ACVIM Required Reading - Gastrointestinal Dz

Question 1

Equine Gastric Ulcer Syndrome (EGUS) is a term used to describe all ulcerative and erosive disorders of the stomach. What two terms are used to further classify these diseases on the basic of anatomical location?

Answer 1

• Equine Squamous Gastric Disease (EGSD).
• Equine Glandular Gastric Disease (EGGD).

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 2

EGSD can be subclassified on the basis of aetiology. What are the two categories of EGSD?

Answer 2

• Primary EGSD: occurs in horses with an otherwise normal gastrointestinal tract.
• Secondary EGSD: occurs in animals with delayed gastric outflow secondary to an underlying abnormality such as
  pyloric stenosis.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 3

Much remains unknown regarding the pathophysiology of EGGD and therefore it cannot be further subclassified at this time. How then should EGGD be described?

Answer 3

• Location: cardia, fundus, antrum or pylorus.
• Gross appearance of lesions: focal/multifocal/diffuse; mild/moderate/severe; flat/raised/depressed; blood clot/haemorrhagic/fibrinosuppurative.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 4

Which breeds/types of horses have the highest and lowest prevalence of ESGD?

Answer 4

• Highest: TB racehorses: 37% untrained, raising to 80-100% within 2 months of commencing training.
• High (~40-90%): racing SBs and endurance horses.
• Mid (~20-60%): pleasure and performance horses in work.
• Lowest (11%): horses rarely competed that are predominantly in their home environment.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 5

What is the prevalence of EGGD?

Answer 5

• Not as well understood (majority lesions pyloric antrum).
• Aus TBs: 47% - 65%.
• Endurance horses: 16% (rest periods), 27–33% (competing).
• UK pleasure horses: 54%.
• UK performance horses: 64%
• 2 studies mixed populations: 57%.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 6

Is there an age, breed or gender predilection for developing ESGD?

Answer 6

• Other factors such as intensity or duration of exercise outweigh any potential age or sex effect.
• A breed effect might be present with Thoroughbreds predisposed to ESGD.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 7

Is there an age, breed or gender predilection for developing EGGD?

Answer 7

There is not enough epidemiologic data available to make firm conclusions.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 8

Do environmental risk factors exist for development of EGUS?

Answer 8

• Significant associations have been shown between ESGD and individual trainers, a metropolitan yard location, a lack of direct contact with other horses, solid barriers instead
  of rails, and talk rather than music radio in the barn.
• Straw feeding and a lack of access to water in the paddock have been associated with an increased risk of EGUS in general.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 9

List nutritional risk factors for development of ESGD.

Answer 9

• High grain (>1% BWt or 2g/Kg starch) intake.
• Intermittent access to water.
• Fasting.
• {Conflicting evidence (protective effect vs no effect) of feeding pasture and high fibre diets.}

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 10

List reported clinical signs associated with EGUS.

Answer 10

• Poor appetite or ‘picky eating’.
• Poor body condition or weight loss.
• Chronic diarrhoea (when part of other dz process?)
• Poor coat condition.
• Bruxism.
• Behavioural changes (aggression, nervousness, self mutilation); nervous show horse has inc risk; aggressive racehorse has dec risk; association w cribbing).
• Acute or recurrent colic (pre-disposes to other GI dysfunction or secondary to other primary GI lesion?)
• Poor performance (not correlated w ulcer severity).

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 11

Is diagnosis of EGUS on the basis of clinical signs recommended?

Answer 11

Although a wide variety of clinical signs might be present in individual cases of EGUS, they are nonspecific and are poorly associated with the presence of EGUS. The committee therefore does not support the practice of diagnosing EGUS based on ‘characteristic’ clinical signs and recommends that EGUS be confirmed by gastroscopy.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 12

What is the preferred diagnostic test for EGUS?

Answer 12

• Gastroscopy.
• Essential to examine the entire stomach, including the pylorus and proximal duodenum, as there is no relationship between ESGD and EGGD, therefore one cannot be used as predictor for the presence or absence of the other.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 13

Discuss clinical pathology tests available for diagnosis of EGUS.

Answer 13

• Sucrose permeability test: showed promise but the diagnostic accuracy has not been reported in clinical cases.
• Faecal albumin or haemoglobin: no association w EGUS.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 14

Describe the recommended ulcer scoring system for EGSD.

Answer 14

Adapted from 1999 EGUS Council:
0 The epithelium is intact and there is no appearance of hyperkeratosis.
I The mucosa is intact, but there are areas of hyperkeratosis.
II Small, single or multifocal lesions.
III Large single or extensive superficial lesions.
IV Extensive lesions with areas of apparent deep ulceration.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 15

Is a hierarchical grading system recommended for EGGD?

Answer 15

• No, given the paucity of information correlating appearance and clinical relevance.
• In the absence of a grading system, terminology
  describing the presence/absence, anatomical location, distribution and appearance of lesions should be used.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 16

Are ulcer appearance and clinical severity correlated in EGUS?

