Mycotoxicoses of ruminants and horses

http://vdi.sagepub.com/Investigation

Journal of Veterinary Diagnostic

http://vdi.sagepub.com/content/25/6/692The online version of this article can be found at:

DOI: 10.1177/1040638713504572

2013 25: 692 originally published online 3 October 2013J VET Diagn InvestSchild

Franklin Riet-Correa, Rodolfo Rivero, Ernesto Odriozola, Maria de Lourdes Adrien, Rosane M. T. Medeiros and Ana LuciaMycotoxicoses of ruminants and horses

Published by:

http://www.sagepublications.com

On behalf of:

Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

can be found at:Journal of Veterinary Diagnostic InvestigationAdditional services and information for

http://vdi.sagepub.com/cgi/alertsEmail Alerts:

http://vdi.sagepub.com/subscriptionsSubscriptions:

http://www.sagepub.com/journalsReprints.navReprints:

http://www.sagepub.com/journalsPermissions.navPermissions:

What is This?

- Oct 3, 2013OnlineFirst Version of Record

- Nov 7, 2013Version of Record >>

at St Petersburg State University on December 8, 2013vdi.sagepub.comDownloaded from at St Petersburg State University on December 8, 2013vdi.sagepub.comDownloaded from

http://vdi.sagepub.com/


http://vdi.sagepub.com/content/25/6/692

http://vdi.sagepub.com/content/25/6/692



http://www.aavld.org

http://www.aavld.org

http://vdi.sagepub.com/cgi/alerts

http://vdi.sagepub.com/cgi/alerts

http://vdi.sagepub.com/subscriptions

http://vdi.sagepub.com/subscriptions

http://www.sagepub.com/journalsReprints.nav

http://www.sagepub.com/journalsReprints.nav

http://www.sagepub.com/journalsPermissions.nav

http://www.sagepub.com/journalsPermissions.nav

http://vdi.sagepub.com/content/25/6/692.full.pdf

http://vdi.sagepub.com/content/25/6/692.full.pdf

http://vdi.sagepub.com/content/early/2013/10/03/1040638713504572.full.pdf

http://vdi.sagepub.com/content/early/2013/10/03/1040638713504572.full.pdf

http://online.sagepub.com/site/sphelp/vorhelp.xhtml

http://online.sagepub.com/site/sphelp/vorhelp.xhtml





Journal of Veterinary Diagnostic Investigation25(6) 692 –708© 2013 The Author(s)Reprints and permissions: sagepub.com/journalsPermissions.navDOI: 10.1177/1040638713504572jvdi.sagepub.com

Review Article

Introduction

Mycotoxicoses are important diseases of ruminants and horses. In South America, where pastoral farming systems predominate, there have been a number of studies published regarding mycotoxicoses of ruminants and horses; however, most of this information has been published in Spanish or Portuguese in journals of limited circulation or in meeting proceedings. The current review reports the epidemiology, clinical signs, and pathology of the main mycotoxicoses affecting livestock, mainly in South America, with an empha-sis on the information necessary for the diagnosis of poison-ing (Tables 1, 2). Comparisons are also made with the occurrence of the same mycotoxicoses on other continents. A description of the details of the laboratory techniques for toxin detection is beyond the scope of this review.

Poisoning by indole-diterpenoid mycotoxins

The 3 main grasses that cause tremorgenic syndrome due to the presence of indole-diterpenoid alkaloids are Paspalum spp., Cynodon dactylon, and Lolium perenne. Paspalum staggers occurs when Claviceps paspali invades the unfertil-ized ovaries of Paspalum spp. during flowering time, replac-ing them with a mass of fungal tissue named sclerotia (Fig. 1A).66 The main indole-diterpenoid tremorgens in C. paspali are paspalinine and paspalitrems A–C.17 This

mycotoxicosis occurs in southern Brazil,66 Uruguay,56 Argen-tina,36 the United States,17 Australia,39 New Zealand,80 Europe,5,44 and South Africa.9,81 Several species of Paspalum can be infected by C. paspali, including Paspalum dilatatum Poiret, Paspalum notatum Flügge, Paspalum distichum L. (syn. Paspalum paspalodes [Michx.] Scribne), Paspalum vaginatum Sw, Paspalum scrobiculatum L., and Paspalum urvillei Steud. In South America and other countries of the southern hemisphere, poisoning occurs from the end of Feb-ruary until early June (i.e., between the end of summer and the start of autumn), when Paspalum spp. is seeding. The disease occurs mainly in rice stubbles 1–2 years after harvest, in cultivated pastures 3–4 years after establishment when the

504572 VDIXXX10.1177/1040638713504572Mycotoxicoses of ruminants and horsesRiet-Correa et al.research-article2013

From the Hospital Veterinário, Centro de Saúde e Tecnologia Rural, Universidade Federal de Campina Grande, Patos, Paraíba, Brazil (Riet-Correa, Medeiros); Dirección de Laboratorios Veterinarios “Miguel C. Rubino”, Laboratorio Regional Noroeste, Ministério de Ganadería, Agricultura y Pesca, Paysandú, Uruguay (Rivero); Instituto Nacional de Tecnología Agropecuaria, Estación Experimental Agropecuaria Balcarce, Balcarce, Argentina (Odriozola); Facultad de Veterinária, Universidad de la República, Estación Mario Cassinoni, Paysandú, Uruguay (Adrien); and Laboratório Regional de Diagnóstico, Faculdade de Veterinária, UFPel, Pelotas, Rio Grande do Sul, Brazil (Schild).

