• EHV-1 causes respiratory infection in all ages, however the disease is more severe in younger animals. It also causes abortion and neurologic disease. (CNS signs are due to thrombotic lesions, not infection of neural tissue) EHV-4, also called  EHV-1², causes respiratory disease, only rarely neurologic or abortion disease.  They are now considered to be 2 separate viruses (fam. Alphherpesvirinae, gen. Varicellovirus)
• Primary replication is in the mucosal epithelium, then a lymphocyte associated viremia develops
• The virus persists in the pregnant mare for long periods with the majority of abortions (90%) occurring within 60 d post-infection; however, the range from infection to abortion is 14 to120 days.
• Abortions may occur from the 5th month to term, but most commonly occur from 8 to 9 months to term.
• Infection of the fetus occurs by migrating leukocytes and/or infection of umbilical blood vessels; primary target organs are the respiratory tract and liver.
• Premonitory signs of abortion are few. 
  • Typically there is a sudden abortion without milk or udder development.
  • The fetus is delivered in a fresh condition, and may even be born alive and die soon after. 
  • Immunity is short after natural infection (3-4 mo) and individuals may be reinfected repeatedly.
• Transmission is by the respiratory route.
• Most mares of breeding age are clinically immune to respiratory disease but not to abortigenic infection.
• Spread of EHV-1 through a herd occurs most commonly without clinical signs.
• The virus can persist in the trigeminal ganglia and can recrudesce in latent carriers. Stressing pregnant mares may trigger abortion.
• Diagnosis of abortion is by histopathology of the fetus. 
  • Fetal lesions include serous pleural and peritoneal fluid, hemorrhages of the entire respiratory tract, petechia of the oral mucosa and conjunctiva, focal hepatic necrosis with intranuclear inclusion bodies in liver and lung*, and a necrotic and friable thymus. 
  • Specimens for submission to the diagnostic lab should include lung, liver and thymus, both frozen and in formalin. 
  • Serology of the mare is of no value because of the time period which has lapsed between maternal infection or viremia and abortion. Diagnosis may also be confirmed by virus isolation or PCR.
• Control is achieved through vaccination programs. 
  • Both modified live and killed vaccines are available. 
  • Controlled studies have showed that both are effective, both had failures.
  •  Recommendations are to vaccinate pregnant mares with 3 doses, given at 5, 7 and 9 mos. of gestation. 
  • (Note: in addition, pregnant mares should be given their annual booster against flu, tetanus, encephalitis, etc. at 10 mos gestation which serves not only to protect them for the coming year and gives them their tetanus booster which is important in case of any postpartum complications but also boosts immunoglobulins at a time when colostrum is being produced so as to provide better protection for the neonate)
• Non-vaccination programs are practiced in some countries. A lower incidence of disease is reported in countries where vaccination is not practiced, however, the disease is common enough in the US that not vaccinating pregnant mares is inviting disaster.

Equine viral arteritis

• The disease was unknown before 1953. In 1953 the virus was isolated, the etiology defined, disease described, etc.
• Studies from which the descriptions of the disease are derived are generally based on an experimentally derived, highly virulent strain (Bucyrus strain) that was made by serial passage and became VERY virulent.
• Some outbreaks of the disease such as the 1984 outbreak in Kentucky during the breeding season, are not associated with abortions. Other outbreaks are associated with significant pregnancy losses.
• Naturally occuring abortion from EVA is not common. It occurs sporadically, sometimes in clusters.
• Majority of abortions occur 23-57 days following exposure, or 6-29 days following the onset of fever in the mare.
• Foals can be born infected and die within 72 hr (appear normal when born or may be born ill, develop respiratory signs or enteritis)
• In a controlled study, mares were bred to carrier stallions, then transported and subsequently housed with mares that were in the 7-11th month of gestation. 
  • All mares became seropositive. 
  • Clinical signs would have gone unobserved but for the experimental protocol which included BID temperatures and weighing of feed given and remaining at the end of the day. 
  • A slight febrile response and mild anorexia was detected. 
  • Of the exposed mares, 10 of 14 pregnant mares aborted. In this study, autolytic changes were not observed in the fetuses. 
  • The virus was isolated from the fetus or the placenta in 8 cases.
• Some breeds (e.g. Standardbreds) have a high incidence of seropositive individuals and disease is almost never seen.
• Other breeds are quite naive and clinical signs (i.e. abortion) are more common.
• There may be some differences in strains of the virus.
• Typically there are no clinical signs in the mare other than abortion.
• After abortion, fetal tissues to collect for laboratory diagnosis are: lung, liver, placenta, fetal fluids - if EAV is the cause of the abortion, it is fairly easy to isolate.
• Transmission is by oronasal and venereal routes. Respiratory shed occurs for about 1.5 - 2 wks
• If a stallion develops clinical signs, control the fever and scrotal edema to prevent temporary sterility
• After infection, mares clear the infection and develop immunity. 
  • However, the virus is shed in the semen and the majority of infectious organisms are in the seminal plasma. 
  • Stallions then become inapparent carriers and remain so for years.
• Need to keep about 90 yds between a shedding stallion and other horses; or between a mare bred to a shedding stallion and other mares
• The disease can be transmitted by AI and has been transmitted by fresh, cooled semen. As the use of transported (fresh cooled or frozen) semen has become more common and international trade in equine semen has increased, reports of abortion due to EVA have become more common as well.
• Control is by use of a MLV vaccine. Once vaccinated, a stallion cannot be distinguished from a naturally infected animal by serology, therefore there is some reluctance towards widespread use of the vaccine. However, virus isolation from the semen can distinguish carriers from vaccinates.

