Equine Disease Quarterly Newsletter

5

consistent with the presence of luteal tissue, indicating that a follicle has ovulated, luteinized andis producing progesterone. When the circulatingprogesterone concentration is above 4 ng/mL,
this is considered adequate for the maintenanceof pregnancy. There are a number of reasons formonitoring and supplementing endogenous progesterone with progestins (synthetic progesterones)
during pregnancy, such as uterine infections, history of pregnancy loss, and luteal insufficiency.
A few important issues regarding laboratory
techniques and progestogens require clarification.
To date, all clinical veterinary diagnostic laboratories use immunoassays to measure circulating progesterone. The specificity of these tests is limitedby the antibodies used in these assays. Due to thestructural similarities among different progestogens
present in late gestation, after day 120 of gestation,
antibodies are unable to differentiate between thosedifferent molecules and therefore can give false or
inaccurate results. In addition, different progesterone antibodies will result in disparate amounts ofcross reactivity; therefore, each progesterone assay
will measure different amounts of progesterone,
producing varying results between laboratories.
It is important to emphasize that the best clinical interpretation for any progesterone result isthe one provided by the clinical laboratory thatmeasured the progesterone, as they have reference

ranges for their specific equine progesterone assay.
The specificity lacking in immunoassays and theinter-laboratory variations can be overcome withthe use of liquid chromatography-mass spectro­
metry (LC-MS). LC-MS has allowed researchers toevaluate changes in different progestogens duringlate gestation and further elucidate links between
placental compromise during late gestation and thechanges associated with specific progestogens. It
would be advantageous for clinical laboratories toswitch to LC-MS to provide diagnostic panels ofgreater specificity and wider array of quantifiable
progestogens.
In summary, current tests for progesterone
in the mare are useful to evaluate the presenceof luteal tissue (P4>1ng/mL) and to ensure thatlevels of circulating progesterone are adequate formaintenance of early pregnancy (P4>4ng/mL)
until about 120 days of gestation. From that point
until term, current clinical tests are somewhat unreliable due to the variety of progestogens present
in maternal circulation. These limitations can beovercome with the use of LC-MS.

Department of Veterinary Science
Maxwell H. Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky 40546-0099
Address Service Requested

F U N D E D B Y U N D E R W R I T E R S AT L LOY D ' S , LO N D O N

JULY 2016
Volume 25, Number 3

C O M M E N TA RY
IN THIS ISSUE
Commentary
International
First Quarter2016  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 2Vector-borne
Diseases .  .  .  .  .  .  .  .  .  .  .  .  . 3

CONTACT:
Alejandro Esteller-Vico, DVM, PhD
aestellervico@uky .edu
(859) 218-1098
Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

National
New Resistance
Genes .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 3•

KENTUCKY

Equine Congenital Cardiovascular Anomalies

C

ongenital cardiovascular malformations arerare in horses with an estimated prevalenceof 0.1-0.5%. Male and female horses are similarly
affected, and a clear-cut breed predilection is notevident. Cardiovascular malformations are broadlyclassified as either simple (a single anomaly) orcomplex (multiple coexisting anomalies). Eachmajor category is further subdivided on the basisof the tissue affected: myocardium (heart muscle),
blood vessels, or valves. Complex malformations
typically involve multiple tissues and have the least
favorable prognoses.
Clinical signs vary in severity and the age of
onset. Typical clinical signs can include stunted
growth, exercise intolerance, heart murmur, tachycardia, respiratory distress, and cyanosis. Affectedhorses are frequently found dead, however not all
horses with cardiovascular malformations display

clinical signs or die from the anomaly. In somecases, the cardiovascular defect is only identified at
necropsy as an incidental finding and is not related
to the cause of death.
Ventricular septal defect (VSD) is the mostfrequently reported congenital cardiac anomaly
in the horse. This anomaly is represented by apatent channel in the interventricular septum thatallows communication between the two ventricles,
which play a critical role in pumping blood. The
channel can result in altered pressures within theheart, the shunting of blood through the channel,
compensatory hypertrophy (enlargement of theheart muscle), and systemic abnormalities (e.g.
cyanosis) in severe cases. Horses with small defects
may be asymptomatic or develop clinical signs at
a later age. VSDs are also components of complex
cardiac anomalies such as Tetralogy of Fallot andtruncus arteriosus.

•
•

•

•
•

Other defects described in the horse include:
Abnormal communications between the atria.
Examples: atrial septal defect and patent foramen ovale.
Abnormal communication between the great
vessels. Example: patent ductus arteriosus.
Malformed great vessels. Example: common
truncus arteriosus (the division between theaorta and pulmonary artery does not develop
and a single vessel leaves the heart).
Abnormally positioned great vessels. Examples:complete transposition (the right ventricle
pumps blood into the aorta and the left ventricle pumps blood into the pulmonary trunk)and double-outlet right ventricle (both theaorta and pulmonary trunk arise from the rightventricle).
Heart valve abnormalities. Example: tricuspid
valve atresia.
Tetralogy of Fallot, which consists of a dextrapositon of the aorta, pulmonic stenosis,
ventricular septal defect, and right ventricular
hypertrophy.

Archives at the University of Kentucky Veterinary Diagnostic Laboratory were searched from2010 to 2015 for cases of congenital cardiovascularmalformations in the horse. Over that period, 18
cases were identified. Fourteen were in Thoroughbreds, two in American Saddlebreds, and one eachin the Arabian and Standardbred breeds. Twelve of
the animals were female and five were male; the sexof one animal was not identified. Ten cases of ventricular septal defect, which included nine simple
and one complex anomalies, were diagnosed. The
complex anomaly was associated with pulmonic
stenosis. Two cases each of Tetralogy of Fallot andtruncus arteriosus with VSD were identified, andsingle cases of atrial septal defect, over-riding aorta,
right ventricular hypoplasia with pulmonary atresia
and moderator band dysplasia were reported.
CONTACT:David Bolin, DVM, PhD
david.bolin@uky.edu(859) 257-8283
Veterinary Diagnostic Laboratory
University of Kentucky
Lexington, Kentucky

Progesterone as a
Diagnostic Tool .  .  .  .  .  . 4KentuckyCongenital Cardiac
Anomolies .  .  .  .  .  .  .  .  .  .  . 5

College of Agriculture,
Food and Environment
Department of
Veterinary Science“Nature doesn’t break, it only bends.” This
quote was recently uttered on a television drama, which depicted an infectious disease
clinician fighting a catastrophic epidemic thatdeveloped following a genetic mutation of a forgotten infectious disease agent. As a pathologist
and former microbiologist, this reference to theconstant evolution of microbes made me ponder,
once again, how such relatively simple organisms
rapidly and continually adapt to their environments to survive and replicate. It is unfortunate,
at least for the host, when the intricate balance
between host, environment, and microbe becomes
offset and results in infectious disease.
This theme was exemplified in April 2016 whenequine infectious disease experts from around theworld gathered for the 10th International Equine
Infectious Diseases Conference in Buenos Aires,
Argentina. The conference, which is held every
four years, provides excellent continuing educationfor equine clinicians and brings together equine
infectious disease researchers who share recent
developments and breakthroughs. The five-day
event addressed infectious diseases of continued
and historical concern, newly recognized andemerging diseases, and important reemerging
infectious diseases of the horse. These motifs wereaddressed in 11 separate sessions on biosecurity,
diagnostics, diseases of working equids, emerging
and reemerging diseases, gastroenterology, international equine movement, neurology, parasitology, theriogenology (reproduction), respiratory
diseases, and infectious diseases of other systems.
Although I enjoyed all of the presentations, I
was particularly taken with the talks on emerging

and reemerging diseases. Emerging viral agentsthat were discussed included: equine enteric coronavirus (a potential cause of necrotizing enteritis),
Theiler’s disease associated virus (the newly identified cause of equine serum sickness), and otherviral causes of hepatitis (equine hepacivirus andequine pegivirus), Bunyamwera virus in Argentina (a cause of nervous disease and/or abortion),and Hendra virus (an acute fatal and zoonotic
disease that frequently affects the respiratory andneurologic systems). Other interesting and noteworthy disease conditions comprised anthelmintic
resistance (resistance of parasitic worms to treatment), the potential role of microbes in equine
polyneuropathy, and strangles-like disease causedby Streptococcus zooepidemicus. The reemergenceof West Nile virus (a cause of neurologic disease)in France and Salmonella Abortusequi (a cause ofabortion and septicemia) in Argentina were also
addressed. Although many of these diseases are
emerging or reemerging in specific locations, onemust be globally aware of them due to the increasing frequency with which equine athletes andbreeding stock are transported around the world.
We may never break nature, but rest assured
that clinicians and infectious disease researchers
will continually attempt to challenge nature anddevelop new modalities to quickly detect, track,
diagnose, treat, and hopefully learn to prevent andcontrol infectious diseases as they occur.
CONTACT:
Alan T. Loynachan, DVM, PhD, DACVP
alan.loynachan@uky.edu(859) 257-8283
Veterinary Diagnostic Laboratory
University of Kentucky
Lexington, Kentucky

