Risk, revolution and preventive medicine

All dogs are pretty much the same, aren’t they? All cats are just little dogs, right? Bad! Of course, every veterinarian understands that each patient is special to their owner and unique as a living organism, but do individual patients need truly individualized care? Further, is the veterinary medical profession at a point where truly individualized care for patients is even available? Let’s start at the beginning.

Prevention as an approach to medicine and health care is not new, however, preventive medicine has certainly evolved over time. Despite a fundamental acknowledgment of disease prevention by Hippocrates in the fifth century BCE, preventive medicine was largely ignored throughout the Middle Ages and leprosy and plague abounded. From the first sanitary act in England in 1388 to early quarantine and isolation efforts in the 1500s, prevention has always cost a fraction of a cure. Indeed, as our understanding of disease and pathology expanded during the 17th and 18th centuries, the introduction of mortality statistics and demographic trends and the invention of vaccines in 1798¹, the prevention of disease has been as coveted as the cure. In 1902, Thomas Fuller wrote in Practical spelling: a textbook for use in business schools, “He who cures a disease may be the most skilful, but he who prevents it is the surest physician.” Fast forward to modern medicine and public health measures are almost exclusively focused on disease prevention.

The progression of veterinary medicine and the integration of preventive measures almost parallels human medicine. Unfortunately, the concept of One Health and its application to disease prevention would not be officially recognized until much later, but I digress. The real cornerstone of preventive medicine in the veterinary field has traditionally been vaccination, nutrition and animal husbandry. These 3 continue to be essential in the prevention of life-threatening diseases such as rabies, distemper, parasitism, nutritional hyperparathyroidism, etc. As veterinary medicine has evolved, recognition of the importance of a healthy microbiome in the long term health of most creatures. In fact, with 70-80% of immune cells being present in the gastrointestinal tissue², the intestinal microbiota has taken on an almost mythical importance in animal health. Transfaunation procedures to help restore normal microbial flora in the gut are more common than ever. Additionally, avoiding oral antibiotics to avoid unnecessarily disrupting the gut microbiome is more common than one might think in veterinary clinics. And speaking of oral issues, molecular analysis can be used to identify feline chronic gingivostomatitis and periodontal disease based on changes in the oral microbiota.³

The gastrointestinal and oral microbiota are not the only centers of the ongoing revolution in the field of prevention in veterinary medicine. Just as human medicine explores the application of genetic analysis, veterinary medicine can now leverage genetic testing to influence current medical and breeding decisions. Genetic analysis appears to have started with a “breed name” approach in which pet owners could submit samples to determine their pet’s purebred status or specific breeds contained in a pet dog. origin unknown. While the novelty of such tests is appealing, little medically applicable information is likely to be gleaned from such superficial analysis. The decision matrix for whether or not to perform a diagnostic test is quite simple in my opinion: will the result of the test change anything? The answer to this question about genetic analysis is evolving. Recent developments in canine genetic analysis testing enable medical intervention and disease prevention.^4.5 Two commercially available canine genetic test panels provide results for more than 200 different health conditions, from joint dysplasia to nasal pigment loss to urolith formation.

Genetic testing and recognition of point mutations and their impact on overall health may enable the most individualized veterinary medical approach to date. For example, if a kitten is determined to have a point mutation associated with kidney disease, the treating clinician may recommend owners start on a low-protein diet from 6 months of age. Additionally, more intensive monitoring of urine output and specific gravity earlier than the traditional recommendations of 7 years or more would be appropriate and would allow for earlier recognition of renal failure followed by more effective intervention. The conversation about avoiding giving table scraps to a Maltese puppy takes on a more serious and meaningful tone if it is determined that the puppy is genetically predisposed to pancreatitis. Currently, several complex diseases are correlated with specific canine genetic markers: hip dysplasia, granulomatous colitis (GC) and idiopathic epilepsy.⁶

Another lesser-known area of ​​research is individual sensitivity to different pharmaceuticals. Point mutations may indicate a propensity for pharmacological sensitivity allowing veterinarians to move beyond the old adage “White on the feet, don’t treat” and make an informed decision about individual patient sensitivities. Imagine being able to predict gastrointestinal disorders associated with the administration of doxycycline? Certainly, if a patient has a propensity to be susceptible to the only effective antimicrobial available for their clinical condition, clinicians should not withhold treatment. Instead, treatment should be initiated with mitigating ancillary care such as antihistamines and even probiotics to support this ever important microbial flora. While genetic testing and the understanding of the ever-increasing role of the gut microbiome are certainly driving a revolution in preventive veterinary medicine, neither exists in a vacuum and both underscore the importance of an approach holistic view of the veterinary patient.

