ACVIM Required Literature - Respiratory Dz

Question 1

Define Exercise Induced Pulmonary Haemorrhage (EIPH) as reported in horses.

Answer 1

• EIPH is defined as the presence of blood detected on tracheobronchoscopic examination after exercise, presence of red blood cells in BAL fluid, or both.
• There is no consensus about the concentration of red blood cells in BAL fluid that is diagnostic of EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 2

Does EIPH produce clinical signs?

Answer 2

• The CSx of EIPH often are considered to include: blood in the airways detected by either tracheobronchoscopy or examination of TTA or BAL fluid, poor performance, epistaxis, abnormalities detected on u/s or radiographic examination of the thorax, coughing, increased RR, respiratory distress or changes in behaviour.
• There is very low quality evidence of consistent clinical abnormalities in horses with EIPH, with the exception of presence of epistaxis after exercise for which there is moderate quality evidence.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 3

Does EIPH affect blood-gas exchange?

Answer 3

There is very low quality evidence of an adverse effect of EIPH on arterial oxygen tension during exercise. There is very low quality evidence of an assoc b/w higher blood lactate concentrations and EIPH during strenuous exercise.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 4

Is EIPH a cause of sudden death?

Answer 4

• There is low quality evidence that EIPH is causally associated with sudden death in race horses.
• There is no evidence of increased risk of sudden death in horses with EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 5

Does EIPH shorten the career of racehorses?

Answer 5

• There is moderate quality evidence that EIPH Grade 1-3 is not assoc with a shorter racing career of TB horses.
• There is moderate quality evidence that TB horses with epistaxis or Grade 4 EIPH have shorter careers.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 6

Is EIPH associated with inflammation in the lung?

Answer 6

• There is low quality evidence that EIPH leads to inflam in either the pulmonary parenchyma or airways.
• There is very low quality evidence that inflammation causes EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 7

Does EIPH cause lesions in the lungs?

Answer 7

• Gross and microscopic EIPH lesions are bilateral and most prevalent in the caudodorsal region of the lung; extend variably along dorsal border but never cranioventral.
• Gross lesions include discoloration of the pleural surface with underlying firm parenchyma that does not fully deflate.
• Pleural discoloration is a consequence of hemosiderin accumulation that is accompanied by pleural and septal fibrosis and angiogenesis.
• Vascular lesions include extensive remodeling of small pulmonary veins charac by accumulation of adventitial collagen and, in some vessels, smooth m hyperplasia.
• Electron microscopy of lungs from recently exercised horses shows breaks in the capillary endothelium and basement membrane, interstitial and intra-alveolar accumulations of erythrocytes, and interstitial edema that are compatible with capillary stress failure consequent to high intravascular pressure.
• There is high quality evidence that some horses with EIPH have extensive and characteristic pulmonary lesions.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 8

Is EIPH a progressive condition?

Answer 8

• There is moderate quality evidence that age is a risk factor for epistaxis/tracheal blood when confounding factors are not taken into account.
• When career duration was included in analyses, years spent racing was a significant), whereas age was not.
• There is moderate quality evidence that EIPH is progressive and related to load of racing.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 9

Does EIPH contribute to the pathogenesis of other diseases?

Answer 9

There is no evidence that EIPH is associated with development of other lung diseases.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 10

Is EIPH heritable?

Answer 10

• There is no published evidence regarding the heritability of EIPH.
• There is very low quality evidence of an association of pedigree with occurrence of epistaxis

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 11

Is EIPH associated with the finishing position in a race?

Answer 11

There is moderate quality evidence that mod to severe EIPH in Thoroughbred race horses is assoc with increased likelihood of inferior finishing position in a race.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 12

Is EIPH associated with the finishing time in a race?

Answer 12

There is very low quality of evidence that EIPH in SB racehorses is not assoc with finishing time in a race.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 13

Is EIPH associated with the distance a horse finishes behind the winning horse in a race?

Answer 13

There is mod quality evidence that TB racehorses with more severe EIPH finish farther behind the winning horse.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 14

Is EIPH associated with race earnings?

Answer 14

There is mod evidence that severity of EIPH in TBs is negatively assoc with a horse’s race earnings.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 15

Is there a dose response relationship between the severity of EIPH and performance?

Answer 15

There is low quality evidence of a dose-response relationship between severity of EIPH in Thoroughbred racehorses and severity of impaired performance.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 16

Is furosemide effective prophylaxis for EIPH?

Answer 16

There is high quality evidence that furosemide (0.5–1 mg/kg administered IV 4 hours before strenuous exercise) decreases the severity and incidence of EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 17

Does furosemide affect pulmonary vascular pressure?

Answer 17

There is moderate quality evidence that furosemide reduces pulmonary vascular pressure during strenuous exercise (treadmill studies).

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 18

Is aminocaproic acid an effective prophylaxis for EIPH?

Answer 18

• There is very low quality evidence that aminocaproic acid affects EIPH severity.
• Two treadmill studies show no effect on tracheobronchial bleeding but small numbers and bias.
  Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 19

Are bronchodilators effective prophylaxis for EIPH?

Answer 19

There is very low quality evidence that bronchodilators affect EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 20

Are corticosteroids effective prophylaxis for EIPH?

Answer 20

There is very low quality evidence that corticosteroids affect EIPH severity.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 21

Are nonsteroidal anti-inflammatory drugs effective prophylaxis for EIPH?

Answer 21

There is very low quality evidence that nonsteroidal anti-inflammatory drug treatment affects EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 22

Is pentoxifylline an effective prophylaxis for EIPH?

Answer 22

There is very low quality evidence that pentoxifylline affects EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 23

Are there other medications that are effective for prophylaxis of EIPH?

Answer 23

• Carbazochrome, equine serum concentrate, conjugated oestrogens, endothelin 1-A antagonist, nedocromil, nitric oxide and sildenafil have been investigated as prophylaxis of EIPH in single studies for each drug.
• The studies provided very low quality evidence that these drugs affect EIPH severity

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 24

Do nasal strips prevent EIPH?

Answer 24

There is low quality evidence that nasal strips decrease severity of EIPH.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 25

Are there other miscellaneous nonpharmacological treatments to prevent EIPH?

Answer 25

The studies provided very low quality evidence that herbal preparations or inhaled water vapor affect EIPH severity.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 26

Does furosemide affect performance of horses running on a racetrack?

Answer 26

There is moderate quality evidence that furosemide administered IV 4 hours prior to racing is associated with improved racing outcomes in TB and SB racehorses.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 27

Does furosemide affect performance of horses running on a treadmill?

Answer 27

There is low quality evidence that furosemide administered IV 4 hours before treadmill exercise results in delayed onset of fatigue and improved energetic cost of locomotion.

Ref: ACVIM Consensus Statement (2015) - EIPH.

Question 28

How can a definitive diagnosis of Rhodococcus equi bronchopneumonia be made?

Answer 28

Bacteriologic culture or amplification of the vapA gene using PCR from a tracheobronchial aspirate (TBA) obtained from a foal with one or more of the following:

(1) Clinical signs of lower respiratory tract disease;
(2) Cytological evidence of septic airway inflammation; or
(3) Radiographic or u/s evidence of bronchopneumonia.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 29

How can a definitive diagnosis of an extrapulmonary Rhodococcus equi infection be made?

Answer 29

• Bacteriologic culture or PCR amplification of vapA from samples from the site of infection if sampling possible.
• If from site which cannot be sampled e.g. uveitis, dx should be based on isolation of R. equi from a TBA or other
  primary sites of infection.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 30

Is a positive culture of R. equi from a nasal swab or faeces diagnostic for R. equi infection in foals?

Answer 30

• No.
• R. equi can be cultured from the faeces of healthy horses even if they live at farms w/o a Hx of R. equi pneumonia.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 31

What is the recommended treatment for infections with R. equi?

Answer 31

• A macrolide (erythromycin, azithromycin, or clarithromycin) plus rifampin based on in vitro activity data, pharmacokinetic studies, and retrospective studies.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 32

What are the advantages of clarithromycin and azithromycin over erythromycin for the treatment of R. equi bronchopneumonia?

Answer 32

• Considerably enhanced oral bioavailabilities especially in the absence of fasting.
• Prolonged half lives.
• Much higher concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar cells.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 33

What criteria are commonly used by veterinarians to determine duration of treatment of R. equi bronchopneumonia?

Answer 33

• Resolution of clinical signs.
• Normalisation of plasma fibrinogen concentrations.
• Radiographic or u/s resolution of lung lesions.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 34

What adverse effects are associated with administration of macrolides to horses and foals?

Answer 34

• Diarrhoea: often self limiting but may become severe; 17-36% foals on erythromycin.
• Hyperthermia: may be fatal; continues 4+ weeks post-tx.
• Fatal enterocolitis in mare ingesting small amounts of macrolides foals transferred to feed/water.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 35

Are long-acting macrolides recommended for treatment of R. equi pneumonia in foals?

Answer 35

• Tulathromycin and tilmicosin: no, both have very poor activity against R. equi.
• Gamithromycin: active against R. equi in vitro; 6mg/kg IM –> bronchoalveolar cell concentrations above the MIC90 for approximately 7 days; tx not recommended until clinical efficacy and safety have been established in foals.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 36

What treatment is recommended for foals infected with macrolide- and rifampin-resistant R. equi isolates or treatment of foals with adverse reactions to the combination macrolide–rifampin?

Answer 36

Macrolide- and rifampin-resistant isolates of R. equi are susceptible in vitro to fluoroquinolones, aminoglycosides, oxazolidinones, and glycopeptide antimicrobials.