Vector-borne Diseases and the Emergent Threat They Pose2

I N T E R N AT I O N A L

First Quarter 2016*

T

Equine Disease Quarterly
Editors

Peter Timoney
Alan Loynachan
Cynthia Gaskill

Staff

Diane Furry
Tawana Brown
Dennis Duross

Correspondence should be
addressed to the editors,
Department of Veterinary
Science, Maxwell H. Gluck
Equine Research Center,
University of Kentucky,
Lexington, Kentucky USA,40546-0099
Telephone (859) 257-4757
Fax (859) 257-8542
Internet address:
http://www.ca.uky.edu/
gluck/index.htm
Material published in the
Quarterly is not subject tocopyright. Permission istherefore granted toreproduce articles, althoughacknowledgment of thesource and author is requested.
The University of Kentucky
is an Equal Opportunity
Organization.

Printed on recycled paper

he International Collating Center, Newmarket, United Kingdom, and other sources
reported the following disease outbreaks.
Three outbreaks of vesicular stomatitis in Colorado in February brought to a conclusion the 2015
occurrence of the disease in the USA. Of the eightaffected states—Arizona, Colorado, Nebraska,
New Mexico, South Dakota, Texas, Utah, andWyoming—the greatest number of outbreaks wasrecorded in Colorado. The 823 reported outbreaks
comprised 329 that were confirmed positive for the
New Jersey serotype of the virus and 494 that werediagnosed based on clinical signs of the disease but
not virologically verified.
Influenza was reported by the UK and the USA;in the latter country, the disease was considered to
be endemic. Outbreaks were confirmed in California and Florida.
Equine herpesvirus 1 and 4 (EHV-1, -4) relateddiseases were recorded in Argentina, Australia,
France, Germany, Ireland, Japan, South Africa,
UK, and the USA. Respiratory disease caused by
EHV-1 was recorded in France (two outbreaks),
Germany (12 cases involving 11 premises), South
Africa (two cases also with intercurrent equine
piroplasmosis), and the UK (one case). Abortiondue to EHV-1 was reported by Argentina (onevaccinated mare), Australia (one), France (four),
Germany (three), Ireland (13 involving nine counties), Japan (51 vaccinated Thoroughbred mares on
19 premises), the UK (14), and the USA (three).
Additionally, single cases of fulminant neonatal
disease due to EHV-1 were diagnosed in the UK.
Outbreaks of EHV-1 myeloencephalopathy wererecorded in France (one 7-year-old mare withintercurrent signs of respiratory infection) andthe USA (eight outbreaks at various premises).
Affected states included Arizona (one), California(two), Florida (one), Georgia (one), Illinois (one),
New Mexico (two), and Pennsylvania (one).
France, Germany, and the USA confirmed
outbreaks of EHV-4 respiratory disease. Twelve
outbreaks were recorded in France; the majority
involved single cases of the disease. The latter wasobserved primarily in weanling foals in the USA.
Limited evidence of EHV-2 and EHV-5 infection

was recorded in the USA.
Strangles was reported by France, Germany,
Ireland, Singapore, Switzerland, and the USA.
Thirteen outbreaks, most involving single cases,
were recorded in France, one in Germany, 11 in
Ireland, one in Singapore, and one in Switzerland.
The disease was stated to be endemic in the USA,with 42 outbreaks confirmed in 14 states, in eightof which multiple outbreaks were reported.
Infection with equine arteritis virus was confirmed in two stallions in Germany, each on adifferent premises.
Canada and the USA reported outbreaks ofequine infectious anemia. Isolated cases on two
farms in Saskatchewan were diagnosed in Canada.
Infection was identified in five of 10 horses on apremises in New York, USA.
Equine piroplasmosis was reported as endemic
by France; Switzerland recorded a single case ofdual infection with Babesia caballi and Theileriaequi, and the USA identified one case of T. equi
infection in a Quarter Horse in New Mexico.
Germany confirmed the presence of Taylorellaequigenitalis in four stallions and one mare. A
single case of infection with equine herpesvirus-3
was diagnosed in Kentucky, USA.
The USA reported 11 cases of abortion due
to Leptospira pomona var kennewicki and several
cases of nocardioform placentitis associated withAmycolatopsis spp or Crossiella spp.
Outbreaks of salmonellosis were recorded byGermany (single case) and the USA (six cases associated with Salmonella Group B and six with untyped Salmonella spp). There was a single report ofrotavirus infection in a foal from Germany. Threecases of infection with Lawsonia intracellularis wererecorded in foals in Kentucky, USA. The USA also
reported several outbreaks of clostridial enteritis in
foals associated with Clostridium perfringens Toxin
Type A.
Rabies was recorded in two horses in the USA,one each in Florida and South Carolina.
Rhodococcal related disease was reported as
endemic in the USA, with numerous outbreaks
diagnosed.
*2015 Fourth Quarter Report for Australia

Vector-borne diseases represent a singularly
serious threat to the health of humans anddomestic livestock species in countries or regionsof the world in which they occur. Historically,
many such diseases were frequently regarded as
geographically restricted in their global distribution and not considered a risk to human and animal populations in far-distant countries in othercontinents or possibly other hemispheres. Major
disease migrations in the last 20 years, however,
have undermined that sense of security. No longer
can the future distribution of specific infectious
agents be predicted with confidence. This wasmost recently exemplified by the explosive andunexpected spread of Chikungunya and Zika
viruses, both human pathogens, from where they
were originally identified in Africa many years ago.
Concerns are further highlighted by the risk of
spreading yellow fever from Angola, Republic ofCongo, and Uganda to European Union member
states and even further afield to inter-tropical zones
in the Americas and Asia.
The most significant group of emerging humanand animal diseases is caused by arboviruses suchas West Nile, Chikungunya, and Zika; they are
single stranded RNA viruses which have spontaneous mutation rates as high as one base per
1,000 bases for each replication cycle. Arboviruses
are transmitted in nature by arthropod vectors.
With the exception of African swine fever virus,
all arboviruses of medical or veterinary medical
importance belong to one of the following fourfamilies: Bunyaviridae, Flaviviridae, Reoviridae,
and Togaviridae. They are maintained in natureby cycling between a host (mammal, bird, reptile,amphibian) that is infected with a particular virus
and a vector (mosquito, tick, sandfly, midge) thatis a carrier and transmits the virus to other hosts.
Some of the most important viral diseases ofhumans are caused by arboviruses, many belonging to the Flaviviridae and Togaviridae families.
These include the following notable examples:yellow fever, dengue fever, Japanese encephalitis(JE), West Nile encephalitis (WNE), Zika virus
infection, Eastern and Western equine encephalomyelitis (EEE and WEE), Venezuelan equine
encephalomyelitis (VEE), and Chikungunya
virus infection. Arboviruses are also the cause of anumber of highly significant equine diseases, themost important of which are African horse sickness(Reoviridae), VEE, EEE, and WEE (Togaviridae),
JE, WNE, and Murray Valley encephalitis (Flaviviridae). It is evident from the foregoing that manyof the listed equine diseases are caused by zoonotic
pathogens.
Of major concern in assessing the health impactof arboviral diseases is the potential of the causal
agents to evolve, giving rise to strains of enhanced
pathogenicity for humans or animals. This is wellexemplified by the emergence of variants of West
Nile virus (lineage 2) in Europe that are highly
pathogenic for horses. The same phenomenon has
also been observed with respect to human infection with Chikungunya virus and most recently,
also, with Zika virus. There is mounting evidence
that strains of Zika virus have acquired marked
neurotropic tendencies, being implicated as acause of neurologic defects in unborn infants andan increased incidence of Guillain-Barre syndromein people.
It is highly likely we will face future threats fromthe emergence of other arboviruses with epidemic
potential. If we are to be successful in preventing
such a threat becoming a reality, we need to identify those viruses with the potential for emergenceand gain a greater understanding of their biology
and epidemiology, complemented by developmentof more effective vector control strategies, active
surveillance, and enhanced ability to diagnose such
infections.
CONTACT:
Peter Timoney, MVB, MS, PhD, FRCVS
ptimoney@uky.edu(859) 218-1094
Maxwell H. Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

N AT I O N A L

Mcr-1 and Other New Resistance Genes: What is the Threat to Horses?

