Mare Reproductive Loss Syndrome (MRLS)

 


Dr. David G. Powell, B.V.SC., F.R.C.V.S., University of Kentucky

 

 

During April and May of 2001 the pregnant mare population of central Kentucky, comprising multiple breeds of horses, experienced a high level of fetal loss. They included early (40-100 day) fetal losses (EFL) plus late term abortions and the birth of weak foals, referred to as late fetal losses (LFL). With no immediate explanation for the cause it was identified as Mare Reproductive Loss Syndrome (MRLS). Also reported during the month of May were an unusually high number of cases of unilateral uveitis and pericarditis among horses of all breeds, ages and sexes. Commencing the last week of April and early May 2002 cases of MRLS were also reported on a number of farms in central Kentucky albeit at a reduced level compared to 2001.

 

Clinical and Pathological Description of MRLS

Veterinarians specializing in equine reproductive practice began examining pregnant mares over 60 days of gestation during the last week of April 2001 utilizing ultrasonography to determine the sex of the fetus. They reported an unusually high number of fetuses were not viable, lacking a heart beat, plus the presence of cloudy, flocculent material in the allantoic and amniotic fluids. Subsequent examination of these cases confirmed the fetus was no longer present. At the same time the University of Kentucky Livestock Disease Diagnostic Center (UKLDDC), Lexington reported a significant increase in the number of late term abortions submitted for post mortem examination. The mare history indicated no premonitory signs. Approximately 550 LFL were submitted from 17 breeds of horses distributed over 32 counties in the state of Kentucky. Pathological lesions associated with these cases included inflammation of the umbilical cord (funitis) and amnion (amnionitis), pneumonia, fetal bacteremia and sometimes placentitis. The findings were suggestive of in utero fetal illness and distress but lacked specificity to permit diagnosis of the inciting cause. Bacterial cultures of the fetus and placenta yielded non-beta hemolytic Streptococci spp. and/or Actinobacillus spp. in over 50% and approximately 20% of the cases respectively. Figures on the number of EFL were less precise with estimates ranging from 20-30% of the pregnant mare population of Kentucky.  Registrations to the Jockey Club of foals born in 2002 provide an accurate figure for the Thoroughbred population in the state. As of September 2002 the Jockey Club reported 11,697 foal registrations, a reduction of 15% compared to the same period in 2001. Kentucky in recent years has produced an annual foal crop that represents 30% of North America’s yearly Thoroughbred foal population.

 

In addition to the reproductive losses an increased number of newborn foals suffering acute respiratory distress were admitted to the local equine veterinary hospitals. These cases required intensive veterinary and nursing care and 50% did not survive. Approximately 30 cases of unilateral uveitis or endophthalmitis involving hemorrhage and fibrin deposition were reported during May among horse of all breeds, ages and sexes. These cases did not respond to treatment leading to loss of sight in the affected eye. During the same time frame approximately 60 cases of pericarditis were reported again among horses of all breeds, ages and sexes. Clinical signs included fever, lethargy, anorexia and muffled heart sounds. Ultrasound examination of the heart revealed a fibrin layer on the epicardium and an abundant amount of fluid in the pericardium. Approximately half of the cases were submitted for post mortem examination at the UKLDDC where it was confirmed that the majority of horses with pericarditis had some degree of peritoneal, pleural and pericardial effusion. Subsequently cases of both eye and heart conditions were included within the ‘Case Definition’ of MRLS.

 

Case Definition of MRLS

  • Two major disease entities LFL and EFL were identified with MRLS which occurred between 4/24/2001 and 6/30/2001 and over a similar period in 2002.

  • In addition to reproductive losses, two other clinical syndromes, unilateral uveitis and pericarditis occurred during this time period.

During April and May 2002 an identical clinical and pathological picture re-emerged with cases of early and late fetal losses as well as cases of pericarditis and uveitis consistent with what was associated with MRLS in 2001. Numbers were significantly reduced as compared to 2001. Cases were less widespread and no cases were reported on farm pastures where there was a complete absence of the eastern tent caterpillar (Malacosoma americanum).

 

Table 1. MRLS Losses 2001/2002

 

 

Early Fetal (EFL)

Late Fetal (LFL)

Uveitis

Pericarditis

2001

2000-3000

550

approx 30

50-60

2002

approx 500

165

6

9

 

 

Epidemiological Studies Undertaken to Investigate MRLS

On May 7, 2001 a questionnaire was faxed to 280 members of the Kentucky Thoroughbred Farm Managers Club to determine the extent and impact of MRLS, particularly EFL on farms in five counties around Lexington. From 158 responses received by May 9 it was estimated that 678 (21%) of 3294 pregnant mares had experienced EFL between 42 and approximately 80 days gestation.

