Review Articles Flashcards
Contact of calves with _____ is the most important risk factor in Johne’s transmission?
Adult cow feces
Johne’s transmission routes are?
feco-oral, colostrum and milk, in utero
Age at which calf susceptibility to MAP exposure reduces development of lesions?
6 months
Improving _______ is more efficient to decrease MAP prevalence in a herd than ___________.
Calf management; test and cull
3 factors that increased the risk of being a MAP infected herd
contamination of udders with manure, group housing of periparturient cows, & presence of more than n 1 cow in the maternity pen
Calves exposed to a contaminated calving pen during ________ were more likely to become infected by MAP.
3 - 10 days
This provided a protective effect to calves from MAP
calving in an individual pen when cows are on grass
MAP positive culture was reduced by _______
attending calvings
Washing cows udders before parturition was associated with increased/decreased risk of infection with MAP
increased
Colostrum from ELISA positive cows increased/decreased risk of being a MAP infected herd
Increased
Calves fed pooled colostrum from multiple cows were at greater/lower risk o testing positive compared to fed from their own cow?
Greater
Which is better, foster cow milk or milk replacer when considering Johne’s
Milk replacer. Calves suckling foster cows had odds ration 2.012 to be ELISA positive compared to milk replacer fed
feeding waste milk decreases/increases MAP infection
increases both ELISA and clinical cases
Does group housing pre-weaned calves during winter decrease MAP in herd?
No, it increases ELISA positive cows in herd
Which bacteria of the URT of cattle is considered the most common bacterial pathogen of BRD?
Mannheimia haemolytica
Which bacteria can be a primary pathogen or a co-infection?
Mycoplasma bovis, potentially synergistic with M haem
For most BRD pathogens, clinical sign resolution occurs…
4 - 6 days after retail temperature returned to less than 40* C.
When does seroconversion occur for BVDV, BRSV, BHV-1, and M bovid?
9 - 21 days, peak b/w 23-40 days.
Clinical signs of BRD resolved up to ___ days after shedding ceased.
at cessation or shedding or up to 3
These APP’s increase as soon as 4 hours after insult
Serum Amyloid A and C reactive protein
These APP’s increase later (24 -48 hours) after insult
haptoglobin or Fibrinogen
Haptoglobin’s sensitivity to diagnose BRD =
61 - 100%
haptoglobin specificity to diagnose BRD =
80 - 100%
SAA Sen & Sp to diagnose BRD =
59-100; 43-94%
Fib Sen and Spec to diagnose BRD =
57-80; 89-95%
Which APP performed better, but not statistically significantly?
Hp > SAA & Fb
The optimal MODS SGI cut point was _____; with Sensitivity and specificity of _____.
8; 92 & 88%
Odds of nonsurvival were _____ when the MODS SGI score was greater than _____
86, 8
Which organ system was most affected in MODS SGI and which one in MODS EQ?
cardiovascular & hepatobiliary
MODS SGI does what?
Predicts 6 month survival from discharge in horses with acute surgical colic.
Definitiion of MODS = ?
the presence of altered organ function in an acutely ill patient such that the homeostasis cannot be maintained without intervention; common sequela to sepsis
MODS One hit model definition…
organ failure develops as the direct result of massive initial insult - sepsis/trauma
MODS Two hit model definition…
prming insult (1st hit) followed by a subsequent insult (2nd hit). Second insult may be small, but enhances inflammation and immune dysfunction
MODS Sustained hit model definition…
continuous insult (ventilator associated pneumonia which causes both the initial and sustains dysfunction
Proposed mechanisms of MODS:
- Cell or tissue hypoxia
- Induction of cellular apoptosis
- Translocation of microbes or components of microbes for GI tract
- Immune system dysregulation
- Mitochondrial dysfunction
MODS likely a complex combination of the above, evidence suggests that immune system dysregulation and subsequent mitochondrial dysfunction might be prevailing pathways.
What are PAMPs & DAMPs?
Pathogen/Danger Associated Molecular Pattern
Pathogen - alert organism to invading pathogen
Danger - markers of endogenous cell damage
What are CARS?
Compensatory anti-inflam response syndrome, limit damage caused by proinflam response while not interfering with pathogen elimination. Can be detrimental and lead to immune system dysregulation when exaggerated or poorly timed (immunoparalysis).
Regarding MODS, what is mitochondrial dysfunction?
Neutrophils activate mitochondrial dysfunction pathways; cytopathic hypoxia (disconnect between adequate oxygen delivery and poor oxygen utilization at tissue level). Results in cellular dysfunction +/- cell death. Can cause cellular hibernation-like state.
Renal dysfunction in MODS can occur in 2 ways:
- ) Regular AKI - renal epithelial necrosis, renal hypoperfusion and ischemia (least common, 22%).