• In 1 study, 18 of 24 isolates were also susceptible to chloramphenicol, tetracycline, and TMPS.
• Currently there are no data to indicate the preferred antimicrobial agent(s) for the tx of resistant infections.
• Oral doxycycline + rifampin has been used with anecdotal success; 10mg/kg PO BID –> serum, pulmonary epithelial lining fluid, and bronchoalveolar cell concentrations above the MIC90 of R. equi isolates for the entire dosing interval.
• Chloramphenicol achieves high conc within phagocytic cells in other species. However, the fact that only 70% of R. equi isolates are susceptible and the potential human health risk make this drug a less attractive alternative.
• High doses of TMPS (30 mg/kg q8-12 h PO) have been used alone or in combination with rifampin in foals with mild or early R. equi pneumonia, or for continued treatment in foals responding well to other antimicrobials.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 37

What ancillary therapies should be administered to foals with R. equi infections if indicated by their clinical signs?

Answer 37

• Nursing care, adequate nutrition and hydration, maintaining the foal in a cool and well-ventilated enviro.
• Humidified oxygen delivered by pharyngeal insufflation in moderately hypoxemic foals, or by percutaneous transtracheal oxygenation in severely hypoxemic patients.
• NSAIDs to reduce fever and impr attitude and appetite.
• Nebulization with saline, antimicrobial agents, or bronchodilators has been advocated but there are no data to either support or refute these therapeutic practices.
• Immune-mediated extrapulmonary disorders e.g polysynovitis generally resolve with successful tx of the accompanying pneumonia.
• Foals with R. equi septic arthritis or osteomyelitis often
  require aggressive local treatment e.g. joint lavage,
  surgical debridement, and IV or intraosseous RLP.
• Abdominal abscesses: surgical removal or marsupialization has been attempted but abdominal adhesions usually result in inability to resect the abscess.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 38

What is the prognosis for survival in foals with R. equi bronchopneumonia?

Answer 38

• Reports vary.
• Referral hospital (severe cases): 59-72%
• On farm: up to 100%.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 39

What is the impact of R. equi infections on future athletic

performance?

Answer 39

Prognosis for performance after successful treatment of uncomplicated R. equi pneumonia should be regarded as excellent.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 40

What factors can be used in screening protocols for identifying subclinical R. equi infections on breeding farms for which there is supporting evidence?

Answer 40

• White blood cell concentrations performed at
  monthly intervals.
• Thoracic ultrasound.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 41

What factors historically used in screening protocols for identifying subclinical R. equi infections have not been proven to be useful?

Answer 41

• Serum concentrations of antibodies against R. equi.
• Serum amyloid A concentration.
• Plasma fibrinogen concentration.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 42

Is treatment of all foals suspected to be subclinically affected with R. equi appropriate?

Answer 42

• Mass antimicrobial treatment of all foals with small subclinical pulmonary abscesses was unnecessary in a recent trial (no adv azith/rif over no tx).
• The extent to which these results may be extrapolated to other farms remains unknown because the proportion of foals that recover without tx may vary by farm, geographic region, and age at which foals lesions are detected.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 43

Is chemoprophylaxis against R. equi infection recommended on breeding farms?

Answer 43

Chemoprophylaxis with macrolides or other classes of antimicrobial drugs is not recommended because of conflicting evidence of efficacy and concerns for promoting resistance of R. equi and other bacteria to these drugs.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 44

Is environmental management recommended for prevention of R. equi on breeding farms?

Answer 44

Although R. equi pneumonia has been positively assoc with the density of mares/foals at farms and airborne conc of virulent R. equi, and neg associated with foaling at pasture, there is inadequate evidence to recommend environmental interventions to control or prevent R. equi pneumonia.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 45

Does administration of R. equi hyperimmune plasma prevent R. equi pneumonia?

Answer 45

• Administration of commercially available and licensed plasma containing antibody against R. equi is recommended as an aid for prevent-ing pneumonia caused by R. equi at endemic farms.
• Transfusion of HIP is not completely effective and therefore does not eliminate the need for screening or careful monitoring of foals at risk.

Ref: ACVIM Consensus Statement (2011) - R. Equi.

Question 46

Is vaccination against R. equi recommended?

Answer 46

• There is inadequate evidence to recommend active immunisation of mares or foals to control or prevent R. equi pneumonia.
• The evidence from mouse models, immune adult horses, and the study of other similar intracellular pathogens strongly suggests that an active immunization strategy to prevent R. equi disease will need to induce antigen-specific Type 1 cell-mediated responses. Antibody responses alone are unlikely to be protective.

Question 47

Isolation of multiple bacterial species from lung or transtracheal aspirate samples is a common finding in foal with R. equi pneumonia. Does the prognosis differ between foals with pure R. equi infections or mixed infections?

Answer 47

Isolation of multiple bacteria or fungi from a TBA along with R. equi does not negatively impact prognosis.

Ref: J. Vet. Intern. Med. 2012; 26(6):1443–1448.

Question 48

What feature of the bacteria is the the

pathogenesis of R. equi pneumonia is dependent on?

Answer 48

• The presence an 85- to 95-kDa virulence-assoc plasmid and the expression of the virulence-assoc protein A (VapA).
• R. equi isolates from horses or their environments are commonly classified as either virulent or avirulent, based on the presence or absence of VapA.

Ref: J. Vet. Intern. Med. 2013; 27(6):1555–1562.

Question 49

Virulent and avirulent isolates of R. equi coexist in equine faeces and the environment and are a source of infection for foals. Does transfer of the virulence plasmid between virulent and avirulent strains of R. equi occur?

Answer 49

• In an in vitro study examining isolates from foals and their environment, transfer of the virulence plasmid occurs with relatively high frequency.
• These findings could impact strategies to control or prevent R. equi through environmental management.

Ref: J. Vet. Intern. Med. 2013; 27(6):1555–1562.

Question 50

Is it necessary to treat all foals with subclinical R. equi with antimicrobials?

Answer 50

• No.
• Randomised, double-blind, prospective study of 108 foals with lesions 5-10cm: tulathromycin, doxy, doxy/rif, azith/rif and saline.
• 88% of control group recovered without need for tx.
• Time to recover shorter with azith/rif vs placebo.
• The proportion of foals that had evidence of dz progression did not differ sig between the tx groups.
• The majority of foals with subclinical pulmonary abscesses

Question 51

Gallium maltolate is a semi-metal compound that has antimicrobial activity against R. equi in vitro and may be an alternative tx for subclinical R. equi pneumonia to reduce resistance-pressure in macrolides. In a field trial comparing clarithromycin and rifampin to gallium maltolate was it proven to be an inferior treatment for subclinical R. equi?

Answer 51

• Gallium maltolate is not inferior to macrolides for treating foals with subclinical pneumonia.
• NB Multiple limitations in this study.

Ref: J. Vet. Intern. Med. 2015; 29(3):932–93.

Question 52

What is the age of presentation and most common clinical signs reported in foals with R. equi pneumonia?

Answer 52

• First CSx usually b/w 3 and 24 weeks of life, with most
  foals showing signs before 16 weeks of age.
• Infections are uncommon among horses > 6mo.
• In a report of 161 foals e R. equi pneumonia: cough (71%), fever (68%), lethargy (53%), and inc respiratory effort (43%).

Ref: J. Vet. Intern. Med. 2011; 25(6):1221–1230.

Question 53

List extra-pulmonary disorders associated with R. equi infection and their reported frequencies.

Answer 53

• Polysynovitis (~24-33%): immune-mediated or septic.
• Abdominal disorders (50% foals presented for necropsy): pyogranulomatous enterotyphylocolitis, pyogranulomatous lymphadenitis of the mesenteric or colonic lymph nodes large intra-abdominal abscesses and peritonitis.
• Ocular lesions incl uveitis, keratouveitis, panophthalmitis.
• Osteomyelitis.
• Septic synovitis (vs polysynovitis above which is a reaction to bacteria which is cleared early).
• Pyogranulomatous mediastinal lymphadenopathy.
• Abscess in liver, kidney, spleen, or nervous tissue/brain.
• Less common EPDs: pericarditis, endocarditis, cellulitis, dermatitis, subcutaneous abscesses, peripheral lymphadenopathy, guttural pouch empyema, pleuritis, sinusitis, myositis, stomatitis, pyometra and omphalitis.
• Immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, and telogen effluvium.

Ref: J. Vet. Intern. Med. 2011; 25(6):1221–1230.

Question 54

Describe the epidemiology of R. equi.

Answer 54

• Inhalation of virulent R. equi is the major route of pulmonary infection.
• Ingestion important route of exposure and likely immunisation but rarely –> pneumonia.
• Incubation period after experiment challenge: 9d - 4wk.
• Incubation period under field conditions is unknown; likely depends on several factors e.g. number of virulent bacteria in air samples, age of foal, host defence mechanisms.
• Most foals on endemic farms become infected early in life –> median age at time of dx is 35-50d on endemic farms.
• In 1 study, foals aged between 3 and 13 days were more susceptible to experimentally induced R. equi pneumonia than foals aged between 14 and 36 days.
• Older foals are also susceptible; experimental infection of 10 foals aged 27-67 days –> infection in all.

Ref: J. Vet. Intern. Med. 2011; 25(6):1221–1230.

Question 55

Describe Rhodococcus equi-phagocytic cell interactions in foals with pneumonia.

Answer 55

• Once inhaled, R. equi is taken up by alveolar macrophages through a process of receptor-mediated phagocytosis incl complement receptor 3 (CR3 or Mac-1) and possibly the macrophage mannose receptor.
• Once engulfed by macrophages, virulent R. equi modify the phagocytic vacuole to prevent acidification and subsequent fusion with lysosomes.
• Bacterial gene expression patterns are altered to accom survival in the intracellular enviro, allow acquisition of essential nutrients e.g. iron, as and promote resistance to host-derived ROIs.
• Uncontrolled intracellular replication of R. equi leads to necrosis of the macrophage.
• If opsonized with R. equi-specific antibody, the fate of the R. equi containing phagosome is altered and lysosome fusion occurs.
• In mouse models killing of R. equi by macrophages depends on TNF-a and IFN-c.
• As opposed to macrophages, neuts from foals and adult horses are fully able to kill R equi –> imp early defence.