R

ecent identification of the mcr-1 resistancegene in bacteria from humans and animals
has focused attention on the emerging epidemicof multidrug resistance. Multidrug resistantGram-negative bacteria, particularly those of theEnterobacteriaceae family (e.g. E. coli, Klebsiella,

34Enterobacter), are not new, as serial waves of resistance mediated by a wide range of genes havebeen encountered. Yet, emergence of mcr-1 is ofconcern because it confers resistance to colistin,an antimicrobial that can be the only option forsome highly drug-resistant infections. Concern has
been expressed that mcr-1 has ushered in the eraof pan-resistant infections, infections where there
are no antimicrobial options.
Equine medicine has not escaped the challenges
posed by resistant bacteria, including multidrug
resistant Enterobacteriaceae. In recent years, there
have been various reports of extended spectrum
beta-lactamase (ESBL) producing Enterobacteriaceae in horse. These are resistant to penicillins
and most cephalosporins, and typically also haveacquired resistance to various other antimicrobials,
limiting treatment options. Susceptibility to only
aminoglycosides (e.g. amikacin) and carbapenems(e.g. meropenem) is a common pattern. ESBLproducing bacteria have been identified in horses
in multiple countries, both in healthy colonizedhorses and horses with clinical infections. Whilecarbapenem use is very limited in horses, carbapenemase-producing Enterobacteriaceae (CPE) and
Acinetobacter, which are resistant to penicillins,
cephalosporins, and carbapenems, and usually arange of other antimicrobials, have been foundin limited numbers in horses. With the common
co-occurrence of resistance to other drug classes,
infections by bacteria such as these approachthe ‘pan resistance,’ from a practical standpoint,considering limitations in antimicrobials that canbe used in horses. Of additional note is the factthat ESBLs found in horses are often the sametypes that are found in people (e.g. CTX-M-15),
highlighting both the potential for zoonotic
transmission and the likelihood that some equine
infections are human in origin.

What does identification of mcr-1 mean tothe equine industry and equine veterinarians?
The likelihood of encountering a horse infectedwith a bacterium possessing mcr-1 is exceedingly
low. However, if bacteria harboring genes suchas these increase in humans, food animals, andthe environment, equine infections are probably
inevitable. Yet, while attracting less attention, theendemic level of resistance to cephalosporins,
fluoroquinolones, and aminoglycosides is likely ofgreater relevance in horses because of their increasing incidence and the limited treatment options.
Regardless, awareness of emerging trends inhumans is important. As new issues emerge inhumans, it is possible that the same problems will
emerge in horses given the close contact between
humans and horses, the potential for interspecies
transmission (in both directions), and the potential for common source infection (e.g. from foodanimals or the environment).
Veterinarians increasingly are encountering
horses infected with multidrug resistant pathogens,and the pathogens of concern continue to change.
Twenty years ago, MRSA and ESBLs in horses wereof little interest. Now, they are far from rare. It isalmost certain that the next 20 years (if not the next
five years) will be accompanied with new antimicrobial resistant pathogens and challenges. There
are no simple answers for battling the scourge ofantimicrobial resistance. However, awareness of theissues, optimizing antimicrobial use, and focusing
on infection control measures to reduce the needfor antimicrobials are important basic and practicalmatters that every equine veterinarian and horsecaretaker can undertake.
CONTACT:
J. Scott Weese, DVM, DVSc, DipACVIM
jsweese@uoguelph.ca
Ontario Veterinary College
University of Guelph
Guelph, ON, N1G2W1Using Progesterone as a Diagnostic Tool during Equine Pregnancy

Progestogens are a class of steroid hormones
largely responsible for sustaining the embryoand maintaining uterine quiescence. In horses, atleast 10 known progestogens are present in maternal
circulation during gestation. To date, only a few ofthem are known to be biologically active. Progesterone, the most renowned of this class of steroid
hormones, is the only one with clinical diagnostic
application. During early pregnancy, progesterone isproduced in the equine ovary by the corpus luteum(CL), and its concentrations remain elevated andpeak between 60 and 120 days of gestation. Fromthat point on, progesterone slowly decreases until
it becomes nearly undetectable around 180 to 200
days of gestation. During late gestation, other progestogens produced by the feto-placental unit are
responsible for maintaining the pregnancy. These
are first detectable by day 60 of gestation and arecompletely capable of maintaining pregnancy fromaround 120 to 140 days of gestation until term.
Circulating progesterone has been used diagnostically to evaluate luteal function during earlypregnancy. When the circulating progesterone (P4)concentration is above 1 ng/mL, this is consideredVector-borne Diseases and the Emergent Threat They Pose2

I N T E R N AT I O N A L

First Quarter 2016*

T

Equine Disease Quarterly
Editors

Peter Timoney
Alan Loynachan
Cynthia Gaskill

Staff

Diane Furry
Tawana Brown
Dennis Duross

Correspondence should be
addressed to the editors,
Department of Veterinary
Science, Maxwell H. Gluck
Equine Research Center,
University of Kentucky,
Lexington, Kentucky USA,40546-0099
Telephone (859) 257-4757
Fax (859) 257-8542
Internet address:
http://www.ca.uky.edu/
gluck/index.htm
Material published in the
Quarterly is not subject tocopyright. Permission istherefore granted toreproduce articles, althoughacknowledgment of thesource and author is requested.
The University of Kentucky
is an Equal Opportunity
Organization.

Printed on recycled paper

he International Collating Center, Newmarket, United Kingdom, and other sources
reported the following disease outbreaks.
Three outbreaks of vesicular stomatitis in Colorado in February brought to a conclusion the 2015
occurrence of the disease in the USA. Of the eightaffected states—Arizona, Colorado, Nebraska,
New Mexico, South Dakota, Texas, Utah, andWyoming—the greatest number of outbreaks wasrecorded in Colorado. The 823 reported outbreaks
comprised 329 that were confirmed positive for the
New Jersey serotype of the virus and 494 that werediagnosed based on clinical signs of the disease but
not virologically verified.
Influenza was reported by the UK and the USA;in the latter country, the disease was considered to
be endemic. Outbreaks were confirmed in California and Florida.
Equine herpesvirus 1 and 4 (EHV-1, -4) relateddiseases were recorded in Argentina, Australia,
France, Germany, Ireland, Japan, South Africa,
UK, and the USA. Respiratory disease caused by
EHV-1 was recorded in France (two outbreaks),
Germany (12 cases involving 11 premises), South
Africa (two cases also with intercurrent equine
piroplasmosis), and the UK (one case). Abortiondue to EHV-1 was reported by Argentina (onevaccinated mare), Australia (one), France (four),
Germany (three), Ireland (13 involving nine counties), Japan (51 vaccinated Thoroughbred mares on
19 premises), the UK (14), and the USA (three).
Additionally, single cases of fulminant neonatal
disease due to EHV-1 were diagnosed in the UK.
Outbreaks of EHV-1 myeloencephalopathy wererecorded in France (one 7-year-old mare withintercurrent signs of respiratory infection) andthe USA (eight outbreaks at various premises).
Affected states included Arizona (one), California(two), Florida (one), Georgia (one), Illinois (one),
New Mexico (two), and Pennsylvania (one).
France, Germany, and the USA confirmed
outbreaks of EHV-4 respiratory disease. Twelve
outbreaks were recorded in France; the majority
involved single cases of the disease. The latter wasobserved primarily in weanling foals in the USA.
Limited evidence of EHV-2 and EHV-5 infection

