JULY 2022 VOLUME 31, NO.3

A PUBLICATION BY THE UNIVERSITY OF KENTUCKY DEPARTMENT OF VETERINARY SCIENCE, MAXWELL H. GLUCK EQUINE RESEARCH CENTER
FUNDED BY:

EQUUS / STANDARDBRED STATION, INC.
M&J INSURANCEIN T HIS IS S U E
INTERNATIONAL, PG. 2
Equine Infectious Diseases
First Quarter 2022
NATIONAL, PG. 3-4
Probiotics in horses:
Potential benefits and how
to choose the right product
Equine Pleuropneumonia
KENTUCKY, PG. 5
Biomarkers for Equine
Athletes: What do weknow?

TH A N K YO U
SPON SO RS

C O MME N TARY
Inflammation and its role in health and disease
We are all familiar with the classic symptoms ofinﬂammation: redness, pain, swelling and heat. This
reaction occurs in response to tissue injury caused by
infection or physical damage.
While inflammation is often viewed as a pathologic
condition, its purpose is to reinstate physiologic
homeostasis in response to damage. The initial, or
acute, inflammatory response is necessary to begin thehealing process by eliminating debris and promoting
cellular regeneration and replacement. Chronic or
persistent inflammation, by contrast, can lead to aworsening of the pathology and further debilitation.
As such, the mechanisms underlying the initiation
and resolution of inﬂammation are tightly regulated.
A number of pro-inflammatory cytokines, which
are proteins used for cellular communication, areinvolved in the induction of this response. Likewise,anti-inflammatory cytokines and other mediatorsserve to dampen and resolve the response once thenoxious stimulus is removed. Therapeutic intervention
can hasten this process by blocking some of the key
intermediaries of the inflammatory response.
While nonsteroidal anti-inflammatory drugs (NSAIDs)
are highly effective in limiting and resolving
inflammatory conditions, they do not address theunderlying cause of the inflammatory response.
They can also interfere with the restorative aspectsof the inflammatory response and delay the return tohomeostasis. This, in addition to their other knownside effects on gastric mucosa, warrants carefulconsideration prior to use. Nevertheless, NSAIDS aresome of the most widely used medications in veterinary
medicine.
Alternative approaches, including the use of nutritional
supplements with anti-inflammatory properties, arewidely available and heavily promoted. While somecontain ingredients with anti-inflammatory properties,
limited data is available regarding dosing, effectivenessand safety, especially for horses.

two articles addressing inflammatory responses. Dr.
Allen Page’s article on the identification of biomarkers
to predict injury risk for Thoroughbred racehorses
is based on the observation that exercise-induced
inflammation is exacerbated in horses at risk formusculoskeletal injury. Exercise is known to induce acertain degree of inflammation required for the repairof skeletal and muscle damage induced by the physicalforces of exercise. However, exaggerated expression ofsome of these pro-inflammatory mediators and otherrelated molecules likely signifies a situation where thedamage is exceeding the capacity of repair mechanisms
leading to a worsening condition and the possibility ofa catastrophic failure. While NSAIDS may be used
to treat post-exercise soreness, their impact on therestorative aspect of the inflammatory response isunknown.
By contrast, Dr. Kate Hepworth-Warren’s article onpleuropneumonia addresses the need for NSAIDS
to reduce inflammation in this condition. The lung isparticularly sensitive to inflammation, where cellular
infiltrates and edema can readily impair its function.
NSAID therapy, in conjunction with antibiotics andother supportive therapies, is key to restoring health in
infected individuals.
The third article by Dr. Jamie Kopper on probiotics
does not directly address their impact on inflammation,
but there is a growing body of information that
identifies linkages between gut microbiota andinflammatory conditions in both humans and animals,
including horses. This area of research is likely to growas horse owners and veterinarians continue to look fornovel ways to modulate the inflammatory response toimprove the horse’s health and wellbeing.
CONTACT:David W. Horohov, PhD
Emeritus Professor
Department of Veterinary Science
Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