Ref: J. Vet. Intern. Med. 2011; 25(6):1221–1230.

Question 56

Describe the adaptive immune response to R. equi in mice and adult horses.

Answer 56

• The strongest evidence for a role of antibody in protection against R. equi is the partially protective effect of passively transferred anti- R. equi hyperimmune equine plasma.
• Because of the facultative intracellular nature of R. equi, CMI mechanisms are of major importance in inf resistance.
• Although both CD4+ (helper) and CD8+ (cytotoxic) T cells contribute to host defense against R. equi in mice, CD4+ T lymphocytes probably play the major role.
• Studies in mice have clearly shown that a Type 1 response, charac by IFN-gamma prod by T helper lymphocytes, is sufficient to effect pulmonary clearance of R. equi whereas a Type 2 response, charac by IL-4 prod, is detrimental.
• Clearance of virulent R. equi in immune adult
  horses is associated with lymphoproliferative responses
  to R. equi antigens, development of R. equi-specific
  cytotoxic T lymphocytes (CTL), and IFN-g induction.

Ref: J. Vet. Intern. Med. 2011; 25(6):1221–1230.

Question 57

Describe the adaptive immune response to R. equi in foals.

Answer 57

• Neonates and perinates have diminished innate immune
  responses, decreased antigen-presenting cell function,
  and are less able to mount type-1 immune responses.
• Age-related deficiencies in R. equi-specific CTL activity has been documented in 3wk old foals. –> n by 8wk old.
• Antigen-presenting cells from foals have significantly lower CD1 and MHC class II expression vs adult horses.
• Young foals are deficient in their ability to prod IFN-c in response to mitogens –> hypoth IFN-g deficiency and Th2 bias might be basis of foals’ susceptibility to R. equi infect.
• However studies demonstration foals are deficient in IL-4 in response to stim with mitogens and after vacc –> clear polarisation toward a Th2 resp is unlikely in neonatal foals.
• Experimental infect of foals with virulent R. equi results in IFN-g induction and Ab resp similar to/greater than adults.
• Oral inoculation with virulent R. equi results in accelerated development of R. equi-specific CTL.
• Collectively, these findings unequivocally demonstrate
  that most foals have the ability to mount protective immune responses to R. equi.
• The basis for the peculiar susceptibility of foals to infection with R. equi is likely complex and multifactorial.

Ref: J. Vet. Intern. Med. 2011; 25(6):1221–1230.

Question 58

What is the the frequency of reactivation and nasal shedding of EHV-1 in horses hospitalised for treatment of acute, severe, gastrointestinal disease?

Answer 58

• In a study of 124 horses admitted to Michigan State Teaching Hospital, none were positive for EHV-1 DNA in buffy coat or nasal swab samples.
• Conclusion: nasal shedding and viremia of EHV-1 in hospitalized critically- ill horses with acute abdominal disorders is extremely rare.

Ref: J. Vet. Intern. Med. 2011; 25(5):1190–1193.

Question 59

A decrease in serum iron (sFe) concentration is an early and sensitive indicator of systemic inflammation caused by tissue necrosis, bacterial infections, or endotoxemia in
horses. What is the response of sFe to experiment infection with EHV-1? is there any difference in sFe concentrations in horses that develop EHM?

Answer 59

• Serum iron concentration decreases significantly in a biphasic pattern after EHV-1 infection.
• There was no significant difference in sFe concentration in horses that developed neurologic disease and those
  that did not in these experimentally infected animals.

Ref: J. Vet. Intern. Med. 2011; 25(5):1190–1193.

Question 60

List the findings of an epidemiologic survey into EIV in the United States which utilised nasal swab samples and patient records from 2,605 equids with acute onset respiratory disease developing between March 2010 to November 2013.

Answer 60

• 230 (9.7%) index cases tested qPCR positive for EIV.
• A higher-than-expected proportion of EIV qPCR-positive horses occurred in the 1–5, 6–10, and 11–15 age groups when compared to the

Question 61

What extrapulmonary disorder has been reported in a horse with Equine Multinodular Pulmonary Fibrosis? What are other reported causes of this condition in horses?

Answer 61

• Hypertrophic osteoarthropathy.
• Presented for hard swellings on the distal radii, distal tibias, proximal metatarsi and left metacarpus and fever.
• Pulmonary abscesses, pulmonary neoplasia, granulomatous pneumonia and rib fracture with pleural adhesions.

Ref: J. Vet. Intern. Med. 2011; 25(1):153–157.

Question 62

Which viral aetiologic agent that is not normally found in horses has been isolated from a horse with pyogranulomatous pneumonia?

Answer 62

• Asinine Herpesvirus-5.
• Pyogranulomatous pneumonia was diagnosed in this case of persistent respiratory disease, and AsHV-5 was detected in lung tissue collected from the affected animal.
• This virus also was detected in nasal secretions from 3 animals in direct contact with the mare, including 2 donkeys and 1 horse.

Ref: J. Vet. Intern. Med. 2012; 26(4):1064–1068.

Question 63

Inflammatory airway disease (IAD) in horses is a widespread, performance-limiting syndrome believed to develop in response to inhaled irritants in the barn environment. Is there any relationship between feeding hay on the ground or in a net and air particulate concentrations or BAL fluid eosinophil proportions?

Answer 63

• > 70% horses had IAD in the first month of training regardless of management group.
• Median respirable particulates were significantly higher when horses were fed from hay nets than the ground.
• Inhalable particulate and respirable endotoxin exposures were sig higher when horses were fed from hay nets.
• Feeding hay from a net resulted in significantly higher BALF eosinophil proportions over time.
• BALF eosinophils were significantly related to respirable particulate exposure.

Ref: J. Vet. Intern. Med. 2014; 28(3):918–924.

Question 64

Do immunological pathways vary according to cytological IAD subtypes, as determined by cytokine expression in BALF samples?

Answer 64

• TNF-a and IFN-gamma concentrations were significantly higher for IAD horses, compared with controls.
• Horses with ‘neutrophil’ subtype had significantly higher IFN-gamma concentrations than ‘neutrophil/metachromatic’ and ‘neutrophil/metachromatic/eosinophil’ subtypes.
• IL-4 conc in BALF was not modified by any condition.
• Data from this study might suggest a predominant Th1-cell response, while cytokine mRNA expression in previous studies revealed either no Th polarisation or a Th2-cell predominance, or a mixed Th1/Th2 response.
• TNF-a concentrations in BALF suggested the
  involvement of pulmonary innate immune response in
  the pathogenesis of IAD.

Ref: J. Vet. Intern. Med. 2014; 28(6):1838–1844.

Question 65

Do racehorses with inflammatory airway disease have increased concentration of circulating acute phase proteins?

Answer 65

Serum amyloid A, C-reactive protein and haptoglobin were not helpful in distinguishing between horses with IAD from horses with exercise intolerance from other causes.

Ref: J. Vet. Intern. Med. 2015; 29(3):940-945.

Question 66

Does an association exist between endoscopic inflammatory scores and mucus scores of upper and lower airways? Do endoscopic findings correlate with the lower airway inflammation measured by bronchoalveolar lavage cytology in horses?

Answer 66

• Tracheal mucus, tracheal septum thickness and bronchial mucus were significantly increased in horses with severe inflammation BALs.
• Tracheal mucus, tracheal septum thickness and bronchial mucus were correlated among themselves but not with upper airways scores.
• BAL neutrophils percentage was correlated with
  tracheal mucus, bronchial mucus and had a weak negative correlation with pharyngitis.
• Conclusion: lower airway endoscopy scores are reflective of lower airway inflammation; however, upper and lower airways are independent in terms of severity of inflammation. Therefore, observing upper airway
  inflammation is not an indication to test for lower airway inflammation.

Ref: J. Vet. Intern. Med. 2011; 25(5):1118–1126

Question 67

Do cytokine expression (mRNA expression of IL-1b, IL-4, IL-8, TNF-a and IFN-g) in BAL cells correlate with cytology in SB racehorses with poor performance?

Answer 67

• Relative expressions of TNF-a/glyceraldehyde 3 phosphate dehydrogenase, IL-4/GAPDH and IFN-g/GAPDH were greater in horses with IAD compared with controls.
• IL-4/GAPDH and IFN-g/GAPDH mRNA expression was inc in horses with inc metachromatic cell counts compared with horses with normal metachromatic cell counts.
• Only the mRNA expression of IL-1b/GAPDH was inc with airway neutrophilia.
• Conclusions: differences in gene expression were associated with the presence of IAD and with specific cell types present in airway secretions of SB racehorses.

Ref: J. Vet. Intern. Med. 2011; 25(2):322–329.

Question 68

Does the mRNA expression of IL-4, IFN-g, IL-17, IL-8, IL-1b, IL-5, IL-6, IL-10, IL-12 and eotaxin-2 vary in horses without airway disease and those with IAD?

Answer 68

• IL-5, IL-1b, IL-6, IL-8, and IL-10 mRNA expression was upregulated in the IAD-total group vs control group.
• The IAD-Neutro group showed inc expression of IL-17, IL-8, and IL-5 and a dec expression of IL-4 vs IAD-Mast group.
• Conclusion: cytokines from the Th2 family play a key role in IAD and a different pathophysiology may be involved in mast cell versus neutrophil BALF accumulation in IAD.

Ref: J. Vet. Intern. Med. 2012; 26(1):153–161.

Question 69

What is the effect of N-Butylscopolammonium bromide on clinical signs and lung function of RAO-affected horses in an experimental model?

Answer 69

• N-butylscopolammonium bromide is a potent bronchodilator, reaching maximum effect 10 minutes after IV admin. This effect dissipates within 1h of drug admin.
• Clinical score at 10 and 30 min after NBB admin was significantly lower than baseline and transpulmonary pressure was significantly lower at 10 mins.

Ref: J. Vet. Intern. Med. 2012;26(6):1433–1438.