 

Following this preliminary survey an in depth field epidemiological study was organized based on a three tiered approach involving 133 farms, pastures on those farms and selected mare populations. Twenty-three volunteers conducted personal interviews of farm owners or managers during June 2001 using a prepared questionnaire previously forwarded to the farm. Data entry and analyses of this extremely comprehensive survey was performed by USDA APHIS personnel in Frankfort, Kentucky and the Centers for Epidemiology and Animal Health, Fort Collins, Colorado. Results indicated that a high incidence of EFL was associated with pregnant mares exposed to high or medium levels of eastern tent caterpillars and cherry trees, farms with a population of more than 50 mares, mares bred in February 2001.

 

Later in the year a number of case control studies were undertaken by Dr Noah Cohen of Texas A and M University and colleagues to identify risk factors associated with cases of pericarditis, EFL and LFL. Their findings indicated that exposure of mares to pasture predisposed to MRLS and also implicated the role of the eastern tent caterpillar.

 

A field study of pregnant mares exposed and not exposed to MRLS in 2001 were monitored through pregnancy to birth of the foal in 2002 by regular ultrasound examination of the fetus. The findings provided no evidence the syndrome exerted an abnormal effect on the fetus and on placental and foal weight at birth.

 

An extensive disease surveillance program for MRLS was established in 2002 incorporating weekly weather data, the number of fetal losses submitted to the UKLDDC, referrals of sick foals to local veterinary clinics and reports from veterinarians undertaking reproductive examinations of pregnant mares.

 

In June 2002 a further questionnaire was sent to members of the Thoroughbred Farm Managers Club seeking to identify farms which did and did not experience EFL in 2002. Of 92 farms, which responded 92.3% of mares, bred prior to April 1,2002 were still pregnant as of June 1.


Economic Impact

The Department of Equine Business at the University of Louisville was commissioned in the summer of 2001 by the Commonwealth of Kentucky, Office of the Governor to quantify the economic loss to the Kentucky equine breeding industry as a result of MRLS.  A survey of 1024 breeders and breeding farm operations involving Thoroughbreds, Standardbreds, Quarter Horses, Paint Horse, Saddlebreds and Tennessee Walking Horses accounting for 96% of all registered foals in the state was undertaken. A response rate of 28% was achieved. It was estimated that 9% of the 2001 foal crop and 26% of the 2002 crop was lost. The total economic loss over a four-year period 2000-2003 was estimated at $336 million.

 

Investigations into the Cause of MRLS in 2001

Preliminary observations indicated that reproductive losses occurred simultaneously over a wide area of central Kentucky on many different farms commencing during the latter part of April. This observation was more indicative of an environmental toxin as distinct from an infectious agent. Investigations by several laboratories have so far failed to implicate a primary disease pathogen. The numerous isolations of opportunistic bacteria were considered to be secondary invaders.  Initial investigations concentrated on the role of environmental toxins including mycotoxins, fungal endophytes, phytoestrogens and chemical compounds including cyanide. During late April and early May 2001 there was an unusually high emergence in central Kentucky of the eastern tent caterpillar, crawling on fence posts, pastures and buildings and filling water troughs and buckets. Field visits had identified the presence of cherry trees in or around pastures containing mares that had experienced MRLS. The majority of these trees containing ‘caterpillar tents’ had been denuded of leaves eaten by the caterpillars. The caterpillars had then left the trees crawling through pasture in search of a source of nutrition.

 

Numerous analyses of pasture and equine samples failed to implicate the role of known mycotoxins, fungal endophytes, phytoestrogens and other chemical compounds.

 

The abnormal weather pattern through April 2001 in central Kentucky comprising low rainfall, high temperatures, punctuated by severe frosts in mid April stimulated an investigation as to the possible involvement of weather as a trigger factor for MRLS. Examination of weather patterns archived by the College of Agriculture’s meteorologist Tom Priddy identified a similar pattern during April 1981. During 1980 and 1981 EFL were reported on a number of farms in central Kentucky among mares bred in February and March of those years.

 

Farm Monitoring and Recommendations for the Prevention of MRLS in 2002.