Answer 16

• There is little evidence to support the notion
  that lesion grade (as assessed visually) correlates with
  clinical signs.
• Assessment of clinical relevance should not be made
  on endoscopic appearance alone. Instead the clinician
  should assess the relevance of an individual’s lesions in
  light of the horse’s recent usage, its history and presenting
  clinical signs.
• Future research on EGUS should focus
  on reporting both clinical and endoscopic outcomes.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 17

Describe the pathophysiology of ESGD.

Answer 17

• Squamous mucosal cells are susceptible to hydrochloric acid (HCl) and volatile fatty acid (VFA) injury in a pH, dose and time dependent manner.
• Damage of the outer cell barrier is induced by HCl, later followed by diffusion into the squamous cells of the stratum spinosum ultimately resulting in ulceration.
• Byproducts of bacterial fermentation of sugars in concentrate diets like VFAs and lactic acid, and also bile acids, have been shown to act synergistically with HCL.
• Exercise increases exposure of squamous mucosa to acidic content and training. Excessive exposure of the squamous mucosa results from the acidic gastric contents being pushed up by the increased intra-abdominal pressure associated with gaits faster than a walk

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 18

Describe the pathophysiology of EGGD.

Answer 18

• Poorly understood.
• The glandular mucosa differs fundamentally from the squamous mucosa in that under normal physiological conditions it is exposed to highly acidic gastric contents with the pH in the ventral stomach 1 to 3.66.
• EGGD is believed to result from a breakdown of the normal defense mechanisms that protect the mucosa from acidic gastric contents e.g. mucus-bicarb layer, mucosal blood flow, surface protective phospholipids.
• The factors that contribute to breakdown of this protective layer are yet to be elucidated.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 19

Do bacterial infection or NSAID administration cause ESGD or EGGD?

Answer 19

• Lack of conclusive evidence at a population level.
• Both gastric-adapted bacteria and opportunistic pathogens might play a role in ESGD; unknown in EGGD.
• Although such bacteria are present in ESGD their role appears to be secondary as the response to acid suppression alone is good.
• Helicobacter-like organisms have been identified in horses affected with EGGD in some studies, whereas other studies have failed to identify such organisms.
• An ulcerogenic capacity has been demonstrated for flunixin, phenylbutazone, and ketoprofen at doses 50% higher than typically recommended, while at clinical doses
  phenylbutazone does not induce EGGD after 15d.
• High prevalences of EGGD have been observed in many populations with disease rates disproportionate to the number of animals likely to receive NSAIDs.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 20

What is the cornerstone of treatment of EGUS? What drugs can be used to achieve this goal and what are their mechanisms of action?

Answer 20

• Gastric acid suppression. Omeprazole is drug of choice.
• Omeprazole: irreversibly impairs the H+, K+ ATPase (proton) pump that secretes HCl with new pumps needing to be made before acid production resumes.
• Ranitidine: competitively blocks the H2 receptor on the parietal cell; efficacy is dependent on maintaining plasma concentrations of the drug.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 21

What is the mechanism of action of sucralfate? When should it be used in treatment of EGUS?

Answer 21

• Likely a combination of adherence to ulcerated mucosa, stimulation of mucous secretion, prostaglandin E synthesis and enhanced blood flow to the glandular mucosa.
• Use for EGGD: a recent study reported a 67.5% healing rate for EGGD of the pyloric antrum using omeprazole at 4 mg/kg PO q24h and sucralfate at 12 mg/kg PO q12h.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 22

What duration of acid suppression is required for healing of gastric ulcers. What dose of omeprazole can achieve this?

Answer 22

• 16h in people; not investigated in horses.
• Once daily dosing of omeprazole is correlated with ulcer healing and in some studies suppresses gastric acid for as little as 12h, so 12h acid suppression may be sufficient.
• 1mg/kg q24h enteric coated; 2mg/kg q24h buffered paste.
• NB all studies on omeprazole –> 70-78% success rate in tx ESGD; only 25% success in tx EGGD in this time.
• 3 weeks equivalent to 4 weeks at 4mg/kg q24h for ESGD.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 23

What treatment guidelines were recommended for ESGD in the 2015 ECEIM Consensus Statement on EGUS?

Answer 23

• Primary recommendation: omeprazole buffered 4mg/kg (lack of clinical data as of yet for lower doses) or enteric coated at 1mg/kg PO q24h.
• Secondary recommendation: omeprazole buffered 2mg/kg PO q24h OR ranitidine 6.6mg/kg PO q8h.
• Treatment duration: 3 weeks.
• Gastroscopy prior to cessation of therapy.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 24

What treatment guidelines were recommended for EGGD in the 2015 ECEIM Consensus Statement on EGUS?

Answer 24

• Primary recommendation: omeprazole buffered 4mg/kg PO q24h or enteric coated 1mg/kg PO q24h plus sucralfate 12mg/kg PO q12h.
• Secondary recommendation: omeprazole buffered 2mg/kg PO q24h plus sucralfate 12mg/kg PO q12h OR nutraceuticals with published efficacy.
• Treatment duration: 4 weeks; additional adjunctive therapies if no response after 8 weeks (and biopsy).
• Gastroscopy prior to cessation of therapy.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 25

Is pharmaceutical treatment recommended for the prevention of ESGD?

