Danger, revolution and preventive medicine

Almost all dogs are the same, right? All cats are just little dogs, right? Wrong – wrong – wronged! Of course, every veterinarian understands that each patient is special to its owner and unique as an organism, but do individual patients really need individualized care? Furthermore, is the veterinary profession at a point where true individualized patient care is available? Let’s start from the beginning.

Prevention as an approach to medicine and healthcare is not new, however, and preventive medicine has certainly evolved with the times. Despite the primary recognition of disease prevention by Hippocrates in the 5th century BC, preventive medicine was largely ignored throughout the Middle Ages, and leprosy and plague spread. From England’s first sanitary act in 1388 to the first efforts at quarantine and isolation in the sixteenth century, prevention has always cost a fraction of the cure. Indeed, as our understanding of disease and pathology expanded during the seventeenth and eighteenth centuries, the introduction of mortality statistics and population trends and the invention of vaccines in 17981The prevention of the disease was as required as the treatment. In 1902, Thomas Fuller wrote in Practical spelling: a text book for use in trade schools“He who cures a disease may be a dowry matter, but he who protects from it is the safest doctor.” Fast-forward to modern medicine and public health measures that focus almost exclusively on disease prevention.

The development of veterinary medicine and the incorporation of preventive measures proceed roughly in parallel with human medicine. Unfortunately, the concept of One Health and its application in disease prevention will not be officially recognized until much later, but I digress. Indeed, the cornerstones of preventive medicine in the veterinary field have traditionally been vaccination, feeding and breeding. These three remain crucial in the prevention of life-threatening diseases such as rabies, tuberculosis, parasitism, dietary hyperparathyroidism, etc. The term health for most creatures. In fact, 70-80% of immune cells are found in the tissues of the gastrointestinal tract2The gut microbiome has acquired near-mythical importance in animal health. Diversion procedures to help restore the normal microflora in the gut are becoming more common than ever. Additionally, avoiding oral antibiotics to avoid unnecessary disturbances in the gut microbiome is more common than one might think in veterinary clinics. And speaking of oral problems, molecular analysis can be used to identify chronic gingivitis in cats and periodontal disease based on changes in the oral microbiome.3

Gastrointestinal and oral microbiota is not the only focus of the ongoing revolution in prevention in veterinary medicine. Just as human medicine is exploring the application of genetic analysis, veterinary medicine can now make use of genetic testing to influence current medical and breeding decisions. Genetic analysis appears to have started with a “name this breed” approach where pet owners can submit samples to determine the pure breeding status of their pets or specific breeds present within a dog of unknown origin. While the novelty of this test is attractive, it is likely that little medically applicable information can be gleaned from such a superficial analysis. The decision matrix for whether or not to take a diagnostic test is fairly simple in my opinion: will the test result change anything? The answer to this question is evolving in connection with genetic analysis. Recent advances in canine genetic testing allow medical intervention and disease prevention.4,5 The two commercially available canine genetic testing panels provide results for more than 200 different health-related problems from hip dysplasia to nasal pigment loss to urine stone formation.

Genetic testing and identification of point mutations and their impact on public health may allow the most private veterinary medical approach to care to date. For example, if a kitten is identified as possessing a point mutation associated with renal disease, the attending physician can make recommendations for owners to feed a low-protein diet as early as 6 months of age. In addition, more intensive monitoring of urinary output and specific gravity earlier than conventional recommendations for 7 years or longer would be appropriate and allow early identification of renal compromise followed by more effective intervention. The conversation about avoiding feeding table scraps to a Maltese puppy takes on a more serious and important tone if the puppy is determined to be genetically predisposed to developing pancreatitis. Currently, several complex diseases are associated with specific genetic markers for dogs: hip dysplasia, granulomatous colitis (GC) and idiopathic epilepsy.6

Another less well-known area of ​​research is individual sensitivity to different pharmaceutical products. Point mutations can indicate a tendency to drug allergies allowing veterinarians to bypass the old adage of “white on feet, don’t treat” and make an informed decision about individual patient sensitivities. Imagine being able to predict the gastrointestinal upset associated with doxycycline administration? Certainly, if a patient has a tendency towards sensitivity to the only available effective antimicrobial for his clinical condition, then physicians should not refrain from treatment. Instead, treatment should start along with palliative adjuvant care such as antihistamines and even probiotics to support those always important microbial flora. While genetic testing and understanding the ever-increasing role of the gut microbiome are certainly driving a revolution in preventive veterinary medicine, neither is in a vacuum and both emphasize the importance of a comprehensive approach to the veterinary patient.