was recorded in the USA.
Strangles was reported by France, Germany,
Ireland, Singapore, Switzerland, and the USA.
Thirteen outbreaks, most involving single cases,
were recorded in France, one in Germany, 11 in
Ireland, one in Singapore, and one in Switzerland.
The disease was stated to be endemic in the USA,with 42 outbreaks confirmed in 14 states, in eightof which multiple outbreaks were reported.
Infection with equine arteritis virus was confirmed in two stallions in Germany, each on adifferent premises.
Canada and the USA reported outbreaks ofequine infectious anemia. Isolated cases on two
farms in Saskatchewan were diagnosed in Canada.
Infection was identified in five of 10 horses on apremises in New York, USA.
Equine piroplasmosis was reported as endemic
by France; Switzerland recorded a single case ofdual infection with Babesia caballi and Theileriaequi, and the USA identified one case of T. equi
infection in a Quarter Horse in New Mexico.
Germany confirmed the presence of Taylorellaequigenitalis in four stallions and one mare. A
single case of infection with equine herpesvirus-3
was diagnosed in Kentucky, USA.
The USA reported 11 cases of abortion due
to Leptospira pomona var kennewicki and several
cases of nocardioform placentitis associated withAmycolatopsis spp or Crossiella spp.
Outbreaks of salmonellosis were recorded byGermany (single case) and the USA (six cases associated with Salmonella Group B and six with untyped Salmonella spp). There was a single report ofrotavirus infection in a foal from Germany. Threecases of infection with Lawsonia intracellularis wererecorded in foals in Kentucky, USA. The USA also
reported several outbreaks of clostridial enteritis in
foals associated with Clostridium perfringens Toxin
Type A.
Rabies was recorded in two horses in the USA,one each in Florida and South Carolina.
Rhodococcal related disease was reported as
endemic in the USA, with numerous outbreaks
diagnosed.
*2015 Fourth Quarter Report for Australia

Vector-borne diseases represent a singularly
serious threat to the health of humans anddomestic livestock species in countries or regionsof the world in which they occur. Historically,
many such diseases were frequently regarded as
geographically restricted in their global distribution and not considered a risk to human and animal populations in far-distant countries in othercontinents or possibly other hemispheres. Major
disease migrations in the last 20 years, however,
have undermined that sense of security. No longer
can the future distribution of specific infectious
agents be predicted with confidence. This wasmost recently exemplified by the explosive andunexpected spread of Chikungunya and Zika
viruses, both human pathogens, from where they
were originally identified in Africa many years ago.
Concerns are further highlighted by the risk of
spreading yellow fever from Angola, Republic ofCongo, and Uganda to European Union member
states and even further afield to inter-tropical zones
in the Americas and Asia.
The most significant group of emerging humanand animal diseases is caused by arboviruses suchas West Nile, Chikungunya, and Zika; they are
single stranded RNA viruses which have spontaneous mutation rates as high as one base per
1,000 bases for each replication cycle. Arboviruses
are transmitted in nature by arthropod vectors.
With the exception of African swine fever virus,
all arboviruses of medical or veterinary medical
importance belong to one of the following fourfamilies: Bunyaviridae, Flaviviridae, Reoviridae,
and Togaviridae. They are maintained in natureby cycling between a host (mammal, bird, reptile,amphibian) that is infected with a particular virus
and a vector (mosquito, tick, sandfly, midge) thatis a carrier and transmits the virus to other hosts.
Some of the most important viral diseases ofhumans are caused by arboviruses, many belonging to the Flaviviridae and Togaviridae families.
These include the following notable examples:yellow fever, dengue fever, Japanese encephalitis(JE), West Nile encephalitis (WNE), Zika virus
infection, Eastern and Western equine encephalomyelitis (EEE and WEE), Venezuelan equine
encephalomyelitis (VEE), and Chikungunya
virus infection. Arboviruses are also the cause of anumber of highly significant equine diseases, themost important of which are African horse sickness(Reoviridae), VEE, EEE, and WEE (Togaviridae),
JE, WNE, and Murray Valley encephalitis (Flaviviridae). It is evident from the foregoing that manyof the listed equine diseases are caused by zoonotic
pathogens.
Of major concern in assessing the health impactof arboviral diseases is the potential of the causal
agents to evolve, giving rise to strains of enhanced
pathogenicity for humans or animals. This is wellexemplified by the emergence of variants of West
Nile virus (lineage 2) in Europe that are highly
pathogenic for horses. The same phenomenon has
also been observed with respect to human infection with Chikungunya virus and most recently,
also, with Zika virus. There is mounting evidence
that strains of Zika virus have acquired marked
neurotropic tendencies, being implicated as acause of neurologic defects in unborn infants andan increased incidence of Guillain-Barre syndromein people.
It is highly likely we will face future threats fromthe emergence of other arboviruses with epidemic
potential. If we are to be successful in preventing
such a threat becoming a reality, we need to identify those viruses with the potential for emergenceand gain a greater understanding of their biology
and epidemiology, complemented by developmentof more effective vector control strategies, active
surveillance, and enhanced ability to diagnose such
infections.
CONTACT:
Peter Timoney, MVB, MS, PhD, FRCVS
ptimoney@uky.edu(859) 218-1094
Maxwell H. Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

N AT I O N A L

Mcr-1 and Other New Resistance Genes: What is the Threat to Horses?

R

ecent identification of the mcr-1 resistancegene in bacteria from humans and animals
has focused attention on the emerging epidemicof multidrug resistance. Multidrug resistantGram-negative bacteria, particularly those of theEnterobacteriaceae family (e.g. E. coli, Klebsiella,

34Enterobacter), are not new, as serial waves of resistance mediated by a wide range of genes havebeen encountered. Yet, emergence of mcr-1 is ofconcern because it confers resistance to colistin,an antimicrobial that can be the only option forsome highly drug-resistant infections. Concern has
been expressed that mcr-1 has ushered in the eraof pan-resistant infections, infections where there
are no antimicrobial options.
Equine medicine has not escaped the challenges
posed by resistant bacteria, including multidrug
resistant Enterobacteriaceae. In recent years, there
have been various reports of extended spectrum
beta-lactamase (ESBL) producing Enterobacteriaceae in horse. These are resistant to penicillins
and most cephalosporins, and typically also haveacquired resistance to various other antimicrobials,
limiting treatment options. Susceptibility to only
aminoglycosides (e.g. amikacin) and carbapenems(e.g. meropenem) is a common pattern. ESBLproducing bacteria have been identified in horses
in multiple countries, both in healthy colonizedhorses and horses with clinical infections. Whilecarbapenem use is very limited in horses, carbapenemase-producing Enterobacteriaceae (CPE) and
Acinetobacter, which are resistant to penicillins,
cephalosporins, and carbapenems, and usually arange of other antimicrobials, have been foundin limited numbers in horses. With the common
co-occurrence of resistance to other drug classes,
infections by bacteria such as these approachthe ‘pan resistance,’ from a practical standpoint,considering limitations in antimicrobials that canbe used in horses. Of additional note is the factthat ESBLs found in horses are often the sametypes that are found in people (e.g. CTX-M-15),
highlighting both the potential for zoonotic
transmission and the likelihood that some equine
infections are human in origin.