This issue of the Equine Disease Quarterly contains

JULY 2022 | 1

I N T E R N AT I ONALFirst Quarter 2022
International Report on equine infectious diseases
The following data was primarily provided by theInternational Thoroughbred Breeders Federation;
International Collating Centre in Newmarket, United
Kingdom (UK); the Equine Disease Communication
Center of the American Association of Equine
Practitioners; and other sources. This report isretrospective and does not claim to be complete.
However, it provides an indication of heightened
activity of contagious or environment-related diseases
among equids. Reports of equine infectious disease
were not received from Central and South America,
most parts of Africa (with exception of the Republicof South Africa) nor from most parts of Asia (withexception of Japan).
Strangles was reported from various regions of North
America and Europe, including the British Isles.
Routine screening revealed eight cases of equine
infectious anemia (EIA) in North America and one casein Italy.
A few outbreaks of equine influenza virus were reported
from regions of North America and from various partsof Europe, including UK and Germany. Equine herpes
virus (EHV)-4 respiratory disease was detected ingroups of weanlings in Kentucky, United States ofAmerica (USA), as well as from isolated cases, mostly
from young stock, in other regions of North America
and Europe.
Pregnant mares in the Northern Hemisphere entered
their most vulnerable period for EHV abortion, thus it
is not surprising that cases of EHV-1 abortion werereported from the Midwest region of the USA, British
Isles, continental Europe and from Japan. Furthermore,
the first quarter of the year in the Northern Hemisphereis also high season for equid herpesvirus-associatedmyeloencephalopathy (EHM). EHM outbreaks werereported from various regions of North America (thehighest number of cases was reported in California,
USA) and from continental Europe. EHM was typicallydetected in one or more horses, while several other incontact animals had fevers and respiratory signs.
There were no reports of West Nile virus encephalitis,
one case of Eastern equine encephalitis virus infectionin Florida, a case of Japanese encephalitis virus
infection in Australia and one case of rabies encephalitis
in Oklahoma, USA.
Miscellaneous:Eleven laboratory submissions tested positive for
Taylorella equigenitalis, the causative agent ofcontagious equine metritis, in Germany and one
submission in the UK. Two cases of equine coronavirus
were diagnosed in continental Europe. Australia
reported a new variant of Hendra virus that was
detected in a horse with clinical signs.
CONTACT:
Lutz Goehring, DVM, MS, PhD, Dip. ACVIM/ECEIM
l.goehring@uky.edu
Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

EQUINE DISEASEQUARTERLYEDITORS
Lutz Goehring
Alan Loynachan
Allen Page
Rebecca Ruby
STAFF
Holly Wiemers
Anita Hatchet

EDQ@uky.edu

Photo Courtesy Mark Pearson Photography

2 | EQUINE DISEASE QUARTERLYN ATIO N A L
Probiotics in horses: Potential benefits and how tochoose the right product
Probiotics have the potential to positively impact
gastrointestinal (GI) health, decrease adverse effects
of antimicrobials on intestinal microbial communities
and improve our ability to prevent or treat colic andcolitis. Additionally, probiotics improve our capacity totreat diseases outside of the GI tract including allergies,
neurological disorders and respiratory disease. Thisis because probiotics have the potential to modify
the population of bacteria present within the GI tract,
improve intestinal barrier function (i.e., “decrease
gastrointestinal leakiness”) and decrease the presenceof pathogenic bacteria like Salmonella. They may
also interact with the immune system, which can havepositive (or negative) effects beyond those that occur
locally within the GI tract.
According to the World Health Organization and Foodand Agricultural Organization, probiotics are defined
as living microorganisms, which when deliveredin adequate amounts, confer a health benefit to thehost. Based on this definition, there are three criteriathat products, marketed as probiotics, should meet:(1) they should contain live microorganisms, (2)the microorganisms should be delivered in adequate
numbers and (3) the microorganisms should dosomething beneficial for the horse. Below, each of thesecriteria are broken down and discussed in reference tothe horse, and advice is provided on how to look for a
product that meets as many of these criteria as possible.
The first criterion is that the product contains live
microorganisms. There are several potential challenges
that microorganisms (typically, bacteria and/or yeast)in probiotics must overcome to remain viable inprobiotics. Most consumers are looking for probiotics
to improve “hind gut” or cecum and/or colonic health,thus microorganisms must survive transit through thehorse’s acidic stomach and small intestine to reachthe cecum and/or colon. Bacteria and yeast are notinvincible and thus, their viability can be adversely
affected during transit. Additionally, they must survive
many conditions that are out of the consumer’s control,
such as manufacturing, shipment and storage.
To improve probiotic viability, choose a product thatlists both storage instructions and an expiration date.
Then, follow the storage instructions appropriately.
Many companies recommend storing their probiotics
in a “cool and dry place.” While this is not specific,
products likely should not experience the extremes ofsummer and winter in a barn.
Second, look for products that advertise “entericprotection” or a mechanism to help the microorganisms
survive transit through the acidic stomach and small
intestine to reach the cecum and colon. If you choose
a product without enteric protection factors, then it
is beneficial to administer the probiotic when hay (orother roughage) is fed.
The second criterion is that microorganisms should beavailable in adequate numbers. Unfortunately, we do
not have a definitive answer for this topic in horses.
In adult humans, it is recommended to use 1 x 106108 colony forming units (CFU) of microorganisms at
the time of consumption. It would seem intuitive that
adult horses should receive at least this many, if not
more, CFU per dose given the size of the horse andthe horse’s gastrointestinal (GI) tract in comparison tothat of a human. However, currently, we do not know