• There are 3 proposed routes of infection. 
  • The first involves the hypothesis that bacterial levels in the uterus can be low enough to allow conception, but multiply during gestation producing placentitis and abortion. The other routes are more plausible. 
  • The second involves hematogenous spread of a pathogen. 
  • The third and most common route involves transcervical migration of the pathogen.
• Etiological agents involved can be almost anything. 
  • Staph, Strep, E coli are commonly implicated and a whole range of organisms have been reported.
  •  Normally there are premonitory signs of an impending abortion, such as udder enlargement, mammary secretions and relaxation of the vulva.

  

  

• Autolysis of the fetus and placenta can make identification of the etiologic agent difficult. 
• After an abortion, the chorionic surface of the placenta should be inspected. 
  • If the infection is an ascending infection through the cervix, a thickened area extending from the cervical star will be evident. 

  

  

  

• The affected portion of the placenta will be thickened, discolored and the villi will be blunted. It may be covered with a brownish, tenacious exudate.

• Pre-partum placental inspection
  
  • Placentitis is a leading cause of abortion and neonatal disease in horses. Early diagnosis is critical to be able to begin effective treatment that can result in the survival of a healthy foal. 
    • Placentitis is initiated either through the hematogenous spread of bacteria to the chorioallantois or through a transcervical route by bacteria ascending through the cervix
    • The ability to diagnose placentitis in utero, before clinical signs of premature lactation or vaginal discharge are observed will improve the chances of successful treatment. 
    • Although it cannot be recommended to examine all mares routinely at intervals for placental abnormalities, mares with a history of problems or at high risk may be periodically examined for signs of placental disease. 
  • Ultrasonographic examination of the placenta may be done either transabdominally or per rectum.
    • Observance of thickening of the uteroplacental unit, separation between the uterus and placenta or exudate between the uterus and placenta are indications of a problem. Because the area of the cervical star is most commonly affected, ultrasound exam of that area per rectum is useful.
  • Reef et al., have described the assessment of fetal well being in utero using a transcutaneous approach. 
    • The uterus is examined at multiple sites, attempting to cover all four quadrants. 
    • Fetal heart rate, the diameter of the fetal aorta, fetal activity, maximum depth of fetal fluids, utero placental contact and utero placental thickness have been found to be related to the pregnancy outcome. 
    • Significant utero placental thickening is consistent with placentitis, while anechoic spaces between the uterus and placenta suggest placental separation. 
  • While observed abnormalities are good indicators of placental disease, the lack of abnormal signs on transcutaneous examination does not mean that placental disease does not exist. 
  • Focal areas of placentitis may go undetected.
  • Most cases of placentitis stem from the spread of bacteria through the cervix, infecting the chorioallantois in the region of the cervical star and spreading from there. 
  • Troedsson et al., have examined the utero placental unit near the cervical os per rectum, near the area where most cases of placentitis would be expected to originate. 
    • Measurements of the combined thickness of the uterus and placenta at the ventral portion of the uterus, near the cervical os, are obtained. 
    • The normal thickness of the utero placental unit is dependent on gestational age (8 mm at 270 to 300 days gestation, 10 mm at 300 to 330 days, 12 mm at greater than 330 days).
    •  Multiple measurements should be taken and the mean value obtained because a single value may be misleading, especially if the image is taken at an oblique angle.