1Corresponding Author: Franklin Riet-Correa, Veterinary Hospital, Centro de Saúde e Tecnologia Rural, Federal University of Campina Grande, Campus de Patos, Patos, Paraíba 58700-000, Brazil. [email protected]

Mycotoxicoses of ruminants and horses

Franklin Riet-Correa,1 Rodolfo Rivero, Ernesto Odriozola, Maria de Lourdes Adrien, Rosane M. T. Medeiros, Ana Lucia Schild

Abstract. In the current study, mycotoxicoses of ruminants and horses are reviewed, with an emphasis on the occurrence of these diseases in South America. The main mycotoxicoses observed in grazing cattle include intoxications by indole-diterpenoid mycotoxins (Paspalum spp. contaminated by Claviceps paspali, Lolium perenne infected by Neotyphodium lolii, Cynodon dactylon infected by Claviceps cynodontis, and Poa huecu), gangrenous ergotism and dysthermic syndrome (hyperthermia) caused by Festuca arundinacea (syn. Festuca elatior) infected by Neotyphodium coenophialum (syn. Acremonium coenophialum), and photosensitization in pastures contaminated by toxigenic Pithomyces chartarum. Other mycotoxicoses in grazing cattle include slaframine toxicity in clover pastures infected by Rhizoctonia leguminicola and diplodiosis in cattle grazing in corn stubbles. The mycotoxicoses caused by contaminated concentrated food or byproducts in cattle include poisoning by toxins of Aspergillus clavatus, which contaminate barley or sugar beetroot by-products, gangrenous ergotism or dysthermic syndrome caused by wheat bran or wheat screenings contaminated with Claviceps purpurea, and acute respiratory distress caused by damaged sweet potatoes (Ipomoea batatas). The main mycotoxicosis of horses is leukoencephalomalacia caused by the fumonisins B1 and B2 produced by Fusarium spp. Poisoning by C. purpurea and F. elatior infected by N. coenophialum has also been reported as a cause of agalactia and neonatal mortality in mares. Slaframine toxicosis caused by the ingestion of alfalfa hay contaminated by R. leguminicola has also been reported in horses.

Key words: Aspergillus clavatus; ergotism; indole-diterpenoid mycotoxins; Ipomoea batatas; leukoencephalomalacia; Pithomyces chartarum; slaframine.

at St Petersburg State University on December 8, 2013vdi.sagepub.comDownloaded from



Mycotoxicoses of ruminants and horses 693

Paspalum spp. substitute the species planted, and in natural pastures with highly fertile soil, such as marshy or irrigated areas.36,56,66 Cattle of various ages and categories, as well as buffalo5 and horses,15 can be affected.

Poisoning by consumption of C. dactylon L. has been reported in cattle in Uruguay,57,70 Argentina,46 the United States,16 and South Africa81 and in horses in California.16 In South Africa, it was determined that the toxicity of this spe-cies was due to infection with Claviceps cynodontis, which contains a mixture of indole-diterpenes, of which paspalit-rems A and B, as well as paspaline and paspalinine, repre-sented major constituents.81 In the South American countries, the disease occurs mainly in the winter months (July and August) when the seeding plant is dry due to severe frosts. Cynodon dactylon is a weed of pastures, crops, and degraded areas. Poisoning occurs mainly in pastures severely invaded by C. dactylon, where this plant becomes the only grass available.

Ryegrass staggers is caused by the endophytic fungi Neotyphodium lolii (syn. Acremonium lolii) in perennial rye-grass (Lolium perenne).75,80 The main indole-diterpenoid tremorgens found in L. perenne are paxilline and lolitrems, primarily lolitrem B,23,30,71,80 which are believed to act on

γ-aminobutyric acid receptors disrupting neuromuscular control.43 Neotyphodium lolii also produce ergopeptide alka-loids, which have been associated with reduced milk produc-tion due to prolactin depression in cattle and sheep, hyperthermia and heat stress in sheep during the summer, and other signs such as reduction of weight gains and fecal contamination of wool (dags) in lambs (Duringer JM, DeLorme MJM, Lehner A, et al.: 2007, A review of the ergot alkaloids found in endophyte-infected tall fescue and perennial rye-grass and their metabolism after ingestion by livestock. In: Proceedings of the 6th International Symposium on Fungal Endophytes of Grasses: no. 13. Fungal endophytes of grasses, ed. Popay AJ, Thom ER, pp. 377–382. Dunedon New Zea-land Grassland Association, New Zealand).23,30,80 Neotypho-dium lolii also produces peramine, which confers resistance against insects including the Argentine stem weevil (Lis-tronotus bonariensis).23,71,80 Ryegrass staggers occurs fre-quently in New Zealand and Australia but has been reported in the United States, Europe, South Africa, and Argentina in sheep, cattle, deer, and horses.47,80 The effects of ryegrass staggers are most serious during the summer and autumn, when the shortage of forage forces livestock to ingest the basal sheath region of the plant, which contains the highest

Table 1. Main features for the diagnosis of mycotoxicosis in grazing livestock in South America.*

Disease/agentSpecies affected Substrate/toxin Epidemiology Clinical signs Pathology Diagnosis

Ryegrass staggers; Neotyphodium lolii

Bovine, ovine, equine, camelid

Lolium perenne; indole-diterpenes

During summer and autumn in overgrazed pastures

Tremors NSL Clinical signs; presence of plant; toxin and endophyte identification

Paspalum staggers; Claviceps paspali

Bovine, equine, buffalo

Paspalum spp.; indole-diterpenes

During autumn at seeding

Tremors NSL Clinical signs; presence of plant with infected seeds

Bermuda grass staggers; Claviceps cynodontis

Bovine, equine Cynodon dactylon; indole-diterpenes

During winter after frosts

Tremors NSL Clinical signs; presence of plant

Ergotism; Neotyphodium coenophialum

Bovine, ovine, equine

Pure pastures of Festuca elatior; ergot alkaloids

During winter Gangrenous ergotism

Necrosis of distal limbs

Clinical signs; presence of plant; toxin and endophyte identificationDuring summer Dysthermic

ergotismNSL

Pithomycotoxicosis; Pithomyces chartarum

Bovine, ovine, deer

Clover/gramineae pastures with dead plant matter; sporidesmin

Mainly in autumn with rains and temperatures of approximately 24°C

Dermatitis and hepatic insufficiency

Liver degeneration and fibrosis

Clinical signs; pathology; spore counting; demonstration of spore toxigenicity

Slobbers; Rhizoctonia leguminicola

Bovine, equine, caprine

Pastures or hay of red clover and alfalfa

During autumn with excessive rainfalls

Salivation NSL Clinical signs; fungi observation; toxin detection

Diplodiosis; Stenocarpella maydis

Bovine, ovine Corn stables; diplonine

By consumption of cob, leaves, and stem of maize

Nervous signs NSL Clinical signs; presence of fungi

* NSL = nonsignificant lesions.




