AKC CHF Parent Club Meeting 2017

1. Genetic Predisposition to Infection by Dr. Urs Giger

Abstract: Dogs with antimicrobial resistant, unresponsive, or unusual infections are due to a primary hereditary immunodeficiency disorder. The microbial host defense can be weakened by secondary or acquired diseases (injury, endocrinopathy, cancer or co-infection) or primary inherited disorders that affect the barriers that keep infection out or functions of white blood cells.

Examples:

1. Ectodermal dysplasia an X chromosomal defect affecting the skin
2. Ehlers-Danlos Syndrome causing stretchy skin and joints due to a collagen defect
3. Mucinosis and Wrinkling in Shar Peis due to a defect in hyaluronic acid synthesis. These dogs also produce amyloid in organs such as the kidneys affecting their function. An assay is available.
4. Primary Ciliary Dyskinesis affects many breeds and is currently being studied at Penn. Affects the respiratory ability to clear infections and often associated with hydrocephalus, male infertility and reverse heart syndrome
5. Immunoglobulin defects of Beagles, German Shepherd and Corgi, a transient or permanent defect of immunoglobulin production necessary to protect the body
6. X-chromosomal Severe Combined Immunodefiency disorder where affected dogs are born without lymph nodes, thymus and have lymphopenia (low lymphocyte counts). Poor prognosis currently believed to be eliminated.
7. Pelger-Huel Anomaly in Aussies and other breeds where the neutrophil cell is not segmented; however, there is no clinical significance to the dog
8. Cyclic Hematopoiesis with color dilution AP3B1 ELANE mutation causing cycles of low wbc (white blood cell production) in collies predispose these dogs to secondary bacterial infections and amyloidosis, and most die less then one year of age.
9. Trapped Neutrophil Syndrome in Border Collies where the bone marrow produces them but cannot be released into the blood cells. Affected dogs die due to their inability to fight infection.
10. Neutrophil adhesion defect in Irish Terriers and Setters where dogs produce neutrophils but they are not able to adhere and fight infection.
11. Avian Tuberculosis usually cannot infect dogs but Miniature Schnauzers and Bassett Terriers having homozygous genetic defects die from the disease despite medical therapy. Unfortunately this condition is zoonotic (contagious to humans) so is of great importance. Currently 10% if US schnauzers are carriers and 15% in Argentina.

With all these diseases it leads us to ask: Is it infectious or is in genetic?

Recent efforts are attempting to consolidating global date on diseases and genetic tests see the following:

WSAVA (wsava.org)

Mendelian Inheritance in Animals (http://omia.angis.org.au)

If you are interested in current clinical trials see: AVMA health study database: search the database for active studies, and AKC CHF website will have a link on their website where open trials are posted

2. Diffuse Large B Cell Lymphoma (DLBCL) of Golden Retrievers Has a Unique DNA Methylation Signature that Yields Biomarkers of Disease by Dr Jeffrey Bryan

Abstract: DNA methylation changes are the earliest and most persistent epigenetic mechanism to control gene expression. DNA hypermethylation change can be reversed, often occur before genetic mutation, and can be more consistent and numerous then mutations in carcinogenesis. The aims of this study were to define the DNA methylation signature of DLBCL that distinguishes it from normal lymphocytes, to develop biomarkers of disease for diagnosis and risk prediction. DLBCL has distinct changes of the methylome from normal B lymphocytes. The methylome in DLBCL is a tumor landscape to be mined for novel early detection biomarkers, therapeutic drug targets, and additional understanding of carcinogenesis.

Methylation is the addition of CH3 on a gene which then can direct a cell what it is to become, since all cells in a body have the same DNA, each cell needs to be directed to its purpose. Removing methylation is done by enzymes after DNA replication.  Methylation generally decreases with age, can be affected by diet, toxins, stress, medication, and can be heritable. That means the expression of genes can be heritable. Epigenetics studies the changes in a body caused by the modification of gene expression, despite inheriting the same genetic code. Epigenetics affects the individual, its offspring, the gonads of the fetus and on. For example, this has been seen in humans DNA of smokers or survivors of the holocaust, where gene expression is present many generations later.

In addition, methylation can help treatment. For example in human lymphoma the DNA methylation changes as the disease progresses  which allow separating diseases that can be responsive to more specific chemotherapy. His project is to define the methylation sequences in DLBCL. DLBCL is one of the worst forms of lymphoma. The next part is to predict the risk of individual dogs, and to treat hyper or hypomethylation with drugs, expand the study to other breeds and preventative medication to dogs at risk. Currently there is a Puppy Up Trial were demethylation drugs are being used.