Question 70

Do elevations in serum haptoglobin, C-reactive protein and serum amyloid A occur in horses with RAO?

Answer 70

• Haptoglobin is a marker of both acute and chronic systemic inflammation in horses with RAO.
• High concentrations of SAA indicate acute inflammation.
• C-reactive protein concentrations are not significantly different in healthy horses and horses with RAO.

Ref: J. Vet. Intern. Med. 2012;26(6):1419-1426.

Question 71

Does a CRI of lidocaine decrease clinical signs and BAL neutrophilic inflammation in horses with an acute exacerbation of RAO?

Answer 71

No.

Ref: J. Vet. Intern. Med. 2012;26(6):1427-1432.

Question 72

Are MAPK and PI3K pathways involved in neutrophil migration toward the airway lumen in horses with RAO?

Answer 72

• MAPK and PI3K pathways regulate neutrophil migration induced by BALF of horses with heaves.
• Inhibition of multiple pathways might be required to completely abolish BALF-induced neutrophil migratory activity and possibly inflammation in heaves.

Ref: J. Vet. Intern. Med. 2013;27(1):164-170.

Question 73

Compared to horses without any clinical signs of respiratory disease, do those with occasional coughing, mucous nasal discharge, or both have an increased risk of developing signs of RAO (frequent coughing, increased breathing effort, exercise intolerance, or a combination of these) as characterized by the Horse Owner Assessed Respiratory Signs Index (HOARSI)?

Answer 73

Yes. Compared to those without signs of respiratory disease, those with occasional mucous nasal discharge and coughing developed signs of RAO more frequently.

Ref: J. Vet. Intern. Med. 2014; 28(2):618–623.

Question 74

Is RAO associated with systemic oxidative stress, as determined by measurement of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in equine erythrocyte lysates and thiobarbituric acid-reactive substances (TBARSs) in erythrocyte lysates and plasma?

Answer 74

• Yes, RAO in horses is associated with systemic oxidative stress.
• A significant increase in the activities of GPx and SOD was detected in RAO-affected horses vs control animals.
• There was no significant difference between groups in terms of the erythrocyte lysate activities of CAT, GR, or TBARs or the plasma concentration of TBARs.

Ref: J. Vet. Intern. Med. 2014; 28(6):1845-1852.

Question 75

Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line. Does inhalation of CpG-ODN in gelatin nanoparticles every 48 hours for 5 treatments improve allergic and inflammatory clinical variables in RAO-affected horses?

Answer 75

Yes. Administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage and an increase in arterial oxygen pressure.

Ref: J. Vet. Intern. Med. 2015; 29(1):286–293.

Question 76

Does omega-3 PUFA supplementation improve clinical signs, lung function, and airway inflammation in horses
with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD)?

Answer 76

• Clinical signs, lung function, plasma PUFA composition, and BALF cytology were evaluated in horses on a pelleted diet only vs pelleted diet + omega-3 PUFA supplement.
• PUFA group had greater improvement in clinical signs (cough score improved 60%), lung function (respiratory effort decreased 48%), and BALF (neutrophils decreased from 23 to 9%) vs placebo (cough score improved 33%, respiratory effort decreased 27%, BALF neutrophils increased from 11 to 17%; P

Question 77

What is the best diagnostic test to identify Streptococcus equi ss equi infection during an acute outbreak of Strangles, when comparing bacterial culture and PCR (prior to and after culture) or nasal swabs, nasopharyngeal swabs and nasopharyngeal lavage?

Answer 77

Nasopharyngeal lavage analysed by a combination of real time PCR directly and after culture or, alternatively, real-time PCR directly on a nasopharyngeal lavage and a nasal/nasopharyngeal swab can identify S. equi in over 90% of acute strangles cases.

Ref: J. Vet. Intern. Med. 2013; 27(3):542–547.

Question 78

What is the effectiveness of vaccinating cattle with commercially available viral antigen vaccines (BHV-1, BVDV, BRSV, PI3) for mitigation of the effects of bovine respiratory disease complex (BRDC)?

Answer 78

• Systematic review and meta-analysis of 31 studies comprising 88 trials.
• In natural exposure trials, beef calves vaccinated with various antigen combinations had a significantly lower BRDC morbidity risk than did nonvaccinated control calves.
• In trials evaluating BHV-1 and MLV BVDV vaccines in experimental challenge models, vaccinated calves had a lower BRDC morbidity risk than did control calves.
• In experimental challenge trials evaluating MLV BRSV and PI3 vaccines, no significant difference in morbidity or mortality risk was found between vacc and control calves.
• The literature provides data but does not provide sufficiently strong evidence to guide definitive recommendations for determining which virus components are necessary to include in a vaccination program for prevention or mitigation of BRDC in cattle.

Ref: J. Am. Vet. Med. Assoc. 2015; 246(1):126-142.

Question 79

What were the main respiratory pathogens isolated from calves in Quebec dairy herds in 2012 with a high incidence
of BRD? Was there an association between the presence of these pathogens and clinical signs of pneumonia, lung consolidation, or average daily gain?

Answer 79

• Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni were isolated in 54, 17, and 12 calves (sample size 95), respectively.
• Mycoplasma bovis was identified by PCR testing or culture in 19 calves, and 78 calves were found to be positive for Mycoplasma spp.
• Bovine coronavirus was detected in 38 calves and bovine respiratory syncytial virus in 1.
• Only the presence of M. bovis was associated with higher odds of clinical signs, lung consolidation, and lower average daily gain.

Ref: J. Vet. Intern. Med. 2015; 29(1):381–387.

Question 80

Is computer aided lung auscultation (CALA) as accurate as pen checking in diagnosis BRD in feedlot steers?

Answer 80

• Comparison of veterinary auscultation and CALA (using a CALA score ≥2 as a cut off) revealed a substantial agreement (kappa = 0.77).
• CALA had relatively high Se (92.9%) and Sp (89.6%) for diagnosing BRD compared with pen checking.
• Conclusions: CALA had good diagnostic accuracy (albeit with a relatively wide CI). Its use in feedlots could increase the proportion of cattle accurately diagnosed with BRD.

Ref: J. Vet. Intern. Med. 2015; 29(4):1112-1116.

Question 81

Describe risk factors for recovery of susceptible and resistant M. haemolytica in feedlot cattle and associations with health outcomes.

Answer 81

• M. haemolytica was recovered from 29% of cattle: 13.1% at arrival and 19.8% at second sampling.
• Nearly half of cattle received antimicrobial drugs (AMDs) parenterally, mostly as metaphylactic treatment at arrival.
• Individual parenteral AMD exposures were associated with decreased recovery of M. haemolytica, whereas exposure in penmates was associated with inc recovery.
• Most isolates were pan-susceptible; AMD exposures were not associated with resistance to any single drug.
• Multiply-resistant isolates were rare but AMD exposures in pen mates were associated with increased odds of recovering multiply-resistant M. haemolytica.
• Conclusions: resistance generally was rare in M. haemolytica. Antimicrobial drug exposures in penmates increased the risk of isolating susceptible and multiply-resistant M. haemolytica, a finding that could be explained by contagious spread.

Ref: J. Vet. Intern. Med. 2015; 29(2):705–713.

Question 82

Does respiratory disease occur commonly in cloned calves? If so, what is the nature of this disease?

Answer 82

• Respiratory disease occurs frequently in cloned calves (22/25 calves in this study).
• 19/22 required INO; 2 remained hypoxaemic despite INO.
• 13/19 were weaned from INO after a median of 70h.
• 9/22 required ventilatory support; 5 were discharged, 3 were euthanised and 1 died due to resp dz.
• Necropsy findings: atelectasis, pulmonary congestion and alveolar damages.
• The most frequent abnormality is hypoxemia because of V/Q mismatch. It is possible to successfully support these calves by INO and mechanical ventilation.

Ref: J. Vet. Intern. Med. 2011; 25(2):373–379.

Question 83

Do clinical examination and lung auscultation have limitations when diagnosing lung consolidation in pre-weaned calves?

Answer 83

• Yes; in an examination of 106 pre-weaned calves. Each preweaned calf was clinically inspected using the Wisconsin calf respiratory scoring chart (CRSC), tx history noted, thoracic ultrasound and auscultation performed.
• Se of auscultation to detect consolidation was 5.9%
• Only 41.1% of calves with consolidated lungs had been treated previously by the producers.
• Se of detection when adding CRSC and prev tx was 71.4%.
• Thoracic ausc is of limited value in dx lung consolidation in calves. U/s assessment of the thorax could be a useful tool to assess BRD detection efficiency on dairy farms.

Ref: J. Vet. Intern. Med. 2014; 28(1):234–242.

Question 84

Clinical leptospirosis in horses is primarily associated
with recurrent uveitis, abortions, stillbirth, neonatal
disease, hemolysis, renal disease, and liver disease. What other disease syndrome has been reported in foals due to Leptospirosis?

Answer 84

• Acute respiratory failure with pulmonary haemorrhage.

Ref: J. Vet. Intern. Med. 2012; 26(3):684–687.

Question 85

How Important Is Mycoplasma bovis as a bovine pathogen?

Answer 85

• M. bovis can be isolated in pure culture from the mammary gland of cows with mastitis and from the joints, tendon sheaths, or periarticular tissues of cattle with arthritis, tenosynovitis, or chronic pneumonia and polyarthritis syndrome (CPPS).
• M. bovis is the predominant pathogen isolated from the middle ear of calves with otitis media.
• Conflicting evidence re importance in BRDC; although M. bovis alone can cause natural and experimentally induced clinical disease, the presence of M. bovis does not always result in disease, and clinical disease does not appear necessary for the maintenance and dissemination of M. bovis in the cattle population.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 86

What Is the prevalence/incidence of M. bovis infection and disease?