Riet-Correa et al.694

lolitrem concentrations. The poisoning can also be caused by ryegrass hay and ryegrass seed screenings. Neotyphodium lolii is transmitted only through the seeds, so the infection is not spread between plants. However, because the infected plants are more resistant to drought and insect attacks, they produce a greater number of infected seeds, and the infection occurs more frequently in the new plants, increasing the tox-icity of the pasture over time.23,39

Another endophyte-related disease associated with tremoring in South America is poisoning by Poa huecu, which has been reported in Argentina. Paxilline has been identified in this type of poisoning, suggesting that the tremors are caused by indole-triterpenoid alkaloids (Towers RN: 1994, Cornezuelo e endofitos como causa de sín-dromes nerviosos y asoleamento en especies pecuarias [Ergot and endophytes causing nervous diseases and hyper-thermia in livestock]. In: Buiatrics Uruguayan XXII Con-ference. Centro Médico veterinário Paysandú, Uruguay, pp. C1–C10. In Spanish).

Poisoning by indole-diterpenoids contained in Paspalum spp., C. dactylon, and ryegrass cause similar clinical signs, which are characterized initially by fine tremors and discrete head nodding, and can be exacerbated by excitement or

movement. Later, the animals display cerebellar ataxia with severe tremors, uncoordinated gait with rigid legs, hyperme-tria, swaying when standing, and a wide-based stance. When affected animals are driven or startled, they can fall to either side, forward or backward, sometimes into unusual posi-tions, and occasionally paddle violently during vigorous attempts to rise (Fig. 1B). After a period of rest, the animals usually rise unassisted. In the more affected animals, tremors became generalized. Generally, the appetite is maintained, but weight loss occurs. Hypersensitivity to noise or move-ment is also observed. Severely affected animals may become recumbent, with generalized tremors, opisthotonus, nystagmus, and salivation. When the animals are removed from pastures, full regression of clinical signs occurs in 7–15 days. Some animals have died as a consequence of accidents or while remaining recumbent.36,46,56,57,66,80

No gross lesions are observed following intoxication, but in the case of Paspalum staggers, many Paspalum seeds are observed in the abomasum contents. Most cases have no his-tological lesions, but some cases with a more prolonged clinical manifestation period have cerebellar lesions, with degeneration and loss of Purkinje cells and the presence of axonal spheroids in the granular layer.38,66

Table 2. Main features for the diagnosis of mycotoxicosis in livestock ingesting grains or grain by-products in South America.*

Disease/agentSpecies affected Substrate/toxin Epidemiology Clinical signs Pathology Diagnosis

Ergotism; Claviceps purpurea

Bovine, equine

Ergot in grains or byproducts; ergot alkaloids

Grain byproducts contaminated by ergotized Lolium multiflorum

Mainly dysthermic ergotism; less frequently, gangrenous ergotism

NSL Clinical signs; presence of ergot and ergot alkaloids

Aspergillus clavatus Bovine, ovine Barley and sugar beet residues; patulin and other toxins

Improper storage of barley, barley residues, or beet residues

Nervous signs and recumbence

Neuronal degeneration

Clinical signs; histopathology; multitoxin and patulin analysis; isolation of A. clavatus

Aflatoxicosis; Aspergillus flavus, and others

Bovine, equine, caprine

Grains or byproducts; aflatoxins B1, B2, G2, and G2

Feeding with grains and grain byproducts; also in nonharvested maize

Unspecific signs of hepatic insufficiency; low milk production and weight gains

Liver fibrosis, megalocytosis, and bile duct proliferation

Lesions and aflatoxin quantification in the food

Poisoning by moldy sweet potatoes; Fusarium spp.

Bovine Damaged sweet potatoes; 3-substituted furans

Ingestion of damaged sweet potatoes

Acute severe respiratory signs

Pulmonary emphysema and edema

Ingestion of sweet potatoes; clinical signs

Leukoencephalomalacia; Fusarium verticillioides

Equine Corn and corn byproducts; fumonisins B1, B2

Corn as main food source

Severe acute nervous signs

Malacia of the white matter of the brain

Corn ingestion; clinical signs; lesions

* NSL = nonsignificant lesions.





This mycotoxicosis is diagnosed by observation of the characteristic clinical signs and the presence of Paspalum spp. infected by C. paspali, C. dactylon, or L. perenne. The main diseases to be considered during differential diagnosis is poisoning by Ipomoea asarifolia, which causes an identi-cal tremorgenic syndrome in ruminants in northeastern Bra-zil, and poisoning by Phalaris spp., which also causes tremors in ruminants in South America62 and other countries. In Phalaris spp., the presence of a characteristic pigmenta-tion of the brain helps in the differential diagnosis of poison-ing. Similar signs are observed following the ingestion of crops or their byproducts containing indole-diterpenoid tox-ins produced by fungi of the genera Aspergillus and Penicil-lium.16 Other diseases that should be considered in the differential diagnosis are hypomagnesaemia, poisoning by swainsonine-containing plants, and cerebellar degeneration caused by Solanum spp.62

Currently, there is no effective treatment for poisoning. The whole herd, or at least animals showing clinical signs, should be gently removed from the infected pastures. In the case of Paspalum staggers, the prevention of intoxication should focus on the suppression of inflorescence. Slashing or mowing may be used to remove seed heads. Paspalum spp. are tolerant of heavy grazing, so high grazing pressure should be maintained during the summer to prevent heavy seeding.

