Consensus Statements Flashcards
With reference to asthma, what is the typical age distribution for mild (IAD) versus severe (RAO)?
RAO 7 yrs plus
IAD any age
Is equine asthma a disease continuum in which horse with IAD should be expected to progress to RAO?
No, although they may be at higher risk.
What are the typical characteristics of racehorses with IAD?
Coughing, increased tracheal mucous and high bacterial counts
List features of the IAD phenotype of asthma that can be used for diagnosis of this condition.
- Poor performance with or without chronic coughing
- Airway mucous grade >2/5 for racehorses >3/5 for sports horses
- BALF neutrophilia, eosinophils and or metachromatic cells
- If PFT available evidence of pulmonary dysfunction seen as lower airway obstruction, hyperresponsiveness, or impaired blood gas exchange
- Exclusion of systemic diseases that could result in these signs.
Are abnormalities on thoracic auscultation expected in horses with IAD?
Usually not but subtle wheezes and increased breath sounds may be heard, particularly with rebreathing examinations.
Which features indicate and increased risk of later development of RAO?
- Occasional cough
- Nasal discharge
List potential contents of the respirable fraction in a stable
- Organic and inorganic particles including
- Fungi
-Moulds - Endotoxins
- Beta-D-Glucan
- Ultrafine particles
- Microorganisms
- Vegetative material
- Inorganic dusts
- Noxious gases
What does the presence of increased eosinophils and mast cells along with Th-2 cytokines such as IL-4 and IL-5 in BALF suggest?
A role for aero allergens
True or false: predominance of metachromatic cells indicates airway hyperreactivity and presence of increased neutrophils has been associated with cough and tracheal mucous?
True
True or false: BALF neutrophilia occurs more commonly in young horses whereas airway eosinophilia has been associated with Coughing?
False. Eosinophilia is more common in young horses (<5yrs) whereas neutrophilia is more often in older horses and associated with coughing.
Which inflammatory mediators are associated with an innate immune response and BALF neutrophilia compared with those suggesting involvement of the adaptive immune system and mast cells?
Increased expression of genes encoding for TNF-a, IL-1B and IFN-y have been linked to luminal neutrophilia and suggest activation of the innate immune response and Th-1 polarisation may be involved in the pathognesis. Likewise mRNA expression of IL-17 and IL-23 have been linked with increased neutrophils while increased IL-4 and IL-5 with the matocytic form supporting implication of the adaptive immune response including Th-2 polarisation.
True or false: there is no conclusive evidence about the relationship between bacterial and viral infections and IAD.
True
What volume of fluid is administered for BAL and what cut off values are proposed for diagnosis of IAD versus RAO?
250-500mL 0.9% NaCl
IAD: neut <5%, eosinophils <1%, metachromatics <2%.
Total nucleated cell count <530 cells/uL
RAO: >25% neutrophils.
True or false: Tracheal mucous score was positively associated with neutrophil percentage but negatively correlated with mast cell percentage
True, by some authors.
True or false: doubling the infusate volume (ie using 500ml instead of the more commonly used 250mL) requires doubling the cut off values?
True. If using 500mL infusate the cut off for IAD neutrophil percent becomes 10% instead of 5%.
True or false: tracheal wash cytology has been correlated well to poor performance.
False. There is a lack of association between TW cytology and poor performance.
Gas exchange is impaired during exercise in horses with IAD, and more sensitive lung function tests such as forced expiration and impulse oscillometry indicate that horses with IAD have detectable airway obstruction. Airway hyperresponsiveness is a prominent feature of IAD, in particular with which cell types?
Increased eosinophils and mast cells.
The development of bronchoconstriction, airway hyperresponsiveness and cough are likely the airways response to what?
Inhaled irritants
How might IAD be differentiated from RAO?
- Severity of exercise intolerance
- Evidence of increased respiratory effort at rest in RAO only
- Severity of airway neutrophilia and mucous.
There is weaker evidence for a role of bacterial bronchitis (Strep zoo, S. pneumoniae) as an aetiological factor in IAD in which horses more commonly?
Typically young horses and those that have recently entered training.
Differentiate IAD from parasitic infections and EIPH from IAD?
The eosinophilic inflammation in BALF from horses with parasitic pneumonitis or eosinophilic pneumonia is usually more severe.
EIPH usually causes macrophagiv bronchiolitis and fibrosis and the haemorrhage is almost exclusively from the caudodorsal lung fields.
True or false: some studies have shown an additive effect on clinical signs, airway neutrophilia and inflammatory cytokines in horses with RAO when combining corticosteroid Tx with measures to improve air quality.
True
List medications for systemic and inhaled treatment of asthma
Systemic:
- Dex 0.05mg/kg SID
- Pred 1.2-2.2mg/kg SID
- Aminophylline 6-12mg/kg BID
- Clenbuterol 0.8-3.2ug/kg BID
- Pentoxifylline 35mg/kg BID
- Omega 3 fatty acids 1.5g DHA SID
Inhaled puffers:
- Beclomethasone 1-8ug/kg BID
- Fluticasone 1-6ug/kg BID
- Albuterol 1-2ug/kg q1-3h
- Ipratropium bromide 0.2-0.4ug/kg q812h
- Dex nebuliser 5mg diluted 1:1 in saline q12-24h
Inhaled nanoparticles of cytosine phosphate-guanosine oligonucleotides have been shown to decreased neutrophil percentage in TW and mucous secretions as well as improve lung function and clinical signs in horses with RAO - what is the mechanism behind this response?