Answer 86

• Mastitis: mycoplasma was identified in bulk tank milk samples in 7–20% of dairies sampled in US; likely underestimate true prevalence b/c mycoplasmas are shed intermittently and mastitic milk is withheld from bulk tanks. - Dairy calves: nasal prev data from >30y ago in California: 34% infected herds, 6% free herds. More recent studies: almost all calves in diseased herds become infected.
• Beef cattle: prev in nonstressed calves is low (0–7%); conversely, prevalence is often high even in the absence of clinical disease for comingled calves, transported calves, or calves at a feedlot.
• Necropsy studies indicate M. bovis can contribute substantially to morbidity and mortality in feedlot cattle.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 87

What are the economic and other consequences of M. bovis Infections?

Answer 87

• One report est costs to US beef industry of US$32m/yr as a result of loss of weight gain and carcass value, and US$108m/yr to US dairy industry due to mastitis.
• Costs of mycoplasma dz include reduced production, drugs and labor for tx, death and culling losses, implementation of dx and control measures, and a portion of the cost of non-pathogen-specific preventive measures.
• Animal welfare consequences, given that the associated dz is often chronic and poorly responsive to treatment.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 88

What do we know about colonisation, persistence, and shedding of M. bovis Infections?

Answer 88

• M. bovis is well adapted to colonization of mucosal
  surfaces, where it can persist without causing CSx.
• URT mucosa is primary site of colonisation after URT exposure; mammary gland after intramammary exposure.
• M. bovis can be isolated from multiple body sites during early infection, partic URT, mammary gland, conjunctiva and urogenital tract; bacteremia has been documented.
• URT mucosa and the mammary gland are most important sites of persistence and shedding of M. bovis.
• Many cattle shed for a few months or less but some can shed intermittently for many months or years –> maintenance of M. bovis within a herd and naive exposure. - Stressful events such as transportation, co-mingling, entry into a feedlot, and cold stress are associated with increased rates of nasal shedding of M. bovis.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 89

How is M. bovis transmitted and what is known about

risk factors for infection and disease?

Answer 89

• Intro of asympt infected animals is thought to be the primary means of M. bovis-free herds become infected.
• Once present, M. bovis can be readily transmitted from infected to uninfected cattle.
• M bovis is difficult to eliminate from multi-age facilities.
• Traditionally regarded as a contagious mastitis pathogen, with udder-to-udder spread major means of transmission.
• Whether URT transmission with internal dissemination to the mammary gland is important in the epidemiology of M. bovis mastitis has not been determined.
• For young calves, ingestion of infected milk is an imp means of M. bovis transmission. However, other means of trans must also be important, as the dz can occur in calves that are fed milk replacer or pasteurized milk.
• Congenital infections appear to occur infrequently.
• M. bovis might be transmitted in respiratory secretions via aerosols, nose-to-nose contact, or indirectly via feed, water, housing, or other fomites.
• Mycoplasmas are susceptible to desiccation and sunlight, but M. bovis can survive for long periods in protected environments with greatest survival in cool, humid conditions e.g. ponds, dirt, recycled sand bedding.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 90

What Is the role of co-infection with other pathogens?

Answer 90

• In some studies but not others an assoc between BVDV infection and M. bovis has been observed.
• Bacterial coinfections in M. bovis-assoc pneumonia and otitis media are extremely common e.g. M. haemolytica, H. somni (feedlot) and P. multocida (younger calves).

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 91

What microbial characteristics are important in

M. bovis pathogenesis?

Answer 91

• Characteristics that enable it to colonise and persist on mucosal surfaces, to invade tissues, and to persist at sites of disease despite an aggressive immune response.
• Molecules involved in adherence, antigenic variation, invasion, immunomodulation, biofilm formation, and production of toxic metabolites are likely important.
• Mycoplasmas lack a cell wall, and exposed membrane proteins facilitate adherence to mucosal surfaces and form the primary interface with the host.
• M. bovis has a large family of immunodominant variable surface lipoproteins; likely impart a vast capacity for antigenic variation in M. bovis populations that contributes to immune evasion and persistence.
• After adherence, many mycoplasmas, including M. bovis, generate products such as phospholipases, hydrogen peroxide, and superoxide radicals which damage host cells. - M. bovis can also form biofilms in vitro that impart increased resistance to desiccation and heat stress.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 92

What role does passive immunity play in the progression of M. bovis infections?

Answer 92

• Strong assoc between FPT and inc risk and severity of
  BRD in calves.
• However, the role of maternal immunity in protection against M. bovis-associated disease is unknown; no assoc b/w post-colostral serum antibody titres against M. bovis and pneumonia in 325 dairy calves.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 93

What role do host immune responses play in the progression of M. bovis infections?

Answer 93

• Innate IR are critical in the early phase of mycoplasma infections; alveolar macrophages v imp in early clearance of mycoplasmas from the lung, however inapprop activation of macro (TNF-a) –> excessive inflammatory response.
• Activation of macro –> recruitment of neuts = prominent cell type in the lungs, middle ear, and joints of M. bovis infected calves; extent of neutrophil recruitment is directly correlated with the severity of mycoplasma disease.
• Although bovine neutrophils are able to kill opsonized M. bovis, unopsonized M. bovis can adhere to neutrophils and inhibit respiratory burst activity.
• Adaptive IR remain poorly defined.
• Adaptive responses that are in place at the time of exposure can help control new infections e.g. prior M. bovis mastitis protects cows from dev severe mastitis.
• Adaptive responses are often ineffective at eliminating est mycoplasma infections.
• How mycoplasmas avoid clearance by the host is not well understood. However, mycoplasmas can induce a broad range of immunomodulatory events that might induce ineffective immune responses, and variation of surface antigens could help mycoplasmas to avoid clearance mediated by adaptive responses.
• Experimental respiratory infection of calves with M. bovis usually elicits a strong humoral response characterized
  by high levels of serum IgG1 and very little IgG2 and local mucosal IgG and IgA responses.
• M. bovis inoculation of the mammary gland results in serum IgG and local mucosal IgG and IgA. responses.
• Humoral responses of naturally infected cattle are more variable but appear to be important in protection from M. bovis (IgG in serum and local immunoglobulins).

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 94

List clinical signs associated with M. bovis mastitis.

Answer 94

• Endemic subclinical dz to severe mastitis outbreaks.
• Cows of any age or stage of lactation are affected, including prepubertal heifers and dry cows.
• Classically more than one quarter is affected, drastic
  dec in milk prod, signs of systemic illness relatively mild.
• Mammary gland might be swollen but usually not painful.
• Secretions vary from mildly abnormal to gritty or purulent, and are sometimes brownish in colour.
• Hx of mastitis that is resistant to tx w antibiotics common.
• Return to production is possible but slow.
• +/- signs of arthritis, synovitis. joint effusion, resp dz.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 95

List clinical signs associated with M. bovis pneumonia.

Answer 95

• Any age; dairy or beef.
• Nonspecific incl fever, tachypnea, dyspnea, and dec appetite +/- nasal discharge and coughing.
• Poor weight gain in chronically affected animals.
• +/- signs of otitis media, arthritis, or both, in the same animal or in other animals in the herd.
• CPPS (polyarthritis in assoc with chronic pneumonia), occurs in beef cattle several weeks after feedlot entry.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 96

List clinical signs associated with M. bovis otitis media.

Answer 96

• Enzootic dz or outbreaks in dairy or beef calves; occurs sporadically in feedlot cattle.
• Early/mild cases: calves remain alert with a good appetite –> fever and anorexia.
• CSx due to ear pain and CN VII deficitis: ear droop, ptosis, nystagmus, circling, falling, vestibular ataxia, head shaking and scratching or rubbing ears.
• Epiphora/exposure keratitis secondary to eyelid paresis.
• Clinical signs can be unilateral or bilateral.
• Purulent aural discharge if the tymp memb has ruptured.
• Concurrent pneumonia, arthritis, or both are common.
• In advanced otitis media-interna, meningitis can develop.
• Spontaneous regurg, loss of pharyngeal tone, dysphagia have also been reported.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 97

List clinical signs associated with M. bovis arthritis, synovitis, and periarticular infections.

Answer 97

• Cases tend to be sporadic and are often concurrent with cases of pneumonia or mastitis, although outbreaks have been reported in calves and dairy cows.
• CPPS is described in feedlot cattle.
• CSx incl acute non-weightbearing lameness with joint swelling, pain, and heat on palpation +/- fever, anorexia.
• Involvement of tendon sheaths and periarticular soft tissues is common.
• Large rotator joints (hip, stifle, hock, shoulder, elbow, and carpal) are most commonly affected.
• Poor response to treatment is a common feature.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 98

List clinical signs of other disease syndromes associated with M. bovis infection.

Answer 98

1. Keratoconjunctivitis. M. bovis can be isolated from the
   conjunctiva of healthy and diseased cattle; involvement in infectious keratoconjunctivitis (IKC) is seldom reported.
2. Meningitis. can occur as complication of otitis media-interna; has been reported with disseminated septic dz.
3. Decubital abscesses. Over the brisket in In 1 report of 50 calves; some had concurrent M. bovis-assoc pneumonia.
4. Cardiac Disease. M. bovis was ID concurrently w H. somni in the hearts of 4/92 feeder calves dying from myocarditis. One report of chronic active fibrinopurulent endocarditis.
5. Genital Disorders. Little evidence to support an important role for M. bovis in naturally occurring bovine repro dz.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 99

How are M. bovis infections diagnosed?

Answer 99

• Serum AB-ELISA: indv titres poorly correlated with infection or dz; on a group level, seroconversion or high titres are predictive of active M. bovis infection.
• Intermittent and low-level shedding, uneven distrib of M. bovis throughout diseased tissue, suboptimal sample handling or culture cond, and the presence of mycoplasma inhibitors in samples likely contrib to low sensitivity.
• Sensitivity of milk culture for diagnosis of mycoplasma intramammary infection low in bulk milk or asymptomatic cows but higher in cows with clinical mastitis.
• Realtime PCR systems with high Se and Sp have been described for detection of M. bovis in clinical samples.
• M. bovis can be detected in situ by IHC on formalin fixed, paraffin embedded tissues or IFAT frozen lung tissue.
• TTW/BAL better than nasal swabs for pneumonia, although isolation of M. bovis not well correlated w dz.
• Joint/tendon sheath aspirates can be submitted.
• Rad/CT/US can aid dx of otitis media/interna.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 100

What are the typical necropsy findings in M. bovis-associated disease?

