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Reproduction: mare reproductive loss syndrome

ISSN 2398-2977


Synonym(s): MRLS, fetal loss syndrome

Introduction

  • During April and May of 2001 and 2002 the pregnant mare population of central Kentucky in the USA, comprising multiple breeds of horses, experienced a high level of fetal loss Mare reproductive loss syndrome: acute onset of EFL / LFL - graphMare reproductive loss syndrome: abortion accessions - graph.
  • Cause: with no immediate explanation for the cause it was identified as Mare Reproductive Loss Syndrome (MRLS). Exposure to the eastern tent caterpillar (ETC), the larval form of Malacosoma americanum during April and May has been identified, based on field and experimental studies, as the principal source for the development of MRLS in horses.
  • Signs: early fetal loss (EFL), late term abortions and birth of weak foals collectively referred to as late fetal loss (LFL), unilateral endophthalmitis and pericarditis in the general equine population of the area.
  • Diagnosis: a combination of clinical, epidemiological and pathological observations within an affected population, with affected populations typically being affected by EFL. LFL, birth of weak foals with acute respiratory distress, fibrinous pericarditis, and unilateral and acute onset exudative endo-ophthalmitis (though not all of these presentations necessarily occur in any one affected population).
  • Treatment: no effective treatment reported for mares showing ultrasonographic signs of EFL. Empirical treatment and intensive nursing care of weak neonates. Cases of pericarditis may be treated with pericardiocentesis, repeated if necessary, and corticosteroids and antibiotics. Cases of endophthalmitis reported not to respond to treatment.
  • Prognosis: unfavorable.

Presenting signs

Geographic incidence

  • In the USA:
    • Kentucky (2001-2002).
    • Also seen in Ohio, Pennsylvania and West Virginia and Tennessee (2001-2002).
    • Florida and New Jersey (2006).
  • In Australia (2004) an abortion storm in mares associated with exposure to caterpillars was reported, which shared some features with MRLS.

Age predisposition

  • All ages of horse susceptible to endophthalmitis and pericarditis.

Breed/Species predisposition

Public health considerations

  • To date, no hazards to public health have been identified.

Cost considerations

  • A study undertaken by the Department of Equine Business at the University of Louisville, USA (summer of 2001), estimated the economic loss to the equine industry of Kentucky, over a four-year period 2000-3003, at $336 million (293 million Euros / £203 million).
  • Subsequent losses in 2002 would raise that figure to approximately $500 million (436 million Euros / £303 million).

Pathogenesis

Etiology

  • Preliminary observations in 2001 indicated that reproductive losses occurred simultaneously over a wide area of central Kentucky on many farms commencing in the latter part of April. This observation was more indicative of an environmental toxin as distinct from an infectious agent.
  • Studies to identify possible toxins included mycotoxins, fungal endophytes, phytoestrogens and chemical compounds all gave negative results. 
  • At the present time the exact etiology of MRLS has not been determined.
  • Experimental studies undertaken by scientists at the University of Kentucky during 2003 suggest that the factor from ETC giving rise to abortion is present in or on the exoskeleton. 
  • Another study demonstrated that irradiated ETC (which would destroy infectious agents carried by caterpillars) could induce fetal loss in late-term pregnant mares.
  • One hypothesis is that MRLS is caused by an ETC-related toxin, with secondary opportunistic bacterial invasion of the fetus.
  • Al alternative hypothesis is that MRLS is caused by the hairs of the caterpillar breaching gastrointestinal mucosal integrity, thus allowing opportunistic bacteria access to the bloodstream, and resulting in bacteremia.
  • The majority of bacteria found in cases of MRLS are non-hemolytic Streptococcus spp and Actinobacillus spp.

Predisposing factors

General

  • Bacterial infection in cases of EFL and LFL represent an ante mortem event and most pathological lesions could be attributable to bacterial infection.
  • However, epidemiological findings and bacterial isolation suggest a secondary role for bacteria. Bacteria gain access to the amniotic fluid and sites with direct contact with this fluid but show little tendency to invade.
  • The high incidence of red bag syndrome suggests premature placental separation indicative of placental damage.

Timecourse

  • Field and experimental studies indicate the onset of both EFL and LFL following exposure to ETC is rapid, a matter of days, whereas the onset of endophthalmitis and pericarditis is more protracted.