   

• 

• Pre-partum treatment
  • If placentitis is diagnosed in utero, treatment should be initiated immediately. 
  • If a vaginal discharge is present a culture and sensitivity may be beneficial in choosing an appropriate antibiotic. 
  • While results of the culture are pending or if no discharge is present, broad spectrum antibiotics should be administered. 
  • Research has shown that in normal pregnancies, without placental disease, that sulfa-trimethoprim can cross the placenta better than penicillin or gentamicin. 
  • However, no studies have been reported examining the ability of various antibiotics to achieve significant levels in the chorioallantois and fetal fluids in cases of placental disease. 
  • Nevertheless, sulfa-trimethoprim is often chosen to begin treatment, not only because of these studies but because of the expected duration of therapy and the ease of oral administration.
  • Treatment also includes progestogen supplementation and pentoxifylline to aid in preventing pregnancy loss. 
  • Depending on the nature of the problem, endotoxin release may be associated with placental disease. 
    • Endotoxin can result in endogenous prostaglandin release leading to abortion or premature delivery. 
    • Exogenous progesterone or progestogen supplementation has been shown by Daels et al., to be effective in preventing abortion associated with prostaglandin release. 
  • The oral progestogen, altrenogest (0.88 mg/kg), is usually used not only because of ease of administration, but because work by Daels et al., has shown it may be more effective than injectable progesterone. 
  • In addition to antibiotics and progestogen supplementation, pentoxifylline (4 gm, p.o., BID) has been recommended (Byars) for its anti-endotoxic effects in cases of placentitis.
    

• If evidence of placentitis exists, treatment consists of: altrenogest (0.088 mg/kg, PO, SID; =1 ml/25 kg = double dose), trimethoprim sulfa (30 mg/kg, PO, BID), pentoxifylline (4 gm, PO, BID)
• A specific cause of placentitis, found primarily in KY and the surrounding area, has been identified as a nocardioform organism, Crossiella equi.  This disease is characterized by an area of placentitis with a tan mucoid exudate located at the base of a uterine horn, near the body of the placenta.  It has been identified in other locations (e.g. Florida).  It occurs sporadically and in 1998 and 1999 was the most common cause of placentitis in KY.

Mycotic abortion

• Abortions result from a placentitis due to fungi, especially Aspergillus sp. Infection is thought to originate from the respiratory tract, through the circulatory system to the uterus and placenta. Alternatively, the transcervical route is also possible. There is a higher incidence in stabled mares.
• Typical gross lesions of placenta include necrotic areas that are difficult to distinguish from bacterial lesions. The chorionic surface may be dry, thick, and leathery. There may be lesions on the fetus, especially the skin. Fungal elements are easily demonstrable in smears and cultures if they are responsible for the abortion.

• Leptospirosis is being increasingly identified as a cause of abortion.  Incidence varies greatly from year to year.

(from M Donahue, B Smith, Equine Disease Quarterly Newsletter, Dept Vet Sci, Gluck Eq Res Center, Univ KY; )

• Leptospira interrogans serovar pomona had been reported to be most often implicated in equine abortion.  However, in the Equine Disease Quarterly Newsletter (Dept. Vet. Sci., Gluck Eq. Res. Center, Univ KY), Drs. M Donahue and B Smith reported of 250 cases diagnosed over the last 16 years (through the 2004 foaling season) 210 (84%) were due to kennewicki and 24 (10%) to grippotyphosa.  The raccoon is the maintenance host for grippotyphosa but the maintenance host for kennewicki was unknown at the time of the report.
• L. bratislava , thought to be "host adapted" in horses may be implicated in some disease processes.
• Many of the general points of information regarding lepto infection in cattle are applicable to horses. Bacteremia occurs after a 4-10 d incubation; pathogenic serovars localize in the kidneys or genital tract; favorable environmental conditions are moist, warm situations; invasion occurs through mucous membranes, soft moist skin, etc.
• Clinical signs in the mare are often unobserved.
• Abortions occur from 6 mos to term. Gross lesions of the fetus vary and may include icterus and a swollen liver and/or kidneys.
• Placental lesions are common.
• Diagnosis is by identification of the organisms and by serology of the mare. 
• No vaccine is currently available. 
• Control is achieved by sanitation and hygiene. 
• Some reports indicate potassium penicillin may be useful in pregnant mares with rising titers. Human studies indicate penicillin, IV, in high doses, may be a reasonable treatment.