What does identification of mcr-1 mean tothe equine industry and equine veterinarians?
The likelihood of encountering a horse infectedwith a bacterium possessing mcr-1 is exceedingly
low. However, if bacteria harboring genes suchas these increase in humans, food animals, andthe environment, equine infections are probably
inevitable. Yet, while attracting less attention, theendemic level of resistance to cephalosporins,
fluoroquinolones, and aminoglycosides is likely ofgreater relevance in horses because of their increasing incidence and the limited treatment options.
Regardless, awareness of emerging trends inhumans is important. As new issues emerge inhumans, it is possible that the same problems will
emerge in horses given the close contact between
humans and horses, the potential for interspecies
transmission (in both directions), and the potential for common source infection (e.g. from foodanimals or the environment).
Veterinarians increasingly are encountering
horses infected with multidrug resistant pathogens,and the pathogens of concern continue to change.
Twenty years ago, MRSA and ESBLs in horses wereof little interest. Now, they are far from rare. It isalmost certain that the next 20 years (if not the next
five years) will be accompanied with new antimicrobial resistant pathogens and challenges. There
are no simple answers for battling the scourge ofantimicrobial resistance. However, awareness of theissues, optimizing antimicrobial use, and focusing
on infection control measures to reduce the needfor antimicrobials are important basic and practicalmatters that every equine veterinarian and horsecaretaker can undertake.
CONTACT:
J. Scott Weese, DVM, DVSc, DipACVIM
jsweese@uoguelph.ca
Ontario Veterinary College
University of Guelph
Guelph, ON, N1G2W1Using Progesterone as a Diagnostic Tool during Equine Pregnancy

Progestogens are a class of steroid hormones
largely responsible for sustaining the embryoand maintaining uterine quiescence. In horses, atleast 10 known progestogens are present in maternal
circulation during gestation. To date, only a few ofthem are known to be biologically active. Progesterone, the most renowned of this class of steroid
hormones, is the only one with clinical diagnostic
application. During early pregnancy, progesterone isproduced in the equine ovary by the corpus luteum(CL), and its concentrations remain elevated andpeak between 60 and 120 days of gestation. Fromthat point on, progesterone slowly decreases until
it becomes nearly undetectable around 180 to 200
days of gestation. During late gestation, other progestogens produced by the feto-placental unit are
responsible for maintaining the pregnancy. These
are first detectable by day 60 of gestation and arecompletely capable of maintaining pregnancy fromaround 120 to 140 days of gestation until term.
Circulating progesterone has been used diagnostically to evaluate luteal function during earlypregnancy. When the circulating progesterone (P4)concentration is above 1 ng/mL, this is consideredVector-borne Diseases and the Emergent Threat They Pose2

I N T E R N AT I O N A L

First Quarter 2016*

T

Equine Disease Quarterly
Editors

Peter Timoney
Alan Loynachan
Cynthia Gaskill

Staff

Diane Furry
Tawana Brown
Dennis Duross

Correspondence should be
addressed to the editors,
Department of Veterinary
Science, Maxwell H. Gluck
Equine Research Center,
University of Kentucky,
Lexington, Kentucky USA,40546-0099
Telephone (859) 257-4757
Fax (859) 257-8542
Internet address:
http://www.ca.uky.edu/
gluck/index.htm
Material published in the
Quarterly is not subject tocopyright. Permission istherefore granted toreproduce articles, althoughacknowledgment of thesource and author is requested.
The University of Kentucky
is an Equal Opportunity
Organization.

Printed on recycled paper

he International Collating Center, Newmarket, United Kingdom, and other sources
reported the following disease outbreaks.
Three outbreaks of vesicular stomatitis in Colorado in February brought to a conclusion the 2015
occurrence of the disease in the USA. Of the eightaffected states—Arizona, Colorado, Nebraska,
New Mexico, South Dakota, Texas, Utah, andWyoming—the greatest number of outbreaks wasrecorded in Colorado. The 823 reported outbreaks
comprised 329 that were confirmed positive for the
New Jersey serotype of the virus and 494 that werediagnosed based on clinical signs of the disease but
not virologically verified.
Influenza was reported by the UK and the USA;in the latter country, the disease was considered to
be endemic. Outbreaks were confirmed in California and Florida.
Equine herpesvirus 1 and 4 (EHV-1, -4) relateddiseases were recorded in Argentina, Australia,
France, Germany, Ireland, Japan, South Africa,
UK, and the USA. Respiratory disease caused by
EHV-1 was recorded in France (two outbreaks),
Germany (12 cases involving 11 premises), South
Africa (two cases also with intercurrent equine
piroplasmosis), and the UK (one case). Abortiondue to EHV-1 was reported by Argentina (onevaccinated mare), Australia (one), France (four),
Germany (three), Ireland (13 involving nine counties), Japan (51 vaccinated Thoroughbred mares on
19 premises), the UK (14), and the USA (three).
Additionally, single cases of fulminant neonatal
disease due to EHV-1 were diagnosed in the UK.
Outbreaks of EHV-1 myeloencephalopathy wererecorded in France (one 7-year-old mare withintercurrent signs of respiratory infection) andthe USA (eight outbreaks at various premises).
Affected states included Arizona (one), California(two), Florida (one), Georgia (one), Illinois (one),
New Mexico (two), and Pennsylvania (one).
France, Germany, and the USA confirmed
outbreaks of EHV-4 respiratory disease. Twelve
outbreaks were recorded in France; the majority
involved single cases of the disease. The latter wasobserved primarily in weanling foals in the USA.
Limited evidence of EHV-2 and EHV-5 infection

was recorded in the USA.
Strangles was reported by France, Germany,
Ireland, Singapore, Switzerland, and the USA.
Thirteen outbreaks, most involving single cases,
were recorded in France, one in Germany, 11 in
Ireland, one in Singapore, and one in Switzerland.
The disease was stated to be endemic in the USA,with 42 outbreaks confirmed in 14 states, in eightof which multiple outbreaks were reported.
Infection with equine arteritis virus was confirmed in two stallions in Germany, each on adifferent premises.
Canada and the USA reported outbreaks ofequine infectious anemia. Isolated cases on two
farms in Saskatchewan were diagnosed in Canada.
Infection was identified in five of 10 horses on apremises in New York, USA.
Equine piroplasmosis was reported as endemic
by France; Switzerland recorded a single case ofdual infection with Babesia caballi and Theileriaequi, and the USA identified one case of T. equi
infection in a Quarter Horse in New Mexico.
Germany confirmed the presence of Taylorellaequigenitalis in four stallions and one mare. A
single case of infection with equine herpesvirus-3
was diagnosed in Kentucky, USA.
The USA reported 11 cases of abortion due
to Leptospira pomona var kennewicki and several
cases of nocardioform placentitis associated withAmycolatopsis spp or Crossiella spp.
Outbreaks of salmonellosis were recorded byGermany (single case) and the USA (six cases associated with Salmonella Group B and six with untyped Salmonella spp). There was a single report ofrotavirus infection in a foal from Germany. Threecases of infection with Lawsonia intracellularis wererecorded in foals in Kentucky, USA. The USA also
reported several outbreaks of clostridial enteritis in
foals associated with Clostridium perfringens Toxin
Type A.
Rabies was recorded in two horses in the USA,one each in Florida and South Carolina.
Rhodococcal related disease was reported as
endemic in the USA, with numerous outbreaks
diagnosed.
*2015 Fourth Quarter Report for Australia