Epidemiology

  • An extensive epidemiological study undertaken in the summer of 2001 on 133 farms in central Kentucky identified high to medium levels of ETC and cherry trees as strongly associated with a high incidence of MRLS.
  • Field and experimental studies in 2002 confirmed the role of the ETC.
  • The overwintered eggs of the insect hatch in the early spring over a 3 week period that is influenced by an increase in mean daily temperatures. In Kentucky, this coincides with about 50% bloom of Forsythia occurring in late March and early April.
  • The emerging larvae   Mare reproductive loss syndrome: Eastern Tent Caterpillar  (caterpillars) build a communal silk shelter (tents)   Mare reproductive loss syndrome: Eastern Tent Caterpillar -   which are visible in tree branches through the months of April and May. 
  • ETC are ravenous feeders and when present in massive population densities   Mare reproductive loss syndrome: Eastern Tent Caterpillar invasion  (as occurred in Kentucky in 2001) rapidly defoliate their natal tree before falling to the ground in search of another food source. It was during this period (late April to early May) that horses in Kentucky were exposed to caterpillars in 2001 and 2002.

Diagnosis

Presenting problems

Client history

  • Horses grazing pastures containing or in close proximity to trees in the plant family Roseaceae, particularly the wild or black cherry that contain overwintered egg masses of the ETC Mare reproductive loss syndrome: ETC egg mass.

Clinical signs

EFL

  • Mares typically present with no outward signs of EFL.
  • Occasionally a mare will show a serosanguineous or purulent discharge from the vulva. 
  • Some mares show membranes protruding from the vulva with the fetus located either in the vagina or uterus. 
  • A small number (<5%) exhibited mild signs of colic Abdomen: pain - adult, abdominal straining or low grade fever 1-3 days before EFL occurs.

LFL

  • Clinical signs in mares experiencing LFL are inconsistent but include restlessness, discomfort, sweating and rarely stiffness resembling acute laminitis followed by an intense and explosive presentation in an attempt to deliver the fetus. 
  • Most mares present with premature placental separation with the appearance of the engorged chorioallantoic membrane (red bag syndrome). 
  • Due to abnormal positioning of the fetus, dystocia Reproduction: dystocia may occur with the mare reluctant to foal in a recumbent position.
  • Some mares show lack of mammary development or waxing prior to delivery.
  • If delivered alive neonates are weak, dehydrated and dyspneic requiring immediate veterinary assistance.
  • Hypothermia, tachycardia and inconsistent respirations are common often with periods of apnea → respiratory arrest. 
  • Placenta is heavy and edematous weighing <40 lb with hemorrhages on the surface of the umbilical cord Mare reproductive loss syndrome: umbilical cord - hemorrhages, particularly the amniotic segment of the cord.
  • Late aborted fetuses are generally of normal size and weight for gestational age.

Unilateral endophthalmitis Eye: panophthalmitis

  • Cases are characterized with acute onset, unilateral endophthalmitis, corneal edema and exudate in the anterior and posterior segments. 
  • Variable degrees of pain, periocular swelling, discharge and hyphema are present.
  • Culture and cytology of aqueous and vitreous samples reported to be unproductive.

Pericarditis Heart: pericarditis

  • Signs include:

Diagnostic investigation

EFL

LFL

  • Detailed post mortem examination of the fetus and placenta if the fetus is dead.
  • Foals born alive but showing signs of respiratory distress require a detailed clinical pathological examination.

Unilateral endophthalmitis

Pericarditis

Gross autopsy findings

LFL

  • Consistent findings in MRLS fetuses and neonates are inflammation of the umbilical cord (funisitis), pneumonia, bacterial infection and hemorrhages.
  • Fetuses are of normal size and weight for gestational age and in a good state of post mortem preservation. The lungs show a variable degree of inflation indicating respiratory efforts at the time of delivery, occasionally providing evidence of pneumonia.
  • Hemorrhages are observed on the pleura and heart. 
  • Some allantochorions are mildly edematous although the majority are of normal size and weight.
  • Hemorrhages are commonly seen on the chorionic and allantoic surfaces. 
  • The most striking changes are observed in the umbilical cord particularly the amniotic segment, these include:
    • Roughening of the surface.
    • A gray-yellow discoloration.
    • Enlargement due to stromal edema.
    • Surface hemorrhages.
    • The allantoic segment retains the normal, smooth glistening appearance. 
    • The amniotic membranes show variable hemorrhage and edema.

Pericarditis

  • Lesions include:
    • Evidence of effusive fibrinous pericarditis with varying degrees of pericardial, pleural and peritoneal effusion. 
    • The epicardium is thickened by granulation tissue. 
    • Myocardial lesions are mild and infrequent but included superficial fibrosis, focal interstitial myocarditis and foci of myocardial mineralization and necrosis.

Histopathology findings

LFL

  • The lungs often contain desquamated cells of amnionic fluid origin and small numbers of neutrophils and macrophages in the alveolar spaces.
  • Bacteria are often present in the alveoli. 
  • Other fetal tissues may show acute hemorrhages. 
  • Umbilical cords have bacteria on the surface with loss of the epithelium and light to heavy infiltrates of neutrophils and macrophages concentrated at the surface of the cord. 
  • Hemorrhages and edema are present in the stroma of the cord. Similar changes are also observed in the amniotic membrane. 
  • Allantochorions occasionally have low numbers of neutrophils in the stroma and extra-embryonic coelom.