- ) Apoptosis (not necrosis), caused by inflammation cytokines and endotoxin. Apoptosis is difficult to appreciate on routine histopath; blood flow typically adequate or increased during sepsis.
Adrenal dysfxn / Critial illness - related corticosteroid insufficiency (CIRCI) = ?
inadequate corticosteroid activity relative to illness severity; describes a reversible dysfxn of any aspect of HPA axis caused by proinflam mediators. Corticosteroid tissue resistance increases in acute inflammatory disease, adequate amounts of cortisol produced, but receptor binding is impaired. CONTROVERSIAL topic in human med.
True of False: HCAI’s (healthcare associated infections) exceeded the number of cases of every notifiable infectious disease in the US and deaths associted w/ HCAIs are among the top 10 dauses of death in US.
True
In VTH’s, which 2 pathogens were identified as common and associated w/ zoonotic infections?
Salmonella & MRSA
Perceived and actual HCAI control are discordant.
40% of hospitals believe to be in top 10% of most effective infection control (false sense of adequacy).
Qualify the evidence of efficacy of nutraceuticals for the alleviation of clinical signs of osteoarthritis.
Poor except for the use of omega - 3 fatty acids in dogs.
Other than Omega 3 Fatty Acids, which other nutraceutical had evidence of efficacy for OA?
Green lipped mussel powder in 3 of 4 studies.
What is the mechanism of action of O3FA?
Lower arachidonic acid concentrations and alter production of eicosanoids to less inflammatory forms.
In cats, which nutraceuticals was found to have beneficial effect?
O3FA, glucosamine, and green lipped muscle powder.
Green Lipped Muscle Powder mechanism of action?
Eicosatetracnoic acid (ETA) dual inhibitor of arachidonic acid oxygenation by both cyclooxygenase and liposygenase pathways
Where does Tritrichomonas foetus live in the bull?
Smegma of epithelial lining of the penis, prepuce, and distal urethra
What age bull is considered chronically infected with T. foetus?
3 - 4 years old or older
What clinical signs can be associated with T. foetus in cows and heifers?
Reproductive failure: endometritis, placentitis, salpingitis, abortion, and puometra.
What reductions in calf crop can occur due to 20-40% prevalence of T foetus in bulls?
14 - 50% loss of calf crop, 12 - 30 days decreased growing period, and decreased weaning weights by 22 - 53 pounds.
T. foetus prevention is achieved by:
limiting unwanted bull exposure, purchase virgin bulls, or bulls from T. foetus negative herds, implement AI.
What % reduction occurred with whole-cell killed vaccination against T. foetus?
20%
Conclusion of review statement = ?
No or limited evidence that vaccines decreased infections or open risk in heifers had a small body of evidence with moderate quality to support it. Some evidence exists that vaccination decreases abortion as the magnitude of effect was large, but low quality eviddence availabel
What is the most common clinical manifestation of disease caused by R. equi?
Pyogranulomatous bronchopenumonia with abscessation.
What is the most common form of R. equi recognized on endemic farms?
Subclinical with sonographic evidence of peripheral pulmonary consolidation or abscessation without manifesting clinical signs
Age of manifestation of R. equi clinical signs
3 - 24 weeks of life; most <16 weeks
Clinical Signs of R. equi in foals
fever, lethargy, cough; anorexia, tachycardia, tacypnea, flared nostrils, increased resp effort and abdominal excursion
Extrapulmonary disorders of R. equi include?
39 identified; immune mediated included; Survival was lower among foals with EPDs than those without. Can occur with and without pneumonia
How does blood culture affect prognosis with R. equi?
Culture positive less likely to survive than culture- negative.
Major route of pulmonary infection for R. equi= ?
Inhalation
Incubation period after intrabronchial challenge with R. equi = ?
9 days heavy inoculum, 2-4 weeks lower inoculum; natural incubation period unknown
Median age of diagnosis of R. equi on endemic farms
35-50 days
What carries virulence in R. equi?
80 - 90 kb plasmid, loss of makes unable to cause disease. Plasmid can enable intracellular replication in macrophages.
What is the significance of the pathogenicity island in R. equi?
It is crucial for virulence of bacterium
What proteins are unique to R. equi? Identify the groupings and which is the most important?
Virulence - associated protein family (Vap). 6 full length vap genes (A, C, D, E, G, H) and 3 truncated pseudogenes (vapF, I, and X). VapA encodes an immunodominant, temperature-iducible, & surface-expressed lipoprotein.
What other 2 factors determine virulence with R. equi?
virR and orf8; each encode a regulatory protein
Pathogenesis of R. equi
Inhaled, taken up by alveolar macrophages through receptor mediated phagocytosis. Receptors used by macrophages engulf complement opsonized are R. equi complement receport 3. Once engulfed by resident macrophages, able to modify the phagocytic vacuole to prevent acidification and subsequent fusion with lysosomes.
