to manage than the acute diseases. I think veterinarians often don t think about vector-borne diseases because of the ways we were taught. Veterinarians in their second and third decade of veterinary practice, like myself, were taught about certain agents that were the only ones recognized at the time. With the advent of better diagnostic tests, we now realize that agents that we didn t previously learn about are actually in our areas. My primary advice to pet owners is to see their veterinarians for yearly to twice-yearly health checks. At that time, veterinarians can give clients information on the appropriate control of vectors. The other important thing for clients to realize is that if their dogs exhibit signs of illness, the owners should see their veterinarians immediately so we can institute appropriate diagnostic tests and therapeutic procedures. On our community practice rotation at the Veterinary Teaching Hospital, we speak with all our clients about how important it is to control potential agents transmitted by fleas and ticks. At wellness examinations, we counsel clients about why flea and tick control products are crucial to their pets health as well as to the health of their families. DR. HOSTETLER: Would you say the same for fleas? DR. MATHER: Definitely. DR. BREITSCHWERDT: Probably even more important for fleas. We 7

have products that are so much better than what they were early in my career. DR. LORENTZEN: A lot of these infections are chronic, so it s important to prevent them in the first place. That s the best approach. Also, we don t have to choose whether to treat fleas or ticks. The products now available are both broad-spectrum and effective. Owners get a lot of value for the money and prevent infection from a number of the vectors that could be threatening their dogs. DR. MATHER: We re working on developing an anti-tick vaccine because ticks transmit multiple agents. To develop a vaccine against each agent is quite costly. We are aiming for a broad-spectrum approach against all of the agents that ticks transmit through both vaccine development and topical products. Conclusion DR. HOSTETLER: If you could give one piece of advice to veterinarians related to canine vector-borne diseases what would it be? DR. LORENTZEN: It s critical for veterinarians to know what s in their practice s dog population. There are some great diagnostic tools as well as great preventives on the market. I m a pet owner whose dog had a CVBD, and I m convinced that she probably led a shorter life because of it. Prevention is the way to go. Bayer deserves a tremendous amount of credit for envisioning a forum that has brought together this group. There s only a small group of researchers involved in the study of these diseases. This discussion has done a tremendous amount to facilitate exchange of information, and to take a more organized and systematic approach to future diagnosis, treatment, and prevention of canine vector-borne diseases across the world. For a company to invest money to gather a group of companion-animal researchers studying just one component of disease is a real tribute to the commitment and the vision that Bayer has to understanding and preventing these infections. DR. HOSTETLER: A substantial part of our profession still isn t looking for CVBDs on a regular basis. When consulting with veterinarians, I ve found that if I encourage them to start looking, they start finding. The geographic distribution of CVBDs is expanding. Just how fast and where they re going next we don t know. Clinical signs are variable, and increased screening and testing are often indicated. Currently, none of these are reportable diseases in the United States. We really have a surveillance challenge and the overall incidence and prevalence are yet to be determined. We need to encourage more veterinarians to look aggressively for CVBDs. REFERENCES 1. Bowman D, Little SE, Lorentzen L, et al. Prevalence and geographic distribution of Dirofilaria immitis, Borrelia burgdorferi, Ehrlichia canis, and Anaplasma phagocytophilum in dogs in the United States: results of a national clinic-based serologic survey. Vet Parasitol 2009;160(1-2):138-148. 2. Beall MJ, Chandrashekar R. Eberts MD, et al. Serological and molecular prevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, and Ehrlichia species in dogs from Minnesota. Vector Borne Zoonotic Dis. 2008 Aug;8(4):455-464. 3. Gaunt SD, Melisa JB, Stillman BA, et al. Experimental infection and co-infection of dogs with Anaplasma platys and Ehrlichia canis: hematologic, serologic and molecular findings, in Proceedings. 5th Int. CVBD Symposium 2010;134-145. 4. Kordick SK, Breitschwerdt EB, Hegarty BC, et al. Coinfection with multiple tickborne pathogens in a Walker Hound kennel in North Carolina. J Clin Microbiol 1999;37(8):2631-2638. 5. Breitschwerdt EB, Maggi RG, Farmer P, et al. Molecular evidence of perinatal transmission of Bartonella vinsonii subsp. berkhoffi and Bartonella henselae to a child. J Clin Microbiol 2010;48(6):2289-2293. 8 2010 Bayer HealthCare LLC, Animal Health Division, Shawnee Mission, Kansas 66201. Bayer and the Bayer cross are registered trademarks of Bayer. All rights reserved.