Article — Artikel

Annual ryegrass toxicity in Thoroughbred horses in Ceres in the Western Cape Province, South Africa

J D Grewara, J G Allenb and A J Guthriea*

affected during the outbreak. The morbid- ABSTRACT ity rate on the farm was 6.7% (8/120), with An outbreak of annual ryegrass toxicity occurred on a Thoroughbred stud in Ceres in the a mortality rate of 1.7% (2/120) and a case Western Cape Province of South Africa. This is the 1st report of annual ryegrass toxicity fatality rate of 25 % (2/8). Seven of the in horses in South Africa, although the condition has been reported in cattle and sheep 8 cases were in the same paddock populations in the past. Annual ryegrass toxicity is characterised by a variety of neurological (Paddock 19) on the farm, and there was a signs including tremors, convulsions, recumbency and in many cases death. The description 29% (7/24) morbidity rate in this paddock. of the outbreak includes the history, clinical presentation and treatment protocol adminis- The only other case occurred in a paddock tered during the outbreak. Various epidemiological variables and their influence in the diagonally across from Paddock 19, and outbreak are also considered. the morbidity rate in this camp was 6.7% Keywords: annual ryegrass toxicity, horse, corynetoxins, neurological, magnesium (1/15). sulphate. Grewar J D, Allen J G, Guthrie A J Annual ryegrass toxicity in Thoroughbred horses in Clinical signs Ceres in the Western Cape Province, South Africa. Journal of the South African Veterinary The index case was initially thought to Association (2009) 80(4): 220–223 (En.). Equine Research Centre, Faculty of Veterinary be colic as the mare was found recum- Science, University of Pretoria, Private Bag X04, Onderstepoort, 0110 South Africa. bent, very uncomfortable and seemingly in pain. She had a severe tachycardia, a lack of borborygmi and severely con- INTRODUCTION The 1st reported cases of ARGT in gested oral mucous membranes. When Annual ryegrass toxicity (ARGT) is an horses occurred in Western and the mare displayed severe convulsions often fatal disease of livestock following were described in 19968. Three different the stud manager opted for euthanasia. ingestion of annual ryegrass (Lolium farms near Perth were affected, 5 horses All other cases developed hypermetria rigidum) seed heads which have been died or were euthanased and 2 affected and cerebellar ataxia, and 5 became contaminated by corynetoxin-producing horses survived following treatment. The recumbent. Some recumbent horses Rathayibacter toxicus through this bacte- authors also indicated that similar cases of developed convulsions with paddling of rium’s association with the nematode ARGT in horses had occurred in South the limbs. None of the cases had an Anguina funesta1. The corynetoxins pro- Australia. In addition, 11 horses died in an elevated temperature. At least 2 horses’ duced are tunicaminyluracil antibiotics outbreak of flood plain staggers during clinical signs became apparent after they which are toxic due to their inhibition of 1991 in New South Wales, Australia9. This had been removed from their original protein glycosylation15. The disease disease is produced by the same toxins paddocks and stabled. Both of the fatali- causes significant central nervous sys- that cause ARGT and occurs when stock ties were mares that were euthanased tem-associated clinical signs that are often eat blown grass (Lachnagrostis filiformis, due to severe clinical signs. Two horses preceded by stressful activities6. These formerly avenacea) infected with relapsed within 6 days of the original signs are owing to cerebellar interstitial R. toxicus that is vectored by the nematode clinical signs but on both occasions re- oedema caused by vascular leakage result- Anguina paludicola5. Equine cases of ARGT sponded to treatment and recovered ing from endothelial damage by the have not been described in South Africa. fully. toxins3,4,12,13. This disease is highly preva- Time to clinical response after treatment lent in certain areas of Australia where CASE HISTORY was varied but, in general, the attending outbreaks occur regularly in sheep and The ARGT outbreak occurred on a veterinarians felt that cases responded cattle populations. ARGT has been Thoroughbred breeding stud farm on the well. The shortest recorded period of described in South Africa, with reports of outskirts of Ceres in the Western Cape clinical response after treatment was high mortalities in sheep near Caledon in Province in South Africa. This region has a 20 min, and in this case the horse was 1979 and 3 more outbreaks in cattle in winter rainfall period that gives rise