Answer 100

• Definitive dx: demonstration of M. bovis in affected tissues by IHC or by culture, PCR, or sELISA
• Pneumonia: multiple necrotic foci filled with dry yellow to white caseous material, raised, 2mm-several cm diam; interlobular septae can contain linear necrotic lesions; extensive fibrosis common; acute fibrinous to chronic fibrosing pleuritis occurs in some cases.
• Histo: subacute to chronic bronchopneumonia that can be suppurative and is usually necrotising.
• Mastitis: mild to severe fibrinosuppurative to caseonecrotic mastitis.
• Otitis media: tympanic bullae contain suppurative to caseous exudate and have often undergone extensive osteolysis.
• Arthritis: nonodorous fibrinous to caseous exudate accompanied by fibrosis. Affected periarticular tissues contain foci of caseous necrosis, linear necrotic lesions, and extensive fibrosis.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 101

Should mycoplasma mastitis be treated?

Answer 101

• No.
• Cows that spontaneously resolve clinical mastitis or become culture negative often remain intermittent, subclinical shedders; regard as permanently infected.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 102

What do we know about antimicrobial resistance

of M. bovis?

Answer 102

• Because mycoplasmas lack a cell wall, the b-lactam antimicrobials are not effective against them.
• Similarly, they do not synth folic acid and are therefore intrinsically resistant to sulfonamides.
• Mycoplasmas are generally susc to drugs that interfere with protein (tetracyclines, macrolides, linosamides, and florfenicol) or DNA (fluoroquinolones) synthesis. However, M. bovis is resistant to erythromycin

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 103

When Might Metaphylactic Antimicrobials be

Indicated for M. bovis-Associated Disease?

Answer 103

• Metaphylactic use of antimicrobials is probably justified when high levels of morbidity and mortality because of M. bovis-associated disease are being sustained or can be expected in high-risk cattle, although M. bovis-specific efficacy data and economic analyses are needed.
• E.g. tulathromycin, florfenicol, tilmicosin.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 104

Can vaccination help control M. bovis-associated disease?

Answer 104

• Despite several vaccines being on the market, attempts to vaccinate cattle against M. bovis-associated disease have been unrewarding in the field.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 105

What biosecurity practices are recommended for control and prevention of M. bovis-associated disease?

Answer 105

• Maintain a closed herd or, if that is not possible, screen and quarantine purchased animals.
• Examine bulk tank culture history of the herd of origin when purchasing heifers or adults or sample bulk tank at least 3 times spaced 3–4 days apart.
• Examine calf-health records to determine if M. bovis-assoc dz e.g. otitis media have been observed.
• When purchasing lactating cows, milk samples should be submitted for mycoplasma detection (culture, PCR, sELISA), keeping in mind the low Se of a single sample.
• Testing purchased dry cows, purchased heifers, and heifers raised offsite at calving and isolating them until results are obtained has been recommended.
• Serology has been used to help identify uninfected groups of cattle before purchase.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 106

What biosecurity and management practices are recommended for control and prevention of M. bovis mastitis?

Answer 106

• Bulk tank testing (culture, PCR, sELISA) should be performed at least monthly, with more frequent sampling
  indicated for large herds, herds undergoing expansion, or
  when managing a mycoplasma problem.
• Sampling of clinical mastitis cases, high somatic cell count cows, and cows and heifers at calving.
• Mastitis records, incl response to tx, should be monitored.
• Small herd or herd trying to maintain free status: eliminate through aggressive surveillance and culling infected cows.
• For expansion herds or dairies where a large proportion of the lactating herd is infected, eradication of M. bovis
  might not be appropriate or economical.
• Attempted elimination of all adult cows with intramammary mycoplasma infections remains the strongly recommended course of action.
• Strict segregation of infected cows has been used
  effectively to limit new infections.
• Strict milking parlor hygiene is recommended to reduce udder-to-udder transmission of M. bovis.
• Bedding found to be mycoplasma positive, usually recycled bedding processed on the farm, should not be used to bed dairy animals of any age.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 107

What biosecurity and management practices are recommended for control and prevention of M. bovis infection in calves?

Answer 107

• Surveillance for M. bovis in calf facilities should incl monitoring of health records and submission of samples from suspect cases for diagnostic testing.
• M. bovis exposure via infected milk can be eliminated by pasteurization or by feeding milk replacer.
• Exposure to infected colostrum could be reduced by pasteurization, by not pooling colostrum, and by not feeding colostrum from cows known to be infected.
• Exposure to airborne M. bovis could be reduced by good
  ventilation, low-stocking density, segregating sick calves.
• All-in, all-out practices or segregation of age groups might also limit transmission of M. bovis in multiage facilities.
• Removing fence-line contact with other cattle and limiting
  the time the calf spends in the maternity area will also
  reduce the potential for exposure.
• Proper sanitization of buckets, housing, and other equipment between uses, wearing gloves, and handling sick calves last could reduce fomite-mediated transmission.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 108

What biosecurity and management practices are recommended for control and prevention of M. bovis infection in stocker and feeder cattle?

Answer 108

• Recommendations focus on maximising respiratory system health and immune function rather than M. bovis-specific measures.
• Strategic antibiotic treatment of high-risk animals on arrival or during an outbreak of BRD might be useful in
  reducing the incidence of mycoplasma disease.
• Segregating affected cattle and keeping the hospital pen separate from new arrivals could reduce exposure.
• Using appropriate hygiene measures for handling
  sick cattle (use separate equipment or personnel or clean
  equipment among animals, feed last, etc) could reduce the
  chances of fomite-mediated M. bovis transmission.

Ref: ACVIM 2011 Consensus Statement - M. bovis.

Question 109

List clinical signs of Strangles.

Answer 109

• Characterised by abrupt onset of fever followed by URT catarrh, as evidenced by mucopurulent nasal discharge and acute swelling with subsequent abscess formation in submandibular and retropharyngeal lymph nodes.
• Older horses often exhibit a mild form of the dz charac by nasal discharge, small abscesses, and rapid resolution; younger horses are more likely to develop severe LN abscessation that subsequently opens and drains.
• Pharyngitis –> dysphagia, anorexia, extended neck.
• Depression, listlessness.
• Pharyngitis, laryngitis, and rhinitis may occur –> bilateral nasal discharge - serous –> mucopurulent –> purulent.
• Nasal and ocular mucosa may become hyperemic, and there may be purulent ocular discharge.
• Lymphadenopathy may cause: external drainage, severe dyspnea, stridor, and dysphagia, marked swelling of the eyelids, severe tracheal compression, asphyxia and death.
• Coughing not significant feature in many cases.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 110

Describe the pathogenesis of Strangles.

Answer 110

• S. equi enters via the mouth or nose and attaches to cells in the crypt of the lingual and palatine tonsils and to the follicular-assoc epi of the pharyngeal and tubal tonsils.
• Translocation occurs in a few hours to the mandibular and suprapharyngeal lymph nodes.
• Complement-derived chemotactic factors generated after interaction of complement with bacterial peptidoglycan attract large numbers of PLNs.
• Failure of neuts to phagocytose and kill the strep appears to be due to a combination of the HA capsule, antiphagocytic SeM protein, Mac protein, and other undetermined antiphagocytic factors released by the org.
• Final disposal of bacteria is dependent on lysis of the abscess capsule and evacuation of its contents.
• Streptolysin S and streptokinase may also contribute to abscess dev and lysis by damaging cell membranes and activating the proteolytic properties of plasminogen.
• Fever occurs 3-14 days after exposure and is assoc with release of the pyrogenic mitogens SePE-H and I.
• The larger the intranasal inoculum of cultured S equi, the shorter the incubation period and the more severe the disease that results.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 111

Describe the pathogenesis of bastard Strangles.

Answer 111

• Spread may be hematogenous or via lymphatic channels channels, which results in abscesses in lymph nodes and other organs of the thorax and abdomen. Metastasis to the
  brain has also been recorded.
• Bacteraemia occurs on days 6 to 12 in horses inoculated intranasally with virulent S equi.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 112

What is the duration of shedding following Strep. equi infection?

Answer 112

• Nasal shedding: usually begins 2-3d days after onset of fever and persists for 2 to 3 weeks in most animals.
• Some animals never shed.
• Some shed for a long time due to GP infection.
• Systemic and mucosal IR are evident 2-3wk after infection and coincide with mucosal clearance.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 113

Discuss development and longevity of immunity to Strangles.

Answer 113

• Systemic and mucosal IR are evident 2-3wk after infection and coincide with mucosal clearance.
• ~75% of horses develop a solid, enduring immunity to strangles after recovery from the dz (lasting >5yr).
• A small proportion become susceptible to dz w/in months.
• Strong serum IgGb responses to surface-exposed
  proteins, incl SeM, Se44.2, Se46.8, Se45.5, and Se42.0, are produced during convalescence.
• SeM-specific IgGa is induced during and shortly after S equi infection. Strong SeM-specific mucosal IgA and IgGb responses occur during acute and convalescent phases.
• Milk from mares that have recovered from strangles contains IgGb and IgA with specificities similar to those found in nasopharyngeal mucus of convalescent horses.
• Colostral antibodies recirculate to the nasopharyngeal mucosa –> resistance to S equi infection until weaning.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 114

Outline the modes of transmission of Strep. equi infection.