Which portion of the immune system is absolutely required for clearance of virulent R. equi in mice?
Functional T lymphocytes, cytokines & direct cytotoxicity
Describe the T lymphocyte responses and their influence of R. equi.
CD4+ (helper) major role and required for clearance of pulmonary infection. Type I response (INF - gamma, helper response) sufficient for pulmonary clearance. Type 2 IL-4 production = detrimental
R. equi clearance in adults
lymphoproliferative responses to R. equi antigen, development of R.equi-specific cytotoxic T lymphocytes (CTL).
Is vaccination of R. equi successful?
No
Define Equine piroplasmosis
An infectious, tick-borne disease caused by the hemoprotozoan parasites Theileria equi and Babesia caballi affecting all equid species.
What is the resevoir of equine piroplasmosis?
persistently infected equid for T. equi, both ticks and horses are reservoirs
Is the complement fixation test considered sensitive to detect persisten infections of equine piroplasmosis?
No, abundant data shown that CFT lacks sensitivity.
Ticks that carry and transmit piroplasmosis
Ixodes, dermacentor, amblyomma, iatrogenic blood transfers
What 3 life stages do both parasites of Equine piroplasmosis go through?
Sporozoite (asexual transmission stage), merozoite (asexual blood stage) and gametocyte (sexual blood stage).
Result of infection by T. equi or B caballi?
Erythrocyte lysis causing anemia; intravascular after merozoite ruptures RBD. Splenic macrophage removal as well. Biochemical structure of RBC membranes changes dramatically during infection with T. equi infection.
Decreased platelet counts have been identified in Equine piroplasmosis affected animals. What are the hypotheses for this?
Immune mediated destruction, splenic sequestration, and/or excess consumption (as seen in DIC). Severe hypercoagulability, SIRS, and MODS may be noted
Which results in a more severe clinical disease?
T. equi > B. caballi
Can neonatal foals be infected in utero?
T. equi present with acute, severe signs. B. caballi rare
Which organ plays a significant role in immunity to Equine piroplasmosis
Spleen
Describe foal immunity to Eq. piroplasmosis
protected from 1 - 5 months after consumption of colostrum of a carrier mare; can be protected up to 9 months of age.
Methods of diagnosing Eq. prioplasmosis: CFT, IFAT, cELISA
Light microscopy, false negative occur even during infection.
- Complement Fixation Test: Not diagnostic test of choice, positive if dilution 1:5; very specific, but not sensitive, especially chronic infection. IgG interference occurs as well.
- Indirect immunofluorescent antibody tests (IFAT); more sens than CFT, good spec.
- Western blot research available
- cELISA regulatory test of OIE for international horse transport. EMA - 1 is highly conserved immunodominant surface ag specific to T. equi. RAP - 1 for B. caballi 25% more cases diagnosed than CFT. NOT available to general practitioner. cELISA can be (+) for 24 months after clearance.
- PCR been for research. able to identify when percent parasitemia = 0.000006%. nested PCR detects 3.6x more infections than microscopy and 2.2x more than standard PCR.
When is treatment of piroplasmosis used?
Decreasing clinical signs and reducing fatalities. Chronic infection in endemic areas maintains life-long immunity.
Treatment for Eq. Piroplasmosis
Imidocarb most effective.
What are the adverse effects of diproprionate salt (ID)?
Primarily anticholinesterase (sweating, agitation, colic, and diarrhea). Tx: atropine/glycopyrolate.
Discuss prevention
Not possible in endemic areas. Regulation of equine movement in non-endemic nations/regions. No vaccine available.
Silymarin is derived from…
It is an extract of milk thistle fruits and seeds, containing 7 flavonolignans
Which is a predominant compound of silymarin?
Silibinin
Discuss pharmacokinetics of milk thistle:
Low bioavailability PO, conjugated by glucuronidation, and excreted into bile and urine w/ minimal phase I metabolism. Fairly insoluble in water & not readily absorbed in intestines
Are liver concentrations higher, lower, or no change in patients with hepatic disease?
Higher, 3 - 5x. Enterohepatic circulation may contribute.
Are pharmacokinetic studies similar across species?
No, dogs mirror humans, cats differ from other species.
Is silibinin treatment effective?
Yes, reduces mortality by 50%.
What evidence is there for silibinin?
Limits biochem and coag parameters, decreases degree of hepatic hemor and necrosis, prevents death. Prevent hepatic enzyme activity and other toxic changes. Protect against iatrogenic toxins?