Inducing a Th-2/Th-1 shift.
As bronchoconstriction has not been shown to be clinically significant in horses with IAD at rest and not well studied during exercise, what would be an additional benefit of clenbuterol?
Increasing mucociliary clearance
What feeding and managements changes should be implemented for horses with IAD?
- Feed complete pelleted diet or haulage.
- Soak hay (decreases dust by 60%)
- Switch to wood shaving bedding
- Feed from the ground to reduce respirable dust
List clinical signs of EIPH
Reported clinical signs:
- Blood in the airways and possibly nares
- Poor performance
- Epistaxis
- Abnormalities on U/S or rads
- Coughing
- Increased respiratory rate (no evidence)
- Respiratory distress or behaviour change (no evidence)
Consensus findings: Very low quality evidence of consistent clinical abnormalities in horses with EIPH with the exception of epistaxis after exercise.
Some horses with EIPH have changes detectable on radiography. Many horses have minimal to undetectable changes and some horses without a history of EIPH can have marked abnormalities. Where are the abnormalities typically identified radiographically?
Cauo-dorsal lung fields.
Does EIPH affect blood-gas exchange?
There is very low quality evidence of an adverse effect of EIPH on arterial oxygen tension, and similarly of higher blood lactate concentrations in horses with EIPH.
Is EIPH a cause of sudden death?
EIPH was considered to have contributed to sudden death during or shortly after racing in 50 of 143 horses for which a cause of death was identified - it may be secondary to other causes of sudden death such as heart failure. It is considered low quality evidence that EIPH is causally associated with sudden death, and there was no evidence of increased risk of sudden death in horses with EIPH.
Does EIPH shorten race careers?
There is moderate quality evidence that EIPH grade 1-3 is not associated with a shorter race career but that grade 4 is associated with a shorter race career.
Is EIPH associated with airway inflammation?
There is low quality evidence that EIPH leads to inflammation in either the pulmonary parenchyma or airways. During intense exercise horses are more likely to bleed into areas that are inflamed, however there is very low quality evidence that inflammation causes EIPH.
Does EIPH result in lesions in the lungs and if so what sort of lesions may be seen?
EIPH can result in both microscopic and gross lesions in the dorso-caudal lung fields bilaterally. Lesions may consist of pleural discolouration secondary to haemosiderin accumulation and this may be accompanied by pleural and septal fibrosis and angiogenesis. Extensive remodelling of small pulmonary veins characterised mainly by accumulation of adventitial collagen and smooth muscle hyperplasia with decreased luminal diameter.
Microscopically in recently exercise horses breaks in the capillary endothelium and basement membrane, interstitial and alveolar accumulations of erythrocytes and interstitial oedema consistent with capillary stress failure may be seen.
True or false: EIPH can be considered progressive with respect to increasing load (ie increased race starts) but not age alone.
True, it is progressive and related to load of racing.
Is EIPH considered a heritable trait?
There is no evidence of heritability however it may be associated with pedigree.
What impact does EIPH have on racing performance?
In thoroughbreds, horses with no evidence or only grade 1 EIPH were more likely to win or finish in the first 3 positions. Horses with tracheobronchoscopic evidence of EIPH were associated with higher likelihood of having an inferior finishing position. There is also evidence that distance behind the winner is associated with increasing EIPH grade.
In standardbreds there is very low quality evidence that EIPH is not associated with finishing time in a race.
Is furosemide effective at reducing or preventing EIPH?
There is high quality evidece that furosemide (0.5-1mg/kg) administered IV 4 hours before strenuous exercise decreases the severity and incidence of EIPH.
What effect does furosemide have on pulmonary vascular pressure?
There is moderate evidence that furosemide decreases pulmonary arterial and pulmonary wedge pressures and hence pulmonary capillary and transmural pressure during intense exercise.
Are aminocaproic acid, bronchodilators, corticosteroids, NSAIDs, pentoxifylline or other treatments including nasal strips effective at reducing EIPH?
Evidence is of low quality but does not support an effective role of other products in preventing EIPH.
Is there evidence to support that furosemide enhances racing performance?
Yes there is evidence that it improves racing speed, finishing position and race earnings in both TB and SB racehorses, and may be associated (low quality evidence) with delayed onset fatigue and improved energetic cost of locomotion in horses on a treadmill.
True or false: the consensus statement strongly recommends that EIPH should be considered a disease and not a variably manifested normal result of strenuous exercise activity?
True.
True or false: The panel found that there is moderate quality evidence that moderate-severe EIPH is NOT associated with decreased athletic performance by TB racehorses?
False. They found that moderate-severe EIPH IS associated with decreased athletic capacity in TB racehorses.
True or false: The panel found no evidence of improved racing performance in TB and SB treated with furosemide?
False. They found high quality evidence for improved performance in TB and SB with treatment with furosemide.
True or false: With respect to S. equi equi younger horses exhibit more severe clinical signs with lymph node abscess formation and rupture whereas older horses are often less severely affected and recover more rapidly.
True
What are the first clinical signs typically seen with S. equi equi and at what stage after exposure do they occur?