Bacteriological findings

LFL
  • Non-beta-hemolytic streptococci and actinobacilli were isolated from umbilical cords, lungs and placentas of 83% of cases. 
  • These bacteria have not historically been routinely isolated from cases of equine abortion except in 1981 when there were reports of EFL occurring on a number of farms in central Kentucky.
Pericarditis
  • Bacteria isolated from pericardial fluid and/or the myocardium includes Actinobacillus spp and Streptococci, supporting the diagnosis of bacterial endocarditis.

Other findings

  • Extensive examination for the presence of viruses and other agents has to date produced negative results.

Differential diagnosis

  • Need to differentiate from abortion resulting from a variety of other causes.
  • Infectious bacterial agents, including equine herpes virus and equine viral arteritis.
  • Chemical and plant toxins.
  • Mycotoxins.

Diagnosis of EFL

  • Ultrasound examination Ultrasonography: reproductive tract - female between 60 and 70 days of gestation indicates the fetus is not viable, lacking a heart beat with the presence of flocculent material in the allantoic and amniotic fluids.
  • Cytological examination of these fluids reveals the presence of squamous epithelial cells, cocci and a rare neutrophil. Subsequent examination confirms the fetus has been expelled.

Diagnosis of LFL

  • Lesions observed in the dead fetus are described under the gross post mortem findings but are not confirmatory of a diagnosis. 
  • Clinical pathological findings in foals born alive but suffering acute respiratory distress indicate dehydration, neutropenia and hypoglycemia.
  • Colostral transfer is impaired with low immunoglobulin levels at 24 h of age. 
  • Blood cultures are rarely positive although non-beta-hemolytic and actinobaccillus are occasionally isolated.

Diagnosis of unilateral endophthalmitis caused by MRLS

  • Culture and cytology of aqueous and vitreous samples are unproductive.

Diagnosis of pericarditis caused by MRLS

  • Echocardiograms Cardiovascular: ECG (electrocardiography) reveal an effusive pericarditis with right-sided heart failure Heart: failure - overview associated with pleural effusion and/or ascites.
  • Analysis of pericardial fluid indicated in the majority of cases a sterile exudate (particularly those with a history of antibiotic treatment), cellular debris and elevated protein levels.
  • In other cases a range of bacteria including non-beta-hemolytic streptococci and actinobacillus were isolated.
  • Hematology indicated leukocytosis Blood: leukocytes and raised fibrinogen levels.

Finding of any of the above in an individual horse or fetus should not be considered diagnostic for MRLS since a pattern of these changes within a population at risk must be present before making a definitive diagnosis. The epidemiological pattern in a defined population with an abrupt and rapid increase in the various clinical manifestations is critical to a diagnosis of MRLS.

Treatment

Initial symptomatic treatment

EFL and LFL

Unilateral endophthalmitis

  • Cases did not respond to treatment.

Pericarditis

Prevention

Control

  • Current management recommendations to minimize MRLS emphasize eliminating the exposure of horses to the ETC. 
  • The wild or black cherry tree is the preferred host to the ETC. ETC can travel long distances (up to 0.25 miles) from their tents in the branches of the cherry tree. Thus host trees outside the boundaries of horse pastures pose a risk. 
  • The caterpillar will also infest other trees including ornamental pear, crabapple and sometimes oak. 
  • Examination of trees during the winter months when no leaves are present will identify fresh egg masses of ETC thereby pinpointing areas for insecticide application.
  • There is no preventive approach to ETC control prior to egg hatch. Insecticides must be applied after egg hatch is complete and tents are visible in trees. There is no benefit to spraying pastures to kill wandering ETC.
  • There are 4 elements to an ETC control program:
    • Timely detection of active ETC tents and feeding caterpillars in trees.
    • Proper application of an appropriate insecticide when ETC populations are judged to be significant. 
    • Protection of applicators, animals and the environment.
    • Follow-up inspections of treated areas after 5-7 days to evaluate results and check for additional tents.