3. How Flow Cytometry Expands Our Understanding of Canine T Cell Lymphoma by Dr Anne Avery

Abstract: Canine lymphoproliferative diseases include a very broad array of disorders ranging from clinically aggressive (acute leukemia) to indolent diseases with long survival times that may not require treatment (T zone lymphoma). The World Health Organization human classification system has been applied to canine lymphoproliferative diseases, and studies have demonstrated the value of this system for determining prognosis, and more recently choosing treatment. A combination of histology/ immunohistochemistry and flow cytometry can be used to classify many types of lymphoma into WHO categories, and can provide accurate prognostic information to owners and clinicians. In addition, the development of a large database of different forms of lymphoma has allowed Dr Avery to identify striking breed-specific predilections which provide the basis for identifying risk factors.

It’s important to classify a patient with lymphoma classified into T or B cell, which can be done easily by a fine needle aspiration cytology flow cytometry at Colorado. The next is to further classify by histopathology (i.e. biopsy), which is well developed system in humans. Currently over 20,000 dogs with lymphoproliferative disease has been tested by lymph node aspirates. By determining what proteins are expressed, and what type of lymphoma, the veterinarian and owner are supplied with references on prognosis and treatment.  For example indolent T zone lymphoma seen in Golden Retrievers and several other breeds has a good prognosis even without any treatment. Dogs have no signs except enlarged lymph nodes (although 10% will get demodicosis).  This is compared to Peripheral T cell lymphoma which is much more aggressive, seen in Boxers and Aussies. Once the lymphoma is defined further genetic studies (GWASP) look for the affected gene and any other associated genes of diseases. They are currently looking for candidates to study dogs associated with a novel T cell Leukemia most common in young Bulldogs. It affects twice as many males, and has a grave prognosis.

4. Chemotherapy and Probiotics by Dr Korinn Saker

Abstract: Dogs receiving chemotherapy drugs as treatment for cancer can suffer from gastrointestinal discomfort, including severe diarrhea, lack of appetite, nausea and weight loss. The side effects may discourage the owner from continuing chemotherapy or, if they are severe enough, may require the anticancer drug protocol to be altered in a way that minimizes its effectiveness. Giving patients probiotics decreased the severity or frequency of gastrointestinal toxicity and inflammation, improved nutritional health, and improve the overall quality of life for dogs undergoing chemotherapy. The results were extremely positive suggesting a benefit from oral probiotic supplementation in dogs receiving doxorubicin.

Purina Fortiflora was used for this study. It is know that gut microbiota affects: GI, circulation, immune function, neuro-emotional and other systems.  Gut imbalances (stress, environmental or emotional), nutritional changes, infection, and disease, lead to GI inflammation. Chemotherapy affects fast growing cells (such as cancer, bone marrow, GI, and hair), thus GI side effects are not uncommon. Dr Saker looked how bacterial affect the GI. In humans, some studies have shown benefits and no ill effects of probiotic but the current conclusion is that more evidence is needed to determine benefits during chemotherapy. Probiotics have been studied in dogs and found to be of some value when use in acute diarrhea, but the science is very limited in veterinary medicine. Dr Saker’s study is double blind and crossover where patients received:  1. a single probiotic (Fortiflora), 2. a multispecies probiotic and 3. a placebo. Real time PCR studies over time showed no change in gut lactobacillus; however, dogs had better fecal scores and less diarrhea days receiving the probiotic.  Although additional studies need to be done, there appears to be benefit during doxorubicin.

5. Bring Genomic Data Back to the Clinic by Dr Matthew Breen with North Carolina’s Lineberger Comprehensive Cancer Center and Dr Moldiano’s Broad Institute.

Abstract: The application of genomics to canine biomedical research has resulted in significant advances as we strive to enhance the health and welfare of our companions. Over the past several years he has recruited tumor tissues and blood samples from thousands of dogs presenting with a variety of cancers, as well as their family members. During the same period they generated a series of sophisticated molecular reagents and resources that complete the genomic “toolbox”. Collectively these tools provided a robust means to interrogate tumor specimens for changes to the genome, which lead to identification of genomic regions and genes associated with cancer. He has demonstrated the presence of numerous genetic signatures associated with canine cancer subtypes and is using these to develop more sophisticated means of cancer diagnosis and prognosis. These studies thus provide a path back to the clinic and offer new tools to help canine cancer patients.

For example, he has identified that 85% of dogs with transitional cell carcinoma (TCC) have a specific mutation in their cancer cells. He has developed a highly sensitive test to detect the mutant bearing cells in a non-invasive free catch urine sample from a dog. The test is currently being used but is not commercially available (contact Dr Breen for more information).