Answer 114

• Purulent discharges from horses with active and recovering strangles are an important source of new S equi infections among susceptible horses.
• A recovered horse may be a potential source of infection for at least 6 weeks after CSx have resolved.
• Long-term, subclinical S equi carriers (10% cases) w GP empyema may shed intermittently for months to years.
• Direct transfer: nose-to-nose transmission.
• Indirect transfer: sharing of contam housing, water sources, feed or feeding utensils, twitches, tack, clothing and equipment of handlers, farriers, vets etc.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 115

How long does Strep. equi persist in the environment?

Answer 115

• Currently there is a lack of field-based proof for prolonged
  environmental persistence of S equi.
• One laboratory- based study documented that the organism survived for 63 days on wood at 28C and for 48 days on glass or wood at 20C.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 116

How is Strep equi isolated from horses?

Answer 116

• Culture: of nasal washes > swabs, or pus aspirated
  from abscesses remains the ‘‘gold standard’’; plate speciments on Columbia CNA agar with 5% sheep or horse blood added; unlike S equi, S zooepidemicus ferments sorbitol and lactose, both are beta haemolytic.
• PCR: designed to detect DNA sequence of SeM, the gene for the antiphagocytic M protein of S equi; 3x more sens than culture and same day return but presumptive until confirmed with culture. PCR is useful to:
• Detect asymptomatic carriers.
• Establish S equi infection status prior to transport.
• Establish S equi infection status following transport prior
  to commingling.
• Determine the success of elimination of S equi from the
  guttural pouch.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 117

Discuss interpretation of SeM-specific antibody ELISA results in horses.

Answer 117

• Does not distinguish between vaccine and infection.
• AB titres peak 5wk post-infection; remain high for 6mo.
• Horses at risk for dev of purpura are hyperresponders and make very strong antibody responses. Such animals, with titers in excess of 1 : 3200, should never be vaccinated.
• Negative: no exposure or exposure w/in 7 days.
• Weak pos (1:200-1:400): very recent or residual antibody from exposure to S equi or vaccine in the remote past.
• Mod pos (1:800-1:1600): 2-3 weeks after exposure or where the infection occurred 6 mo to 2 yr previously.
• High pos (1:3200-1:6400): 4-2 weeks after infection or 1-2 weeks following inj vacc or 2-4 wks after intranasal vacc. Vaccination is contraindicated if antibody 1 : 1,600 or more.
• Very high pos (>1:12800): often found in horses with a metastatic abscess or purpura hemorrhagica.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 118

Discuss available vaccines for protection against S. equi infections in horses.

Answer 118

1. Extract vaccines:
   - IM or SC.
   - Elicit serum antibody responses 7-10d later.
   - Naive horses and foals: 2-3 doses q2wk.
   - Boosters years; one month prior to foaling.
   - Horses that have had strangles w/in the previous year, with signs of strangles or titres >1:1600 should not be vacc.
2. Attenuated live intranasal vaccine:
   - Schedule: 2 doses at 2-3wk intervals; annual boosters.
   - Should only be admin to healthy, nonfebrile animals free of nasal discharges.
   - Live vaccine should not be used during an outbreak except in horses with no known contact with infected or exposed animals.
   - No data are available about colostral antibody levels following admin of intranasal vaccine to broodmares.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 119

List all aspects of an outbreak-control strategy for S. equi infected farms.

Answer 119

• Stop all horse movements on/off the affected premises.
• Implement hygiene measures immediately.
• Segregate strangles cases and contacts.
• Take rectal temp at least once daily to detect, promptly segregate, and possibly treat new cases.
• Screen all convalescing cases following clinical recovery
  and their contacts via swab or lavage of the nasopharynx.
• Collect swabs/lavage fluid at weekly intervals
  following recovery over several weeks and test for S equi by conventional culture and PCR.
• Because PCR can detect dead as well as living bacteria,
  pos PCR results are regarded as provisional –> URT and GP endoscopy; collect lavage samples for PCR/culture.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 120

Outline treatment of horses harbouring S. equi in their guttural pouches.

Answer 120

• Repeated lavages of pus-filled pouches via rigid or indwelling catheters using isotonic saline or polyionic fluid.
• Topical and systemic penicillin (topical gelatin benz pen).
• Topical installation of 20% (w/v) acetylcysteine solution; denaturing and solubilizing activity by disrupting disulphide bonds in mucoprotein molecules, thus reducing mucus viscosity and so theoretically facilitating natural drainage.
• Chondroid removal using a memory-helical polyp retrieval basket through the biopsy channel of the endoscope.
• Scarring of the pharyngeal openings of the GPs may preclude natural drainage and endoscopic access
  to the GPs –> Sx or endoscopically guided laser treatments to break down scar tissue and allow access to the pouches.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 121

Outline recommended treatment of horses with early clinical signs of S. equi infection.

Answer 121

• During an outbreak, immediate antibiotic therapy (3-5d) of new cases in early acute phase with fever and depression may be curative and may prevent focal abscessation.
• Antibiotic tx will inhibit synth of protective antigens and the dev of protective immunity will not be stim, so the horses will be highly susceptible to reinfection once tx is discont if the horse remains exposed to infected horses.
• No evidence that early tx increases the risk of bacteraemia, septicaemia and metastatic abscessation.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 122

Outline recommended treatment of horses with lymph node abscessation due to S. equi infection.

Answer 122

• Antibiotic therapy is contradicted UNLESS horse is febrile, depressed, anorexic, and especially manifesting dyspnea as result of partial upper airway obstruction.
• Therapy should be directed toward enhancing maturation
  and drainage of the abscesses.
• Topical treatments e.g. icthamol or a hot pack.
• Surgical drainage is sometimes indicated if abscesses do not rupture spontaneously; however, it is critical to wait until the abscess has matured and thinned out ventrally.
• Daily flushing of the open abscess with a 3–5% povidone iodine solution until the discharge ceases.
• NSAIDs may improve the horse’s demeanor by reducing fever, pain, and inflammatory swelling at the site of the abscesses and may encourage eating and drinking.
• Rarely: IVFT, feeding via NGT, tracheostomy.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 123

What is the recommended antibiotic for treatment of S. equi infection?

Answer 123

• Penicillin.
• Anecdotally TMPS improves S. equi infection.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 124

What are the complication and mortality rates associated with S. equi infection?

Answer 124

• Overall complication rate is approximately 20%.
• In a study of 74 horses, 20% had complications of which 40% died vs. overall case fatality rate of 8%.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 125

List sites of metastatic spread of S. equi infection (Bastard Strangles).

Answer 125

• Most common: lung (suppurative bronchopneumonia), LNs, mesentery, liver, spleen, kidneys, and brain.
• Extension of infection to sinuses or guttural pouches.
• Also reported: myocarditis, endocarditis, panophthalmitis, periorbital abscesses, ulcerative keratitis, paravertebral abscesses, septic arthritis, and tenosynovitis.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 126

How is Bastard Strangles diagnosed?

Answer 126

• Varies depending on the site of infection and whether there are concurrent signs of classic strangles.
• Bronchopneumonia, GP empyema, or sinusitis –> culture.
• Internal abscesses:
• • Hx of exposure to S equi or low-grade fever responsive to penicillin.
• • Laboratory results consistent with chronic infection e.g. elevated SeM-specific antibody titers, anemia, hyperfibrinogenemia, and hyperglobulinemia.
• Mesenteric abscesses may be accompanied by an immune ascites with elevated SeM-specific antibody in ascitic fluid.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 127

How is Bastard Strangles treated?

Answer 127

Long-term antimicrobial therapy, and appropriate local treatment or drainage of abscesses if possible.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 128

Describe the pathophysiology of purpura haemorrhagica.

Answer 128

• PH is an aseptic necrotizing vasculitis charac primarily by oedema and petechial or ecchymotic haemorrhage.
• Appears to be a vasculitis caused by the deposition of immune complexes in blood vessel walls.
• Commonly assoc w S. equi infection but other aetiologies also possible.
• A pre-existing high serum antibody titer to S equi antigens
  may predispose horses to the development of purpura.
• Studies have suggested an association between the development of purpura and antibodies of the IgA isotype.
• The immunologic basis for the high conc of IgA and low conc of IgG during the acute stages of purpura is not understood; proposed explanations incl uncontrolled expansion of B cell populations that prod IgA, failure of IgA removal mechanisms, delayed, defective or suppressed prod of IgG, and neutralisation or excess utilisation of IgG.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 129

Outline the clinical signs and diagnosis of purpura haemorrhagica.

Answer 129

• Vary from mild and transient to severe, fatal dz.
• S/C oedema, most frequently involving the head, limbs, and/or trunk, and petechiation and ecchymoses of the MM.
• Severe edema may result in oozing from the skin surfaces, and sloughing of the skin may occur.
• Vasculitis may affect other sites e.g. GIT, lungs, and muscle –> colic, resp prob, muscle soreness.
• Skin histo: leukocytoclastic vasculitis
• Isolation of the organism and demonstration of elevated IgA and IgG titers to S equi are also supportive.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 130

Outline the treatment and prognosis of purpura haemorrhagica.

Answer 130

• Corticosteroids are the primary treatment for purpura.
• Antibiotic therapy.
• NSAIDs in some cases.
• Supportive care incl IVFT, hydrotherapy, bandaging.
• 1/4 and 3/22 cases died.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 131

Describe S. equi-associated infarctive myositis.

Answer 131

• Likely a manifestation of purpura hemorrhagica.
• Severe vasculopathy characterized by infarction of skeletal muscle, skin, GIT and lungs.
• Present with muscle stiffness, lameness and elevations in muscle enzymes in conjunction with other signs, such as abdominal pain and subcutaneous swelling.
• Histo: acute coagulative necrosis of muscle with infarctions +/- pulmonary hemorrhage or GI infarctions.
• Px guarded.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 132

Describe S. equi-associated rhabdomyolysis with progressive atrophy.