High grazing pressure also helps decrease soil contamination by ergot and prevents heavy infection for the next year (Riet-Correa F, Rivero R, Dutra F, et al.: 2007, Micotoxicosis en animales domésticos en pastoreo [Mycotoxicosis in grazing domestic animals] In: Jornadas Uruguayas de Buiatría, Pay-sandú. Buiatrics Uruguayan XXXV Conference, Paysandú, Uruguay, vol. 35, pp. 116–131). The only way to prevent C. dactylon poisoning is to avoid grazing livestock in severely infected pastures during the winter. Nevertheless, the risk of C. dactylon poisoning is very low, because despite the numerous pastures invaded by this species in South America, poisoning is rare. The prevention of ryegrass staggers is based on the avoidance of heavy grazing during the dry sea-son, thereby forcing livestock to graze the lower part of the pastures. Pastures that are at least 30 cm high can be consid-ered nontoxic. Pastures infected with L. perenne can be replaced by noninfected ryegrass, but this measure is unsuc-cessful because compared to infected ryegrass, noninfected ryegrass is more susceptible to environmental conditions and less resistant to nematodes and insects. As a consequence, noninfected ryegrass dies and is substituted by endophyte-infected plants, which originate from seeds remaining in the soil. Another possible solution is to replace toxic ryegrass with seeds infected by a strain of N. lolii, which do not pro-duces penitrems.23 AgResearch Ltd. developed AR6 novel endophyte, which produces peramine and ergovaline to con-trol the Argentine stem weevil and African black beetle (Het-eronychus arator), but does not produce lolitrem B; however, lambs on AR6 pasture could be more vulnerable to heat stress due to ergovaline than lambs grazing endophyte-free pastures.1

Ergotism

Ergot alkaloids produced by Claviceps purpurea and Fes-tuca arundinacea Scribe (syn. Festuca elatior L.; tall fescue) infected with Neotyphodium coenophialum (syn. Acremo-nium coenophialum) cause diseases in ruminants and horses, including gangrenous ergotism (also known as fescue foot in cases of F. elatior poisoning), dysthermic ergotism (also known as summer toxicosis, hyperthermia, idiopathic bovine hyperthermia, and dysthermic syndrome), and a reproductive form (causing agalactia or hypogalactia).6,10,35,59,65,77,80 Fes-cue poisoning has also been associated with necrosis of the abdominal fat in cattle.78 Nervous ergotism caused by C. purpurea, as it is known in human beings, has not been fully documented in domestic animals, and the reported cases were most probably caused by indole-triterpene alkaloids in Claviceps paspali.

Claviceps purpurea is a fungus that infects the ovaries of crops and grass seeds, forming an sclerotium (ergot), which is larger than the seeds, with a black or dark brown color and a hard consistency (Fig. 2A, 2B). In South America, the fungus can affect several species of grasses including Holcus lana-tus, Setaria spp., Polypogon chilensis (syn. Chaetotropis

Figure 1. A, Paspalum notatum infected by Claviceps paspali. B, bovine with nervous signs due to Cynodon dactylon poisoning.





Figure 2. A, Claviceps purpurea sclerotia infecting Festuca elatior seeds. B, C. purpurea sclerotia compared with ryegrass (left) and oat (right) seeds.

chilensis), Poa pratensis, Festuca spp., and Phalaris spp., but most outbreaks in the region have been associated with the ingestion of grains or their byproducts contaminated with Lolium multiflorum L. (annual ryegrass) infected with C. pur-purea.59 Lolium multiflorum is a weed that affects winter cul-tures, mainly wheat; hence, the main cause of ergotism in cattle in Uruguay is the contamination of wheat bran and wheat screenings contaminated with annual ryegrass seeds infected by C. purpurea (Fig. 2B). Oats harvested from areas severely contaminated by C. purpurea–infected ryegrass have been responsible for outbreaks of agalactia and neonatal mortality in horses.65 Ergotism has also been reported in ani-mals grazing on ryegrass pastures severely contaminated by C. purpurea.59

The toxicity of F. elatior is due to infection by the endo-phyte fungus Neotyphodium coenophialum, which produces ergot alkaloids.77 This mycotoxicosis is very important in the southwestern United States but has also been reported in sev-eral other countries,10,80 including Argentina (Villahoz MD, Moras EV, Barboni AM, et al.: 1984, Reproductive problems of pregnant mares grazing fescue pastures in Argentina. In: Proceedings of 10th Congress on Animal Reproduction and Artificial Insemination, vol. 2, pp. 100–102, June 10–14, Urbana-Champaign, Illinois)35,50 and Uruguay.61 The endo-phyte is transmitted only through the seed, but because non-infected plants are less resistant to drought and environmental stress, they die and are replaced by endophyte-infected plants originating from seeds that remain in the soil.80

Ergot alkaloids are generally classified in 2 main groups: ergoline alkaloids, which include lysergic acid, lysergol,

lysergic, acid amide, and ergonovine; and ergopeptine alka-loids, which include ergotamine, ergocristine, ergosine, ergocryptine, ergocornine, and ergovaline. Ergovaline is probably the most active ergot alkaloid produced by N. coe-nophialum, and the ergopeptine alkaloids ergotamine, ergo-cristine, ergosine, ergocornine, and ergocryptine are the main toxins in C. purpurea (Duringer JM, et al.: 2007, A review of the ergot alkaloids).24,77

The vasoconstrictive effect of ergot alkaloids through interactions with dopaminergic, adrenergic, and serotonergic receptors cause constriction of the arterioles, resulting in gan-grenous ergotism or hyperthermia.24 In temperate climates, gangrenous ergotism occurs during the winter, and dysther-mic ergotism occurs during the summer. In cold climates, vasoconstriction causes ischemia, endothelial degeneration, thrombosis, and ischemic necrosis.59 At temperatures higher than 25°C, vasoconstriction of peripheral blood vessels causes reduced blood flow to the skin, reducing heat loss when ambient temperatures are high and leading to heat stress and hyperthermia.16,59 In the reproductive form of ergotism in horses, hypogalactia or agalactia occurs as a result of decreased prolactin secretion and inhibition of mammary gland development at the beginning of lactation or as a result of lower milk production during lactation.6,24,77 A 2011 review is available concerning the endocrine disruptive effects of ergopeptine alkaloids on lactogenesis and steroidogenesis on pregnant mares.24 Fibrosis and thickening of placenta are most likely due to vasoconstriction of the placental vessels.6,65