Vector-borne diseases represent a singularly
serious threat to the health of humans anddomestic livestock species in countries or regionsof the world in which they occur. Historically,
many such diseases were frequently regarded as
geographically restricted in their global distribution and not considered a risk to human and animal populations in far-distant countries in othercontinents or possibly other hemispheres. Major
disease migrations in the last 20 years, however,
have undermined that sense of security. No longer
can the future distribution of specific infectious
agents be predicted with confidence. This wasmost recently exemplified by the explosive andunexpected spread of Chikungunya and Zika
viruses, both human pathogens, from where they
were originally identified in Africa many years ago.
Concerns are further highlighted by the risk of
spreading yellow fever from Angola, Republic ofCongo, and Uganda to European Union member
states and even further afield to inter-tropical zones
in the Americas and Asia.
The most significant group of emerging humanand animal diseases is caused by arboviruses suchas West Nile, Chikungunya, and Zika; they are
single stranded RNA viruses which have spontaneous mutation rates as high as one base per
1,000 bases for each replication cycle. Arboviruses
are transmitted in nature by arthropod vectors.
With the exception of African swine fever virus,
all arboviruses of medical or veterinary medical
importance belong to one of the following fourfamilies: Bunyaviridae, Flaviviridae, Reoviridae,
and Togaviridae. They are maintained in natureby cycling between a host (mammal, bird, reptile,amphibian) that is infected with a particular virus
and a vector (mosquito, tick, sandfly, midge) thatis a carrier and transmits the virus to other hosts.
Some of the most important viral diseases ofhumans are caused by arboviruses, many belonging to the Flaviviridae and Togaviridae families.
These include the following notable examples:yellow fever, dengue fever, Japanese encephalitis(JE), West Nile encephalitis (WNE), Zika virus
infection, Eastern and Western equine encephalomyelitis (EEE and WEE), Venezuelan equine
encephalomyelitis (VEE), and Chikungunya
virus infection. Arboviruses are also the cause of anumber of highly significant equine diseases, themost important of which are African horse sickness(Reoviridae), VEE, EEE, and WEE (Togaviridae),
JE, WNE, and Murray Valley encephalitis (Flaviviridae). It is evident from the foregoing that manyof the listed equine diseases are caused by zoonotic
pathogens.
Of major concern in assessing the health impactof arboviral diseases is the potential of the causal
agents to evolve, giving rise to strains of enhanced
pathogenicity for humans or animals. This is wellexemplified by the emergence of variants of West
Nile virus (lineage 2) in Europe that are highly
pathogenic for horses. The same phenomenon has
also been observed with respect to human infection with Chikungunya virus and most recently,
also, with Zika virus. There is mounting evidence
that strains of Zika virus have acquired marked
neurotropic tendencies, being implicated as acause of neurologic defects in unborn infants andan increased incidence of Guillain-Barre syndromein people.
It is highly likely we will face future threats fromthe emergence of other arboviruses with epidemic
potential. If we are to be successful in preventing
such a threat becoming a reality, we need to identify those viruses with the potential for emergenceand gain a greater understanding of their biology
and epidemiology, complemented by developmentof more effective vector control strategies, active
surveillance, and enhanced ability to diagnose such
infections.
CONTACT:
Peter Timoney, MVB, MS, PhD, FRCVS
ptimoney@uky.edu(859) 218-1094
Maxwell H. Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

N AT I O N A L

Mcr-1 and Other New Resistance Genes: What is the Threat to Horses?

R

ecent identification of the mcr-1 resistancegene in bacteria from humans and animals
has focused attention on the emerging epidemicof multidrug resistance. Multidrug resistantGram-negative bacteria, particularly those of theEnterobacteriaceae family (e.g. E. coli, Klebsiella,

34Enterobacter), are not new, as serial waves of resistance mediated by a wide range of genes havebeen encountered. Yet, emergence of mcr-1 is ofconcern because it confers resistance to colistin,an antimicrobial that can be the only option forsome highly drug-resistant infections. Concern has
been expressed that mcr-1 has ushered in the eraof pan-resistant infections, infections where there
are no antimicrobial options.
Equine medicine has not escaped the challenges
posed by resistant bacteria, including multidrug
resistant Enterobacteriaceae. In recent years, there
have been various reports of extended spectrum
beta-lactamase (ESBL) producing Enterobacteriaceae in horse. These are resistant to penicillins
and most cephalosporins, and typically also haveacquired resistance to various other antimicrobials,
limiting treatment options. Susceptibility to only
aminoglycosides (e.g. amikacin) and carbapenems(e.g. meropenem) is a common pattern. ESBLproducing bacteria have been identified in horses
in multiple countries, both in healthy colonizedhorses and horses with clinical infections. Whilecarbapenem use is very limited in horses, carbapenemase-producing Enterobacteriaceae (CPE) and
Acinetobacter, which are resistant to penicillins,
cephalosporins, and carbapenems, and usually arange of other antimicrobials, have been foundin limited numbers in horses. With the common
co-occurrence of resistance to other drug classes,
infections by bacteria such as these approachthe ‘pan resistance,’ from a practical standpoint,considering limitations in antimicrobials that canbe used in horses. Of additional note is the factthat ESBLs found in horses are often the sametypes that are found in people (e.g. CTX-M-15),
highlighting both the potential for zoonotic
transmission and the likelihood that some equine
infections are human in origin.

What does identification of mcr-1 mean tothe equine industry and equine veterinarians?
The likelihood of encountering a horse infectedwith a bacterium possessing mcr-1 is exceedingly
low. However, if bacteria harboring genes suchas these increase in humans, food animals, andthe environment, equine infections are probably
inevitable. Yet, while attracting less attention, theendemic level of resistance to cephalosporins,
fluoroquinolones, and aminoglycosides is likely ofgreater relevance in horses because of their increasing incidence and the limited treatment options.
Regardless, awareness of emerging trends inhumans is important. As new issues emerge inhumans, it is possible that the same problems will
emerge in horses given the close contact between
humans and horses, the potential for interspecies
transmission (in both directions), and the potential for common source infection (e.g. from foodanimals or the environment).
Veterinarians increasingly are encountering
horses infected with multidrug resistant pathogens,and the pathogens of concern continue to change.
Twenty years ago, MRSA and ESBLs in horses wereof little interest. Now, they are far from rare. It isalmost certain that the next 20 years (if not the next
five years) will be accompanied with new antimicrobial resistant pathogens and challenges. There
are no simple answers for battling the scourge ofantimicrobial resistance. However, awareness of theissues, optimizing antimicrobial use, and focusing
on infection control measures to reduce the needfor antimicrobials are important basic and practicalmatters that every equine veterinarian and horsecaretaker can undertake.
CONTACT:
J. Scott Weese, DVM, DVSc, DipACVIM
jsweese@uoguelph.ca
Ontario Veterinary College
University of Guelph
Guelph, ON, N1G2W1Using Progesterone as a Diagnostic Tool during Equine Pregnancy

Progestogens are a class of steroid hormones
largely responsible for sustaining the embryoand maintaining uterine quiescence. In horses, atleast 10 known progestogens are present in maternal
circulation during gestation. To date, only a few ofthem are known to be biologically active. Progesterone, the most renowned of this class of steroid
hormones, is the only one with clinical diagnostic
application. During early pregnancy, progesterone isproduced in the equine ovary by the corpus luteum(CL), and its concentrations remain elevated andpeak between 60 and 120 days of gestation. Fromthat point on, progesterone slowly decreases until
it becomes nearly undetectable around 180 to 200
days of gestation. During late gestation, other progestogens produced by the feto-placental unit are
responsible for maintaining the pregnancy. These
are first detectable by day 60 of gestation and arecompletely capable of maintaining pregnancy fromaround 120 to 140 days of gestation until term.
Circulating progesterone has been used diagnostically to evaluate luteal function during earlypregnancy. When the circulating progesterone (P4)concentration is above 1 ng/mL, this is consideredEquine Disease Quarterly Newsletter

5

consistent with the presence of luteal tissue, indicating that a follicle has ovulated, luteinized andis producing progesterone. When the circulatingprogesterone concentration is above 4 ng/mL,
this is considered adequate for the maintenanceof pregnancy. There are a number of reasons formonitoring and supplementing endogenous progesterone with progestins (synthetic progesterones)
during pregnancy, such as uterine infections, history of pregnancy loss, and luteal insufficiency.
A few important issues regarding laboratory
techniques and progestogens require clarification.
To date, all clinical veterinary diagnostic laboratories use immunoassays to measure circulating progesterone. The specificity of these tests is limitedby the antibodies used in these assays. Due to thestructural similarities among different progestogens
present in late gestation, after day 120 of gestation,
antibodies are unable to differentiate between thosedifferent molecules and therefore can give false or
inaccurate results. In addition, different progesterone antibodies will result in disparate amounts ofcross reactivity; therefore, each progesterone assay
will measure different amounts of progesterone,
producing varying results between laboratories.
It is important to emphasize that the best clinical interpretation for any progesterone result isthe one provided by the clinical laboratory thatmeasured the progesterone, as they have reference

ranges for their specific equine progesterone assay.
The specificity lacking in immunoassays and theinter-laboratory variations can be overcome withthe use of liquid chromatography-mass spectro­
metry (LC-MS). LC-MS has allowed researchers toevaluate changes in different progestogens duringlate gestation and further elucidate links between
placental compromise during late gestation and thechanges associated with specific progestogens. It
would be advantageous for clinical laboratories toswitch to LC-MS to provide diagnostic panels ofgreater specificity and wider array of quantifiable
progestogens.
In summary, current tests for progesterone
in the mare are useful to evaluate the presenceof luteal tissue (P4>1ng/mL) and to ensure thatlevels of circulating progesterone are adequate formaintenance of early pregnancy (P4>4ng/mL)
until about 120 days of gestation. From that point
until term, current clinical tests are somewhat unreliable due to the variety of progestogens present
in maternal circulation. These limitations can beovercome with the use of LC-MS.