• This organism causes abortion in mares, septicemia in foals and testicular lesions in stallions. The incidence has decreased to near non-existence but is reported in some areas of the world. Transmission is by ingestion or possibly venereal. Diagnosis is by recovery of the organism. Control is by isolation and hygiene and a bacterin has been available.

• The usual outcome of twins is abortion, stillbirth, mummification or dystocia.
• It has been considered to be the most important cause of abortion, with EHV-I under control. However, with the advent of early pregnancy diagnosis with ultrasound, the incidence has decreased greatly.
• Multiple ovulations are common, up to 35% in some breeds. However, twins are not common.
• The difference between the double ovulation rate and the lower incidence of twins is explained by the natural reduction hypothesis developed by Ginther.
  •  Natural reduction results when both vesicles become fixed in the same horn (unilateral fixation). 
  • The developing embryos have a trilaminar portion of the trophoblast and a bilaminar portion. 
  • The trilaminar portion is responsible for uptake of nutrients and gas exchange and if the trilaminar portion of one vesicle gets covered by the bilaminar portion of the other, it will die. 
  • Therefore the natural reduction hypothesis explains why in the majority of twins, one vesicle dies and the other survives. 
  • If one vesicle becomes fixed in each horn (bilateral fixation) neither vesicle will die and both twins survive, at least for a period of time. 
  • Eventually, there is inadequate uterine capacity (placental insufficiency) and fetal death with subsequent abortion or mummification ensues.

  

• Diagnosis of twins is best accomplished with ultrasound.

• A high degree of accuracy can be achieved. The initial pregnancy exam should be performed at 14 d post ovulation. If 2 CL's are observed on ultrasound, but only one vesicle is seen, repeat the exam in a few days. Rectal palpation is not as accurate as ultrasonography. If the embryos are in different horns, 2 bulges are palpable from 20-50+ d but if they are in the same horn they may be difficult to detect. Other methods of detection such as elevated eCG levels or fetal EKG are less reliable, more difficult and do not provide information early enough to manage the situation properly. Unfortunately, when mares are bred without proper supervision, a diagnosis of twins is often made at the time of abortion.

• The AVMA has established liability guidelines regarding twins which it may be wise to review.
• Various management guidelines have been proposed to handle the problem of twins and there are some points of discussion.
• Some persons recommend to avoid breeding when multiple follicles present. However, this will reduce the overall pregnancy rate and delay conception until later in the season. Most breeders won't be happy with this.
• Others recommend "Splitting follicles" or breeding between ovulations. This is not a good idea in my opinion because you're breeding after ovulation when progesterone is beginning to rise, uterine defenses are less effective and mechanical clearance is becoming less effective.
• In my opinion, it is best to breed regardless of whether or not 2 follicles are present and worry about twins when and if they occur.
• The important point is to perform the pregnancy exam early, before fixation occurs, when one vesicle can be easily crushed and the likelihood of the other surviving is high.
• At any rate, it is important to diagnose twins before the endometrial cups are established. Once the endometrial cups are in place (about 30 days), if pregnancy loss occurs (for example as a result of a twin reduction attempt) the mare will not cycle normally and the chance of getting her back in foal that breeding season is slight.
• Others recommend waiting for natural reduction. Although Ginther estimates a 5 in 6 chance of reduction to a singleton pregnancy by 45 d, this is based on assumptions of a 20% double ovulation rate and a 70% conception. If either rate is higher , the incidence of twin pregnancy could be higher. Moreover, if a mare owner has only one or two mares or it happens to be his best mare that has twins, odds may not be as important as reality.

Ginther's 'Twinning Tree'

• Manual rupture - before 16 days
  • Manual rupture of one vesicle as early as possible (i.e. before 16 d) is the best management practice in my opinion. When twins aren't discovered until too late, other options such as ultrasound guided twin reduction or therapeutic abortion can be discussed with the mare owner.
• Aspiration of one conceptus
  • This involves a transvaginal aspiration of the fluids from one conceptus.
  • A heavy sedative is given
  • A transvaginal probe is inserted into the vagina and a the conceptus visualized
  • A long needle is inserted through the vagina, into the fetus and all the fluid is quickly removed using an aspiration pump.
  • The success rate is not good (30%). A theory on the problem is that the fluid leaks from the aspirated fetus and undermines the other fetus, thereby killing it too.