In addition, he has begun to define genetic lesions that correlate with prognosis. For example, in working with canine lymphoma they have developed a genetic test that allows us to predict how long dogs diagnosed with lymphoma, at time of diagnosis, will respond to doxorubicin based chemotherapy. They have also developed a test that can differentiate histocytic malignancies from other round cell cancers. Histiocytic cancers are especially common in Burners and Flat Coat Retrievers; however, 70% get misdiagnosed as lymphoma instead of histiocytoma. Currently the test is 78% sensitive and 95% specific.  This test is being offered at Sentine Biomedical out of NC State with all profits going back to AKC CHF. Another test is being developed at Sentinel Biomedical to tell you which type of lymphoma and how it will respond to the standard CHOP or doxorubicin therapies.  Yet another test that can identify about 20% of dogs with osteosarcoma that have a high likelihood of survival beyond 18 months if treated with amputation and standard of care chemotherapy.

With so many dogs involved, he has initiated a nationwide study of canine cancers that involves gathering data about each dog’s history and exposures, and than geospatially mapping of the cancer cases. The data is being consolidated to identify possible environmental concerns that are affecting our dogs and possibly our own health.

Additionally, Dr Breen discussed  a new drug, Tinovia, which  appears to work on resistant lymphoma with a new technology that allows it to soak into diseased cells, with one potential serious side effect of lung fibrosis, especially in Westies.

6. The Effects of an Omega-3-Fatty Acid Rich Diet with Rehabilitation on Recovery, Activity, and Osteoarthritis in Dogs Following Tibial Plateau Leveling Osteotomy Surgery for Cranial Cruciate Ligament Disease by Dr Wendy Baltzer

Abstract: Can an omega-3-fatty acid rich diet improve recovery and activity of dogs after surgery for cranial cruciate ligament disease? Is rehabilitation of dogs following cruciate ligament surgery worth all the money and hassle? The answer is yes! In a double blinded (owners and veterinarians were blinded), placebo-controlled clinical trial, which followed the recovery of dogs after cruciate ligament surgery for 6 months, fed Purina Proplan Veterinary Diets JM Joint Mobility had reduced lameness, reduced inflammation on the operated joint, and reduced progression of arthritis comparted to dogs fed a commercial adult dog food (pedigree used) . Owners saw less lameness when the dogs were trotting, running, or making sharp terms in the dogs fed Purina JM diet. Rehabilitation also improved the dogs’ recovery and slowed the development of arthritis. Dogs that had rehabilitation exercise with both home and underwater treadmill treatments were more physically active, even 3 months after treatment, than dogs that did not have postoperative therapy. Providing a diet rich in omega-3-fatty acids and rehabilitation dogs after surgery for cruciate ligament rupture can have lasting beneficial effects helping dogs to return to a more active, healthy lifestyle.

This study was statistically significant (<<P.05) and rehabilitation started 8 weeks post TPLO. Dividing dogs into 4 group post TPLO for 6 months: regular food and no PT, regular food and PT, Proplan JM only, and Proplan JM and PT.  The average TPLO takes 6 months to recover to normal weight bearing (determined by force plate analysis). Non-steroidal anti-inflammatory drugs (NSAID) helped pain and inflammation, but did not inhibit arthritis comparted to omega-3-fatty acids decreased inflammation and arthritis. She tried NSAID and PT, and found this not better to PT alone.

The level of omega-3-fatty acids in ProPlan JM is 180 mg/kg/day of EPA and DHA. In comparison, this is 20 capsules or more (for a 50lb dog) of some of the most concentrated DHA and EPA supplements available on the market. In addition, Proplan JM contains high protein then maintenance diets which are believed to help muscle development during rehabilitation. Glucosamine and chondroitin supplements are not included in the diet and current research is finding that they may provide prevention for osteoarthritis in younger dog but not after its development. This study concentrated on the omega-3-fatty acids and post operative PT providing impressive results reduced healing time to 8 weeks, improved weight bearing, improved owner’s perception and slowed arthritis.

7. Canine Lyme Disease- Is the Clock Ticking

Abstract: Lyme disease is a poorly understood condition in dogs. The range of Borellia-infected ticks, responsible for transmitting Lyme disease, continues to expand in the US and Canada resulting in many infected dogs. Infected dogs rarely show signs of illness, however, Lyme disease can be severe (e.g.. kidney disease). This talk reviewed the current knowledge of canine Lyme disease risk and forecasted emergence and recommendations for prevention and control. Primary results from a large and on-going US and Canada study were presented.

The ixodes tick (also called black legged or deer tick) is the most common carrier of Lyme disease. It’s life cycle involves an egg which develops into larval stage (6 weeks feeds on rodents and birds), then nymph ( 8 weeks this is believed to be the cause of Lyme disease in people also feeds on other mammals) , then adult tick (current belief is that  this is the cause of Lyme in the dog and feeds on other mammals). Most dogs infected with Lyme show no signs, with 5% showing signs several months after infection. The signs may include lameness, arthritis, fever, decreased appetite with some resolving quickly with or without treatment. There are 1-2% infected dogs that develop an ultimately fatal form Lyme nephritis with some breed predilection in Labs and Goldens.