Answer 25

• Prevention should be approached on a case by case basis, wherein the greater the ability to impact on risk factors, the lower the need for additional treatment.
• Omeprazole is typically used at 1.0 mg/kg PO once
  daily for prevention of ESGD.
• Efficacy of omeprazole as a prophylactic for EGGD is unclear with 23% of horses experiencing worsening of their EGGD grade in a series of recent studies, despite tx.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 26

List the nutraceuticals for which scientific evidence of their efficacy in prevention or treatment of EGUS is available.

Answer 26

• A combination antacid (magnesium hydroxide), pectin-lecithin complex and Saccharomyces cerevisiae has shown promise as a prophylactic agent for ESGD and EGGD.
• A feed supplement consisting of salts of organic acids in
  combination with B-vitamins might be beneficial in the
  management of ESGD.
• A preparation containing sea buckthorn berries appeared to have protective effects against the development of EGGD, but not ESGD, in a fasting model of disease.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 27

Outline nutritional recommendations for management of EGUS.

Answer 27

• Continuous access to good quality grass pasture is considered ideal OR free choice or 4-6 meals/day hay.
• Feed grain and concentrates as sparingly as possible. Sweet feed should be avoided as a large quantity of VFAs could be produced w >1-2kg/meal. Grains like barley and oats can be substituted to decrease fermentation to VFAs.
• Do not exceed 2g/kg BWt starch/day (or 1g/kg/meal).
• Concentrate meals should not be fed lower gastric acid output and inc Pg synth in gastric juice.
• Water should be provided continuously.
• Inc risk of ESGD when electrolyte pastes or hypertonic solutions are fed straight therefore mix with feed or water.

Ref: ECEIM Consensus Statement (2015) - EGUS.

Question 28

According to the 2012 ACVIM Consensus Statement what proportion of US cattle herds contain animals infected with Mycobacterium avium subsp. paratuberculosis (MAP)?

Answer 28

• 70% of all US dairy herds.
• 5–10% of US beef herds.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 29

What factors make diagnosis of Johne’s disease in ruminants a challenge?

Answer 29

• The fastidious growth requirements of MAP in vitro.
• Long in vivo incubation period (“eclipse” phase).
• Blunted humoral immune response.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 30

List the advantages, disadvantage, sensitivity and specificity of bacterial culture of faecal samples as a method of Johne’s Disease diagnosis.

Answer 30

• Adv: positive result confirms the presence of viable MAP, allows for strain typing, amount of MAP and shedding risk.
• Disadv: longer incubation period vs PCR of 4-16 wk.
• Sensitivity: approximately 60% relative to necropsy.
• Specificity >99%; false +ve ‘pass through’ if just ingested.
• Culture can be performed on faecal samples from indv animals, on pooled samples, or on samples from the enviro and manure storage areas such as a lagoon or slurry pit.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 31

List the advantages, disadvantage, sensitivity and specificity of detection of MAP DNA in faecal samples as a method of Johne’s Disease diagnosis.

Answer 31

• Adv: dec test turnaround time compared with culture, allows est of amount of MAP shed in faeces.
• Disadv: does not confirm the presence of viable organisms and does not permit strain differentiation.
• Sensitivity and specificity vary w test, but for one commercially available method similar to culture.
• Can be applied to pooled samples and samples collected from the environment and manure storage.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 32

List the advantages, disadvantage, sensitivity and specificity of detection of MAP antibodies in serum and milk as a method of Johne’s Disease diagnosis.

Answer 32

• • Adv: major cost savings advantage vs PCR, great adv in throughput and turnaround time vs culture.
• Sensitivity: limited by biology of the immune resp to MAP –> ABs usually not prod until late in infection after faecal shedding has begun; est 30% for milk and serum ELISA.
• Quantitative results (ELISA OD or S/P ratio), which correlate well with the likelihood of (and level of) fecal shedding of MAP.
• ELISA superior to AGID for subclinically infected cattle but AGID useful for diagnosis in clinically affected cattle.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 33

List the advantages and disadvantages of detection of a cell-mediated immune response to MAP as a method of Johne’s Disease diagnosis.

Answer 33

• Incl intradermal johnin test, and an in vitro assay of antigen-induced gamma-interferon release from lymphocytes of test subjects.
• Adv: offer promise in early detection before antibodies or fecal shedding of MAP are detectable.
• Disadv: because of cost, variable test performance,
  or both, neither of these methods is recommended.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 34

What are the recommendations for diagnosis of MAP infection in individual animals with clinical signs as per the 2012 ACVIM Consensus Statement?

Answer 34

• Antibody tests, fecal culture, and fecal PCR will all perform with comparable sensitivity (>90%).
• If clinical disposition of the animal depends on the results, then one of the more rapid methods should be employed. - If MAP has never been diagnosed in the herd, organism detection to confirm the diagnosis is preferred.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 35

What are the recommendations for diagnosis of MAP infection to determine herd status via environmental testing as per the 2012 ACVIM Consensus Statement?