Department of Veterinary Science
Maxwell H. Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky 40546-0099
Address Service Requested

F U N D E D B Y U N D E R W R I T E R S AT L LOY D ' S , LO N D O N

JULY 2016
Volume 25, Number 3

C O M M E N TA RY
IN THIS ISSUE
Commentary
International
First Quarter2016  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 2Vector-borne
Diseases .  .  .  .  .  .  .  .  .  .  .  .  . 3

CONTACT:
Alejandro Esteller-Vico, DVM, PhD
aestellervico@uky .edu
(859) 218-1098
Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

National
New Resistance
Genes .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 3•

KENTUCKY

Equine Congenital Cardiovascular Anomalies

C

ongenital cardiovascular malformations arerare in horses with an estimated prevalenceof 0.1-0.5%. Male and female horses are similarly
affected, and a clear-cut breed predilection is notevident. Cardiovascular malformations are broadlyclassified as either simple (a single anomaly) orcomplex (multiple coexisting anomalies). Eachmajor category is further subdivided on the basisof the tissue affected: myocardium (heart muscle),
blood vessels, or valves. Complex malformations
typically involve multiple tissues and have the least
favorable prognoses.
Clinical signs vary in severity and the age of
onset. Typical clinical signs can include stunted
growth, exercise intolerance, heart murmur, tachycardia, respiratory distress, and cyanosis. Affectedhorses are frequently found dead, however not all
horses with cardiovascular malformations display

clinical signs or die from the anomaly. In somecases, the cardiovascular defect is only identified at
necropsy as an incidental finding and is not related
to the cause of death.
Ventricular septal defect (VSD) is the mostfrequently reported congenital cardiac anomaly
in the horse. This anomaly is represented by apatent channel in the interventricular septum thatallows communication between the two ventricles,
which play a critical role in pumping blood. The
channel can result in altered pressures within theheart, the shunting of blood through the channel,
compensatory hypertrophy (enlargement of theheart muscle), and systemic abnormalities (e.g.
cyanosis) in severe cases. Horses with small defects
may be asymptomatic or develop clinical signs at
a later age. VSDs are also components of complex
cardiac anomalies such as Tetralogy of Fallot andtruncus arteriosus.

•
•

•

•
•

Other defects described in the horse include:
Abnormal communications between the atria.
Examples: atrial septal defect and patent foramen ovale.
Abnormal communication between the great
vessels. Example: patent ductus arteriosus.
Malformed great vessels. Example: common
truncus arteriosus (the division between theaorta and pulmonary artery does not develop
and a single vessel leaves the heart).
Abnormally positioned great vessels. Examples:complete transposition (the right ventricle
pumps blood into the aorta and the left ventricle pumps blood into the pulmonary trunk)and double-outlet right ventricle (both theaorta and pulmonary trunk arise from the rightventricle).
Heart valve abnormalities. Example: tricuspid
valve atresia.
Tetralogy of Fallot, which consists of a dextrapositon of the aorta, pulmonic stenosis,
ventricular septal defect, and right ventricular
hypertrophy.

Archives at the University of Kentucky Veterinary Diagnostic Laboratory were searched from2010 to 2015 for cases of congenital cardiovascularmalformations in the horse. Over that period, 18
cases were identified. Fourteen were in Thoroughbreds, two in American Saddlebreds, and one eachin the Arabian and Standardbred breeds. Twelve of
the animals were female and five were male; the sexof one animal was not identified. Ten cases of ventricular septal defect, which included nine simple
and one complex anomalies, were diagnosed. The
complex anomaly was associated with pulmonic
stenosis. Two cases each of Tetralogy of Fallot andtruncus arteriosus with VSD were identified, andsingle cases of atrial septal defect, over-riding aorta,
right ventricular hypoplasia with pulmonary atresia
and moderator band dysplasia were reported.
CONTACT:David Bolin, DVM, PhD
david.bolin@uky.edu(859) 257-8283
Veterinary Diagnostic Laboratory
University of Kentucky
Lexington, Kentucky

Progesterone as a
Diagnostic Tool .  .  .  .  .  . 4KentuckyCongenital Cardiac
Anomolies .  .  .  .  .  .  .  .  .  .  . 5

College of Agriculture,
Food and Environment
Department of
Veterinary Science“Nature doesn’t break, it only bends.” This
quote was recently uttered on a television drama, which depicted an infectious disease
clinician fighting a catastrophic epidemic thatdeveloped following a genetic mutation of a forgotten infectious disease agent. As a pathologist
and former microbiologist, this reference to theconstant evolution of microbes made me ponder,
once again, how such relatively simple organisms
rapidly and continually adapt to their environments to survive and replicate. It is unfortunate,
at least for the host, when the intricate balance
between host, environment, and microbe becomes
offset and results in infectious disease.
This theme was exemplified in April 2016 whenequine infectious disease experts from around theworld gathered for the 10th International Equine
Infectious Diseases Conference in Buenos Aires,
Argentina. The conference, which is held every
four years, provides excellent continuing educationfor equine clinicians and brings together equine
infectious disease researchers who share recent
developments and breakthroughs. The five-day
event addressed infectious diseases of continued
and historical concern, newly recognized andemerging diseases, and important reemerging
infectious diseases of the horse. These motifs wereaddressed in 11 separate sessions on biosecurity,
diagnostics, diseases of working equids, emerging
and reemerging diseases, gastroenterology, international equine movement, neurology, parasitology, theriogenology (reproduction), respiratory
diseases, and infectious diseases of other systems.
Although I enjoyed all of the presentations, I
was particularly taken with the talks on emerging

and reemerging diseases. Emerging viral agentsthat were discussed included: equine enteric coronavirus (a potential cause of necrotizing enteritis),
Theiler’s disease associated virus (the newly identified cause of equine serum sickness), and otherviral causes of hepatitis (equine hepacivirus andequine pegivirus), Bunyamwera virus in Argentina (a cause of nervous disease and/or abortion),and Hendra virus (an acute fatal and zoonotic
disease that frequently affects the respiratory andneurologic systems). Other interesting and noteworthy disease conditions comprised anthelmintic
resistance (resistance of parasitic worms to treatment), the potential role of microbes in equine
polyneuropathy, and strangles-like disease causedby Streptococcus zooepidemicus. The reemergenceof West Nile virus (a cause of neurologic disease)in France and Salmonella Abortusequi (a cause ofabortion and septicemia) in Argentina were also
addressed. Although many of these diseases are
emerging or reemerging in specific locations, onemust be globally aware of them due to the increasing frequency with which equine athletes andbreeding stock are transported around the world.
We may never break nature, but rest assured
that clinicians and infectious disease researchers
will continually attempt to challenge nature anddevelop new modalities to quickly detect, track,
diagnose, treat, and hopefully learn to prevent andcontrol infectious diseases as they occur.
CONTACT:
Alan T. Loynachan, DVM, PhD, DACVP
alan.loynachan@uky.edu(859) 257-8283
Veterinary Diagnostic Laboratory
University of Kentucky
Lexington, Kentucky

Equine Disease Quarterly Newsletter

5

consistent with the presence of luteal tissue, indicating that a follicle has ovulated, luteinized andis producing progesterone. When the circulatingprogesterone concentration is above 4 ng/mL,
this is considered adequate for the maintenanceof pregnancy. There are a number of reasons formonitoring and supplementing endogenous progesterone with progestins (synthetic progesterones)
during pregnancy, such as uterine infections, history of pregnancy loss, and luteal insufficiency.
A few important issues regarding laboratory
techniques and progestogens require clarification.
To date, all clinical veterinary diagnostic laboratories use immunoassays to measure circulating progesterone. The specificity of these tests is limitedby the antibodies used in these assays. Due to thestructural similarities among different progestogens
present in late gestation, after day 120 of gestation,
antibodies are unable to differentiate between thosedifferent molecules and therefore can give false or
inaccurate results. In addition, different progesterone antibodies will result in disparate amounts ofcross reactivity; therefore, each progesterone assay
will measure different amounts of progesterone,
producing varying results between laboratories.
It is important to emphasize that the best clinical interpretation for any progesterone result isthe one provided by the clinical laboratory thatmeasured the progesterone, as they have reference

ranges for their specific equine progesterone assay.
The specificity lacking in immunoassays and theinter-laboratory variations can be overcome withthe use of liquid chromatography-mass spectro­
metry (LC-MS). LC-MS has allowed researchers toevaluate changes in different progestogens duringlate gestation and further elucidate links between
placental compromise during late gestation and thechanges associated with specific progestogens. It
would be advantageous for clinical laboratories toswitch to LC-MS to provide diagnostic panels ofgreater specificity and wider array of quantifiable
progestogens.
In summary, current tests for progesterone
in the mare are useful to evaluate the presenceof luteal tissue (P4>1ng/mL) and to ensure thatlevels of circulating progesterone are adequate formaintenance of early pregnancy (P4>4ng/mL)
until about 120 days of gestation. From that point
until term, current clinical tests are somewhat unreliable due to the variety of progestogens present
in maternal circulation. These limitations can beovercome with the use of LC-MS.