A monitoring program published by the University of Kentucky’s College of Agriculture for managing the risk of MRLS in 2002 was issued in the fall of 2001. Thirteen farms were selected as ‘sentinels’ on which pasture and mare (blood and urine) samples were obtained at intervals of two weeks from March 1 through June 30. Detailed records of animal and pasture histories were maintained and samples examined for a variety of environmental toxins. Where EFL or LFL cases occurred additional samples from the mare were obtained and the fetus if found submitted to the UKLDDC for examination. Contingency measures to reduce the risk of MRLS included minimizing or eliminating the exposure of pregnant mares to the eastern tent caterpillar, keeping pregnant mares away from cherry trees, frequent clipping of pastures on which pregnant mares grazed and offering hay to horses at pasture.

Research Projects

 

Several projects were undertaken during 2002 within the College of Agriculture as well as studies in collaboration with two local equine practices in Lexington, Hagyard-Davidson-McGee Associates and Rood and Riddle Equine Hospital. Finance for these projects was provided from federal funds, the local horse industry, the Grayson Jockey Club Foundation and many private sources.

 

Four challenge studies were completed involving the exposure of pregnant mares to the eastern tent caterpillar. The results of those studies are summarized in Table 2. For the first time it was possible to reproduce MRLS under experimental conditions. Information derived from field and experimental observations provides evidence as to the source of MRLS, involving the eastern tent caterpillar. It does not at this stage indicate cause but does narrow the field of investigation considerably. Additionally it does simplify the recommendations to horse owners and farm managers to reduce the incidence of the disease by controlling the incidence of the eastern tent caterpillar.

 

Table 2. Results of Experimental Challenge Studies involving the Eastern Tent Caterpillar, April- July 2002. 

 

Caterpillar/Frass

Frass

Control

Study No. 1

7/10

7/9

3/10

Study No. 2

3/8

0/8

1/8

Study No. 3

4/5

0/5

0/5

Study No. 4

6/6

 

0/5

 

 

Communications

In addition to investigating MRLS during 2001 a significant amount of time was spent in providing factual up to date information regarding the syndrome to the equine industry and the media, locally, nationally and internationally. The interest the syndrome generated and the voracious appetite for information proved to be a challenging and at times an almost overwhelming task. Early in May 2001 an MRLS web site to address these needs was established by the Department of Veterinary Science in collaboration with the Department of Agricultural Communications at www.uky.edu/Agriculture/VetScience/gluck1.htm. This has proved to be a useful and effective means of communication and by the end of 2001 had been accessed on 33,000 occasions.  The Department of Veterinary Science web site continues to be the primary source of information and by the end of March 2003 had been accessed on 48,000 occasions. The MRLS surveillance data referred in the section on epidemiological studies is updated weekly plus regular summaries of results from the monitoring program undertaken on the sentinel farms. Advice on management strategies to control MRLS including reduction of the eastern tent caterpillar population are also provided.

 

A ‘list server’ was established so that those who requested updates would receive them as they were posted. Several organizations including the Kentucky Association of Equine Practitioners, The Jockey Club and the Kentucky Thoroughbred Owners and Breeders regularly forward the information on their web site to members. Additionally the Bloodhorse and the Thoroughbred Times, two weekly equine publications, regularly post information on their websites and their journals. Overall coordination of the flow of information is vested in an Equine Industry Task Force comprising farm managers and owners representing several horse breeds, practicing equine veterinarians, USDA and state veterinarians and scientists from the University of Kentucky’s College of Agriculture. Guidance on the operation of the monitoring program and recommendations for control of MRLS is provided by a small ‘oversight group’ derived from members of the Task Force.

 

In August 2002, a Workshop to discuss information pertaining to MRLS was held at the Maxwell H. Gluck Equine Research Center sponsored by the Grayson Jockey Club Equine Research Foundation, Keeneland Association, and the University of Kentucky Equine Research Foundation.  The Proceedings to be published in the spring of 2003 provide a comprehensive review of current knowledge relating to MRLS.  A “Think Tank” sponsored by the Kentucky Association of Equine Practitioners was held in January 2003 focusing on procedures to identify the causal agent(s) of MRLS. 

 

Scientific Collaboration

This investigation has since April 2001 involved an enormous number of individuals at the industry, veterinary and scientific level. Each individual in their unique way has contributed to piecing together what has progressively become an increasingly complex puzzle. If and when the final picture is put together that identifies and controls MRLS it will be the result of a concerted and dedicated team effort.