Tick control is the key. Humans should wear white and use 20-30% DEET, picaridin or permethrin treated clothing.  The current best control in dogs is using tick prevention and vaccination. The previous ACVIM (American College of Veterinary Internal Medicine) consensus statement is anything but a consensus on vaccination for Lyme. There have been many new potentially safer and more effective vaccines that a new statement is expected to be released, but there is no debate that effective tick control is critical.  Additionally, removing tick environments near the home by mowing the grass or using gravel or wood chips as a boundary around the yard. The current study continues to better define Lyme disease in dog and he is also studying the prevalence of Leptospirosis in North America.

It’s recommended to check your local area: CAPVet.org

8. Bartonellosis: The Dog that Changed the Course of My Research, Career, and Life by Dr Edward Breitschwerdt who received this year’s AKC CHF Award of excellence.

Abstract: Bartonella species are fastidious Gram-negative bacteria that are highly adapted to a mammalian reservoir host and within which the bacteria usually cause a long-lasting, intra-erythrocytic  (RBC) endotheliotropic blood stream infection. These facts are of particular importance to veterinarians, physicians, diagnosticians, public health officials, and pet owners as an increasing number of animals have been identified as reservoir host for zoonotic Bartonella species. Among examples, Bartonella henselae, Bartonella koehlerae, and Bartonella clarridgeae have co-evolved with cats. Bartonella vinsonii subsp, berkhoffii and Bartonella rochalimae have co-evolved with dogs and wild canines, and Bartonella bovis has co-evolved with cattle. Importantly, the list of reservoir –adapted Bartonella species, including a large number of recently identified bats and rodent species, continues to expand exponentially as new Bartonella spp. and their reservoir hosts are discovered throughout the world.

Bartonella is a zoonotic infectious disease of worldwide distribution, caused by an expanding number or recently discovered Bartonella species. Of comparative medical importance, Bartonella are transmitted by several arthropod or insect vectors, including fleas, kits, lice, sand flies, ticks and potentially mites and spiders. Prior to 1990, there was only one named Bartonella species (B. bacilliformis), where there are now over 36 species of which 17 have been associated with an expanding spectrum of disease in dog and human patients. Recent advances in diagnostic techniques have facilitated documentation of chronic bloodstream infections with Bartonella spp. in healthy and sick animals, and in immunocompetent and immunocompromised human patients with cardiovascular, neurologic, and rheumatologic symptoms.

In 1993, I examined a 3 year-old Lab that had experienced a chronic, insidious and progressive illness during the proceeding 9 months. Dr Kordick, then a PhD student in my research lab, successfully isolated a Bartonella species from this dog, representing the first time this genus of bacteria was isolated from a dog anywhere in the world. Subsequently, in collaboration with bacteriologist at the CDC, the newly isolated bacteria was defined as microbiologically unique and named Bartonella vinsonii subsp. Berkhoffii. The young Lab served as the foundation for a large research program that has generated an important and controversial body of medical evidence related to canine and human bartonellosis. Not only are dogs our best friends, but naturally-infected dogs continue to provide important comparative medical insights that have enhanced our understanding of human bartonellosis.

In recent years, physicians, veterinarians, and other scientist have called for a ONE HEALTH approach to this emerging zoonotic infectious disease. Comparative medical research is needed to more fully define disease manifestations, to clarify the pathogenesis of disease induced by this stealth pathogen, to validate effective treatment regimens, and to develop vaccines and other strategies to prevent zoonotic disease transmission from animals to humans. With additional research, it is likely that the genus Bartonella and the disease bartonellosis will represent major microbiological and clinical paradigm changers in the future.

Bartonella has been challenging to find and define, killing and infecting humans since 1885, a medical student in Peru, then World War II infecting solders through lice, killing more soldiers then gunshots, and again in the 1900’s causing cat scratch fever in humans. In 1990’s with AID’s epidemic causing Peliosis hepatitis and Bacillary Angiomatosis .  Effective treatments are currently being studied but currently include doxycycline, amoxicillin, enrofloxin and rifampin for 4-6 weeks.

Current canine research is looking at Bartonella and association with hemangiosarcoma, hopefully soon to be studied. According to the WHO (World Health Organization), human cancers caused by infections (viruses, bacteria, etc.) are likely to grow as we learn more about these agents.