the optimal dose to administer a horse. Until an answer
has been determined, consider choosing products thatprovide a total number of CFUs per microorganismand per dose for their product. A repeated concern forprobiotics is that independent research has identified
discrepancies between label claims and actual contents
when certain products have been evaluated, raisingconcerns for quality control. Thus, finding a company
that is willing to provide information on quality control
and testing would also be desirable.
Finally, the product should provide a health benefit tothe horse. In humans, a large body of research has been
conducted to identify beneficial microorganisms, assess
whether theoretical benefits translate to patient benefits
and to evaluate potential adverse effects. Unfortunately,
microorganisms that are beneficial for people may notprovide benefit to horses given differences in diets,
eating style (grazing) and GI physiology (i.e., hind gut
fermentation).
Few studies have evaluated probiotics for potential
beneficial and adverse effects in adult horses and foals.
A handful of different organisms and products havebeen evaluated in adult horses and were found to haveno clinical effect or potential positive effects, such as
improved clearance of sand accumulation in the colon,
decreased duration of diarrhea and decreased sheddingof Salmonella. Currently, there is not enough research
to make blanket statements or recommend specificmicroorganisms for specific benefits.
The potential for adverse effects must be considered.
In three studies utilizing neonatal foals, the use ofprobiotics was associated with an increased risk ofdiarrhea and need for veterinary care. Although it
has not been documented in neonatal foals, probiotic
microorganisms administered to human neonates havebeen identified in blood cultures, indicating bacteremia
or fungemia. Finally, recent work has identified thepresence of antimicrobial resistance genes in probiotics
marketed for horses – whether these genes are beingtransferred to the horse’s normal intestinal microbiota
and/or pathogenic bacteria, like Salmonella, has yet to
be determined.
In conclusion, probiotics have the potential to improve
not only the GI health of horses but their general healthas well. Currently, many products are on the market
which can be confusing to choose from. More researchis needed to determine basic questions like whichmicroorganisms should be administered to horses (adults
and foals) and in what quantity to result in benefit. And,at least in foals, there does appear to be a real risk fornegative side effects, so careful consideration should begiven to this age group. In selecting a product, look fora product that provides you with necessary information
to make an informed choice, including a list of the
product’s microorganism(s), statement of the quantityof microorganism per dose, storage instructions andan expiration date and, ideally, a product that provides
scientific references that support the health benefits ofthe product.