Gangrenous ergotism and hyperthermia caused by C. pur-purea31,59 and F. elation35,61 have been reported frequently in cattle in Uruguay, Argentina, and southern Brazil. The repro-ductive form of ergotism has been diagnosed in horses that ingested C. purpurea in southern Brazil65 and Uruguay59 and in horses that ingested F. elatior in Argentina (Villahoz MD, et al.: 1984, Reproductive problems of pregnant mares graz-ing fescue pastures). In Uruguay and southern Brazil, mor-bidity due to hyperthermic ergotism varies from 25% to 70%, and, generally, spontaneous deaths do not occur.31,59 The morbidity of fescue foot can vary from 6% to 80%, depending on the amount of tall fescue grass and the degree of contamination. Fertilization with nitrogen and drought stress can increase the toxicity of the grass.6 Lower weight gains have also been observed in cattle without clinical signs.80 Poisoning occurs at different times of the year, with plants at different stages of growth. In cattle in Uruguay and Argentina, the gangrenous form occurs in the winter, and hyperthermic ergotism occurs in the summer. The disease does not occur in paddocks with fescue contents below 50%.35 The occurrence of ergotism has become rare in Uru-guay and Argentina, most likely due to the use of tall fescue mixed with other grasses such as clovers and ryegrass and also to the marketing of controlled seeds with endophyte infection rates of less than 5%. In outbreaks of agalactia due to C. purpurea ingestion, reported morbidity rates are 7–90%, with foal mortality rates of up to 50%.65





In cattle, gangrenous ergotism is characterized by a dry gangrene of the limb extremities. Initial clinical signs include lameness with swelling and redness of the skin of the coro-nary band and fetlock, and, in dairy cattle, reduced milk pro-duction. Subsequently, the skin becomes gangrenous and shows cracks, sometimes with purulent exudate under the necrotic skin. Gangrenous lesions are separated from normal skin by a clear line. The horn also separates from the under-lying tissues, the skin sloughs off, and the rupture of tendons and ligaments may result in loss of the hoof.59,61 The general condition of animals is not greatly affected, although some animals may show skin necrosis at the edge of the ears, the tip of the tail, and the udder.59,61

Dysthermic ergotism in cattle is characterized by heat stress with a high body temperature (40–42°C), rough hair, dyspnea, decreased feed intake and weight gains, reduced milk production, increased water intake, and polyuria. Diar-rhea and nasal discharge are occasionally observed. When environmental temperatures increase, affected cattle seek out any shade available, stay in water ponds, and show severe respiratory distress with an extended neck, open mouth, drooling, and tongue exposition. During the hotter hours of the day, the clinical signs are more evident than during the night or on cold days. Some animals may show signs of lameness and gangrenous ergotism in the limbs, ears, and tail 30–60 days after ingestion. Death can occur when infected animals are exposed to ambient temperatures of more than 30°C. With the withdrawal of the contaminated food, the clinical signs disappear slowly over a course of 2–3 weeks. Abortions, agalactia, retained placenta, and reproductive failures such as infertility and anestrus may occur during and after the occurrence of hyperthermic ergotism.31,59,61

In cases of F. elatior poisoning in cattle, adipose tissue necrosis in the abdominal cavity has also been described. This change is detected by rectal palpation as hard masses that range from 1 cm in diameter to large masses that are only partially palpated on the dorsal surface. Such lesions, which may or may not occur simultaneously with dysthermic ergot-ism, may cause digestive disorders and calving problems.78

Gangrenous ergotism is a rare disease in sheep,34 but digestive lesions can be observed in sheep experimentally poisoned by C. purpurea.22 Poor weight gains and hyperther-mia can be observed in sheep grazing tall fescue and in lambs grazing perennial ryegrass contaminated by N. lolii, which also produces ergot alkaloids.59,80 In horses, mainly in mares during the last month of gestation, the main form of ergotism is reproductive and is characterized by a lack of mammary gland development and agalactia. In most cases, agalactia is permanent after birth, but some mares can produce milk after parturition if ergot alkaloids are removed from the food. Pre-mature release of the chorioallantoid also occurs, and the placenta is heavier, thickened, and fibrotic and must be man-ually broken. Gestation may be prolonged, and some mares have dystocia. Abortion, embryonic death, and anestrus have also been reported.6,65 The foals born to affected mares are

weak, without mammary reflex, and neonatal mortality can be higher than 50%.65 Newborn foals had decreased serum triiodothyronine concentration, hypothyroidism, and signs of dysmaturity, including marked decrease in muscle mass, long fleshy hooves, and delayed eruption of incisor teeth.6,7 After the removal of food contaminated by ergot alkaloids, the frequency of agalactia, other reproductive signs, and neo-natal mortality rapidly decreases.65

Histologically, the lesions of gangrenous ergotism display coagulation necrosis of the skin and subcutaneous tissue, with proliferation of granulation tissue in the deeper layers. The muscular layer of arterioles is hyperplasic, with narrow-ing of the vessel lumen and of subcutaneous tissue.59 In the reproductive form in horses, placental lesions are character-ized by a thickening of the allantochorion and the degenera-tion of the chorionic epithelium. In foals, jaundice and enlarged, yellow livers with severe vacuolation of hepato-cytes can be observed.65 No macroscopic lesions have been reported in cases of hyperthermic ergotism in cattle. Histo-logically, the only lesions observed in the cases described in Brazil were pulmonary emphysema and hypertrophy of the muscular layer of the bronchioles.31