• Twin Reduction by Cervical Dislocation (as told by Karen Wolfsdorf)

  • Best time to perform surgery is between 75 to 85 days

  •  Ultrasound to locate and identify fetuses, choose the one with the least surface area or closest to the tip of the horn

  • Give Banamine pre-op

  • Give 0.5 cc detomidine

  • Clip and give local block

  • Give another 0.5 cc detomidine

  • Give 1.0 cc propantheline (This is critical – if skip this, uterus will be too turgid to be able to perform task - availabel from HGD Pharmacy)

  • Grid incision (big enough to permit arm in abdomen)

  • Locate fetus, dislocate cervix by rolling between thumb and second finger (bigger fetuses – sort of like popping a cork on a bottle)

  • Routine closure

  • Post-Op Banamine q 12 h for 2 d

  • Double dose Regumate for 30 d

  • Pen/Gent for 3 d, then 7 more d of SMZ

• Much of the tall fescue is infested with an endophyte (Neotyphodiun, formerly Acremonium, coenophialum).
• Fescue infected with this endophyte actually performs better than noninfected fescue. 
• The problem occurs when mares graze this fescue during gestation.
• Abortion, stillbirth, prolonged gestation, dystocia, thickened placenta, agalactia, increased mare mortality and weak foals result.
• Abnormal cyclicity, lower d 14 pregnancy rates, and increased EED are also seen in mares grazing on infected fescue.
• The endophyte acts like a dopamine agonist.
• Treatment is aimed at either remove the mares from the fescue at 300 d of gestation which will prevent problems or treating affected mares with a dopamine antagonist such as domperidone.

• To cause pregnancy loss, the trauma would have to be quite severe and there are few documented cases. It is unlikely that a bump would cause any problem.

• The equine umbilical cord is quite long and tortuous. It is normally twisted in utero. To be significant and be implicated as the cause of an abortion, the torsion must be accompanied by edema and congestion indicating impaired blood flow.

• Nutritional support for the first 35-40 d is from the yolk sac and histotrophe. 
• Initial attachment of the placenta begins around d 45 or 60 but is not complete until 100 (+) days and is delayed in mares with significant endometrial pathology.
• Twins, body pregnancy, and mares with endometrial atrophy or fibrosis are examples of situations where inadequate placental attachment occurs. 
• In mares which have a long gestation (e.g. >365 d), and deliver a small foal, especially older mares or those with history of endometritis, this may indicate retarded fetal growth resulting in nutritional deprivation of the fetus. 
  • Slower maturation of the fetus and later maturation of the systems involved in initiation of parturition are responsible for the prolonged gestation. 
  • This is one of the reasons it is important to examine the placenta after delivery. Areas of hypoplastic or aplastic villi may be observed which may lead to further diagnostic measures (biopsy of corresponding areas or hysteroscopy) or aid in management decisions.

• Poor nutrition has been associated with pregnancy loss between 7-13 wks gestation and has been advocated by some as a tool for managing twin pregnancy. This area should be re-examined now that ultrasound is available.
• Good nutrition ("Flushing") caused by a change in pasture or sudden lush growth of pastures has been associated with relaxation of the cervix, possibly allowing an ascending infection. Estrous behavior and breeding if a stallion is present has been observed under these circumstances. Natural breeding may result in an ascending placentitis as the stallion normally ejaculates into the uterus.

• although horse owners worry about it, has never been associated with causing abortion.

Mare Reproductive Loss Syndrom

• Kentucky in 2001
• Early loss - 90 days
• Associtated with 
  • More time in pasture
  • Eastern Tent Caterpillars
  • White Clover
  • Cherry Trees
  • Bred during February
  • Larger farms
  • Pasture feeding hay (increased exposure to other causes?)

• Vaccination of mares against herpesvirus at 5, 7 and 9 months of gestation and against EAV when indicated will reduce the chance of abortion. 
• A Caslick's suture should be placed if indicated by perineal conformation.
• Pregnant mares should be separated from other horses, especially from new stock, young stock, etc.
• Prophylactic progestogen (altrenogest) may be administered if indicated, i.e. in situations where endogenous prostaglandin release is likely. 
• Although there are few instances where the need for exogenous progestogen can be documented, and overuse cannot be condoned, altrenogest is safe to use in pregnant mares and there may be circumstances where it can be viewed as cheap insurance.