to recumbent at the time of treatment. Two 1980, all in the Western Cape Province20. the occurrence of wild annual ryegrass other cases took between 1 and 1.5 h to One of the outbreaks in cattle was near throughout the region. The farm involved show visible signs of improvement and Prince Albert Hamlet, which is within fed locally produced oaten hay as rough- 1 animal only stood up from recumbency 10 km of Ceres. age to all mares throughout the summer 6 h after treatment. In the last case the aEquine Research Centre, Faculty of Veterinary Science, months in 2008/2009. The outbreak mare only allowed her foal to suckle the University of Pretoria, Private Bag X04, Onderstepoort, commenced on 7 February 2009 and the day following treatment. 0110 South Africa. bDepartment of Agriculture and Food, Western Australia, last new case was seen on 11 February 2009. A post mortem was not performed on the Locked Bag 4, Bentley Delivery Centre, WA, 6983, The morbidity of the disease decreased index case in the outbreak; however, a full Australia. dramatically following removal of the post mortem was performed on the mare *Author for correspondence. E-mail: [email protected] oaten hay on 8 February 2009. that was euthanased on 8 February 2009. Received: July 2009. Accepted: October: 2009. Six mares, 1 colt and 1 yearling filly were This mare presented with cerebellar

220 0038-2809 Tydskr.S.Afr.vet.Ver. (2009) 80(4): 220–223 ataxia that included hypermetria and weight for these horses. In general the the removal of the toxic feedstuff, indicat- incoordination. She later collapsed and dose used was approximately 100 mg/kg. ing that a continual intake of the toxin is had muscle fasciculation while recumbent The recommended route of administra- required for clinical signs to develop. and had a seizure prior to sedation and tion of this drug is subcutaneous but no An important consideration in this eventual euthanasia. On post mortem a negative effects of intravenous adminis- outbreak is that cutting of the oat crop moderate pulmonary oedema was found tration were noted during the outbreak. was delayed by 2–3 weeks. This additional with mild hydropericardium and The MgSO4 treatment was repeated as period would have allowed the ryegrass subendocardial haemorrhage in the left required if animals continued to show to complete reproduction and the ventricle. A haemorrhagic ascites was also any central nervous signs. A dose was also seed heads to reach full maturity. Toxin noted and the bladder had prolapsed given in the evening to affected animals production within the bacterial galls com- through the vagina prior to euthanasia. as a prophylactic against convulsions mences during flowering, rapidly increases Histopathological examination of repre- during the night. Other drugs used in- during seed set, and the maximum con- sentative coronal sections of the brain cluded 1 mg/kg flunixin meglumine centrations of toxin are reached at the showed no specific lesions. (Finadyne®, Shering-Plough AH) as well time that the seeds become fully mature22. as approximately 0.08 mg/kg dexametha- In addition, conditions for ryegrass Diagnosis sone sodium phosphate (Calvasone, growth within the oat crop may have The diagnosis was based on the presence Norbrook®). Recumbent animals were varied due to contouring in the field, of central nervous system associated treated with a regimen of intravenous causing run-off water to concentrate in clinical signs that are typical of ARGT7 and fluids which included dimethyl sulphoxide different sections. As the crop was cut the positive identification, by the Stellen- and Norcal PMD (Norbrook®). The latter sequentially and the bales taken to storage bosch Provincial Veterinary Laboratory, contains calcium borogluconate, dextrose in the order that they were prepared, of seeds contaminated with bacterial and magnesium hypophosphite. In there may have been groups of bales in galls, found within bales of oaten hay 2 cases which were severely affected and the storage facility that contained greater being fed to the horses. deemed to be in severe shock, a combina- levels of ryegrass seed. These groups of tion of 100 mg per horse of prednisolone bales may therefore have contained Epidemiological considerations sodium succinate (Solu-Delta-Cortef®, higher levels of toxin and could have been A 4.5 ha, contoured field of farmland Pfizer AH) and 500 to 1000 m per horse of fed closer to the time of the outbreak. was hired in Ceres by the stud for the hydroxyethyl starch (HAES-steril® 6%, All the horses on the farm were fed purpose of planting oats and making Fresenius Kabi) was administered intra- the contaminated