Answer 35

• Organism detection tests applied to samples of manure collected from 6 on-farm cow congregation areas, alleyways etc. –> 70– 80% sensitivity.
• Adv: most cost-effective method to determine if a herd is infected or likely uninfected.
• Allows entry to some MAP control programs.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 36

What are the recommendations for diagnosis of MAP infection to determine herd status via individual animal testing as per the 2012 ACVIM Consensus Statement?

Answer 36

• To estimate prevalence within a herd, samples for ELISA
  testing (serum, milk) or indv faecal samples for organism detection can be collected from every animal in the herd, from a random statistical subset of animals, or from targeted animals (based on age and BCS).
• Organism detection methods can be applied to individual
  samples or pooled for cost savings.
• Cows over 36 months of age are usually targeted.
• Choice of strategy is determined by size of herd, costs, and goals of the producer including regulatory program.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 37

What are the recommendations for diagnosis of MAP infection to determine herd status via bulk milk tank testing as per the 2012 ACVIM Consensus Statement?

Answer 37

• Organism detection methods have not shown sufficient sensitivity to warrant recomm for their use at this time.
• Studies on sensitivity of ELISA applied to bulk tank milk have yielded mixed results; some = insufficient Se/Sp; a more recent largescale study employing modified ELISA cut-offs –> 85% sensitivity to detect herds with a 3% or higher seroprevalence, with 96% specificity.
• The evidence in favor of employing these tests is weak.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 38

Why would you determine an individual cow’s MAP infection status in a known infected herd?

Answer 38

• May facilitate colostrum management, segregation of cows at calving, and culling of fecal shedders to reduce enviro MAP load & risk of exposure for susceptible animals.
• E.g. control protocol: limit access of all test-positive cows to calving pens, use of colostrum only from all ELISA neg
  animals, but only “high positive” are targeted for culling.
• For commercial herds, with MAP apparent prevalence >5%, use of a serum or milk ELISA is recommended.
• In herds with

Question 39

What are the recommendations for diagnostic testing for eradication of MAP from an infected herd as per the 2012 ACVIM Consensus Statement?

Answer 39

• Diagnostic testing to identify MAP infected animals for culling will be a component of the plan for most infected herds attempting eradication.
• Choice of tests is dictated by how aggressively
  producer wishes to pursue eradication, which hinges on economic factors e.g. starting prevalence, and whether income from selling seed stock is a goal.
• The cost will generally be inversely related to the rapidity - Moderate evidence: reports of eradication of MAP from infected herds using a combination of test-cull and management recommendations are scarce.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 40

What are the recommendations for diagnostic testing of herd addition, embryo transfer recipients, herd sires etc. for eradication of MAP from an infected herd as per the 2012 ACVIM Consensus Statement?

Answer 40

• It is not appropriate to rely on diagnostic tests of purchased animals to avoid introduction of MAP-infected animals into herds, especially when

Question 41

What are the recommendations for diagnosis of MAP infection in sheep, goats and camelids as per the 2012 ACVIM Consensus Statement?

Answer 41

• Both of the ELISA kits commercially available in the US have similar Se and Sp for use in sheep and goats as cattle.
• Sheep strains of MAP are difficult to cultivate in vitro, but a modified liquid culture method with good sensitivity has been developed in Aus; testing faecal samples in pools of 50 –> 95% confidence of detecting 2% prev in the flock.
• Testing by PCR is more sens than culture of individual
  fecal samples from experimentally infected sheep.
• Goats, culture for MAP has low Se therefore PCR recomm.
• Serologic tests have not been useful in camelids, and organism detection by PCR on faeces is recomm.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 42

What are the recommendations for maintaining a MAP free status in a cattle herd as per the 2012 ACVIM Consensus Statement?

Answer 42

• Do not introduce animals from herds with Johne’s dz or from herds with an unknown Johne’s dz status.
• Do not participate in auctions/shows where there is a risk that animals will be reintroduced into the herd following prolonged contact with animals with unknown status.
• On-farm calf rearing according to management
  and hygiene procedures described below
• Off-site (commercial) calf rearing accepts only calves
  from MAP-tested unsuspected herds.
• Breed rather than buy replacement heifers.
• Avoid applying manure from farms with Johne’s dz or unknown status to pastures or forage crops or using equipment potentially contaminated with such manure/soil.
• Demand and enforce biosecurity measures from visitors.
• Document the herd status with a long-term monitoring
  system through use of a repeated dx testing scheme.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 43

What are recommendations for management of calves on MAP infected diary farms as per the 2012 ACVIM Consensus Statement?

Answer 43

• Do not allow sick, lame, or Johne’s disease testpositive
  cows in group maternity pens.
• Maintain clean pen bedding by adding 25Lb straw/cow/day and 100 square feet of space/cow.
• Keep cows in calving pens clean; limit manure on flanks, legs, udders, and teats.
• Remove or isolate calves from cows within 10 minutes of calving or before standing attempts are made.
• Do not feed colostrum from cows of unknown MAP status.
• Clean teats to ensure sanitary colostrum collection.
• Do not pool colostrum.
• Heat tx colostrum—60°C (140°F) for 60 mins. Use standard plate and coliform counts to monitor effectiveness.
• Store colostrum at 3–4°C for 0-3d, then discard or freeze.
  Raise calves well-separated from adult cattle.
• Feed calves milk replacer or pasteurised milk –> minimises, but does not eliminate, the risk of MAP infection.
• Even with effective pasteurisation, post-pasteurisation contamination with MAP is possible. Uncontaminated milk replacer powder is MAP-free.
• Prevent contamination of calf grain, water, feeding implements, and calf pens by manure from adult cattle.
• For heifers originating from high prev herds test for MAP faecal shedding at 7-14mo.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 44

What are recommendations for management of calves on MAP infected beef farms as per the 2012 ACVIM Consensus Statement?