The diagnosis of ergotism must be established by clinical signs, pathological changes, and the presence of C. purpurea sclerotia in the food or F. elatior contamination by N. coeno-phialum, which can be confirmed by microscopic observa-tion of leaf sections stained with aniline blue. The determination of the number of infected plants is important for confirmation of the diagnosis and to provide an indica-tion of the toxicity of a pasture of tall fescue. Clinical signs are likely to occur when at least 50% of the plants in a pas-ture are infected. Infection of 15% of the plants can lead to a reduction in daily weight gains. Milk production may be affected in some animals when the ambient temperature is high and 8% of the plants are infected.61 However, the per-centage of infected plants is not the only factor that deter-mines the toxicity of a pasture. Other factors, such as the botanical constitution, the percentage of fescue, and the nitrogen fertilization of the pasture, as well as the duration and type of grazing animal, can influence the toxicity. The diagnosis of C. purpurea presents difficulties when animals are fed with products or ground-based grains, in which the milled sclerotia cannot be identified. In such cases, labora-tory tests are needed to detect the presence of C. purpurea or ergot alkaloids. Ergot alkaloids can be identified in food by thin-layer chromatography, enzyme-linked immunosorbent assays, and high-performance liquid chromatography.10,33 Urinary ergot alkaloids can be determined in animals that are still ingesting the contaminated food.10

After diagnosis of the disease, grazing animals should be removed from fescue pastures infected by N. coenophialum or ryegrass pastures contaminated by C. purpurea. Contami-nated feed should also be removed from penned animals. Treatment should be symptomatic; gangrenous lesions are slowly reversible in milder cases but are not reversible in





Figure 3. Bovine with severe dermatitis due to pithomycotoxicosis. Inset: spore of Pithomyces chartarum. Bar = 30 µm.

severe cases. For the prevention of gangrenous ergotism, grains or byproducts should be inspected for the presence of C. purpurea. As a weed in crops, L. multiflorum should be controlled by the use of herbicides, which is difficult due to increasing resistance to herbicides. Crop seeds should be free of ryegrass seeds. In areas invaded by ryegrass, the preven-tion of seeding will prevent soil contamination by ergot, which can overwinter to infect ryegrass the following year.

Endophyte-free fescue seeds are available or can be obtained by treating seeds with fungicides or by using seeds after 12–15 months of storage. In Uruguay, fescue seeds must have infection rates below 5%.61 Endophyte-free fescue provides excellent livestock performance, but is less resistant to drought and insect attacks.80 If endophyte-free fescue is planted in an area previously occupied by infected fescue, the culture will rapidly revert to an endophyte-infected pas-ture as seeds in the soil germinate and the endophyte-free plants die.80 A better approach is the use of fescue infected by endophytes, called novel endophytes, which produce little or no ergot alkaloids but still produce toxins against insects.3,80 The only way to use toxic pastures is to allow grazing only for short periods, alternating grazing fescue pastures with other species. However, one should consider the possibility of lower weight gains and a drop in production.

Intoxication by Pithomyces chartarum (pithomycotoxicosis)

Pithomyces chartarum is a saprophytic fungus distributed in temperate, subtropical, and tropical regions. It is usually found on dead vegetable matter at the base of the pasture. The spores (Fig. 3) of pathogenic strains of the fungus pro-duce sporidesmins A–H, but sporidesmin A is the most clini-cally relevant. Sporidesmins B–H are of low biologic significance. Sporidesmin causes cholestasis and pericholan-gitis, resulting in hepatic photosensitization of sheep, cattle, deer, and camelids. The poisoning, known as facial eczema, is an important disease in New Zealand in perennial ryegrass pastures, but has also been reported in the United States, Canada, England, South Africa, The Netherlands, Uruguay,

and Argentina.75,80 In New Zealand, the disease is more com-mon in sheep than in cattle. In contrast, pithomycotoxicosis has only been reported in cattle in Uruguay and Argentina because sheep are rarely grazed in cultivated pastures with high productivity (Riet-Correa F, et al.: 2007, [Mycotoxico-sis in grazing domestic animals]).45,54 In Brazil, many out-breaks of hepatogenous photosensitization caused by Brachiaria spp. were misdiagnosed as pithomycotoxicosis, but it is now well known that the toxicity of Brachiaria spp. is caused by steroidal lithogenic saponins,58 and almost none of the P. chartarum strains from Brazil and Colombia pro-duce sporidesmin.11,18 Analyses carried out in P. chartarum isolated from pastures of Uruguay showed that 60% of the strains were pathogenic (Towers N: 1994, Eczema facial [Facial eczema]. In: Buiatrics Uruguayan XXII Conference, Paysandú, Uruguay. Centro Médico veterinário Paysandú, Uruguay, pp. G1–G9. In Spanish). In contrast, nearly all New Zealand isolates produce sporidesmin.18

Pithomycotoxicosis has been detected since the 1970s in Uruguay and Argentina,45,50,54 where it is the main cause of hepatogenic photosensitization. This disease occurs in culti-vated pastures of white, red, or subterranean clover mixed with ryegrass (Lolium rigidum), Festuca arundinacea, Phalaris spp., Avena sativa, or other gramineae. The follow-ing 2 epidemiological conditions are necessary for pastures to be toxic: environmental conditions must be favorable for fungal growth, and pathogenic strains of P. chartarum, capa-ble of producing sporidesmin, must be present. For the fun-gus to multiply, conditions with suitable humidity and temperature are required, as well as a suitable and abundant substrate. The most favorable conditions for fungal growth occur during cloudy days with rain, temperatures above 16°C (optimal temperature is 24°C), and relative humidity of more than 80%. The repetition of these favorable growth conditions significantly increases the number of spores. In South America, outbreaks occur in the late summer and autumn, when climatic conditions and pastures are suitable for fungal growth.54 Intensive grazing practices facilitate the ingestion of large numbers of spores present in the pasture litter. Pastures with plenty of dead plant material, as in those used for seed production, mixed pastures with wheat or oats, pastures that cannot be baled due to adverse weather condi-tions, and pastures that have been mowed can become toxic. Hay produced from contaminated pastures or pastures that receive rain may also be toxic, as can round bales that are exposed to rain or high humidity levels.54