Answer 132

• ID is some QH, some had PSSM, others no underlying myopathy.
• CSx: malaise, rapid progressive atrophy of the epaxial and gluteal muscles.
• Muscle enzymes were elevated.
• Muscle biopsies revealed chronic active rhabdomyolysis
  with regeneration, prominent macrophage infiltration, atrophy of fast-twitch fibers, and lymphocytic vasculitis –> fibrosis around blood vessels over time.
• May be an immune response resulting from similarities between the amino acid sequence of an S equi protein and equine myosin in certain horses.
• Tx: corticosteroids; ABs if signs of concurrent infection.
• Muscle mass may return to normal with tx.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 133

Describe S. equi-associated glomerulonephritis and myocarditis.

Answer 133

Streptococcal antigens have been suggested as a trigger for development of myocarditis and proliferative glomerulonephritis.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 134

Describe S. equi-associated agalactia.

Answer 134

• Has been reported in broodmares with strangles.
• Thought to be secondary to the fever, anorexia, and lethargy associated with infection not active infection of the mammary gland.

Ref: ACVIM 2005 Consensus Statement - Strep. equi.

Question 135

List the minimum criteria used to define IAD in horses.

Answer 135

1. Inclusion criteria:
   - Poor performance, exercise intolerance, or coughing,
   with or without excess tracheal mucus.
   - Nonseptic inflammation detected by cytologic examination of BALF or pulmonary dysfunction based on evidence of lower airway obstruction, airway hyper-responsiveness, or impaired blood gas exchange at rest or during exercise.
2. Exclusion criteria:
   - Evidence of systemic signs of infection (fever,
   hematologic abnormalities compatible with infection).
   - Increased respiratory efforts at rest (ie, heaves).

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 136

List clinical signs seen in horses with IAD.

Answer 136

• CSx: chronic, intermittent cough, increased mucoid airway
  secretions, and decreased performance.
• Cough can occur at rest or during exercise; absence of cough does not rule out IAD.
• Multiple specks of mucus along the length of the trachea, a pool of mucus at the thoracic inlet, or a continuous stream of variable width.
• Relationship between nasal discharge and IAD as defined in this consensus is currently unknown.
• Thoracic auscultation usually WNL, but some horses can exhibit increased breath sounds or subtle wheezes, particularly during rebreathing manoeuvres.
• IAD in racehorses –> poor racing performance, delayed recovery of RR after exercise, exaggerated resp effort during exercise.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 137

Describe the pathogenesis of IAD in horses.

Answer 137

• Noninfectious agents are likely to be central to the
  development of IAD.
• Introduction of horses to a stable is a risk factor for IAD = high dust enviro; dust may include a variety of organic and inorganic particles including endotoxin, (1R3)-b-D-glucan, ultrafine particles, micro-organisms, mite debris, vegetative material, inorganic dusts, and noxious gases.
• The presence of high eosinophil or mast cell counts in BALF from some horses with IAD suggests that aeroallergens might contribute to the dev of this syndrome.
• Contribution of enviro pollutants, cold, dry environments, and infectious agents to dev of IAD is unknown.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 138

Describe cytologic findings on analysis of transtracheal wash fluid and bronchoalveolar lavage fluid in horses with IAD.

Answer 138

• TTW cytology is deemed insufficient for the diagnosis of IAD as defined here in the absence of BALF cytology or pulmonary function testing.
• BALF: most commonly BALF cytologic profile in IAD is inc INCC w mild neutrophilia, lymphocytosis, and monocytosis; two other profiles mainly in young horses w IAD are charac by inc mast cell and eosinophil counts.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 139

Describe diagnostic imaging findings in horses with IAD.

Answer 139

• Supportive of the diagnosis of IAD and exclusionary of
  alternative dx but insufficient for diagnosis of IAD.
• In one study, a bronchial pattern was observed more frequently in horses with IAD, radiographic changes were not statistically assoc with abnormal BALF cytology or pulmonary function tests.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 140

Describe pulmonary function testing in horses with IAD.

Answer 140

• Several studies have documented neg impact of IAD on lung function both at rest and during exercise.
• Gas exchange is impaired during exercise in horses w IAD. - Lung function tests such as forced expiration and forced oscillation mechanics indicate that horses with IAD have airway obstruction.
• Airway hyper-responsiveness is a prominent feature of horses with IAD.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 141

List differential diagnoses for IAD in horses.

Answer 141

• RAO.
• Upper airway disease.
• Bronchopneumonia/pleuropneumonia.
• Viral respiratory infections.
• EIPH.
• Thoracic neoplasia.
• Lungworm.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 142

Outline therapy for IAD in horses.

Answer 142

• Environmental change.
• Control of airway inflammation: systemic or inhaled corticosteroids, inhaled mast cell stabilisers.
• Bronchodilators: probably most efficacious when combined with anti-inflammatory therapy, because the underlying mechanism of this disease is most likely related to persistent airway inflammation.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 143

Outline prevention strategies for IAD in horses.

Answer 143

• Reduce exposure of the horse’s airways to respirable
  particles by:
  i) Use feedstuff and bedding that generate low dust and endotoxin concentrations.
  ii) Inc removal of airborne particles and noxious gases by improving ventilation in the building.
• Changing bedding material from straw to cardboard can cut respirable dust concentrations in half and reduce mould concentration to negligible concentrations.
• Replacing hay feed and straw bedding by wood shaving bedding and a complete pelleted diet was shown to decrease the respirable dust burden by 97%.
• Low-dust beddings are shredded paper and peat moss.
• The activity in the barn also affects dust exposure with peak concentrations occurring during the day especially at the time of feeding and cleaning stalls.
• Different feed and bedding materials may have variable conc of endotoxin, which can directly irritate airways.

Ref: ACVIM 2007 Consensus Statement - IAD.

Question 144

Describe the Porcine Respiratory and Reproductive Syndrome virus (PRRSV).

Answer 144

• Family: Arteriviridae.
• Genus: Arterivirus.
• Enveloped RNA virus.
• Species specific, highly resistant to cold temps, and highly variable because of its high mutation rate and potential for recombination.

Ref: J. Am. Vet. Med. Assoc. 2015; 246(12):1304-1317.

Question 145

Describe within-farm transmission of PRRSV.

Answer 145

• Routes of shedding include saliva, nasal secretions, semen, urine, feces, and mammary gland secretions.
• Transmission may occur through multiple common routes, including intranasally, orally or intramuscularly.
• Prolonged infection is a hallmark of PRRSV, up to 200d.
• Vaccination appears to reduce shedding.
• PRRSV is highly susceptible to inactivation by heat, common disinfectants and drying.
• At temperatures between –20°C and –80°C, PRRSV can be stable for months to years, but infectivity is quickly lost when pH of a solution is 7.5.
• It is assumed that pigs with maternal immunity are not likely to have that immunity wane over the suckling period. - Pigs born to infectious sows are assumed to be infectious.
• In one model herd closure together with acclimatisation
  of gilts and repeated mass immunisation was the scenario that resulted in the highest number of iterations that achieved stable status.

Ref: J. Am. Vet. Med. Assoc. 2015; 246(12):1304-1317.

Question 146

Describe between-farm transmission of PRRSV.

Answer 146

• Live pigs and semen:
  – Testing serum with PCR assays is more sensitive and detects PRRSV in infected boars earlier than does testing semen with PCR assays NOT pooled.
  – Practices to reduce risks assoc w entry of gilts include purchasing gilts from PRRSV-neg sources and isolation of purchased gilts prior to entry into a herd.
  – Acclimatisation of gilts to provide immunity to PRRSV by intentional exposure to wild-type PRRSV or vaccination followed by a period sufficient to ensure they are no longer shedding virus reduces spread of the virus.
• Vehicles: an amount of live virus sufficient to infect
  PRRSV-neg pigs can remain in unwashed trailers transporting infected weaned pigs in faeces for 120h at 4°C. Risk in reduced by a comb of disinfection and drying.
• People: methods to reduce risks assoc w drivers incl use of disposable plastic boots, boot baths w bleach, changing boots and coveralls, washing hands etc.
• Tools, equipment, and supplies: mechanical trans of PRRSV via fomites has been confirmed, with a higher frequency of transmission in cold weather.
• Food and water: conflicting reports of transmission from infected pork to live pigs.
• Non-swine animals and insects: houseflies and mosquitoes are vectors, not stable flies in one study; insect screens superior to pyrethrins for reducing bites; results looking at non-swine animals as reservoir are inconsistent.
• Air: aerosol tranmission occurs; amount may vary w isolate; air filters reduce risk of transmission.

Ref: J. Am. Vet. Med. Assoc. 2015; 246(12):1304-1317.

Question 147

Describe control and elimination programs for PRRSV at the farm level.

Answer 147

• Classification as per the AASV scheme from positive unstable to negative.
• Control of PRRS starts in the sow herd, with the intent of weaning pigs with a low prevalence (ideally zero) of PRRSV. - 2 fundamental strategies to accomplish this:
  i) Maintaining a uniform level of immunity through vaccination, strategic exposure to live virus from the herd, or both; based on the rationale that some immunity in a herd is better than no immunity.
  ii) Goal of eliminating PRRSV from the sow herd via depopulation, partial depopulation, test and removal, and
  herd closure.

Ref: J. Am. Vet. Med. Assoc. 2015; 246(12):1304-1317.

Question 148

Describe considerations in testing for PRRSV.

Answer 148

• Infection with PRRSV does not result in pathognomonic clinical signs.
• Both serum and oral fluid specimens are suitable for
  nucleic acid (PCR assay) or antibody-based testing, but
  each has advantages and disadvantages.
• Detection of nucleic acid reflects current circulation of pathogens.
• Antibodies are abundant in serum and can be readily detected in oral fluid; cost of antibody assays is substantially less than that of PCR-based assays.
• In contrast to nucleic acids, antibodies provide
  a prolonged window of detection because they reflect
  both recent and past exposure history.
• At the farm level, antibody assays are compatible with continuous monitoring of population immune status by use of control charts.
• Point-in-time detection of pathogens or nucleic acid may be useful for pathogen charac or vaccine development.

Ref: J. Am. Vet. Med. Assoc. 2015; 246(12):1304-1317.