Genetic-based preventive care may sound like Star-Trek things to most practitioners (and it kind of is), but there is no reason for veterinarians to fear the future or avoid incorporating all available tools into treatment regimens. However, talking with geneticists can be intimidating. The world of genetics, of course, has its own vocabulary. So, what are the most common, albeit important, terms to know and why? An important term to understand is “hack”. Penetrance is the potential for a clinical condition to occur when a particular gene or mutation is present.7 For example, if shih-tzu has the SLC2A9 (Exon) mutation – chr38 And that mutation is 80% penetrable and is associated with the development of a urethra, and this dog is almost certain to develop urinary stones in their lifetime versus if the mutation had only 5% penetration. Another term for art when discussing genetic testing for prevention is “linkage.” Linkage is the tendency of genes or DNA segments that are close together on a chromosome to be inherited together.9 These trends are important when relying on Correlation Analysis. Linkage analysis is a technique used to infer the presence of a disease-causing gene by identifying other known genetic markers close to the target gene and usually jointly inherited. It’s basically the genetic analysis equivalent to guilt by association. Positive dogs by analyzing associations are a little more difficult to interpret. For example, if a corgi is positive for the FGF4-chr12-chr12 gene, your dog may not be more likely than any other corgi to develop intervertebral disc disease (IVDD), experience an IVDD event, or require surgical intervention for IVDD. However, if a corgi has multiple copies of this mutation, the dog is approximately 46 times more likely to be susceptible to IVDD.10 And approximately 5 to 15 times more likely to need surgical intervention11 For a juvenile IVDD of a Corgi without a mutation. Such tough statistics and professional language would surely encourage more cartilaginous breed lovers to buy at least another set of ladders for their cuddly pups, right?

While preventive veterinary medicine may not be the latest clinical approach, it certainly has stood the test of time better than any other. With the evolving understanding of the importance of the gut microbiome in the immune response and the breakthrough pace of genetic discoveries, preventive veterinary medicine has certainly become popular again. So let’s put our fire hose on long enough to begin the search for clinical fire prevention rather than just get to the scene in time to put it out.

references:

  1. Protective medicine. 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 throughout life and the role of nutrition in improving treatment strategies. Nutrients. 2021; 13 (3): 886. Published in 2021 March 9. doi: 10.3390 / nu13030886
  3. Dolieslager SM, Riggio MP, Lennon A, et al. Identification of bacteria associated with chronic gingivitis in cats using culture-dependent and culture-independent methods. veterinarian microbiol. 2011; 148 (1): 93-98. doi: 10.1016/j.vetmic.2010.08.002
  4. Lip T, Muller EJ, Rossje B, Phil M. Genetic testing in veterinary dermatology. veterinarian 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 available DNA variant tests for genetic diseases and genetic predispositions in dogs and cats: an update. Gene hum. 2021; 140 (11): 1505–1515. doi: 10.1007/s00439-021-02256-5
  6. Hayward G, Castelhano MG, Oliveira KC, et al. Complex diseases and phenotype mapping in pet dogs. nat common. 2016; 7: 10460. Published 2016 Jan 22. 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, Kokkonen M, Anderson H, et al. Examination of genetic panels of nearly 100 mutations is revealing new insights into the breed distribution of risk variants for genetic disorders in dogs. PLUS ONE. 2016; 11(8): e0161005. Published 2016 Aug 15. 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 The nitrogen in 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. Butcher K, Dickinson F, Giovrida M, et al. The phenotypic effects of FGF4 Retrogenes on intervertebral disc disease in dogs. Genes (Basel). 2019; 10 (6): 435. Published 2019 Jun 7. doi: 10.3390 / genes10060435

Leave a Comment