Pyrexia with lethargy. 3-14 days after exposure. Pyrexia is persistent and may exceed 42C and may persist until lymph node abscesses rupture.
True or false: Squeezing the larynx will often cause marked pain, stridor, or gagging followed by coughing and endoscopically pharyngeal lymphoid hyperplasia and pharyngeal compression from enlarged lymph nodes may be seen in cases of S. equi equi
True
Which lymph nodes are commonly and less commonly involved with S. equi equi.
Submandibular and retropharyngeal commonly involved; parotid and cranial cervical occasionally involved.
What is the usual temporal relationship between infection and rupture of abscesses with S. equi equi?
Typically rupture between 7days and 4 weeks after infection - thick fibrous capsule.
In a horse that displays expulsion of large amounts of purulent discharge during coughing, eating or when the head is lowered what might you suspect?
Guttural pouch empyema. Approximately 50% of horses with guttural pouch empyema exhibit an intermittent unilateral nasal discharge and cough.
What is the pathogenesis of infection with S. equi equi?
The bacterium attaches to cells within the crypts of the lingual and palatine tonsils and to the follicular-associated epithelium of the pharyngeal and tubal tonsils. Ligands responsible for binding may include exposed surface proteins such as SzPSe. A few hours after infection the organism is difficult to detect on mucosal surfaces but is visible within epithelial cells and subepithelial tonsillar follicles. Thus, nasal or nasopharyngeal samples may be culture negative in early stages of infection. Translocation occurs in a few hours to the mandibular and retropharyngeal lymph nodes that drain the pharyngeal and tonsillar region. Complement-derived chemotactic factors attract large numbers of neutrophils although gross abscessation isn’t visible for 3-5 days.
What factors of S. equi equi prevent phagocytosis?
Thought to be a combination of the hyaluronic acid capsule, anti-phagocytic SeM protein, H factor binding Se18.9, Mac protein and other undetermined antiphagocytic factors released by the organism.
What is the time progression to shedding with S. equi equi?
Nasal shedding usually begins 2-3 days after onset of fever and persists for 2-3 weeks in most animals, although up to 6 weeks post nasal discharge ceases is possible, or longer if guttural pouch or sinus colonisation occurs. Some asymptomatic horses will still shed.
Systemic and mucosal immune responses are evidence 2-3 weeks after infection and coincide with mucosal clearance.
What influence does the size of inoculum have on disease occurrence and severity with S. equi equi?
Lower numbers of bacteria are likely to be efficiently removed by the mucociliary clearance mechanisms.
Inocula of less than 10^6 CFU don’t consistently cause disease.
The larger the intranasal inoculum, the sohrter the incubation period and more severe the disease.
What percentage of horses develop convalescent immunity post S. equi equi?
Approximately 75% if not treated with antibiotics. However 20-25% of convalescent horses become susceptible to a second attack of the disease within several months.
True or false: It is appropriate to consider that all (strangles) recovered horses may be potentially infectious for at least 6 weeks after their purulent discharges have dried up.
True.
What is the survival of S. equi equi in the environment?
Fairly rapid death of the bacteria on fencing and in soil of 1-3 days. May remain viable in water for 4-6 weeks.
What are the pro’s and con’s of different testing strategies for S. equi equi and the temporal relevance of these?
- A needle aspirate from an enlarged or abscessed lymph node is the optimal sample for confirmation
- Moistened nasopharyngeal swabs (false negatives possible in early stages and with intermittent GP shedding), nasopharyngeal lavage (false negatives possible in early stages and with intermittent GP shedding), and guttural pouch lavage (best for detection of carriers; false negative may occur if lymph nodes have not yet ruptured into the pouch) may be useful however the bacteria will often not be isolated from these sites during the early stages of disease, so a negative doesn’t rule out disease.
- Washes have increased sensitivity compared to swabs.
What culture medium should be used for S. equi equi isolation?
Columbia CNA agar with 5% sheep or horse blood added.
True or false: Presence of other beta-haemolytic strep such as Strep zoo can complicate interpretation of cultures as zoocins produced bby Strep zoo will kill S. equi equi and so strangles abscesses that rupture quickly can become colonised and dominated by S. zoo
True.
During which periods is culture potentially unsuccessful or of low yield with S. equi equi?
During incubation, early clinical phases and when the bacterial count is low during convalescence - recovery can be as low as 40%.
S. equi equi may not be present on the mucosal until 24-48 hours after the onset of fever - what approach can be used to enable early recognition, isolation and limited transmission of disease?
Daily temperature monitoring
What genes do PCR look for when testing for S. equi equi?
- The antiphagocytic M protein of S. equi (SeM sequence)
- A superantigen-encoding gene seeI (qPCR)
Which antibodies does the S. equi equi ELISA test for and how quickly do they peak and return to normal?
Antigen A (N-terminal fragment of SEQ_2190 or Se75.3)
Antigen C (N-terminal fragment of SeM)
Peak titres are seen about 5 weeks after exposure and typically remain elevated for at least 6 months. This combined antigen A and C ELISA overcomes the problem of cross reactivity with Strep zoo and provides a similar sensitivity but greater specificity compared with the whole SeM antibody titre.
List different antibody responses and how these can be used to interpret risk for secondary complications with S. equi equi.