The toxicity of pastures depends on the number of toxic P. chartarum spores in the dead plant material and the toxicity of the individual P. chartarum strains. More than 40,000 spores of pathogenic strains per gram of dead vegetation can cause photosensitivity, leading to a severe drop in milk pro-duction, while 100,000 spores/g can lead to death.54 In Uru-guay, the disease was very frequent from 1970 to 2000, but the number of outbreaks has decreased, most likely due to the use of high-quality soils, previously used for pastures, for





grain production. Morbidity is variable, with rates of 5–10%, while mortality ranges from 1% to 10%.54

In cattle, the first clinical signs may be transient diarrhea, depression, anorexia, and severe reductions in milk yields from milking cows. Subsequently, subcutaneous edema can be observed, followed by dermatitis affecting exposed, non-pigmented, uncovered areas of the skin (perineum, external face of the udder, nose and muzzle, lips, ears, and periorbital region; Fig. 3). Jaundice, salivation, and nasal and ocular dis-charges are frequent. The tongue may be ulcerated on the ventral surface, because of exposure to the sun when the ani-mal licks its nostrils. Some affected animals seek shade, have continuous movements of the head, and exhibit other signs of pain. Sometimes the skin peels from a large area, mainly on the face. More severe cases may be fatal during the acute phase, without presenting photosensitization. Intravascular hemolysis, anemia, hemoglobinuria, and abortions have also been described.54 In sheep, the most characteristic sign is dermatitis of the face; hence, the disease is called facial eczema. The ears are edematous, and the animals display photophobia and seek out any available shade. Jaundice, subcutaneous edema, and other signs of liver failure are also observed. Acutely affected sheep and cattle can die without presenting photosensitization. In severe cases, edema, hem-orrhages, and even necrosis may be observed in the urinary bladder.54,75,80

The serum activities of gamma-glutamyl transferase and aspartate aminotransferase and the serum concentrations of bilirubin are increased in affected animals. Gamma-glutamyl transferase is the best indicator of the disease, and high serum concentrations may persist for periods of 3–6 months. During outbreaks, the analysis of blood enzyme activities may reveal that most animals without clinical signs are suf-fering liver damage with production losses and increased susceptibility to other diseases. Resistant animals show no increase in serum gamma-glutamyl transferase activities.80

In acute cases, jaundice occurs, and the liver is yellowish and enlarged. The gallbladder is also enlarged and shows edema of the wall. In cases of longer evolution, the liver may be yellowish or whitish due to periportal fibrous tissue pro-liferation. These lesions are most marked in the left lobe, which in chronic cases may be atrophic and fibrous.54,80 His-tologic changes primarily affect the bile ducts, causing degeneration and necrosis of the epithelium, followed by proliferation of epithelial bile duct cells and periportal fibro-sis. The periportal hepatocytes may show diffuse vacuoliza-tion or necrosis. In chronic cases, there is severe periportal fibrosis and atrophy of the parenchyma.54,80

Presumptive diagnosis is based on clinical signs and the occurrence of the disease in pastures with dead plant mate-rial, especially during the fall. The macroscopic and histo-logical lesions are also suggestive of the diagnosis, but the spores in the pasture must be counted for confirmation. However, because not all strains of P. chartarum produce sporidesmin, at least in regions where the disease has not

been previously diagnosed, it is also necessary to know if the strains are sporidesmin producers. Enzyme-linked immuno-sorbent assays and high-performance liquid chromatography methods can be used to detect sporidesmin in body tissues and grass.18,80 The differential diagnosis should be made with plant poisoning that causes hepatic photosensitization, mainly Brachiaria spp. and Panicum spp., which contain lithogenic steroidal saponins and cause a disease similar to pithomycotoxicosis. Histologically, the liver lesions induced by saponin-containing plants are characterized by the pres-ence of crystals in the bile ducts or within macrophages. The presence of foamy macrophages in the liver is also a charac-teristic of Brachiaria spp. poisoning.58 Poisoning by plants such as Lantana spp., Myoporum laetum, Stryphnodendron spp., Enterolobium spp., and Senecio spp. should also be considered in the differential diagnosis.62

All ruminants must be removed from the infected pas-tures. Affected animals should be placed in permanent shadow with food and water and treated symptomatically if necessary. These pastures should not be used again until their conditions have changed or until the spore count demon-strates a nontoxic fungal concentration. For prophylaxis, pasture management practices should be used to prevent the accumulation of dead plant matter. When these conditions occur, the pastures can be monitored for toxicity by spore counting. However, in countries where not all P. chartarum strains are toxic, this practice can overestimate the risk of poisoning.18 Reducing grazing pressure can also reduce toxin intake, as the highest toxin levels are generally in those parts of the pasture closest to the ground. In New Zealand, other practices have been used to prevent facial eczema, including dosing the animals with zinc salts to protect them against the toxic effect of sporidesmin, spraying the pastures with fungi-cides to reduce spore production, and breeding sheep or cat-tle with increased resistance to the toxin.75 The substitution of toxigenic strains of P. chartarum by nontoxigenic strains was proposed in New Zealand as a way to control facial eczema. Unfortunately, nontoxigenic strains, initially repre-senting 80–90% of the isolates, did not persist in the pastures and constituted only 4% of the strains after 4 months.80 How-ever, survival of nontoxigenic strains may not be a problem in South American countries where P. chartarum constitutes a high percentage of the nontoxigenic strains.18

Diplodiosis

Diplodiosis is a mycotoxicosis caused by Stenocarpella maydis (syn. Diplodia maydis) in cattle and sheep grazing maize harvested fields. Stenocarpella maydis produce a thick mass of mycelium in the cob, leaves, and stem of maize (Fig. 4A), and after maturation, the fungi forms black, pinhead-sized pycnidia (Fig. 4B).32,48,60 A substituted β-cyclopropylamino acid toxin named diplonine was identi-fied in S. maydis and found to cause nervous signs in guinea pigs, similar to those observed in ruminants.76





Figure 4. Maize infected by Stenocarpella maydis (syn. Diplodia maydis). A, fungus is forming a thick mass of mycelium. B, masses of black pycnidia. Inset: pycnidia of S. maydis. Bar = 20 µm.