Answer 44

• Remove cow-calf pairs from calving area as soon
  as possible after calving.
• Maintain segregated calving areas for MAP positive cows.
• Ensure access to a clean water source; ponds may become MAP-contam and serve as a source of infection.
• Herd sires are MAP test-negative in bull-bred herds.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 45

A killed vaccine in an oil base is available for vaccination of ruminants against Johne’s Dz. Why is its use more widespread in sheep than cattle? What is its efficacy in terms of preventing disease progression and MAP shedding in cattle?

Answer 45

• Limited use as can interfere w bovine tuberculosis testing.
• Good success with control in sheep: Gudair –> 90% reduction in within-flock prevalence in vaccinated flocks.
• Prevents the progression of infected cattle to clinical dz in most cases; effect on reduction of bacterial shedding is less pronounced, effect on prevalence of infected animals is limited. Therefore must use w good management plan.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 46

The phenotype (infection status) shown by individual animals is a combination of genetically determined factors (susceptibility and resistance genes) and environmental factors (exposure to MAP). How can genetic selection be used as a tool to control MAP infections within herds?

Answer 46

• Genetic effects can be quantified best at sire level using phenotype of daughters.
• Heritability estimates range from 1- 18%; majority 9-12%.
• Genetic selection strategies are probably most suited to breeding more resistant animals, rather than using individual animal genetic marker profiles.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 47

What is the goal of treatment of animals with Johne’s Disease?

Answer 47

• There is currently no cure for Johne’s Dz.
• Tx is usually aimed at reducing CSx of weight loss and diarrhea, but cannot be expected to prevent shedding of the organism or clear the organism from tissues.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 48

What medications are registered for treatment of Johne’s Disease in North America?

Answer 48

• There are no drugs approved for treatment of paratuberculosis in North America, although monensin is approved for control in Canada.
• Tx confined to exceptional production or sport animals to allow for the collection of embryos or semen, and tx of pet animals that will be managed in a way to prevent contamination of the environment with MAP.
• With the exception of monensin, none of these drugs is approved for use in food animal species and tx is lifelong, therefore owners are relinquishing the possibility of salvage of these animals for human food if they try tx.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 49

What is the recommended treatment protocol for ruminants with clinical Johne’s disease as per the 2012 ACVIM Consensus Statement?

Answer 49

• Once-daily oral treatment with rifampin (10–20 mg/kg) and isoniazid (10–20 mg/kg).
• Monensin should be included if it can be legally administered for its label claims (prevention of coccidiosis in goats [22 ppm in feed] and beef cattle [200 mg/head/day], increased milk production efficiency in dairy cattle [410 mg/head/day]).

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 50

Does MAP have zoonotic potential for transfer from infected ruminants to humans?

Answer 50

• MAP has been incriminated as a triggering agent for
  Crohn’s disease in genetically susceptible individuals.
• Aetiology of Chron’s dz is multifactorial; likely an aberrant host–pathogen interaction to antigens in the GIT; many scientists believe MAP is one such organism.
• MAP primarily infects ruminants, but has also been reported in nonruminants, including nonhuman primates. There is extensive MAP strain sharing among species.
• Evidence that humans are exposed to MAP through foods
  derived from infected animals is strong and evidence of
  exposure via domestic water supplies is weak.
• Evidence for MAP assoc with Crohn’s disease is strong, but association must not be confused with causation.
• The strength of evidence that MAP is a cause of Crohn’s disease is moderate.

Ref: ACVIM Consensus Statement (2012) - Johne’s Dz.

Question 51

What genetic characteristics of GI nematodes promote development of anthelmintic resistance?

Answer 51

• Rapid rates of nucleotide sequence evolution.
• Large pop resulting from the high fecundity of each indv nematode –> exceptionally high level of genetic diversity.
• Population structure consistent with high levels of gene flow (dissemination).
• As a result, these helminths have the genetic potential to respond rapidly and successfully to chemical attack and the means to ensure dissemination of their resistant genes by host movement from farm to farm.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 52

What are the three classes of anthelmintics currently used in small ruminants?

Answer 52

1. Benzimidazoles: incl albendazole, fenbendazole.
2. Cholinergic agonists: incl levamisole/morantel.
3. Macrocyclic lactones or avermectins and milbemycins: incl ivermectin, moxidectin.
   Resistance to all 3 classes has been reported in US.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 53

List the important GI parasites of small ruminants. To which is there the most resistance?