- Strong antibody response >1:3,200 may be at risk of developing purpura haemorrhagica
- Detection of recent infection evidenced by 4-fol increase in antibody titre in pared sera 10 days apart
- High titre >1:12,800 supports an existing diagnosis of purpura haemorrhagica or bastard strangles
- A vale of >1:3,200 would suggest vaccination is contraindicated due to increased risk of purpura haemorrhagica in these animals.
- Serologic values are not a measure of protection and also cannot be used to determine carrier status.
True or false: Horses with S. equi equi treated with antibiotics mount a reduced immune response and remain susceptible to reinfection.
True.
How are paired S. equ equi ELISA results interpreted?
- Negative results on both samples (taken 10-14days apart) in a horse with no clinical signs indicates the horse is safe to return to the herd.
- Horses that test positive with either antigen shoudl be investigated further by means of guttural pouch endoscopy and washes for qPCR
What is the earliest stage at which testing should be implemented at the end of a Strangles outbreak to determine persistent carriers and subclinically infected horses
No sooner than 3 weeks after resolution of clinical signs of the last clinical case.
List the vaccines available for Strangles and their type as well as reported efficacy
- Single purified M-protein antigen extract (StrepvaxII) schedule is 3 doses 3 weeks apart then booster annually. Reduction in clinical attach rate of only 50%.
- Attenuated live intranasal vaccine (Pinnacle IN) schedule is 2 doses 2-3 weeks apart and annual booster. Concern regarding reversion of virulence or slowly progressive disease post vaccination. Other invasive procedures should not be done concurrently and not give to foals <1yr. May be PCR positive for up to 6 weeks. Don’t use if history of strangles in past year. Risk of purpura haemorrhagica.
- Live attenuated sub-mucosal vaccine (Equilis StrepE) provides immunity from expirmental challenge for around 3 months. Cannot differentiate infected from vaccinated based on serology. Painful injection site reactions can occur and rarely bacterial replication post vaccination has occurred.
Does passive transfer of immunity occur with S. equi equi and how does vaccination of the dam influence this?
IgGb isotypes predominate, and are distributed to the serum and nasal secretions. Pre-partum extract vaccination of the mare significantly increases colostral levels of these antibodies. Don’t tend to have IgA titres
List components of a screening programme prior to introduction to a strangles free herd.
Isolate for a minimum of 3 weeks with strict biosecurity and disinfection protocols
Paired serology (unless vaccinated)
Guttural pouch endoscopy, culture and PCR testing
What percentage of Strangles animals in an outbreak become carriers?
10% have persistent GP empyema and 40% will be culture or PCR positive >40 days after initial diagnosis.
What is the traffic light approach to cohorting in a strangles outbreak?
Red: horses with 1 or more clinical sign
Amber: horses that have had direct or indirect contact with an infected horse in the red group and may be incubating. Monitor temperature twice daily, if febrile, move to red group.
Green: those with no known direct or indirect contact with affected animals. Monitor temperature twice daily, if febrile, move to red group.
True or false: 1 endoscopically guided guttural pouch lavage qPCR on cases and heir contacts to screen for carriers provides increased efficiency and sensitivity over 3 nasopharyngeal washes over 3 weeks.
True.
What approach should be considered in cases that continue to test positive for Strangles despite endoscopically normal GP?
Systemic antibiotics and radiography to assess for sinusitis - if purulent discharge at nasomaxillary opening it should be sampled.
Which disinfectants are most effective with S. equi equi?
- Clean with foaming soap agent to remove organic material and rinse then thorough soak in liquid disinfectant such as hypochlorites (bleach), quarterary ammonium compounds, phenolic compounds, accelerated hydrogen peroxide.
What are the main risks of antibiotic treatment of S. equi equi cases and when is it indicated versus not indicated?
- Antibiotic treatment could limit synthesis of protective antibodies.
- Possible delay in abscess maturation or recurrence of abscessation after treatment ceases.
- Evidence is lacking that antibiotics increase the risk of bastard strangles.
Consider antibiotics in cases where: - Acutely infected animals have a very high fever and malaise before abscess formation (may be curative and prevent abscessation; premature discontinuation may result in prolonged disease rather than shortened)
- Profound lymphadenopathy and respiratory distress
- Metastatic abscessation
- Purpura haemorrhagica treated with corticosteroids
- Guttural pouch infections (treat locally and or systemically to eliminate carrier status)
- Don’t use as a preventative in animals that may have been exposed
True or false: Once external lymphadenopathy is detected antibiotic treatment is generally ineffective
True
Complication rate with S. equi equi increases with duration and intensity of exposure - up to what percentage can experience complications? And what case fatality rates have been reported
Up to 20%. Fatality up to 8.1-9.7% in large farm outbreaks.
List reported sequelae to Strangles.
- Anaemia
- Agalactia
- Myocarditis
- Endocarditis
- Panophthalmitis
- Periorbital abscesses
- Ulcerative keratitis
- Paravertebral abscesses
- Meningitis
- Funiculitis
- Septic arthritis
- Tenosynovitis
What clinical and clinicopathologic findings would support a diagnosis of metastatic strangles in a case where internal abscessation is identified?
- History of exposure to S. equi
- Intermittent low grade fevers responsive to penicillin
- High SeM titres
- Evidence of chronic infection eg anaemia, hyperfibrinogenaemia, neutrophilia, hyperglobulinaemia.