9. Characterization of the Hematologic Response to Ehrlichia canis Infection by Dr Anne Avery.

Abstract: Ehrlichia canis is a rickettsia that infects canine monocytes (type of white blood cells) and causes a variety of unique clinical and hematologic signs, including monoclonal gammopathy and clonal expansion of CD8 T cells. E. canis infection can be confused in dogs with a clinical suspicion of T cell leukemia, because common diagnostic methods (flow cytometry and clonality) may not be able to distinguish between these entities. The goals of this study conducted at Ross University in St, Kitts where E. canis is endemic, were to better define the nature of the hematologic response to naturally acquired E. canis infection. This data allows us to diagnose T cell leukemia in clinical situation where patients also have evidence of E. canis exposure.

E canis causes a pancytopenia (low blood cells) but some have an increase in lymphocytes which appear large.  Most dogs did not have severe disease, but there appears to be a roll of genetics, co-infection or strain. For example German Shepherds appear to have a clinically severe disease. E. canis infection needs to be differentiated from the similar clinical appearance of leukemia or lymphoma. She found expanded CD8 T cells and defined the clonality on T cell assays to help differentiate elevated lymphocytes due to E canis infection compared to lymphoma or leukemia.

10. Canine Cognition: A Neuropsychological Approach by Dr Bill Milgram

Abstract: Cognition in dogs, as in humans, refers to the mental experiences (thoughts) and cognitive level refers to mental capabilities. Both depend on processes that are not directly observable but are inferred from behavior. His research has focused on characterizing cognition, understanding how cognition develops early in life, how it changes with advanced age and whether it can be modified with the use of drugs, nutritional supplements, or behavior interventions. Our focus on the importance of the development of interventions differentiates our approach from a purely academic approach that seeks to understand comparative similarities and differences between canine and human cognition. They view cognition through a neuropsychological perspective, which assumes that cognition consists of a limited set of district cognitive domains, with each associated with distinct underlying neural structure. To this end, they have developed a battery of neuropsychological test protocols that target each of these domains and they have used these tests to study the effects of age and the various interventions on cognitive abilities. Their research has demonstrated that canine cognitive abilities decline in a domain specific manner. For example, episodic memory, which relates to the ability to learn complex tasks declines relatively in life, while working memory, which refers to sort term recall and use of information remains relatively intact until later in age.

There are also notable individual differences in the effect of age on cognitive decline. Some dogs show surprisingly little change. Others develop cognitive dysfunction syndrome (CDS), which becomes apparent because of obvious changes in the dog’s everyday behaviors. Although behavior changes associated with CDS are at least partially distinct from neuropsychological cognitive changes, they have been able to show that interventions to provide neuropsychological improvement can also reduce or stabilize behavior changes associated with CDS. This suggests a possible common underlying structure between CDS and our neuropsychological measures of cognition.

They found to improve cognitive function with age it helps to previously train to do the cognitive function.   In a study he created 4 diet groups: 1. Antioxidants alone (which did little by itself), 2. Control, 3. Behavior enrichment (which showed some improvement) and 4.  Behavior enrichment and antioxidant diet which did the best in discrimination learning and reversal task.  Another study used medium chain triglycerides (MCT), which showed significant improvement in visual acuity and reversal learning in laboratory Beagles. This study was then done in pet animals with CDS and tested in 30 and 90 days after supplementing. They improved in all categories of CDS: social, disorientation, anxiety, sleep, house training and activity. There were 3 groups in this study: 1. Control, 2. 6.5% MCT and 3. 9% MCT. Both groups with MCT improved; however, there were palatability problems at the 9% level.

11. Searching for Genetic Risk Factors for Canine Epilepsy in Whole Genome Sequences by Dr. Gary Johnson

Abstract: Epilepsy is a neurologic disorder characterized by recurrent seizures. He presented background information about epilepsy in the dog, describe various subtypes of canine epilepsy and how they related to other episodic canine diseases, and summarize our current understanding of the disease mechanisms that underlie seizures. Also, he is working to provided conclusions about the effect of gender and age on the risk of developing epilepsy, based on information about the > 2000 epileptic dogs that provided samples for their DNA repository. In addition, he summarized the past efforts to identify mutation.

Idiopathic epilepsy is suspected to have a genetic predisposition; however, in the past most GWASP have failed in locating. They have found the genetic defect in some neurologic diseases such as Border Terrier’s leukoid encephalopathy, Ridgebacks that start with twitching, and syndromic epilepsy, a neonatal epilepsy in Standard Poodle but there had been so much pleomorphism in epileptic dog’s GWASP.  This failed to provide identification. Currently using whole genome sequencing which makes it feasible to look at every gene. This has been used to find Falconi Syndrome in Basenjis. They are currently looking at 400 priority genes (found in epileptic humans), then compare it to the mass array of 2000 epileptic dogs and 4000 controls.  There’s a lot of work to be done.

12. Exploring the Role of the Gut Microbiome in Epilepsy by Dr Karen Munana

Abstract: Epilepsy is the most common nervous system disorder of dogs affecting 0.75% of the canine population (1% of the human population). Approximately 1/3 of dogs with epilepsy fail to achieve adequate seizure control with anti-seizure medication, and are considered to have drug resistant epilepsy. These dogs are known to have increased disease complications and shorter lifespan associated with poor seizure control, and account for much of the financial burden of epilepsy management.