Material published in the
Quarterly is not subject
to copyright. Permissionis therefore granted toreproduce articles, althoughacknowledgment of the source
and author is requested.
Maxwell H. Gluck
Equine Research Center
Lexington, Kentucky USA,40546-0099
Telephone (859) 257-4757
Fax (859) 257-8542
gluck.ca.uky.edu

CONTACT:
Jamie Kopper, DVM, PhD, DACVIM, DACVECC
Iowa State University
jkopper@iastate.edu
515-294-1500

JULY 2022 | 3

Equine Pleuropneumonia
Pleuropneumonia is the term applied to pneumonia when
it extends from the main airways (bronchopneumonia)
to the thin membrane on the surface of the lung (thepleura) and the surrounding thoracic cavity. Once abacterial pneumonia reaches the pleura, horses respondby producing large volumes of proteinaceous fluid.
Pleuropneumonia is the most severe form of pneumonia
and often requires long-term hospitalization andintensive care to resolve. Horses with pleuropneumonia
often have endotoxemia, thus they can develop many
complications, including laminitis and death.
Pleuropneumonia is most commonly associated withlong-distance transportation (shipping fever), but
it also develops following esophageal obstruction(choke) and secondary aspiration pneumonia. Stressis often considered a contributing cause of shipping
fever because travel is known to weaken host immune
responses against infection. However, the position of
the horse’s head and the way they are fed during travel
likely play a more important role. Normally, horses
have their heads down for long periods of time, whichallow them to easily clear debris from their trachea andlower airways. Horses that are transported with theirheads tied in elevated positions have decreased ability
to clear their airways. In addition to head position, hay
is often placed in a bag directly in front of the horse’s
nose, so they are constantly inhaling debris and bacteriathat then settles in the lower airways and incites
inflammation and infection.
Pleuropneumonia does not always develop immediately
and can go unnoticed for days to weeks after the inciting
event. Obvious clinical signs include cough, increased
respiratory rate and effort and purulent (pus-like) nasal
discharge coming from both nostrils that often has a fetid
odor. Subtle signs include fever (greater than 101.5°F),
weight loss, decreased appetite and malaise. It is
important to note that horses with pleuropneumonia do
not always develop nasal discharge or cough. Diagnosisof pleuropneumonia is confirmed via imaging of thelungs and sampling of the airways to identify bacterial
infection. Ultrasound is the most frequently employedmode of imaging, as it is portable and can be easily
performed in ambulatory practice. Ultrasound canidentify and measure fluid in the thoracic cavity, whichis the hallmark of pleuropneumonia. Ultrasonography
can only be used to image the surface of the lung, so
radiography may also be performed to assess the deeper
lung tissue.
Once pleuropneumonia has been identified via
ultrasound, pleural fluid can be sampled for bacterial
culture and microscopic evaluation. Bacterial culture
and antimicrobial susceptibility testing ensure thathorses will be treated with targeted antimicrobial
therapy. In normal horses, the mediastinum (thedivision between the right and left side of the thoracic
cavity) has small slits in it that allow movement ofsmall amounts of fluid from one side of the thorax

4 | EQUINE DISEASE QUARTERLY

to the other. In pleuropneumonia, large amounts ofinflammatory materials (fibrin, leukocytes and cellulardebris) obstruct these openings so there is complete
separation of the two sides. Once this has occurred, it ispossible for different bacteria to cause infections in theseparate thoracic spaces, thus samples should be takenfrom both sides. In addition to sampling pleural fluid,a transtracheal wash should also be performed and thefluid cultured for bacteria. Adjunct diagnostics may beutilized to assess a horse’s systemic health and include
a complete blood count, measurement of acute phase
proteins (e.g., serum amyloid A), chemistry panel andblood gas analysis.
The pillars of therapy for pleuropneumonia include
drainage of pleural fluid, antimicrobial therapy andsupportive care. Indwelling chest tubes may be placed
to facilitate constant drainage and allow for lavage andadministration of intrathoracic medication. Intravenous
antimicrobial administration is preferred over oral
or intramuscular routes to reach higher drug levels in
diseased tissue. Antimicrobials may also be nebulized
to increase penetration into the lower airways while
avoiding potential adverse systemic effects. Largevolumes of fluid can be lost each day from the thoracic
cavity, therefore intravenous fluid therapy is often
required to ensure adequate hydration. Non-steroidal
anti-inflammatory agents are administered to reduce
inflammation, attenuate endotoxemia and provide
analgesia. Supplemental oxygen, bronchodilators,
intravenous nutrition, plasma transfusions, cryotherapy
for laminitis prevention and surgical intervention may
also be warranted.
As the infection begins to resolve and lungs heal, horses
can be transitioned from injectable to oral antimicrobials.
Many horses are discharged for long-term antimicrobial
therapy at home, and treatment may be necessary for
multiple months. Once pleuropneumonia has resolved,
horses can slowly return to work, and many go back totheir previous level of performance.
CONTACT:
Kate L. Hepworth-Warren, DVM, DACVIM (LAIM)
Clinical Assistant Professor of Equine Internal Medicine
North Carolina State University College of Veterinary Medicine

