Thanks to a range of scientific and clinical advancements, veterinary diagnostics, along with disease management and treatment options, have come a long way since the 1970s.
The development and application of clinical innovations in both human medical and veterinary diagnostics have evolved dramatically over the last five decades.1-7 Today, diagnostic, management, and treatment options are improved even further by focusing on the individual patient, as in personalized medicine for people and companion animals.3,8 Additional factors, including One Health and significant advancements in the field of genetics, have further improved diagnostics for both human and veterinary patients.
VETERINARY DIAGNOSTICS BY GENETICS, ORGAN AND FUNCTION
It may be surprising to readers that there is so much more literature on veterinary diagnostics than there is for humans. It becomes more understandable when we recognize that animals often serve as models before any findings are adapted to humans.8 While an equal number of studies have been done in livestock and wildlife,15 this review primarily covers a selected group of studies in companion animals.
Behavioral disorders and the brain: Stress, whether emotional, physical, chemical or metabolic, plays a major role in behavior as measured by biomarkers of cellular oxidative stress.9,17,18,19 Recent studies have shown that cannabinoids (CBD) help control stress not only in people but also in veterinary patients. Over a six-month study period, a once daily dose of broad-spectrum THC-free CBD was shown to be efficacious and safe in relieving stress anxiety from being left alone or during car travel.20 Additionally, the importance of the gut-brain axis in regulating the microbiome and gut health has resulted in improved diagnostics, management, and therapy.9,19,21-24 Several commercial entities now offer microbiome analyses for pet animals.24
Bleeding disorders: A recent major breakthrough in gene therapies for humans with hemophilia A (factor VIII deficiency) and B (factor IX deficiency), has led to effective and safe cures for these disorders, albeit at a very high cost in the millions of dollars.25,26 The commercial products are Roctavian (valoctocogene roxaparvovec) for hemophilia A,25 and Hemgenix (etranacogene dezaparvovec) for hemophilia B.26 Hopefully, these research and therapeutic advances will soon be applied to parallel companion animal hemophilias, although obtaining the needed funding will be challenging. In beagles with delayed post-operative hemorrhage (DPOH), a missense G96E mutation encoding for alpha-2 antiplasmin in the F7 gene was found at exon 5, with glycine26 substituted by glutamic acid136; this mutation has a frequency of 31% in the breed.12 The effect of this genetic variant on bleeding susceptibility was reported as mild to moderate.8,12 More recently, another missense variant mutation in the SERPINEF2 gene encoding alpha-2 antiplasmin was identified by GWAS on chromosome 9, with a relatively high prevalence in Scottish deerhounds that were also affected by DPOH.10
Platelet lysates for human cell therapy not only provide for improved hemostasis but also contribute to regenerative medicine by helping control inflammation and infection, and supporting wound healing.27 Parallel studies with platelet lysates are ongoing in companion animals, including horses.28, 29
Cancers: Diagnostics for the early detection of cancers in humans and animals, in addition to the conventional techniques of pathology, biopsy and histology, now include nanotechnology, genetic copy number variations, cytological grading systems, specialized ultrasound, cellular and serum biomarkers, flow cytometry, stem cell technologies, patterns of lymphocytic infiltrates, immunohistochemical expression, expression of sex hormone receptors, and liquid biopsies.1,2,5,6,9,14,30-33
Cardiac disorders: Controversial issues surrounding the diagnosis and causes of canine heart disease, specifically dilated canine cardiomyopathy, have escalated to include genetic predisposition, dietary components, environmental inhalant and contact exposures, vaccines, toxins, parasiticide preventives and others.9,21,22
CRISPR applications: The decades-long genomic revolution culminated in the recent Nobel Prize-winning CRISPR Cas9 and Cas11-13 research and its ensuing patent disputes between the University of California, Harvard University and MIT’s Broad Institute.8,34 This has since evolved to include novel genome editing tools such as Prime and PASTE.34
Endocrine and metabolic disorders: Endocrine disruption, deficiencies, and excess production have been recognized for many years, especially when involving the diet and microbiome, and pituitary, thyroid, pancreas, adrenal, and parathyroid glands.9,35-38 Studies of the pituitary-thyroid and adrenal axes, and the novel reference laboratory in-clinic/bedside diagnostic testing of humans and companion animals, have made diagnosis more accurate along with emphasizing the need for species-specific reagents and dynamic metabolic testing.3,7,9,35-38
Parallel concerns apply to the increasing number of metabolic disorders, with emphasis on expanding global numbers of inflammatory conditions; autoimmune disorders, especially diabetes, thyroiditis, and Addison’s disease; infectious and antibiotic-resistant microbial diseases; increasing gluten sensitivities; and the widespread issues arising from obesity in people and pet animals.9,39,40