 

Mare Reproductive Loss Syndrome Suggested Reading List

Following is a suggested reading list of articles, papers and other publications relevant to mare reproductive loss syndrome. The list is arranged in chronological order, with each year’s publications additionally arranged alphabetically by author.

 

The Morris Library at the Gluck Equine Research Center maintains and updates this list, as well as retaining copies of the various publications. For further information, to request an article be added to the list, or receive updates of the list please contact: Gracie Hale, Morris Library, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546. Phone: 859-257-1192 Fax: 859-257-8542, Email: ghale@uky.edu

 

1. Fitzgerald, T. D. The Tent caterpillars. Ithaca: Comstock Publishing Associates; 1995. (Cornell series in arthropod biology).

 

2. Mare reproductive loss syndrome. Journal of Equine Veterinary Science. 2001; 21(5):217-218.

 

3. Mare reproductive loss syndrome. Journal of Equine Veterinary Science. 2001; 21(12):587-588.

 

4. Bush, L. Mare reproductive loss syndrome (MRLS). In: Southern Extension and Research Activity Information Exchange Group-8. Tall Fescue Toxicosis Workshop; Chapel Hill, Tenn. s.l.: s.n.; 2001: 21-23.

 

5. Cohen, N.; Carey, V.; Donahue, J.; Seahorn, J.; Slovis, N., and Reimer, J.  Report of pericarditis case-control study: prepared for the Governor's Task Force on the Mare Reproductive Loss Syndrome.  2001.

 

6. Dwyer, R. M. MRLS epidemiological study. Equine Disease Quarterly. 2001; 10(1):5-6.

 

7. Gray, S. L.; Cross, D. L.; Gimenez, T.; Bridges, W. C.; McMillan, P. D., and Evans, P. Factors associated with mare reproductive loss syndrome in Central Kentucky and surrounding areas. In: Southern Extension and Research Activity Information Exchange Group-8. Tall Fescue Toxicosis Workshop; Chapel Hill, Tenn. s.l.: s.n.; 2001: 48-49.

 

8. Harrison, L. R. Kentucky equine abortion storm and related conditions. Proceedings of the United States Animal Health Association. 2001; (105):227-229.

 

9. Kane, E. and Kilby, E. Death in the Bluegrass: an epidemic of lost pregnancies, dead foals and sick horses strikes Central Kentucky and beyond, challenging researchers and veterinarians to identify the cause and staunch the unprecedented loss of equine lives. Equus. 2001; (287):60-68.

 

10. Powell, D. G. Commentary (MRLS). Equine Disease Quarterly. 2001; 10(1):1.

 

11. Powell, D. G. Mare reproductive loss syndrome (MRLS). Equine Disease Quarterly. 2001; 9(4):4-6.

 

12. Thalheimer, R. and Lawrence, R. G. The Economic loss to the Kentucky breeding industry from Mare Reproductive Loss Syndrome (MRLS) of 2001: prepared for the Office of the Governor, Commonwealth of Kentucky. 2001.

 

13. Mare reproductive loss syndrome. Journal of Equine Veterinary Science. 2002; 22(8):349-350.

 

14. Mare reproductive loss syndrome returns, but losses are fewer - Evidence further suggests that eastern tent caterpillar is culprit. Journal of the American Veterinary Medical Association. 2002; 221(2):179-180.

 

15. Asbury, A. C. MRLS Workshop. The Horse. 2002; 19(10):22.

 

16. Bain, F. T. and Williams, N. M. The Mare reproductive loss syndrome (MRSL): fetal and neonatal problems. In. Proceedings of the 2002 American College of Veterinary Internal Medicine Veterinary Medical Forum.; Dallas, Tex.  2002. Available at: http://www.vin.com/Members/Proceedings

 

17. Dwyer, R. M.; Garber, L.; Traub-Dargatz, J.; Meade, B., and Pavlick, M. Dissecting an outbreak of mysterious etiology: mare reproductive loss syndrome. In: Proceedings of the 2002 American College of Veterinary Internal Medicine Veterinary Medical Forum.; Dallas, Tex.  2002.

Available at: http://www.vin.com/Members/Proceedings

 

18. Dwyer, R. M.; Garber, L.; Traub-Dargatz, J.; Meade, B.; Pavlick, M., and Walker, J. An epidemiological investigation of mare reproductive loss syndrome: breaking ground on a new disease. Society for Veterinary Epidemiology and Preventive Medicine. 2002; 44-47.