What is purpura haemorrhagica?
An aseptic necrotising vasculitis that is caused by deposition of immune complexes in the blood vessel walls associated with S. equi infection as well as other non-S. equi antigens.
What are the main forms of myositis that can occur as sequelae to S. equi equi?
- Infarctive myositis: a severe vasculopathy characterised by infarction of skeletal muscle, skin GIT and lungs. Titres often exceed 1:6,400
- Rhabdomyolysis with acute myonecrosis involves direct invasion of the muscle by the bacteria resulting either in a toxic shock like syndrome or direct toxic effects of the bacteria.
- Rhabdomyolysis with progressive atrophy characterised by chronic active rhabdomyolysis with rgeneration, macrophage infiltration, atrophy of fast-twitch fibres and lymphocytic vasculitis. Atrophy may resolve in some cases.
What is the pathogenesis of EHV-1 and the potential development of abortion or EHM?
- Primary EHV-1 infection occurs at the respiratory epithelium resulting in erosion of the URT mucosal surface and viral shedding for 10d after infection (longer in EHM).
- Cell to cell spread results in the presence of virus in respiratory tract lymph nodes within 24-48h after infection
- A leukocyte-associated viraemia is established which is directly responsible for delivery of EHV-1 to other tissues.
- Viraemia can persist for at 14 days and is a pre-requisite for abortion or EHM as it allows for transport of the virus to the vasculature of the pregnant uterus or the CNS where infection of endothelial cells occurs.
- In the CNS the typical result is disseminated ischaemic necrosis of the spinal cord (grey and white matter and brainstem).
- In the reproductive tract the viraemia affects endothelial cells in small arterioles in the glandular layer of endometrium at the base of microcotyledons, leading to vasculitis, microcotylednoary infarction, perivascular cuffing and trans-placental spread of virus at the site of vascular lesions, hence abortion. The foetus is usually virus positive. The uterine ednothelial cells have an increased susceptibility during late pregnancy, hence abortions tend to be 3rd trimester.
What percentage of horses with EHV-1 develop EHM or abortion if pregnant?
EHM is fairly rare - approximately 10%
Abortion - attack rates can be as high as 50%
It has been suggested that magnitude of cell-associated viraemia is an important factor for the development of EHM - why?
Infection with the DNApol D752 strain (up to 75%+ of EHM cases are this strain) leads to higher magnitude and duration of viraemia
What signalment of horse is more often susceptible to EHM and what does this imply?
Older horses are generally more susceptible. This suggests a possible role for immunological status in the pathogenesis of EHM as older horses typically demonstrate a greater IFN-y based cellular response to EHV-1
A single nucleotide polymorphism (SNP) in the DNA polymerase (DNApol) gene has been associated with EHM. Which strain is associated with this SNP and what proportion of EHV-1 viruses carry this genotype?
D752. Thought to be 5-20% of viruses carrying this genotype.
Which strain of EHV-1 has been most commonly associated with cases of abortion?
N752 (responsible for 95-98% of EHV-1 abortion outbreaks in US, UK and other countries). * note: still responsible for between 15-25% of neurological outbreaks so not “non-neuropathic”.
True or false: Targeted mutation of the D752 to the N752 genotype in a neurovirulent isolate resulted in attenuation of virulence, specifically reduced levels of viraemia, reduced capacity to cause neurological disease and reduced severity of other clinical signs, providing support for the hypothesis that the D752 variant has increased neuropathic potential
True.
What is the likely mechanism behind infection of EHV-1 in foals in the first weeks of life?
Reactivation of virus in latently infected mares
Where is latency established with EHV-1 and in approximately what proportion of horses?
Latency is established in both the lymphoreticular system and the trigeminal ganglion. Prevalence of latency is thought to be in excess of 60%. The recommendation is that clinicians should presume that the majority of horses are latently infected with EHV-1.
What are the clinical implications of sub-clinical shedding of EHV-1
Thought to be fairly rare and when it does occur it is likely at very low levels that might not pose a contagious threat to other horses, hence spread of EHV-1 among adults is typically accompanied by clinical disease, either abortion of EHM.
What are the two proposed scenarios for the origin of the high risk neuropathogenic D752 variants in EHV-1 outbreaks?
- Reactivation of the D752 genotype from a horse latently infected with this genotype.
- Spontaneous mutation from a lower risk N752 genotype to the higher risk D752 genotype.
Both of these scenarios may occur.
List the known and suspected risk factors for development of EHV-1 disease (respiratory, abortion and neurologic)
Known risk factors:
- Presence of EHV-1 and susceptible horses within a herd
- Presence of an infected, shedding horse in the herd
- Season (majority of EHM occurs in late autumn, winter and spring, abortion occurs in third trimester)
- Age (EHM can occur in all ages but is largely restricted to >3-5yo; respiratory disease associated with EHV-1 is infrequent in horses >2yo)
- Past exposure produces a limited period of protection (3-6mo) however repeat EHM has not been reported, and repeat abortions from consecutive pregnancies are rarely reported.
- Horses with high fever, particularly high fevers occurring several days after the initial onset of fever are more likely to develop EHM.