Genetic-based preventative care might sound like Star-Trek stuff to most practitioners (and it sort of is), but there’s no reason for vets to fear the future or avoid integrating all available tools into treatment regimens. However, talking with geneticists can be daunting. The world of genetic medicine naturally has its own vocabulary. So what are the most common, yet important, terms to know and why? An essential term to understand is “penetrance”. Penetrance is the likelihood of a clinical condition occurring when a particular gene or mutation is present.^seven For example, if a shih-tzu has SLC2A9 (Exon) – chr3 mutation⁸ present and this mutation has 80% penetrance and is linked to the development of uroliths, then this dog is almost certain to develop uroliths in its lifetime compared to if the mutation only has 5% penetrance . Another term in the art when talking about genetic testing for prevention is “linkage”. Linkage is the tendency of genes or DNA segments that are close to each other on the chromosome to be inherited together.⁹ These trends are important when relying on “linkage analysis”. Linkage analysis is a technique used to infer the presence of a pathogenic gene by identifying other genetic markers known to be close to the target gene and usually co-inherited. It’s essentially the equivalent of a genetic test of being guilty by association. Dogs that are positive via linkage analysis are a little more difficult to interpret. For example, if a corgi is positive for the FGF4-chr12-chr12 gene, the dog may not be more likely than any other corgi to develop intervertebral disc disease (IVDD), experience an IVDD event, or require intervention. surgery for IVDD. However, if the corgi has multiple copies of this mutation, the dog is approximately 46 times more likely to have an IVDD event.^ten and about 5 to 15 times more likely to require surgery¹¹ for an IVDD event than a corgi without the mutation. Such precise statistics and professional jargon are sure to encourage more lovers of chondrodystrophic breeds to buy at least one more set of stairs for their beloved puppies, right?

Although preventive veterinary medicine may not be the newest clinical approach, it has certainly stood the test of time better than any other. With the evolving understanding of the importance of the gut microbiome in immune response and the rapid pace of genetic discovery, preventive veterinary medicine is definitely in vogue. So let’s lay our fire hose down long enough to start looking to prevent clinical fires rather than just getting to the scene in time to put them out.

References:

1. Preventive medecine. Encyclopædia Britannica, Inc. Accessed August 11, 2022. https://www.britannica.com/science/preventive-medicine
2. Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The interaction between the gut microbiome and the immune system in the context of infectious diseases across the lifespan and the role of nutrition in optimizing treatment strategies. Nutrients. 2021;13(3):886. Published March 9, 2021. doi:10.3390/nu13030886
3. Dolieslager SM, Riggio MP, Lennon A, et al. Identification of bacteria associated with feline chronic gingivostomatitis using culture-dependent and culture-independent methods. Veterinary microbiol. 2011;148(1):93-98. doi:10.1016/j.vetmic.2010.08.002
4. Leeb T, Müller EJ, Roosje P, Welle M. Genetic testing in veterinary dermatology. Veterinary Dermatol. 2017;28(1):4-e1. doi:10.1111/vde.12309
5. Rokhsar JL, Canino J, Raj K, Yuhnke S, Slutsky J, Giger U. Web resource on DNA variant testing available for inherited diseases and genetic predispositions in dogs and cats: an update. Hum Genet. 2021;140(11):1505-1515. doi:10.1007/s00439-021-02256-5
6. Hayward JJ, Castelhano MG, Oliveira KC, et al. Complex mapping of diseases and phenotypes in the domestic dog. Nat Common. 2016;7:10460. Published January 22, 2016. doi:10.1038/ncomms10460
7. NCI Dictionary of Genetic Terms. National Cancer Institute. Accessed August 11, 2022. https://www.cancer.gov/publications/dictionaries/genetics-dictionary/expand/P
8. Donner J, Kaukonen M, Anderson H, et al. Genetic panel screening of nearly 100 mutations reveals new insights into the breed distribution of risk variants for canine inherited disorders. PLoS One. 2016;11(8):e0161005. Published August 15, 2016. doi:10.1371/journal.pone.0161005
9. NCI Dictionary of Genetic Terms. National Cancer Institute. Accessed August 11, 2022. https://www.cancer.gov/publications/dictionaries/genetics-dictionary/expand/L
10. Brown EA, Dickinson PJ, Mansour T, et al. FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proc Natl Acad Sci USA. 2017;114(43):11476-11481. doi:10.1073/pnas.1709082114
11. Batcher K, Dickinson P, Giuffrida M, et al. Phenotypic effects of FGF4 Retrogenes on intervertebral disc disease in the dog. Genes (Basel). 2019;10(6):435. Published June 7, 2019. doi:10.3390/genes10060435