Gastrointestinal disorders: As the critical importance of the microbiome in balancing the gut-brain and gut-lung axes has evolved, new diagnostic and therapeutic approaches have become available, including stem cell infusion and fecal transplantation (microbial restoration therapy) from healthy, matched donors.9,21,22,24,38-43 Commercial availability now extends to animal patients.9,21,39,41,42
Genetic disorders: Many of the conditions discussed above occur more often in people and animals carrying a specific heritable trait or a predisposition to them.8-14,25,26,34-37,39
Hematologic disorders: In addition to the bleeding disorders already discussed, other human and animal blood disorders have been documented.9,44,45 Companion animal blood typing is performed for the purposes of identifying the transfusion needs of patients and blood donors; establishing techniques in regenerative and stem cell medicine; and determining potential mismatched blood type mating that can lead to hemolytic disease of newborn dogs, cats, horses, and livestock.9,44-47
Hepatic disorders: As a major organ for the production of coagulation proteins and hematopoietic cell storage, as well as reticuloendothelial cell function and clearance, the liver plays a pivotal role in health and disease conditions.8,9 Similar physiological and pathological functions apply to humans and other species.48-51
Infectious diseases and prevalence: Microbial infections from bacteria, viruses, fungi (including yeast), protozoa, phages, and parasites are much more prevalent than the other conditions discussed above. However, the world-wide success rate for early and accurate identification is hampered by factors such as the varying ability of even the most accurate tests to predict clinical results, their turn around time for completion, and their increased cost.1-7,43,52-57 Adding to this challenge is the ever-increasing development of microbial strains becoming resistant to standard antimicrobials, which now require novel, more costly therapies with limited availability that need to be given for extended periods in both people and animals.1,3,4-7,43,51,52, 56, 57
Regarding the prevention of infectious diseases, vaccines play a preeminent role but have been plagued by controversy ever since the SARS-CoV-2 pandemic of COVID-19 and the advent of life-saving mRNA vaccine technology.57 Similar vaccine hesitancy and naysayers are vocal in veterinary medicine, such that refusal to vaccinate has led to the inevitable increased risk of vaccine-preventable infectious diseases, suffering and even death.58,59 Issues regarding vaccine safety and adverse events include injection site sarcomas, adjuvant-induced autoimmune reactions, thimerosal (mercury) and aluminum heavy metal content, and squalene content, as well as the immunizing volume of vaccine needed for very small versus larger pets.58,59
Renal and urinary tract disorders: Like the liver, the kidneys detoxify the body of small proteins, drugs, and fluids in relation to the glomerular filtration rate. Congenital abnormalities and acquired disorders affect kidney size, number, anatomy (hypoplasia, dysplasia, polycystic), and function in humans and animals.9 At least 14 dog breeds have heritable, familial renal disease or are genetically predisposed, ranging from the small Shih Tzu to the much larger Doberman Pinscher, Akita, and Alaskan Malemute, where the renal disease is associated with dwarfism.60 Disorders of the urethra, ureters (e.g. ectopic ureter especially in female pups), and bladder also occur.60
Respiratory disorders: Interest in human respiratory disorders, as exemplified over the years by infections like bacterial and parasitic pneumonia, tuberculosis, and the common cold, has grown exponentially with the advent of the COVID-19 pandemic, and co-infections with seasonal human influenza virus, rhinoviruses, enteroviruses, and respiratory syncytial virus.1,57,61 In animals, similar issues and controversy have arisen with the zoonotic transmission of these novel coronavirus variants from people to wildlife and pets, and vice versa.59 Other respiratory infections in animals include canine parainfluenza virus 5, with improved diagnostic identification.43,54 The current global spread of virulent avian influenza (bird flu) H5N1-N8 strains from migrating wild birds has devastated commercial and backyard poultry flocks. Certain mammals like the red fox are also susceptible,62 although it very rarely causes respiratory infection in humans.62 The importance of the gut-lung axis and the role of the microbiome have also been explored with regard to respiratory disorders.24,56
Improved diagnostics that help us find disease processes faster and earlier often lead to better outcomes for our animal patients. The scientific advances of the last 50 years have greatly enriched our ability to get to the bottom of our patients’ health problems, so we can implement a treatment or management plan as soon as possible.
Dr. Jean Dodds received her veterinary degree in 1964 from the Ontario Veterinary College. In 1986, she established Hemopet, the first non-profit national blood bank program for animals. Today, Hemopet also runs Hemolife, an international veterinary specialty diagnostics service. Dr. Dodds has been a member of many committees on hematology, animal models of human disease and veterinary medicine. She received the Holistic Veterinarian of the Year Award from the AHVMA in 1994, has served two terms on the AHVMA’s Board of Directors, chairs their Communications Committee, and currently serves on the Board of the AHVMF, as well as its Research Grant and Editorial Committees.