- Introduction of new horses to a herd commonly precedes an outbreak of EHV-1, and specifically EHM
- Clinical infection with D752 biovar is more commonly detected in horses with EHM than N752 but both can cause EHM.
- Breed and sex are risk factors, with females more often affected and ponies and smaller breeds less often affected with EHM.
Suspected Risk Factors
- Geographic region appears to be associated with development of EHM (very rare in Aus/NZ)
- Outbreaks of EHV-1 diseases are anecdotally associated with stressors such as weaning, commingling, transportation, concurrent infections
What diagnostic tests are available for EHV-1 and what is the gold standard?
Gold standard is virus culture and isolation
- PCR of nasal or nasopharyngeal swabs as well as buffy coat.
- Paired serum samples 7-21days apart showing 4-fold+ increase in serum antibody titre by serum neutralising or complement fixation tests (more useful testing in-contact horses as antibody levels have often already peaked by the time clinical signs show so you don’t get a rise)
How do you interpret the results of various EHV-1 PCR test result?
- Positive EHV-1 blood sample: viraemia and most likely active infection. Latent infections are unlikely to give a positive on blood
- Negative EHV-1 on blood indicates absence of detectable viraemia
- Positive EHV-1 on nasal swab indicates shedding of infectious virus (quantitative result will give more information about level of risk posed)
- Negative EHV-1 result on nasal swab indicates absence of detectable virus shedding.
What are the advantages of knowing the viral load?
Enables better characterisation of the stage of disease, assessment of risk of exposure to other horses, enables monitoring response to treatment, magnitude of viraemia can help predict the severity of infection and risk of progression.
What are the typical features of CSF from a horse with EHM?
Xanthochromia, increased protein concentration with or without monocytic pleocytosis. PCR is usually unrewarding due to low viral numbers
Why is an EHV-1 antibody titre in CSF not diagnostic during the acute phase?
It reflects leakage of blood into the CSF as a result of the EHM lesions.
What are the histologic features of EHM and what post-mortem diagnostic tests can be done on the CNS?
Vasculitis and thrombosis of small blood vessels in the spinal cord and brain are consistent with EHM.
Virus antigen detection in the CNS via immunohistochemistry, in situ hybridisation and PCR testing may be rewarding.
Is there evidence that current vaccination protocols protect against EHM?
No
Control of cell-associated viraemia is thought to be critical for the prevention of abortion and likely neurological disease too. Hence vaccination aims at stimulating those immune responses that reduce or eliminate cell-associated viraemia. Hence is it mucosal or serum antibodies that need to be stimulated and where?
Mucosal antibodies which prevent infection of the respiratory tract and hence limit shedding.
Which vaccines are effective at inducing mucosal antibody production?
- Modified live vaccine Rhinomune performs well in controlling respiratory infection and shedding. Doesn’t claim to protect against abortion.
- Inactivated adjuvanted vaccines Pneumabort K and Prodigy. PNeumabort K decreased incidence of abortion in vaccinated mares in 1 study however an other study found no difference in occurrence of abortion.
List the recommended management protocols to reduce the risk of EHV-1 outbreak.
- Segregation of pregnant mares from all other horses
- Isolate for at least 3 weeks when entering the farm including those returning after leaving the farm.
- Subdivide pregnant mares into small physically separated groups for the duration of their gestation.
- Reduce stress by maintaining the social structures, avoid prolonged transport, relocation, poor nutrition, parasitism, environmental exposure and en masse weaning of juveniles.
How long should quarantine be implemented after an outbreak of EHV-1?
A minimum of 28 days after the occurrence of any new cases.
Alternatively, quarantine for 14 days then test all horses by qPCR of nasal swabs on 2 consecutive days before lifting quarantine. It can be further augmented by monitoring rectal temperature twice daily during the 14 days - 14 days without fever can constitute the quarantine, followed by PCR testing.
True or false: Virus is unlikely to survive in the environment in infectious form for more than 21 days.
True
True or false: given our poor understanding of the efficacy of corticosteroids their use is currently reserved for EHM cases presenting in recumbency or with severe ataxia, in which the prognosis is guarded for survival.
True.
What is the bioavailability of acyclovir versus valacyclovir?
Acyclovir is low, below that required for viral inhibition
Valacyclovir is 35-40%.
How is R. equi pneumonia definitively diagnosed?
PCR amplification of the vapA gene obtained from a foal with clinical signs of LRT disease, cytological evidence of septic airway inflammation or radiological/ultrasonograhpic evidence of bronchopneumonia. PCR does not replace culture as it does not identify other bacterial pathogens or determine in vitro susceptibility testing.
Why is diagnosis of R. equi enterocolitis challenging?
Faecal shedding of R. equi does not confirm R. equi as the cause of enterocolitis.
True or false: The current state of knowledge precludes serology to be used as a diagnostic test for R. equi pneumonia.
True
True or false: Detection of R. equi from a foal without clinical signs of respiratory disease, cytological evidence of septic airway inflammation, or ultrasonographic/radiographic evidence of pulmonary lesions is still indicative of clinical disease
False - it is probably an incidental finding in that case
Why is detection of R. equi via PCR more likely to yield false positive results than culture?
More likely to identify small numbers that may be present as environmental contaminants.
Why is the vapA gene the only one recommended for PCR of R. equi?
Detection of other R. equi genes would mean detection of environmental isolates that lack the virulence plasmid and hence don’t cause disease.