Drug resistance in epilepsy is thought to involve both genetic and environmental factors, but the mechanisms that lead to drug resistance are poorly understood.

Within the past several years, there has been extensive research on the relationship between the gastrointestinal tract (GI) and nervous system. The term “microbiota-gut-brain axis” is used to describe the complex bidirectional signaling that occurs between the GI tract and the nervous system, and emphasizes the newly recognized role of intestinal microbes in these interactions. This system is considered vital for maintaining health, and can influence an individual’s susceptibility to disease.  For example, alterations in the population of intestinal bacteria of the Lactobacillus group are thought to play a role in the development and progression of several neurological disorders, including anxiety/depression, autism, multiple sclerosis and Alzheimer’s disease. Lactobacillus bacteria are capable of producing gamma-aminobutyric acid (GABA), one of the main chemical used to transmit signals in the brain, and an increase in GABA levels in the GI tract is associated with increased levels in the brain. Oral administration of Lactobacillus microbes has been demonstrated to have beneficial therapeutic effect in experimental models of neurological disease, as well as in recent clinical trials on depression and anxiety disorders in humans.

An unexplained link between disorders and the GI tract and epilepsy has been recognized for some time. Humans with gluten sensitivity can have numerous neurological symptoms including seizures, and some children with celiac disease are at increased risk for developing epilepsy. Furthermore, a recent large scale study demonstrated that adults with newly diagnosed IBD have a greater risk of developing epilepsy compared to a similar group without GI disease. This recognized association between disease of the GI tract and epilepsy let her to hypothesize that alterations in the intestinal microbes might influence the development and progression of epilepsy similar to what has been described for other neurologic disorders. They are currently undertaking a study that aims to explore differences in intestinal bacterial populations among epileptic dogs and healthy housemates, and evaluate how antiepileptic drugs affect the growth rates of intestinal bacteria. The study will provide preliminary information on the relationship between GI microbes and epilepsy. Research in this area has the potential to further our understanding of epilepsy and drug resistance in dogs, and ultimately leads to more successful management of the disorder. She is currently recruiting 15 pairs of dogs that live together: one normal and one with epilepsy.

13. Epilepsy and Nutrition by Dr. Rowena Packer in place of Dr. Holger Volk

Abstract: Every practitioner and breeder has had the experience dealing with a dog with epilepsy. Most veterinary practitioners also have had the experience that despite an ever-increasing number of available antiepileptic drugs, the majority of dogs will continue to seizure and suffer from quality-of-life limiting side-effects. Epilepsy is not caused by one single disease; it can be caused by a plethora of disease processes. Recurrent seizures are the basis for the definition of epilepsy and seizures can be seen as the cardinal clinical signs. As epilepsy is a complex, multifactorial brain disease, new management strategies should reflect this and new more multimodal (holistic) approaches to epilepsy management are needed. The ‘right mix’ in epilepsy management usually needs to include antiepileptic drug(s) medication tailored to the individual case, a balanced and potentially specialized nutritional plan, a reduction of potential seizure triggers and stress factors, and a treatment plan for comorbidities. The role of nutrition in epilepsy management is currently heavily debated. Until recently there has been only anecdotal evidence that nutrition can influence seizure control. It has been known that salt content in a diet can influence pharmacokinetics of the antiepileptic drug potassium bromide. However, that nutrition could have a direct impact o epilepsy management has just recently been shown. A ketogenic diet based on medium chain triglycerides (MCT) has recently been shown to improve seizure control and reduce behavioral comorbidities in some dogs with idiopathic epilepsy when fed as an adjunct to antiepileptic drug treatment. Fourteen percent of dogs became seizure free when fed the MCT diet and 48% of dogs showed a greater then 50% or greater reduction in seizure frequency. New management options are needed for epilepsy and nutrition might play one factor in its successful management.

Hypoallergenic diets and seizures were studied in 1994 and found to have no benefit.  Then omega-3-fatty acids showed a weak associated improvement that needs more studying. At this time the ketogenic diets wit MCT have shown statistical improvement. Previous studies were done with Purina bright minds and now Proplan Veterinary Neurology diet. There is a current study using distilled MCT supplementation which should be completed by the end of the year.

Royal Veterinary College has pet epilepsy tracker App which can be very useful

14. Harmonizing of Genetic Testing for Dogs by Dr. Brenda Bonnett

Abstract: There is widespread consensus amongst the veterinary and research communities on the need for a collaborative, international effort to address challenges surrounding effective use of genetic health testing (GT) in dogs. There are currently no mandatory accreditations of standardization for GT for companion animals, putting the health of many individual dogs and their progeny at risk, frustrating veterinarians and consumers, and negatively impacting the reputations of GT, in general. There is a need not only for transparency of the overall quality of commercial entities, and of the specific tests/products they are offering, but also for better information and counselling to support the global dog community, veterinarians and consumers.