hay, but ARGT only oaten hay. The cutting of the crop was venously. All cases received a standard became apparent in 2 paddocks. A possible delayed for 2–3 weeks due to late seasonal vitamin and mineral supplement which explanation for this is that the wild rains and was baled soon after 26 Novem- included sodium glycerophosphate and ryegrass in these paddocks was also toxic. ber 2008. The affected oaten hay was fed vitamins B12, B6 and B5 (Kyrophos As this ryegrass was not examined for for 9 weeks, from the time it was baled Metabolic-V, Kyron Laboratories). seeds contaminated with bacterial galls it until the 2nd day of the outbreak. The is not known whether this was the case. timeline associated with this outbreak DISCUSSION However, it takes several years for the was consistent with a toxin exposure, as This is the 1st description of ARGT in populations of the nematode and bacte- the cases showed a clear indication of horses in South Africa. The outbreak rium in annual ryegrass to reach levels a point epidemic. The mode of cases described has similarities to an outbreak that present a risk to livestock11. occurred on the same day as the index of ARGT in horses previously described in It was evident to the farm management case on 7 February 2009. The 2nd day of Western Australia8. The clinical manifes- and attending veterinarians during this the outbreak gave rise to 3 cases with a tations of the disease were similar and outbreak that clinical signs were precipi- single case occurring on 11 February. The both were associated with a specific tated by stress, particularly during the affected oaten hay was removed on 8 source of toxin and feeding of this source afternoon. February is one of the hotter February. for a specific period. This period may months of the year in the Western Cape The feeding pattern of the affected range from several days to weeks in dura- Province and it is likely that the high oaten hay was consistent for all paddocks. tion14 and depends on the level of contam- temperatures, particularly in the after- The hay was fed on the ground and ination of the source and the quantity noon, contributed to the stress that led to always in the same position within each being fed. In the outbreak described here clinical manifestation of ARGT. Weather paddock. Annual ryegrass is a weed that the affected oaten hay was fed for 9 weeks data from the nearest weather station is found throughout the province on prior to the outbreak, and had been fed (Worcester, 34.2 km away) revealed that roadsides and grows sporadically on for a similar period to most of the horses 7 February 2009, the day the outbreak many farms. Wild ryegrass in the paddocks on the farm. began, was the hottest day of the year to on the affected farm was not examined for The corynetoxins produced by R. toxicus24 date, with a maximum of 37.3 °C and a the presence of seeds contaminated with are cumulative toxins in spite of having a minimum of 20.5 °C. The thermoneutral bacterial galls. short (4-hour) plasma half-life14,21. It seems zone of horses falls between 5 and 25 °C17 an anomaly to have a point epidemic due so in the prevailing environmental condi- Treatment to a cumulative toxin but the sudden onset tions these horses were under some degree Horses showing clinical signs of ARGT of the outbreak of ARGT described here is of heat stress. Wind speed data were not were immediately treated with magnesium typical of many of the outbreaks of ARGT available for Ceres. sulphate (MgSO4 50 %, Kyron Laborato- seen in all species in Australia and is prob- Two horses relapsed within a week and ries) solution intravenously using a treat- ably due to the disease requiring a the treatment regimen was reinstated ment regimen previously described for stress-associated trigger1,6. In this outbreak based on the severity of the clinical signs. horses with annual ryegrass toxicity environmental temperature was thought This is a reasonably high proportion (ARGT)8. The initial dosage ranged from to be a likely trigger. In the current out- given that 2 of the 8 cases were eutha- 60–200 mg/kg using 500 kg as an average break, only 1 clinical case occurred after nased due to poor prognosis and were