Why is weekly quantitative culture of faeces for R. equi recommended as a monitoring tool for early infections?
Faecal concentration of R. equi increases at around the same time as respiratory disease appears, according to some studies.
What is the most appropriate method for measuring effective drug concentrations with antimicrobials intended to treat lower airway infections?
Measurement of drug at the site of infection such as PELF and BAL cells
In one study the combination clarithromycin-rifampin was significantly more effective than erythromycin-rifampin or azithromycin-rifampin, especially in foals with severe radiographic lesions. However these results must be interpreted with caution - why?
Foals were not randomly distributed to treatment groups and there was likely biases from retrospective data.
True or false: false treated with a macrolide and rifampin for R. equi often developdiarrhoea which is self-limiting and often does not necessitate treatment cessation
True
What is the incidence of diarrhoea in foals treated with erythromycin-rifampin for R. equi?
17-36%
What precautions should be made for foals treated for R. equi in hot or humid weather?
Idiosyncratic reaction characterised by severe hyperthermia should be monitored for.
Why should rifampin not be used alone?
It increases the chance of resistance developing as a result of mutations in the RNA polymerase beta subunit encoded by the rpoB gene.
What is the approach to treatment in foals with R. equi, including extra-pulmonary disorders?
- Nursing care, including nutrition, IVFT, electrolyte/acid base balance
- Antimicrobials
- Intranasal humidified oxygen
- NSAIDs
- Nebulisation with saline +/- antibiotics +/- bronchodilators may be effective but no studies to confirm
- Limit exercise in foals with polysynovitis
- Additional therapy such as lavage, debridement and regional perfusions may be necessary in foals with septic arthritis or osteomyelitis
- Intra-abdominal abscessation rarely responds to prolonged treatment.
What is the prognosis for foals with R. equi with and without screening protocols?
Prognosis as reported from a referral hospital in which severe cases are more prevalent, the survival was 59-72%.
On a farm with a screening programme survival was 100% but likely included treatment of foals that would have resolved without intervention.
True or false: prognosis for racing performance after successful treatment of uncomplicated R. equi pneumonia should be regarded as excellent?
True.
Implementing a screening programme for controlling R. equi pneumonia on farms is recommended - why?
R. equi pneumonia is an insidius disease and clinical signs may not be apparent until pathologic changes are well progressed - detection in early stages of disease will improve therapeutic outcome as advanced progression of disease is associated with poorer prognosis.
True or false: Serum concentrations of antibodies against R. equi, serum amyloid A and fibrinogen are useful as a screening test.
False.
True or false: Many foals with subclinical pulmonary lesions recover without treatment. Treatment of foals with pulmonary lesions with azithroycin-rifampin accelerated recovery compared with placebo.
False. Many foals will recover without treatment, and initiating treatment in subclinical cases does not accelerate recovery compared with placebo.
At what soil pH is the odds of recovering virulent R. equi increased? pH<6 or pH >6?
pH <6 seems to be associated with increased odds of isolating virulent R. equi from soil samples
True or false: There is currently no evidence that R. equi affected foals should be isolated from other foals? Justify your answer
True. Reasons to isolate would include increased aerosolised virulent bacteria from pneumonic foals compared with the environment and increased shedding in faeces compared with normal foals. However there is no evidence to support isolation as normal foals are exposed to virulent bacteria in the environment anyway and there is no evidence to support R. equi being contagious amount foals.
Administration of hyperimmune plasma to foals is recommended as a preventative treatment for R. equi pneumonia, however administration of regular plasma (non-hyperimmunised) is not recommended as prophylaxis - why?
The benefit of hyperimmune plasma seems to come from immunoglobulins predominantly directed against VapA and VapC which requires immunisation of plasma donors.
Which antibody responses will likely need to be stimulated in order to provide effective protection of foals to R. equi infection?
- Likely needs to induce antigen-specific Type 1 cell-mediated responses
- Likely needs to include CD4 Th1 lymphocytes that secrete INF-y in response to R. equi antigens and possibly also CD8 T lymphocytes that recognise and kill infected cells.
List objective negative prognostic factors in the setting of structural heart disease.
- Progressive chamber remodelling and dysfunction
- Great vessel enlargement
- Development of PHT
- Development of CHF
- Development of potentially dangerous or complex ventricular rhythms.
Horses with PHT, CHF or complex ventricular arrhythmias are unsafe to ride.
List cardiovascular characteristics that indicate the need for echocardiography.
- A previously diagnosed functional murmour that is louder on serial examinations
- A grade 3-6/6 left sided murmour compatible with MR or AR
- A grade 4-6/6 right sided murmour compatible with TR
- Suspected VSD or other congenital lesion
- Continuous or combined systolic-diastolic murmours
- Clinically important arrhythmias
- Suspected myocardial injury
- Suspicion of CHF.
List components of a complete echocardiographic study.
- Morpholic lesions
- Motion abnormalities
- Cardiac chamber and great vessel size
- Cardiac valve function
- Blood flow disturbances
- Global and regional ventricular systolic function
- Estimates of haemodynamic variables including pressure gradients and volumetric flow
- Ventricular diastolic function and filling pressures.
True or false: Tricuspid valve regurgitation and pulmonary artery dilatation are used as surrogates for the identification of PHT.