The International Partnership for dogs (IPFD), an independent, multi-stakeholder organization, has been recognized as the appropriate body to create and oversee an online resource to: catalog information from commercial test providers (CTPs) on measures of quality, host expert reviews of genetic tests; coordinate a program for standardizing testing; assemble resources for genetic counselling and education; and provide the foundation for future developments. The basis of this program is the voluntary participation from CTPs and multi-stakeholder collaboration. The initiative, the Harmonization of Genetic Testing for Dogs (HGTD) parallels resources developed from human genetic testing (e.g. Eurogentest). As almost all genetics experts have an affiliation with a CTP, the HGTD resource will utilize panels of qualified experts to provide collective expert opinion. The online platform of the IPFD (DogWellNet.com is a breed specific international database), demonstrated her can be continually expanded to accommodate the growing catalog of CTPs, expert reviews, and resources.

Research in GT and genomics and the subsequent development of tests continues at a rapid pace. Issues of quality and the complexities of applications of test- for different scenarios and for different breeds-has not received adequate attention. Many breeders breed clubs, their veterinarians, and advisors are overwhelmed by the challenges of integrating scientific developments into sound breeding decisions. The lack of transparent information on the quality of CTPs and test; the confusion and frustration of consumers and the financial and personal costs to them; is a crisis in the making.

The IPFD Harmonization of Genetic Testing in Dogs is a major step towards improving access to information, and encouraging and standardizing best practices for GT. This resource will aid international kennel clubs, breed clubs, breeding advisors, veterinarians, and the end-user to make informed decisions regarding laboratories and testing for the health and welfare of their dogs. This, in turn, will lead to better translation of research developments to practical and effective applications. They plan to launch in 2018, labs will pay to participate and supported by AKC CHF grant 2328A.

15. Semen Evaluation, Quality, and the Effects of Aging by Dr. Stuart Meyes

Abstract: Semen quality in dogs has not been assessed in a longitudinal study that includes endpoints of female fertility and pregnancy. While the use of artificial insemination with chilled semen in increasingly used in canine reproduction, the resultant level of predictability and the odds of fertile mating for dogs is still not fully understood. This research provides, for the first time, comprehensive semen evaluation in a large population of dogs in which fertility has been tracked. Duplicate ejaculates were obtained from 39 male Labrador retriever from Guide Dogs for the Blind (San Rafael, CA) breeding program. Sperm endpoints were determined in fresh semen and extended chilled semen at 48 hour post-collection. Evaluation including total and progressive motility, average path velocity, morphology, membrane lipid peroxidation, presence of sperm reactive oxygen species, sperm chromatin structure, and mitochondrial DNA copy number. Male age ranged from 1 to 10 years, and were grouped as young (Y; 1-2 years, n=21), middle-aged (M; 4-6 years, n=13), and senior (S; 7 years and older, n=5) for analysis. The effects of age and sperm state (fresh vs chilled) on the above sperm endpoints were determined using a linear mixed effects model. Semen endpoint values for all parameters were established for this group of fertile males. Progressive motility was only lower in the senior male chilled samples compared to all other groups, (P<0.05). Velocity decreased with increasing age and was lower overall in chilled samples (P<0.05). Percent morphologically normal sperm was lower in senior dogs compared to the other age groups (P<0.05). The presence of reactive oxygen species was lower in chilled samples compared to fresh (P<0.05).  No differences were seen in total motility, membrane lipid peroxidation, mitochondrial DNA coy number, with regard to the conception rate, or average litter size between age groups or between fresh and chilled samples. They observed no effects from semen quality on fertility of fecundity regardless of age, despite the differences found in semen quality. The use of advanced laboratory tests to evaluate sperm parameters beyond the standard motility, morphology, and concentration will open investigation to more specific and sensitive fertility tests in canine reproduction.

It is known that human male fertility declines in the 40’s.  This includes increased DNA fragmentation, microvascular changes in the testes, and decreased hormone production by the pituitary and hypothalamus. The same has not been supported in dogs with his study. In addition, it must be considered that Guide Dogs for the Blind do select for fertility which is not necessarily done by other purebred dog breeders. There is a clear association with increasing inbreeding coefficient and decreasing fertility. Smaller studies done on other breeds of subfertile males have show decreased motility, increased reactive oxidase production, decreased viability and decreased normal morphology. The next study is to study 50-60 males with less than ideal fertility using his comprehensive semen evaluation.