K EN TU CKY
Biomarkers for Equine Athletes: What do we know?
Another simple and readily available test
is serum amyloid A (SAA), a sensitivemarker of inflammation, which is often
used to diagnose and monitor horses
with infectious processes, such asbacterial infections. While research has
shown SAA isn’t useful for detectionof orthopedic (bone) injuries, there
is potential that it may be useful for
detection of some soft-tissue injuries.
One of the major focuses of equinemusculoskeletal research is detecting
injuries in racehorses before theyoccur. Most racehorses that sustain
fractures during training or racing
Photo Courtesy Mark Pearson Photography have preexisting bone or soft tissue
damage. This tissue damage should
If you spend any time keeping up on the latest lead to inflammation and the release of proteins or
research, even in general press articles, you’ll other biomarkers. Additional research has looked at theeventually come across mention of a “biomarker.” At quantification of multiple proteins, which are thought
its most basic definition, a biomarker is an indicator to be joint or bone-specific, to predict injuries inof biological activity or occurrence. The Food and racehorses. While this work has shown limited success
Drug Administration further defines a biomarker as in the U.S. and internationally, it has only been based
a “characteristic that is measured as an indicator of on relatively small populations of injured horses. The
normal biological processes, pathogenic processes or limited number of horses makes it difficult to predict
responses to an exposure or intervention, including how well these results will hold up within the racing
therapeutic interventions.” In other words, a biomarker population as a whole.
is something that is produced by the body which may
be measured at higher or lower levels during health Another exciting development with biomarkers andor disease. While many people may think biomarkers racehorse injuries comes from our lab at the University
are only detected in the blood, it is important to point of Kentucky Gluck Equine Research Center, where weout that they can also be measured using radiography, have been using messenger RNA (mRNA) to monitor
microscopy or with physiologic monitoring (like heart a variety of different aspects of racing, including
rate or blood pressure).
the occurrence of catastrophic racing injuries. With
mRNA, we are able to identify approximately 75% ofWithin the context of horses, a recent cursory Google horses that are at risk for fracture using three different
Scholar search for “equine” and “biomarker” retrieved markers. Taken together, changes in these three markers
more than 19,000 entries, which is not surprising given (IGF-1, MMP-2 and IL-1RA) suggests that horses withthe broad definition of a biomarker. The addition of catastrophic injuries have underlying inflammation.
“injury” to the search criteria decreased the number However, the level of inflammation may be so lowof entries to approximately 10,000. This confirms that it is difficult to directly measure using currently
that there is an ever-evolving push to understand available technologies, a limitation that isn’t applicableand decrease injuries and lameness in horses using to mRNA analysis. We recently began a large-scalebiomarkers. Nowhere is this more apparent than with study to validate this research and expect to haveequine athletes, where the drive to improve both results in late 2023. Ultimately, we believe that mRNA
welfare and performance go hand in hand. Research biomarkers have the potential to provide an economic
in this field involves looking at currently available and effective tool to the racing industry that can be usedand validated tests, as well as the identification of new to identify horses at risk for fracture. In the future, webiomarkers and tests to detect them.
also hope to expand this work into other equine athletic
disciplines for use as a monitoring and/or training tool.
Work from Cornell University, where researchers havea strong interest in liver enzymes and function, hassuggested that gamma-glutamyl transferase (GGT) is CONTACT:
Allen Page, DVM, PhD
elevated in racehorses with maladaptation to training Scientist/Veterinarianand poor performance. While it is not yet known Gluck Equine Research Center
whether the elevated enzyme concentrations are the University of Kentucky
cause of poor performance, use of GGT as a biomarker
could become more mainstream since testing is readily
available at most veterinary labs.

JULY 2022 | 5