Answer 53

• Haemonchus contortus (most resistance).
• Telodorsagia circumcinta.
• Trichostrongylus axei.
• Nematodirus spp.
• Cooperia spp.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 54

Describe the faecal egg count reduction test for determination of anthelmintic resistance in nematodes.

Answer 54

• The modified McMaster technique is used to determine pre- and post-treatment fecal egg counts.
• Once resistant helminths are documented, the species should be determined through larval identification.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 55

Describe egg hatch assays/larval development tests for determination of anthelmintic resistance in nematodes.

Answer 55

• Eggs from feces are incubated with concentrations of
  the anthelmintic to be tested and the eggs are allowed to
  hatch. A dose-response curve is generated.
• Adv: a single fecal sample can be tested simultaneously for all available classes of anthelmintics.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 56

What route of administration of anthelmintics is recommended in small ruminants in the US?

Answer 56

Oral only.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 57

When underdosing or administering a drug in a manner that results in suboptimal drug absorption or bioavailability, or both, partially resistant worms are more likely to survive, mate and produce homozygous, fully resistant worms. How call anthelmintics be used in small ruminants to maximise efficacy?

Answer 57

• Evaluation of the efficacy of anthelmintics on each farm is essential to any on-going control program via FECRT or larval development assays.
• Never rotate anthelmintics within a grazing season.
• If other helminths such as tapeworms, which require a drug to which GI nematodes are already resistant, the drug effective against Haemonchus and the drug for these other helminths should be used concurrently.
• For most anthelmintics, efficacy is related directly to duration of the contact between drug and parasite; therefore full dose must lodges in rumen, bind to rumen particulate matter and be released slowly down the GIT.
• Presenting a drench to the buccal cavity, rather than pharynx/oesophagus, can stimulate closure of the oesoph groove –> bypass rumen; therefore always admin via a drenching gun, or syringe with a drench adapter.
• Increasing the duration of contact between drug and parasite can be accomp by repeated dosing 12h apart (this is especially true for the short-acting benzimidazole drugs).
• Withholding of food from animals overnight before drenching may increase the efficacy of benzimidazole anthelmintics, but not ivermectin or levamisole.
• The simultaneous use of anthelmintics in different drug families even where each drug in the combination is ineffective may have value in many situations.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 58

Outline strategies for prevention of anthelmintic resistance in GI parasites of small ruminants.

Answer 58

• Prevention of resistance must be aimed at reducing the rate with which resistance alleles accumulate.
• Strategies must be in integrated early on in the process of resistance evolution, before there is any clinical evidence of reduced drug effect.
• Following practices that ensure maintenance of an adequate level of refugia and maximise the likelihood that drug treatment will kill partially resistant parasites.
• Using 2 anthelmintics together has a synergistic effect –> clinically relevant increases in the efficacy of treatment. This synergistic effect is most pronounced when level of resistance is low. Once high-level resistance to both drugs is present, the synergistic effect is unlikely to produce acceptable levels of efficacy.
• Drug rotation no longer recommended as accelerates resistance, therefore recommended to use a single drug until resistance develops.
• Maintain refugia through selective deworming:
• • 20–30% of animals harbour 80% of the worms.
• • Treatment of animals with low worm burdens does little to control parasites, but removes an imp source of refugia.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 59

How can biosecurity protocols be used to decreased resistance in GI worms of small ruminants?

Answer 59

• Quarantine (on dry lot where faeces can be removed) every new addition to the flock, dose with triple-class anthelmintic therapy, and perform FECRTs.
• Feed should be withheld for 24h before tx, then moxidectin, levamisole, and albendazole should be admin consecutively (do not mix drugs together).
• Fourteen days later FEC sould be zero and faecal flotation should yield very few or no eggs.
• After this tx animals should be placed on a contaminated pasture not a clean pasture as any surviving worms will be triple resistant and there will be no refugia on pasture to dilute the future transmission of any eggs that are shed.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 60

Young lambs/kids and pregnant ewes/does should be dewormed routinely, however in adult ewes/sheep the FAMACHA system can be used to guide strategic deworming. Describe this program.

Answer 60

• Ocular mucous membranes of sheep and goats are categorised by comparison with a laminated color chart of sheep conjunctivae to assess degree of anaemia caused by H. contortus burden.
• On farms where low to mod levels of resistance to one or more drugs (60–95% reduction in FERC) have been dx, a useful strategy to help gain the full benefits of treatment and resistance prevention could be to use these ‘‘less-effective’’ drugs, to give a sufficient reprieve from infection until the next FAMACHA examination.
• This strategy will help preserve the efficacy of the still fully effective drugs for use in severely affected animals while decreasing egg contamination of pastures.
• Borderline tx score 3 mm pink (PCV 18-22%).
• Tx score 4 mm pink-white and 5 mm white (PCV

Question 61

Describe how pasture management can be used to reduced anthelmintic resistance in GI parasites of small ruminants.