Define microparticles
small membrane-derived vesicles, are derived from many cell types and released into the circulation. Can express antigens, contain cell surface proteins, cytoplasmic contents, and nuclear components from their cell of origin that determines their composition, characterization, and transfer of biologic information.
Where do microparticles come from?
shear stress, complement activation, proapoptotic stimulation, or cellular damage.
Which enzymes are significant to phospholipid membrane stabilization?
Phophatidylserine, phophatidylethanolamine, flippases, floppases, and scramblases. Become redistributed when cellular activation occurs.
What mineral is significant in microparticle fromation?
Calcium
Describe microparticle generation:
Cytoskeletal disruption after cellular activation (phospholipid asymmetry) initiated by stimuli (shear, oxidative, cytokine stresses, complement activation, hypoxia, apoptosis, cell damage, & agonist induced (in platelets). Membrane contracture and budding occur –> Microparticle generation that are proinflammatory and procoagulant.
What are the roles of Microparticles?
Involved in tightly controlle dbiologic functions: inflammation, hemostasis, transfer of surface proteins, angiogenesis, binding sites for coagulation (PS), enhance platelet adhesion to endothelium, tissue factor function, and thrombin production. ROLE OF MICROPARTICLES dependent on source of origin.
Finish the thought: “MPs could exert…
either beneficial or deleterious effects in disease states depending on cellular origin, stimulus for production, and the clinical setting.
Which is the most common chrnoic airway disease of the athletic horse?
IAD, cough, poor performance, excess mucus in the airways.
Describe the pulmonary function of RAO horses.
mucus accumulation, airway wall thickening, and bronchoconstriction, increased lung resistance, transpulmonary pressures, functional residual capacity, decreased dynamic lung compliance and arterial oxygen tension. Chronic respiratory acidosis.
Is RAO reversible?
Yes
Treatments for RAO?
IV bronchodilators (atropine, N-butylscopolammonium) or aerosol bronchodilators (ipratorpium bromide & albuterol)
What provides the lowest potential for respirable particulate & fungal release?
Late harvest, 2nd cutting hay baled at 85% dry matter, and haylage.
Which bedding is preferable for management or reduction of RAO?
Wood chips (not straw or poor hay) and pelleted feed.
In regards to R. equi genetic susceptibility, what association has been identified (SNP)?
IL-7 receptor gene and increased concentrations in CFU of TBA (no validation population though).
With Genome Wide Association Studeis, what association has been made regarding R. equi?
Comparisons among 3 groups (pneumonia, sub-clinical pneumonia, and no pneumonia) identified a significant association of a region on chromosome 26 that included the gene for the transient receptor potential cation channel, subfamily M member 2 (TRPM2).
Advances in genomic understanding of R. equi susceptibility include:
a gene related to innate immunity associated with R. equi pneumonia and likely multigenic.
What are p - glycoproteins (p-gp)?
most well characterized drug transporter in the ATP binding cassette (ABC) protein superfamily is encoded by the ABCB1 (MDR-1 gene). It is a unidirectional tranposrt from intra to extra-cellular.
What happens as a result of p-gps in relation to tumor cells?
For tumor cells, relatively low intracellular concentrations of anticaner drugs.
What is the function of p-gp?
protective for mammalian organisms by decreasing their exposure to potentially toxic xenobiotics.
Give an example of a p - gp defect (MDR1) defect.
MDR-1 mutant/mutant dogs that experience severe neurological toxicosis because of defective blood-brain barrier and accumulation of ivermectin in brain tissue
How do p - gp inhibitors act (Mechanism of action)?
- blocking the drug binding site either competitively, noncompetitive or allosterically
- interferring with ATP hydrolysis which is required for P-gp function
- altering the integrity of cell membrane lipids
* Competitively and noncompetitively blocking drug binding sites
What diseases are associated with alterations of eqine intestinal microbiota?
acute colitis, equine grass sickness, and laminitis
Which phyla predominate the health horse microbiota?
Firmicutes (46 - 70% in feces), Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Spirochaetes. Greater clostridiales in healthy horses compared to diseased horses.
Definition of probiotics per World Health Organization
live micro-organisms, that when adminstered orally at adequate concentrations, provide a beneficial effect beyond that of the nutritional value.
Are probiotics sustained beyond treatment period?
No, minimal duration of therapy beyond administration.
What are the 4 main mechanisms of action of probiotics to prevent colonization of the digestive tract by pathogenic strains or prevent disease?
1 - modulation of the host innate and acquired immune system
2 - antimicrobial production
3 - competitive exclusion
4 - inhibition or inactivation of bacterial toxins
What are produced by probiotics? (Antimicrobial)
fatty acids, lactic acid, and acetic acid
What evidence exists for use of probiotics to decrease Salmonella shedding in horses?
Very little.
