The mare reproductive loss syndrome and the eastern tent caterpillar: a toxicokinetic/statistical analysis with clinical, epidemiologic, and mechanistic implications.

Manu Sebastian, University of Kentucky
Marie G Gantz, University of Kentucky
Thomas Tobin, University of Kentucky
J Daniel Harkins, University of Kentucky
Jeffrey M Bosken, University of Kentucky
Charlie Hughes, University of Kentucky
Lenn R Harrison, University of Kentucky
William V Bernard, Rood and Riddle Equine Hospital
Dana L Richter, Michigan Technological University
Terrence D Fitzgerald, SUNY Cortland

*Published as #331 from the Equine Pharmacology, Therapeutics, and Toxicology Program at the Maxwell H. Gluck Equine Research Center and the Department of Veterinary Science, University of Kentucky and Kentucky Agricultural Experiment Station Article #03-14-102 with the approval of the Dean and Director, College of Agriculture and Kentucky Agricultural Experiment Station. Supported by grants from the USDA Agriculture Research Service Specific Cooperative Agreement #58-6401-2-0025 for Forage-Animal Production Research, the Kentucky Department of Agriculture, the Kentucky Thoroughbred Association Foundation, the Horsemen’s Benevolent and Protective Association, and Mrs. John Hay Whitney. ©Thomas Tobin

Abstract

During 2001, central Kentucky experienced acute transient epidemics of early and late fetal losses, pericarditis, and unilateral endophthalmitis, collectively referred to as mare reproductive loss syndrome (MRLS). A toxicokinetic/statistical analysis of experimental and field MRLS data was conducted using accelerated failure time (AFT) analysis of abortions following administration of Eastern tent caterpillars (ETCs; 100 or 50 g/day or 100 g of irradiated caterpillars/day) to late-term pregnant mares. In addition, 2001 late-term fetal loss field data were used in the analysis. Experimental data were fitted by AFT analysis at a high (P < .0001) significance. Times to first abortion (“lag time”) and abortion rates were dose dependent. Lag times decreased and abortion rates increased exponentially with dose. Calculated dose × response data curves allow
interpretation of abortion data in terms of “intubated ETC equivalents.” Analysis suggested that field exposure to ETCs in 2001 in central Kentucky commenced on approximately April 27, was initially equivalent to approximately 5 g of intubated ETCs/day, and increased to approximately 30 g/day at the outbreak peak. This analysis accounts for many aspects of the epidemiology, clinical presentations, and manifestations of MRLS. It allows quantitative interpretation of experimental and field MRLS data and has implications for the basic mechanisms underlying MRLS. The results support suggestions that MRLS is caused by exposure to or ingestion of ETCs. The results also show that high levels of ETC exposure produce intense, focused outbreaks of MRLS, closely linked in time and place to dispersing ETCs, as occurred in central Kentucky in 2001. With less intense exposure, lag time is longer and abortions tend to spread out over time and may occur out of phase with ETC exposure, obscuring both diagnosis of this syndrome and the role of the caterpillars.