True
What characteristics of a mitral regurgitation jet might lead to underestimation of the severity of MR?
An eccentric, wall-hugging or flat jet.
List negative prognostic indicators for horses with MR.
- Mod-severe MR
- Endocarditis
- Ruptured chordae tendinae
- Flail leaflet
- Severe valvular thickening
- Concurrent PA dilatation
- Increased TR velocity
- Significant MR with AF or tachycardia
True or false: Bounding or hyperdynamic arterial pulses suggest haemodynamically severe AR with LV volume overload.
True
True or false: A flail leaflet is detected frequently, and indicates a torn or avulsed portion of the valve.
False: a flail leaflet is detected rarely and indicates a torn or avulsed portion of the valve
What does premature closure of the mitral valve indicated?
Markedly increased LV end-diastolic pressure, indicative of severe AR.
Detection of hyperkinetic arterial pulses, or a pulse pressure of >60mmHg suggests that progression of AR is likely or unlikely?
Likely.
What are the exercise and re-examination recommendations for a horse with severe AR?
Not to be ridden by a child or used as a school horse.
Re-examine twice yearly, then annually thereafter if no further progression.
What are the common echo findings associated with clinically significant TR?
- Structural or motion abnormalities of the tricuspid valve with RA or RV enlargement
- Jet width is wider at the origin
- Jet tends to occupy a larger area in the RA
- Jet is oriented centrally or toward the lateral RA wall.
- If jet velocity is >3.5m/s (PHT is suspected)
Which breeds are predisposed to VSDs?
Welsh Mountain Ponies, Arabians and Standardbreds.
What are the types of VSD (based on location) and which is most common?
- Perimebranous (most common) - located ventral to the tricuspid leaflet and below the junction of the right and non-coronary cusps of the aortic valve
- Subarterial (also called subpulmonic) beneath each semilunar valve
- Muscular (also called apical)
- Malalignment - when the aorta straddles part of the ventricular septum - increased risk of aortic valve prolapse.
How should a VSD be measured?
The largest systolic diameter of the defect in two mutually perpendicular planes.
True or false: There is usually some enlargement of the left side of the heart with a left-right shunt, however cardiac dimensions usually fall within normal with small shunts. Moderate to severe enlargement of the LA and LV is concerning and increases the risk for AF, PHT and CHF.
True.
What factors might indicate a greater shunt volume?
- Lower shunt velocities (<4m/s)
- Higher pulmonary artery ejection and mitral inflow velocities
List the most important prognostic criteria for an isolated VSD.
- Size of the VSD
- Size of the cardiac chambers
- Maximal shunt velocity
- Presence of significant AR or MR
- PHT
- CHF
What condition would you be suspicious of if you identify a continuous machinery murmour loudest on the right side of the thorax with bounding arterial pulses?
Aorto-cardiac fistula.
What condition would you be suspocious of if you identify a grade 1-3/6 holosystolic and early-mid diastolic murmour loudest dorsal to the aortic valve with concurrent bounding arterial pulses and tachycardia in a Friesian?
Aorto-pulmonary fistula.
List potential causes for development of cardiac arrhythmias
- Isolated electrical disorders
- Structural heart disease
- Metabolic and endocrine disorders
- Systemic inflammation
- Hypotension, haemorrhage, anaemia and ischaemia
- Autonomic influences
- Toxicosis/envenomations
- Drugs
What might resting tachycardia indicated in a horse with AF?
- Underlying heart disease
- Sympathetic nervous system stimulation (stress or pain)
- Presence of an accessory atrio-ventricular conduction pathway (uncommon)
What does atrial flutter represent?
A slow macro-reentry variation of AF.
With respect to the atrial rate, how might you differentiate atrial flutter from atrial fibrillation?
Atrial flutter atrial rate = 170-275bpm
Atrial fibrillation atrial rate = 275-500bpm
True or false: AF induces time-dependent electrical and structural remodelling within the atria, factors which are known to promote its persistence. These changes might also decrease the chances of successful cardioversion.
True.
True or false: rapid ventricular response to AF and complex ventricular ectopy are contraindications for quinidine treatment? Justify
True. Due to the proarrhythmic effects of quinidine and the risk of polymorphic VT.
Which drugs and supplements should be avoided in horses post cardioversion?
Furosemide (if you have to give it, supplement with oral KCl)
NaHCO3
Thyroid hormones
True or false: horses with APCs that are overdriven during exercise and those with occasional APCs during exercise are considered unsafe to ride.
False. These horses are considered as safe as their age-matched peers. The risk for development of AF should be appreciated.
What are the typical auscultation findings with a VT?
Rapid, usually regular rhythm with variable intensity and often booming heart sounds (bruit de cannon), but may sound irregular due to intermittent aortic valve opening.
List recommendations for horses with ventricular arrhythmias.
- Horses with occasional VPCs at rest or during exercise or with sustained accelerated idioventricular rhythm that is overdriven by exercise can be ridden with caution by an informed adult
- Horses with sustained monomorphic VT should be rested and treated.
- Horses with symptomatic or complex ventricular arrhythmias should be rested and treated, and only ridden by informed adults.
- Rigorous exercise is not recommended for horses tht showed ventricular arrhythmias in the setting of moderate or severe structural heart disease, and should only be ridden by an informed adult.