Department of Veterinary Science
Maxwell H. Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky 40546-0099
Address Service Requested

F U N D E D B Y U N D E R W R I T E R S AT L LOY D ' S , LO N D O N

JULY 2016
Volume 25, Number 3

C O M M E N TA RY
IN THIS ISSUE
Commentary
International
First Quarter2016  .  .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 2Vector-borne
Diseases .  .  .  .  .  .  .  .  .  .  .  .  . 3

CONTACT:
Alejandro Esteller-Vico, DVM, PhD
aestellervico@uky .edu
(859) 218-1098
Gluck Equine Research Center
University of Kentucky
Lexington, Kentucky

National
New Resistance
Genes .  .  .  .  .  .  .  .  .  .  .  .  .  .  . 3•

KENTUCKY

Equine Congenital Cardiovascular Anomalies

C

ongenital cardiovascular malformations arerare in horses with an estimated prevalenceof 0.1-0.5%. Male and female horses are similarly
affected, and a clear-cut breed predilection is notevident. Cardiovascular malformations are broadlyclassified as either simple (a single anomaly) orcomplex (multiple coexisting anomalies). Eachmajor category is further subdivided on the basisof the tissue affected: myocardium (heart muscle),
blood vessels, or valves. Complex malformations
typically involve multiple tissues and have the least
favorable prognoses.
Clinical signs vary in severity and the age of
onset. Typical clinical signs can include stunted
growth, exercise intolerance, heart murmur, tachycardia, respiratory distress, and cyanosis. Affectedhorses are frequently found dead, however not all
horses with cardiovascular malformations display

clinical signs or die from the anomaly. In somecases, the cardiovascular defect is only identified at
necropsy as an incidental finding and is not related
to the cause of death.
Ventricular septal defect (VSD) is the mostfrequently reported congenital cardiac anomaly
in the horse. This anomaly is represented by apatent channel in the interventricular septum thatallows communication between the two ventricles,
which play a critical role in pumping blood. The
channel can result in altered pressures within theheart, the shunting of blood through the channel,
compensatory hypertrophy (enlargement of theheart muscle), and systemic abnormalities (e.g.
cyanosis) in severe cases. Horses with small defects
may be asymptomatic or develop clinical signs at
a later age. VSDs are also components of complex
cardiac anomalies such as Tetralogy of Fallot andtruncus arteriosus.

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Other defects described in the horse include:
Abnormal communications between the atria.
Examples: atrial septal defect and patent foramen ovale.
Abnormal communication between the great
vessels. Example: patent ductus arteriosus.
Malformed great vessels. Example: common
truncus arteriosus (the division between theaorta and pulmonary artery does not develop
and a single vessel leaves the heart).
Abnormally positioned great vessels. Examples:complete transposition (the right ventricle
pumps blood into the aorta and the left ventricle pumps blood into the pulmonary trunk)and double-outlet right ventricle (both theaorta and pulmonary trunk arise from the rightventricle).
Heart valve abnormalities. Example: tricuspid
valve atresia.
Tetralogy of Fallot, which consists of a dextrapositon of the aorta, pulmonic stenosis,
ventricular septal defect, and right ventricular
hypertrophy.

Archives at the University of Kentucky Veterinary Diagnostic Laboratory were searched from2010 to 2015 for cases of congenital cardiovascularmalformations in the horse. Over that period, 18
cases were identified. Fourteen were in Thoroughbreds, two in American Saddlebreds, and one eachin the Arabian and Standardbred breeds. Twelve of
the animals were female and five were male; the sexof one animal was not identified. Ten cases of ventricular septal defect, which included nine simple
and one complex anomalies, were diagnosed. The
complex anomaly was associated with pulmonic
stenosis. Two cases each of Tetralogy of Fallot andtruncus arteriosus with VSD were identified, andsingle cases of atrial septal defect, over-riding aorta,
right ventricular hypoplasia with pulmonary atresia
and moderator band dysplasia were reported.
CONTACT:David Bolin, DVM, PhD
david.bolin@uky.edu(859) 257-8283
Veterinary Diagnostic Laboratory
University of Kentucky
Lexington, Kentucky

Progesterone as a
Diagnostic Tool .  .  .  .  .  . 4KentuckyCongenital Cardiac
Anomolies .  .  .  .  .  .  .  .  .  .  . 5

College of Agriculture,
Food and Environment
Department of
Veterinary Science“Nature doesn’t break, it only bends.” This
quote was recently uttered on a television drama, which depicted an infectious disease
clinician fighting a catastrophic epidemic thatdeveloped following a genetic mutation of a forgotten infectious disease agent. As a pathologist
and former microbiologist, this reference to theconstant evolution of microbes made me ponder,
once again, how such relatively simple organisms
rapidly and continually adapt to their environments to survive and replicate. It is unfortunate,
at least for the host, when the intricate balance
between host, environment, and microbe becomes
offset and results in infectious disease.
This theme was exemplified in April 2016 whenequine infectious disease experts from around theworld gathered for the 10th International Equine
Infectious Diseases Conference in Buenos Aires,
Argentina. The conference, which is held every
four years, provides excellent continuing educationfor equine clinicians and brings together equine
infectious disease researchers who share recent
developments and breakthroughs. The five-day
event addressed infectious diseases of continued
and historical concern, newly recognized andemerging diseases, and important reemerging
infectious diseases of the horse. These motifs wereaddressed in 11 separate sessions on biosecurity,
diagnostics, diseases of working equids, emerging
and reemerging diseases, gastroenterology, international equine movement, neurology, parasitology, theriogenology (reproduction), respiratory
diseases, and infectious diseases of other systems.
Although I enjoyed all of the presentations, I
was particularly taken with the talks on emerging

and reemerging diseases. Emerging viral agentsthat were discussed included: equine enteric coronavirus (a potential cause of necrotizing enteritis),
Theiler’s disease associated virus (the newly identified cause of equine serum sickness), and otherviral causes of hepatitis (equine hepacivirus andequine pegivirus), Bunyamwera virus in Argentina (a cause of nervous disease and/or abortion),and Hendra virus (an acute fatal and zoonotic
disease that frequently affects the respiratory andneurologic systems). Other interesting and noteworthy disease conditions comprised anthelmintic
resistance (resistance of parasitic worms to treatment), the potential role of microbes in equine
polyneuropathy, and strangles-like disease causedby Streptococcus zooepidemicus. The reemergenceof West Nile virus (a cause of neurologic disease)in France and Salmonella Abortusequi (a cause ofabortion and septicemia) in Argentina were also
addressed. Although many of these diseases are
emerging or reemerging in specific locations, onemust be globally aware of them due to the increasing frequency with which equine athletes andbreeding stock are transported around the world.
We may never break nature, but rest assured
that clinicians and infectious disease researchers
will continually attempt to challenge nature anddevelop new modalities to quickly detect, track,
diagnose, treat, and hopefully learn to prevent andcontrol infectious diseases as they occur.
CONTACT:
Alan T. Loynachan, DVM, PhD, DACVP
alan.loynachan@uky.edu(859) 257-8283
Veterinary Diagnostic Laboratory
University of Kentucky
Lexington, Kentucky