16. An Update on Canine Brucellosis: A Call for Interdisciplinary Action by Dr. Angela Arenas

Abstract: Canine infection by Brucella spp. constitutes a serious problem for dog breeders and a pet owner; leading not only to huge economic cost associated with reproductive losses, but is also considered a public health concern because of its zoonotic potential. New evidence suggests the emergence or reemergence of canine brucellosis in the US. The increase in canine brucellosis cases is a direct result of the persistence of this organism in the host, the low dose required for infection, lack of protective vaccines, and the difficulty in diagnosing infected animals. A comprehensive review of the current status of the disease, the mechanism of infection, pathogenesis, zoonotic potential, preventive measures that can be adopted in managing the disease as well as the current advancements towards the development of new vaccines and diagnostic test.

Although canine brucellosis is endemic in sub-Saharan and Latin America, it is reemerging at a fast pace in the US. Two species are found most commonly in dogs, B. canis and B. suis. B. suis was eradicated in domestic swine but is found in 18% of feral swine. This disease is on the rise and is highly pathogenic to humans. B suis is on he increase in the south especially in feral dogs. The incidence of B canis in the US is unknown due to the lack of testing but believed to be 28% worldwide. Brucella in dogs is only reportable in 18 states and currently there are no interstate requirements for travel. The signs of brucellosis in female dogs are late 45 to 59 day abortion, vaginal discharge, reabsorption of fetus, intermittent reproductive failure and some are asymptomatic. In male dogs the signs include inflammation of the testes, prostate, scrotal edema and dermatitis, and again some are asymptomatic. Both male and female dogs can have anterior uveitis or discospondylitis . Transmission is aerosol and ingestion, but healthy appearing puppies is a major source. Treatment is generally not recommended, euthanasia is due to the zoonotic and possibly ineffective treatment. If euthanasia is declined treatment is neuter and long coarse of antibiotics (doxycycline, enrofloxin, rifampin) with variable success. Serology is repeated until antibodies are no longer detected.

Diagnostic tests:

1. Serology: used for screening and done first but  has low sensitivity and specificity (RSAT, ME-RSAT, AGID, Elisa)
2. IFA screening, usually done 2^nd at labs after the above is positive. Positive suggest Brucella but is not confirm since low specificity and sensitivity
3. Culture is the gold standard but is difficult since the bacteria are released cyclically. Blood cultures may require multiple attempts and best to take when the do has a fever and prior to antibiotics. Cultures should be done on aborted material, semen or vaginal discharge when suspected.

Attenuated modified live vaccines are starting to be developed and currently tested in Guinea pigs. The vaccine needs to be tested in pregnancy, and a new diagnostic test since serology will become positive in vaccinated dogs.

17. Canine Pyometra by Marco Coutinho da Silva

Abstract: Pyometra is a potentially life-threatening infection of the canine uterus. The incidence of occurrence has been reported to be 9-15.2% with aged, nulliparous bitches most at risk. This presentation discusses the reasons why dogs are susceptible to developing pyometra, as well as address treatment options and prognosis for life and reproduction. Often the therapy suggested for pyometra is spaying the female. However, some genetically valuable females can be successfully treated using a combination of prostaglandins, dopamine agonist, antibiotics, and supportive care. Currently available treatment protocols are costly, time-consuming, and not without risks themselves, often limited to healthy breeding bitches without evidence of renal compromise. An educated decision is best made by being knowledgeable. The breeder must remember that pyometra will reoccur; treatment has significant side effects, takes time and expense, and requires careful management of future breedings.

Dogs are predisposed to pyometra due to long periods of high estrogen followed by a long 2 months of high progesterone. It is a progressive disorder after several heat cycles which can also lead to cystic endometrial hyperplasia. This occurs due to repeated production of uterine “milk” during heat cycles, with a closed cervix and relaxed uterine muscle leading to the glands becoming clogged and cystic.

Pyometra develops and secondary infection fills the uterus with purulent material (pus). The number one bacteria found in pyometra is E. coli, and then secondly to E coli includes a normal variety found in the dog’s body naturally. As the uterus continues to fill up due to infection, it becomes significantly enlarged. The bitch has a high white blood count, may or may not have vaginal discharge, drink and urinate more, anorexia, vomiting, depression, fever,  and may further develop into septic shock or death.

Aglepristone, an anti-progestin drug not currently available in the US may have a place in the future to treat pyometra but at this time is only available after obtaining a USDA permit to import.

His study involved isolating 23 bacteria from pyometra, 16 were E coli. Of the 16 E coli, 14 o them had a strain that produced a biofilm. This biofilm in the uterus promotes reoccurrence of pyometra and prevents the body’s natural defense mechanism. He demonstrated clinically relevant strains of E coli that produce a biofilm in vitro and vivo. Future studies are exploring how to remove the biofilm.