0038-2809 Jl S.Afr.vet.Ass. (2009) 80(4): 220–223 221 therefore not candidates for a relapse. safe18. Nevertheless, use of HES in ARGT REFERENCES This clinical feature must be taken into cases should be considered with caution 1. Allen J G 2004 Annual ryegrass toxicity. consideration in the event of other ARGT until more is understood about the extent In Plumlee K H (eds) Clinical veterinary toxicology. Mosby, St Louis, Missouri: 422– outbreaks. Of the 42 mares on the farm of damage to the cerebellar vasculature in 424 during the outbreak, 40 were pregnant, this disease. If the damage is extensive 2. Bath G, de Wet J 2000 Annual rye grass and while abortion was not seen in enough to allow HES across the blood toxicity. In Bath G, de Wet J (eds) Sheep and this outbreak it has occurred in ovine brain barrier the disease will be exacer- goat diseases. Tafelberg Publishers, Cape cases of ARGT in the past2,20. bated, as more fluid will be drawn into Town: 137–140 3. Berry P H, Howell J M, Cook R D 1980 No specific antitoxin or antidote against the cerebellar interstitium. Morphological changes in the central the corynetoxins produced by R. toxicus is nervous system of sheep affected with available, so symptomatic treatment is all experimental annual ryegrass (Lolium CONCLUSION that can be attempted in cases of ARGT.In rigidum) toxicity. Journal of Comparative ARGT is well known and described in Pathology 90: 603–617 this outbreak MgSO4 was used to prevent Australia. It has been described to a lesser 4. Berry P H, Howell J M, Cook R D, Richards muscle contractions associated with con- degree in South Africa, possibly owing to R B, Peet R L 1980 Central nervous system vulsions. This salt is used in human medi- misdiagnosis or a lack of reporting. The changes in sheep and cattle affected with cine to prevent the convulsions associated natural or experimental annual ryegrass circumstances leading to this outbreak with eclampsia and it acts by preventing toxicity. Australian Veterinary Journal 56: were as follows: later than usual cutting the release of acetylcholine at the neuro- 402–403 19 and baling of the oaten hay led to maxi- 5. Bertozzi T, Davies K A 2009 Anguina muscular junction (NMJ) . During out- mum toxicity in the affected ryegrass paludicola sp. n. (Tylenchida: Anguinidae): breaks of ARGT in sheep and cattle the nematode associated with Rathayibacter within the hay; heat stress, associated generally only clinically affected animals toxicus infection in Polypogon monspeliensis with the very hot weather in February, and in Australia. are treated with MgSO4. Since horses are Lachnagrostis filiformis provided a stress trigger; increased toxin more valuable and found in smaller Zootaxa 2060: 33–46 ingestion just prior to the clinical out- 6. Botha C J, Venter E 2002 Annual rye grass numbers it is probably advisable to treat break may have occurred because specific In Plants poisonous to livestock southern Africa all horses potentially exposed to the toxin (CD ROM). Department of Paraclinical bales contained higher concentrations of as it is inexpensive and could provide a Sciences, Faculty of Veterinary Science, form of prophylaxis to prevent develop- toxin. Once the disease was diagnosed University of Pretoria, Pretoria. ment of the clinical signs. It is important and the toxic hay removed, the morbidity 7. Bourke C A 1994 Tunicaminyluracil toxicity, of the disease decreased rapidly, with only an emerging problem in livestock fed grass not to use MgSO4 concurrently with 1 new case and 2 relapses occurring. The or cereal products. In Colegate S M, Dorling calcium because this provides a greater P R (eds) -associated toxins: agricultural, source of Ca2+ at the NMJ, which decreases treatment of ARGT was symptomatic, but phytochemical and ecological aspects. CAB In- the effectiveness of Mg2+ in preventing it is important to consider treating all po- ternational, Wallingford, Oxon: 399–404 muscle contraction19. The attending tentially in-contact horses with MgSO4 8. Creeper J H, Vale W, Walsh R 1996 Annual ryegrass toxicosis in horses. Australian veterinarians also recommend the use of during an outbreak. Avoiding the use of calcium as part of the the treatment Veterinary Journal 74: 465–466 an indwelling intravenous catheter for 9. Davis E O, Curran G E, Hetherington W T, regimen should also be considered. The the MgSO4 treatment as it decreases Norris D A, Wise G A, Roth I J, Seawright the stress associated with repeated injec- use of anti-inflammatory drugs may be A A, Bryden W L 1995 Clinical, pathological tions. useful to reduce inflammation associated and epidemiological aspects of flood plain staggers, a corynetoxicosis of livestock Flunixin meglumine has anecdotally with muscle damage due to convulsions. Should the causative organisms of ARGT grazing Agrostis avenacea. Australian Veteri- been used to good effect in cattle affected nary Journal 72: 187–190 by ARGT in Australia (JGA, pers. obs.) and become more widespread, horse owners 10. Dieterich H J, Reutershan J, Felbinger T W, South Africa (P le Roux, private veterinar- should ensure that the hay they