Answer 61

• A safe pasture has not had sheep/goats on it for 6mo during cool/cold weather or 3mo during hot, dry weather.
• Weaning sheep and goats at 2mo of age and rotating them through pastures ahead of the adults will minimize the exposure of susceptible animals to large numbers of infective larvae.
• Keeping pastures short.
• Low stocking density; general rule 5-6 goats/acre.
• Heavily contam pastures can can be tilled and reseeded.
• Ewe or doe in periparturient relaxation of resistance will be a source of eggs for the environment.
• Strategic deworming to remove arrested or recently emerged larvae before they contaminate the pasture will reduce pasture contamination.
• Tx 2wk after a rain that removes recently acquired
  worms before they can begin passing eggs also will
  decrease pasture contamination.
• Providing sufficient dietary protein is vital during the periparturient period and during rapid growth, so that animals will tolerate the worm burden better as well as increase the animals’ resistance to infection.
• When plants high in condensed tannins are grazed, there is evidence that the incoming larvae are adversely affected as well as providing bypass protein for the host.
• Cattle and small ruminants can be grazed together where each consumes the parasites of the other, which reduces
  available infective larvae for the preferred host species.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 62

Which breeds have been reported to have genetic resistance to Gi parasitism?

Answer 62

• Scottish Blackface, Red Maasai, Romanov, St. Croix, Barbados Blackbelly, and the Gulf Coast Native.
• Katahdin sheep not as well proven.
• Crossbreeding for parasite resistance diminishes production traits therefore can breed for resistant individuals within a breed (cull parasitised animals; select for resistance on basis of FECs).

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 63

What nutritional interventions can be made to improve resistance to GI parasitism in small ruminants?

Answer 63

• Increased protein intake –> abolishment of the periparturient egg increase in lambing ewes; immunity is closely related to protein repletion and GI nematodes inc demand for AAs by the sheep.
• Supplementation with phosphorus has been shown to
  prevent worm establishment.
• Cobalt deficiency also has been associated with reduced immunity to gastrointestinal nematodes.
• Adequate copper values are necessary for development of immunity to gastrointestinal nematodes.
• Recent work suggests that treatment of lambs with copper oxide wires orally reduces H contortus burdens. However, copper toxicosis would be a concern associated with this treatment.
• The addition of molybdenum at a concentration of 6–10 mg/d decreased worm burdens in lambs.

Ref: ACVIM Consensus Statement (2006) - Anthelmintic Resistance of GI Parasites in Small Ruminants.

Question 64

Describe the Bovine Viral Diarrhoea Virus (BVDV).

Answer 64

• Family: flaviviridae.
• Genus: pestivirus.
• Enveloped, single-stranded RNA virus.
• Two species: BVDV1 (12 subgenotypes), BVDV2 (2 subgenotypes).
• In the US there are 3 major subtypes: BVDV1a, BVDV1b, BVDV2a.
• Exists as non-cytopathic (90%) or cytopathic biotypes.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 65

What is the prevalence and host range of BVDV?

Answer 65

• Species that are susceptible to BVDV include cattle, sheep, pigs, goats, bison, captive and wild cervids, New and Old World camelids.
• Prevalence US cattle: 40-90% indv level, 28-53% herd level,

Question 66

Describe the epidemiology of acute BVDV infections.

Answer 66

• The source of most acute infections is cattle PI with BVDV, although acutely infected cattle can be a source of virus to other susceptible cattle.
• The most effective route of transmission appears to be nose-to-nose contact.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 67

List the clinical signs of acute BVDV infections.

Answer 67

• Majority are subclinical/inapparent infections; may display mild fever, leukopenia, anorexia, and dec in milk prod.
• Diarrhoea.
• Depression.
• Oculonasal discharge.
• Anorexia.
• Decreased milk production.
• Oral ulcerations.
• Pyrexia.
• Leukopenia charac by lymphopenia and neutropenia.
• Immunosupression (leukopaenia and diminished function of immune cells) –> inc susc to other infectious dz agents e.g. BRDC polymicrobial infections.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 68

List the clinical signs of the haemorrhagic form of acute BVDV infections.

Answer 68

• Charaterised by thrombocytopaenia.
• Platelet dysfunction.
• Bloody diarrhoea.
• Epistaxis.
• Petechial haemorrhages.
• Ecchymotic haemorrhages.
• Bleeding from injection sites or insect bites.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 69

Describe reproductive BVDV infection in bulls.

Answer 69

• Bulls infected with BVDV are capable of shedding virus in semen which can survive cryopreservation and processing of semen for artificial insemination –> infect cows.
• Acutely infected bulls shed lower conc in semen than PIs.
• Protection from a systemic immune response because of a blood-testes barrier is believed to be the mechanism for the localised, prolonged testicular infection.
• Uncertainty currently exists regarding whether bulls with a prolonged testicular infection can become viremic and infectious to other animals.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 70

Describe reproductive BVDV infection in cows.

Answer 70

• Infection of pregnant cattle –> foetal infection.
• Potential outcomes: PI, abortion, embryonic or fetal resorption –> repeat breeding, congenitally malformed offspring, mummification, congenital infections manifesting as normal calves or calves of poor vigor.
• Embryonic/fetal death and abortion most common during the first trimester, however mid- and late-term abortions and stillbirths can be caused by BVDV.
• Congenital malformations (100-150d): cerebellar hypoplasia, hypomyelinogenesis, hydranencephaly, alopecia, cataracts, optic neuritis, brachygnathism, hydrocephalus, microencephaly, thymic aplasia, hypotrichosis, pulmonary hypoplasia, growth retardation.
• Infection of cattle before insemination reduces conception rates; could be due in part to ovarian infection and dysfunction as a result of BVDV viremia.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 71

Describe the pathophysiology of persistent infection with BVDV in cattle.