Available foliar sprays

  • Bacillus thuringiensis (Bt):
    • Bt based insecticides derived from a toxin produced by a soil microbe. They are specific to caterpillars by disrupting the digestive tract and must be eaten. 
    • Bt insecticides must therefore be applied to foliage within 3 of the nest and not to the nest itself. 
    • Bt products are effective against small caterpillars but are less so as the larvae grow older. The residual life appears to be 3-5 days and is nontoxic to the environment.
  • Bifenthrin and other pyrethroids:
    • These provide the most effective, rapid and longest lasting of the foliar insecticides. 
    • They are toxic to the nervous system of the caterpillar and are effective against and large larvae so can be applied when the majority of larvae have emerged (2-3 weeks after first hatch). 
    • Many pyrethroids are Restricted Use pesticides in the United States because of potential environmental harm. 
  • Carbamate insecticides:
    • These attack the nervous system and act as a contact and stomach poison can be sprayed directly on caterpillars. 
    • Agricultural product labels contain a 14 day grazing/harvest wait. 
  • Injection technique:
    • Injection of the base of the tree with bidrin, applied during the same time period when foliar sprays are used has provided excellent control of ETC in large trees. 
    • The insecticide is carried in the sap to the leaves and kills the caterpillars as they feed.  
    • It has proved highly effective against young ETC but less effective against older, larger larvae (2 or longer).
  • All insecticides should be used with due regard to spray drift, and to environmental contamination.

Surveillance

  • Increased surveillance during the 2002 and 2003 included reporting weekly the number of equine fetuses submitted to the Livestock Disease Diagnostic Center in Lexington. 
  • Also equine practitioners regularly reported the number of EFL and referrals of neonates to local veterinary intensive care clinics. 
  • Selected mares and pastures on twelve farms in central Kentucky were used as sentinels in 2002 and 2003 for regular monitoring of a variety of parameters from February to June.

Communication

  • The interest generated by the outbreak was extensive and at times overwhelming. 
  • To address the need to provide rapid and up to date information an MRLS Website was established in May 2001 and continues to be available.

Outcomes

Prognosis

EFL

  • Very few mares that lost their fetuses and were bred back in the 2001 breeding season became pregnant: 
    • The primary reason was their refusal to cycle normally due to the presence of eCG (equine chorionic gonadotrophin) in the blood circulation.
    • The eCG levels are maintained due to the persistence of endometrial cups produced by the placenta before the pregnancy was lost.
  • The majority of these same mares experienced no problems when they were bred in 2002 (by which time the endometrial cups had been resorbed).

LFL

  • No problems were experienced by mares who had experienced LFL due to MRLS in 2001 when they were bred in 2002.

Unilateral endophthalmitis

  • Cases did not respond to treatment.

Pericarditis

  • Between 33-50% of cases died or were euthanized.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • McDowell K J et al (2010) Invited review: the role of caterpillars in mare reproductive loss sydrome: a model for environmental causes of abortion. J Anim Sci 88 (4), 1379-1387 PubMed.
  • Sebastian M M et al (2008) Review paper: mare reproductive loss syndrome. Vet Pathol 45 (5), 710-722 PubMed.
  • Volkmann D et al (2008) Hormone profiles of mares affected by the mare reproductive loss syndrome. Repro Dom Anim 43 (5), 578-583 PubMed.
  • Potter D A, Foss L, Baumler R E & Held D W (2005) Managing Eastern tent caterpillars Malacosoma americanum (F) on horse farms to reduce risk of mare reproductive loss syndrome. Pest Management Sci 61 (1), 3-15 PubMed.
  • Cohen N D, Carey V J et al (2003) Case-control study of late-term abortions associated with mare reproductive loss syndrome in central Kentucky. JAVMA 222 (2), 199-209 PubMed.
  • Cohen N D, Carey V J et al (2003) Descriptive epidemiology of late-term abortions associated with the mare reproductive loss syndrome in central Kentucky. J Vet Diag Invest 15 (3), 295-297 PubMed.
  • Cohen N D, Donahue J G et al (2003) Case-control study of early-term abortions (early fetal losses) associated with mare reproductive loss syndrome in central Kentucky. JAVMA 222 (2), 210-217 PubMed.
  • Dwyer R M (2003) Fitting the pieces of the puzzle: mare reproductive loss syndrome update. Equine Vet Educ (American Edition) 5 (1), 56-58 VetMedResource.
  • Dwyer R M, Garber L P et al (2003) Case-control study of factors associated with excessive proportions of early fetal losses associated with mare reproductive loss syndrome in central Kentucky during 2001. JAVMA 222 (5), 613-619 PubMed.
  • Hughes C, Lehner F et al (2003) A simple and highly sensitive spectrophotometric method for the determination of cyanide in equine blood. Toxicol Mech Methods 13 (2), 129-138 PubMed.
  • Fitzgerald T D, Jeffers P M & Mantella D (2002) Depletion of host derived cyanide in the gut of the eastern tent caterpillar, Malacosoma americanum. J Chem Ecology 28 (2), 257-268 PubMed.
  • Morehead J P, Blanchard T L, Thompson J A & Brinsko S P (200