feed and Eltzschig H K 2003 Penetration of intrave- ian, pers. comm., 2009). Although no the ryegrass in paddocks are both free of nous hydroxyethyl starch into the cerebro- spinal fluid in patients with impaired specific reason for this being effective was toxic seed galls. Currently the Stellen- bosch Provincial Veterinary Laboratory blood–brain barrier function. Anesthesia & obvious, the anti-inflammatory proper- Analgesia 96: 1150–1154 ties of this drug may have limited the visually examines ryegrass seed for the 11. Finnie J W 2006 Review of corynetoxins toxic bacterial galls. In Australia an ELISA poisoning of livestock, a neurological muscle damage caused by clonic and 16 tonic contractions. for the bacterium is used commercially disorder produced by a nematode-bacterium 23 complex. Australian Veterinary Journal 84: In the current outbreak, HES (hydroxy- and an ELISA for the corynetoxins has also been developed. It may be worth 271–277 ethyl starch) was used to treat horses with 12. Finnie J W, Mukherjee T M 1987 Ultra- signs of shock. As starch increases the implementing these assays in South structural changes in cerebral blood vessels osmotic pressure in the blood, interstitial Africa. of sheep injected with tunicamycin. Journal fluid is drawn into blood vessels, increas- of Comparative Pathology 97: 217–220 ACKNOWLEDGEMENTS 13. Finnie J W, O’Shea J D 1988 Pathological ing blood volume and therefore increas- and pathogenetic changes in the central ing mean arterial blood pressure. In The authors wish to thank the Ceres nervous system of guinea pigs given humans, there is evidence that HES does Veterinary Hospital, in particular Drs tunicamycin. Acta Neuropathologica 75: not cross damaged blood-CSF barriers Freeman and Wium, for their referral and 411–421 but it is still not clear whether it crosses assistance. Thanks also to Dr P le Roux 14. Jago M V, Culvenor C C 1987 Tunicamycin 10 and corynetoxin poisoning in sheep. Aus- the blood brain barrier . If HES crossed (private practitioner), Dr J C Stroebel tralian Veterinary Journal 64: 232–235 the blood-brain barrier in horses with (Stellenbosch Provincial Veterinary 15. Jago M V,Payne A L, Peterson J E, Bagust T J ARGT it might cause a greater osmotic pres- Laboratory), Dr J. Myburgh (University of 1983 Inhibition of glycosylation by coryne- sure within the already compromised in- Pretoria) and Dr P.J. Pieterse (University toxin, the causative agent of annual rye- terstitial tissue. Studies in humans have, of Stellenbosch) who assisted the consult- grass toxicity: a comparison with tunica- mycin. Chemico-Biological Interactions 45: however, shown that the use of HES to ing veterinarians during the outbreak. 223–234 improve cranial blood pressure in patients Thanks also to the South African Weather 16. Masters A M, Gregory A R, Evans R J, with severe cranio-cerebral injury is Service. Speijers J E, Sutherland S S 2006 An

222 0038-2809 Tydskr.S.Afr.vet.Ver. (2009) 80(4): 220–223 enzyme-linked immunosorbent assay for 19. Sadeh M 1989 Action of magnesium sulfate 23. Than K A, Cao Y, Michalewicz A, Edgar J A the detection of Rathayibacter toxicus, the in the treatment of preeclampsia-eclampsia. 1998 Development of an immunoassay for bacterium involved in annual ryegrass Stroke 20: 1273–1275 corynetoxins. In Garland T, Barr A C (eds) toxicity, in hay. Australian Journal of Agricul- 20. Schneider D J 1981 First report of annual Toxic plants and other natural toxicants. CAB tural Research 57: 731–742 ryegrass toxicity in the Republic of South International, Wallingford, Oxon: 49–54 17. Morgan K 1998 Thermoneutral zone and Africa. Onderstepoort Journal of Veterinary 24. Vogel P,Petterson D S, Berry P H, Frahn J L, critical temperatures of horses. Journal of Research 48: 251–255 Anderton N, Cockrum P A, Edgar J A, Jago Thermal Biology 23: 59–61 21. Stuart S J, Leury B J, Edgar J A 1992 Plasma M V, Lanigan G W, Payne A L, Culvenor 18. Neff T A, Doelberg M, Jungheinrich C, clearance of tritiated-tunicamycin in sheep. C C 1981 Isolation of a group of glycolipid Sauerland A, Spahn D R, Stocker R 2003 Proceedings of the Nutrition Society of Austra- toxins from seedheads of annual ryegrass Repetitive large-dose infusion of the novel lia 17: 137–137 (Lolium rigidum Gaud.) infected by Coryne- hydroxyethyl starch 130/0.4 in patients 22. Stynes B A, Bird A F 1983 Development of bacterium rathayi. Australian Journal of Experi- with severe head injury. Anesthesia & annual ryegrass toxicity. Australian Journal mental Biology and Medical Science 59: Analgesia 96: 1453–1459 of Agricultural Research 34: 653–660 455–467

0038-2809 Jl S.Afr.vet.Ass. (2009) 80(4): 220–223 223