Mare reproductive loss syndrome
Reviewing the speed with which ETCs produced late-term abortions in 2002 experiments, the nonspecific bacterial infections in the placenta/fetus were assigned a primary driving role.
The question then became how exposure to the caterpillars produced these non-specific bacterial infections of the affected placenta/fetus and also the uveitis and pericarditis cases.
About 15% of cardiac output goes to the late-term fetus, at which point the septic barbed setal fragments are positioned to penetrate placental tissues which lack an immune response.
What became MRLS was first noted on April 26, 2001, by Dr. Thomas Riddle of Lexington, Kentucky, who observed an unusual number of equine in utero early fetal deaths in 60-day-old fetuses he was examining by ultrasound for sex determination.
Of foals conceived during the spring of 2000, and then close to term, at least 600 were lost, the so-called late fetal losses (LFLs).
[2][citation needed] Coincident with the MRLS syndrome in May 2001, Kentucky was experiencing an extraordinarily heavy infestation of eastern tent caterpillars (ETCs).
One to three days prior to the EFLs, several mares showed mild colic symptoms, abdominal straining, or low-grade fever.
Placentas were observed to carry a pale brown hue as opposed to their usual dark reddish-brown color.
[8][9][10] In 2002, investigators' attention was drawn to the highly toxic Brazilian Lonomia obliqua caterpillar setae and their enzymatic fibrinolysin toxin.
[13] The septic penetrating setal emboli (SPSE) hypothesis is the most probable mechanism of action for ETC exposure leading to MRLS.
[8] Reviewing the speed with which ETC dosing produced LFLs in controlled experiments and the barbed nature[1] of ETC hairs (setae),[14] and thereafter)[15] intestinal blood vessel penetration by barbed ETC setal fragments, followed by their systemic distribution following cardiac output (SPSE) and then distant tissue penetration by these distributed fragments to tissues with reduced immune responses, i.e., the early- and late-term fetus, the eye, and the heart/pericardial space/fluid, followed by bacterial proliferation in the reduced immune response tissue (fetus, eye, pericardial fluid) would both quantitatively account for and mechanistically link all four MRLS syndromes, including most particularly the unique and unprecedented single-eye lesions.
ETC setal fragments distributing bacteria to immune competent tissues, as occurred in all horses in central Kentucky during the ETC/MRLS do not appear to produce any observable clinical responses.
The probability of an MRLS event is, all other things being equal, directly related to the proportion of cardiac output delivered to the tissue in question.
In fact, based on the incidence of single-eye events, estimates of the actual number of circulating setal fragments on the order of ten per day, the small number of which accounts for the lack of clinical signs in ETC MRLS horses and the difficulty in culturing bacteria from the bloodstream of MRLS mares.
[8] The pathogenesis of MRLS was found[14] to depend simply on the mechanical properties of the barbed setal fragments and their ability to transport bacterial pathogens through the cardiovascular system and distribute them by tissue penetration to poorly immune-protected tissues such as the early and late fetus, the eye, and the pericardial fluid.
This proposed pathogenesis, SPSE hypothesis of MRLS, was communicated privately among colleagues and university administrators,[14] and then publicly at the Bain Fallon lectures, the Gold Coast, Australia, July 2002, and the following month to participants the First International Symposium on the Mare Reproductive Loss Syndrome.
In 2003 (Memorial Day Weekend), compelling statistical evidence in support of this probabilistic mechanism developed when a combined analysis of 2012 and 2013 LFL abortion rate data showed their time courses closely followed a probabilistic mathematical equation called accelerated failure time model (AFT).
[8][16] At about this time during the fall of 2003, colleagues who had been provided the prepublication draft of the AFT analysis paper were performing necropsies on pigs that had been dosed with ETCs.
Discussing rumors of these findings with Dr. Terry Fitzgerald, he noted that similar intestinal microgranulomas had been observed previously in ETC-dosed rats by colleagues experimenting with ETCs, and he shared some H and E section of such a rat intestinal ETC setal microgranuloma slides for inclusion in a second paper.
[8] A simple intuitive model of AFT analysis is to imagine what happens when a person armed with a machine gun appears at the door of a crowded ballroom and shoots randomly into the room.
However, if the shooter just happens to be shooting very slowly, then the time to the first death will be relatively longer and the frequency of hits is low, which is of course the longer "lag time period" and low frequency one sees with MRLS in a normal year when the caterpillars are rare (or an experimental dose of caterpillars is small).
She put Tobin in touch with the investigating veterinarian, Dr. Nigel Perkins, who at that time understood the Kentucky MRLS outbreak to be black cherry tree/cyanide-driven.
Considering the difficulty that certain groups in Kentucky had in accepting the theory of caterpillars causing MRLS, the long-time familiarity of a traditional camel-herding culture with the concept of caterpillar-driven abortions is interesting.