Answer 71

• Occurs when foetus infected at days 45-125d gestation.
• Immunotolerance is specific to the infecting NCP strain of BVDV, and postnatal PI animals can respond immunologically to heterologous strains of BVDV therefore seropositive status cannot be utilised dx to rule out PI.
• Virus is found in many tissues in PI animals and shed from multiple sites, including nasal and ocular discharges, urine, semen, colostrum/milk, and feces.
• Vertical trans rate is 100%; all PI cows –> PI offspring.
• Most PI calves are born weak, stunted, and die shortly after birth or fall behind their cohorts as they mature.
• Some PI calves are born without obs abnormalities.
• PI animals can have an impaired immune resp, making them more susceptible to pathogens –> early death.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 72

Describe mucosal disease of cattle persistently infected with BVDV.

Answer 72

• Occurs when a PI becomes super-infected with a CP.
• The origin of the CP BVDV can be external e.g. MLV containing CP BVDV, or internal as the result of mutations of the NCP BVDV (the PI biotype) –> CP BVDV.
• Multiple clinical forms: acute fatal mucosal disease, chronic mucosal disease, chronic mucosal disease with recovery, and delayed onset mucosal disease.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 73

Describe diagnostic tests for BVDV.

Answer 73

• Virus isolation = gold standard; use serum, whole blood, semen, nasal swabs, and various tissues; buffy coat is preferred antemortem sample, lymphoid tissue necropsies.
• Antigen detection methods such as IHC and antigen capture ELISA (ACE) are rapid and inexpensive; performed to detect PIs on skin biopsies of young animals that would test neg by virus isolation and ACE on serum because of inhibition of the tests by acquired colostral antibodies.
• IHC and ACE do not detect acutely infected animals.
• RT-PCR: high sensitivity has allowed it to be adapted for pooled testing of tissues, whole blood, serum, or milk; economic for herd screening, but pooled samples need to be frequently validated.
• Serologic testing: difficulty in differentiating response to a natural infection, vaccination, or transfer of maternal ABs; can be used to assess vaccine efficacy and to test sentinels to determine if BVDV exposure has occurred in the herd.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 74

What are the three key aspects of elimination/prevention programs for control of BVDV in cattle herds?

Answer 74

1. Identification and elimination of PI animals.
2. Enhancing immunity through vaccination.
3. Implementing biosecurity measures to prevent BVDV exposure of susceptible cattle.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 75

Describe techniques to detect BVDV PI animals in breeding herds.

Answer 75

• All calves, replacement heifers, bulls, and non-pregnant cows without calves should be tested for PI status before entry of the bull.
• Negative calf indicates a negative PI status for the dam.
• Dams of test-pos calves need to be tested for PI status. Dams that test negative could reenter the breeding herd.
• Pregnant cattle should be segregated and their calves be tested before return to the breeding herd.
• Because the occasional acutely infected animal might be PCR, IHC, or ACE positive, valuable cattle should be retested after 30 days using virus isolation or RT-PCR assays on blood samples.
• Indv testing is very expensive so can be more economic to use evaluation of production records, BVDV evaluation of aborted fetuses, use of sentinel animals, pooling strategies by RT-PCR testing, and BVDV testing on sick or dead cattle.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 76

Describe vaccine programs for BVDV.

Answer 76

• Modified-live and inactivated vaccines containing both BVDV1 and BVDV2 strains are now widely available.
• Inactivated: disadv that 2 doses are req –> compliance.
• Effectiveness has been to limit transmission and clinical dz rather than completely prevent infections with BVDV.
• Protection against fetal infections after BVDV vaccination varies, being influenced by use of inactivated or modified live vaccine, the timing of challenge, and the degree of homology between vaccine and challenge strains.
• Preconditioning cattle by preweaning and vaccinating against BVDV and other respiratory pathogens before commingling and shipping reduces the incidence of bovine respiratory disease in feedlot cattle.

Ref: ACVIM Consensus Statement (2010) - BVDV.

Question 77

What biosecurity practices can be employed to keep a herd BVDV free.

Answer 77

• All purchased cattle should be isolated and tested for PI status before entry into the herd.
• Isolation of new cattle for 3 weeks before entry into the herd should prevent trans from acutely infected animals.
• Purchased pregnant cattle should be isolated and their offspring tested to ensure that they are free of BVDV.
• Semen should only be used from bulls that have been tested for BVDV infection.
• Exposure of cattle to other ruminants at exhibitions should be limited, and animals should be quarantined for 3 weeks before reentry into the breeding herd.
• Elimination of fence-line contact with neighbouring livestock and sanitation of equip and people entering farm.

Ref: ACVIM Consensus Statement (2010) - BVDV.