 

19. Fitzgerald, T. D.; Jeffers, P. M., and Mantella, D. Depletion of host derived cyanide in the gut of the eastern tent caterpillar, Malacosoma americanum. Journal of Chemical Ecology. 2002; 28(2):257-268.

 

20. Green, E. M. MRLS outbreak response in Florida: the ripple effects. In: Proceedings of the 2002 American College of Veterinary Internal Medicine Veterinary Medical Forum.; Dallas, Tex.  2002. Available at: http://www.vin.com/Members/Proceedings

 

21. Kane, E. and Kilby, E. The plan pays off: 20/20 hindsight and targeted science guide Kentucky horse breeders through a foaling season free of ugly surprises. Equus. 2002; (299):54-61.

 

22. Morehead, J. P.; Blanchard, T. L.; Thompson, J. A., and Brinsko, S. P. Evaluation of early fetal losses on four equine farms in central Kentucky: 73 cases (2001). Journal of the American Veterinary Medical Association. 2002; 220(12):1828-1830.

 

23. Powell, D. G. Commentary (MRLS). Equine Disease Quarterly. 2002; 10(4):1.

 

24. Powell, D. G. Mare reproductive loss syndrome. Journal of Equine Veterinary Science. 2002; 22(3):108-110.

 

25. Powell, D. G. Mare reproductive loss syndrome (MRLS). In. Bluegrass Equine Reproduction Symposium; Lexington, Ky. Lexington: Hagyard-Davidson-McGee Associates, PLLC; 2002.

 

26. Powell, D. G. An Update on mare reproductive loss syndrome (MRLS) in Kentucky. In. Conference Proceedings Society for Theriogenology, American College of Theriogenologists;  Colorado Springs, Colo. Nashville: Society for Theriogenology; 2002: 147-152.

 

27. Priddy, T. MRLS degree days - what it means. Equine Disease Quarterly. 2002; 10(4):5-6.

 

28. Reimer, J. Pericarditis outbreak: management and prognosis. In. Proceedings of the 2002 American College of Veterinary Internal Medicine Veterinary Medical Forum.; Dallas, Tex.  2002.

Available at: http://www.vin.com/Members/Proceedings

 

29. Swerczek, T. W. Saprotrophic fungi and bacteria and commensal bacteria that infect frost-damaged pastures may be contributing to microbial overgrowth and lesions associated with the Mare Reproductive Loss Syndrome. Journal of Equine Veterinary Science. 2002; 22(6):234-236.

 

30. Taylor, J. R. Theory of ammonia toxicity as the mechanism of abortion in the Mare Reproductive Loss Syndrome. Journal of Equine Veterinary Science. 2002; 22(6):237-239.

 

31. Vince, K. J.; Riddle, W. T.; LeBlanc, M. M.; Estes, R., and Stromberg, A. J. Ultrasonographic appearance of fetal fluids between 55 and 176 days of gestation in the mare: effect of mare reproductive loss syndrome. Proceedings of the Annual Convention of the American Association of Equine Practitioners. 2002; (48):350-352.

 

32. Williams, N. M. Mare reproductive loss syndrome: pathologic findings. Equine Disease Quarterly. 2002; 10(4):4-5.

 

33. Brown, S. E. The MRLS mystery. The Horse. 2003; 20(2):66.

 

34. Cohen, N. D.; Carey, V. J.; Donahue, J. G.; Seahorn, J. L.; Donahoe, J. K.; Williams, D. M., and Harrison, L. R. Case-control study of late-term abortions associated with mare reproductive loss syndrome in central Kentucky. Journal of the American Veterinary Medical Association. 2003; 222(2):199-209.

 

35. Cohen, N. D.; Donahue, J. G.; Carey, V. J.; Seahorn, J. L.; Piercy, D.; Donahoe, J. K.; Williams, D. M.; Brown, S. E., and Riddle, T. W. Case-control study of early-term abortions (early fetal losses) associated with mare reproductive loss syndrome in central Kentucky. Journal of the American Veterinary Medical Association. 2003; 222(2):210-217.

 

36. Dwyer, R. M.; Garber, L. P.; Traub-Dargatz, J. L.; Meade, B. J.; Powell, D. G.; Pavlick, M. P., and Kane, A. J. A case-control study of factors associated with excessive proportions of early fetal losses associated with mare reproductive loss syndrome in central Kentucky during 2001. Journal of the American Veterinary Medical Association. 2003; 222(5):613-619.

 

37. Herbert, K. S. Pasture monitoring in Kentucky. The Horse. 2003; 20(2):16-17.