Diplodiosis is the most important mycotoxicosis of sheep and cattle in southern Africa32 and has also been reported in cattle in Brazil60 and Argentina48 in corn stubbles during the autumn and winter (April–September). The morbidity rate is 5–75%, the mortality rate is 2–20%, and animals of different ages are affected.60

Clinical signs in cattle include weeping, salivation, mus-cle tremors, ataxia, and dysmetria with exaggerated flexion of the limbs during gait. A wide-based stance and stiff gait are also observed. Some animals become recumbent and may develop opisthotonus and extension of the limbs. The first clinical signs occur 2–10 days after consumption of moldy maize. After being removed from stubble, the animals recover in 7–10 days.48,60 Stillborns and neonatal mortality can occur in pregnant cows and sheep without clinical signs following the ingestion of contaminated corn.32 There are no significant gross lesions. Histologically, spongiosis (status spongiosus) of the cerebellar and cerebral white matter may be observed in cases of long duration.32 In Argentina, moder-ate to severe myelin degeneration has been observed in the white matter of the cerebellum.48 Spongiosis has also been observed in lambs and calves that die around the time of par-turition.32

The diagnosis of diplodiosis must be established by the observation of nervous signs in cattle grazing in corn stub-bles during the winter. The main differential diagnosis is

with tremorgenic diseases caused by indole-diterpenoid mycotoxins and with poisoning by Ipomoea asarifolia and Phalaris spp. Poisoning by Aspergillus clavatus shares simi-lar signs with diplodiosis but has a higher mortality rate. A detailed histologic examination of the central nervous sys-tem should help in the differential diagnosis, mainly in cases of neonatal mortality when the dams do not show clinical signs.

There is no specific treatment for diplodiosis. After the observation of clinical signs, the herd must be removed from the corn stubbles immediately. Because the pycnidia of the fungus overwinter in the soil, maize residues should be removed from the area (i.e., by deep early plowing or burn-ing) to decrease contamination of the next crop. Alternating maize cultures with other cultures can also help control corn contamination by S. maydis.

Slaframine poisoning

Slaframine is an indolizidine alkaloid produced by the fun-gus Rhizoctonia leguminicola, which infects leguminous pastures, mainly Trifolium pratense (red clover or rotklee) and Medicago sativa (alfalfa or lucerne).21 In the liver, slaframine is metabolized to 6-ketoimine, which is similar to acetylcholine. This active metabolite causes excessive salivation and other parasympathomimetic effects.21 Rhi-zoctonia leguminicola causes a disease called “blackpatch” in leguminous plants, characterized by dark patches up to 1–3 mm in length on the leaves or stems (Gough FJ, Elliott ES: 1956, Blackpatch of red clover and other legumes caused by Rhizoctonia leguminicola sp. nov. Bulletin 387T, West Virginia University Agricultural Experiment Station, Morgantown, West Virginia. Available at: http://archive.org/stream/blackpatchofredc387goug#page/n1/mode/2up). Rhi-zoctonia leguminicola also contains swainsonine, which may be responsible for some of the clinical signs observed in the disease.21

Slaframine poisoning, known as slobbers, has been reported in the United States and other countries and pri-marily affects cattle and horses, although goats may also be affected.21,82 In Uruguay (Riet-Correa F, et al.: 2007, [Mycotoxicosis in grazing domestic animals]) and Argen-tina,50 the disease has been observed in cattle grazing red clover. In the Brazilian state of São Paulo, slobbers was diagnosed in horses that ingested alfalfa hay, which was produced in southern Brazil (state of Paraná) and stored for 4 months before consumption.8 In Uruguay and Argentina, the disease has been reported to occur during the fall (April–June), apparently as a result of excessive rainfall (Riet-Correa F, et al.: 2007). Poisoning also occurs by the ingestion of alfalfa or red clover hay, in which 5–10% of the original toxicity remains after 10 months.21

In cattle, clinical signs are decreased milk production, salivation, lacrimation, and piloerection. Some animals may show frequent urination, stiff gait, dyspnea, bloat, and


http://archive.org/stream/blackpatchofredc387goug#page/n1/mode/2up




increased frequency of defecation (Riet-Correa F, et al.: 2007, [Mycotoxicosis in grazing domestic animals]).50 Horses show light to intense drooling accompanied by con-stant movement of the tongue.8 Salivation appears 5–6 hr after ingestion of the contaminated food, and the animal recovers 24 hr after removal of the contaminated diet. A pre-sumptive diagnosis can be made by the observation of saliva-tion in animals ingesting leguminous pastures or hay. Rhizoctonia leguminicola poisoning can be confirmed by microscopic observation or fungal isolation from the typical black spots on the plants. To detect slaframine activity, pas-tures, hay, or their extracts can be administered to guinea pigs to induce salivation. The toxin can be identified by gas chromatography and mass spectrometry. The differential diagnosis includes vesicular stomatitis and salivation in indi-vidual horses caused by choking, oral trauma, oral foreign bodies, dental problems, glossitis, and treatment with the drug imidocarb, which causes salivation by reversible inhibi-tion of cholinesterase.8 In cattle, the main differential diag-nosis is with foot and mouth disease and vesicular or ulcerative stomatitis. Affected animals may be treated with atropine to reduce the salivation.50 There is no practical way to control R. leguminicola in the pastures or hay, but seeds can be treated with fungicides to avoid transmission to fungus-free areas (Gough FJ, Elliott ES: 1956, Blackpatch of red clover and other legumes).

Aflatoxicosis

Aflatoxins are a group of hepatotoxic metabolites (primar-ily aflatoxins B1, B2, G1, and G2) produced by some strains of Aspergillus, mainly A. flavus and A. parasiticus, at temperatures of 24–35°C and humidity greater than 14%.43,49 Aflatoxin B1 is biotransformed by liver micro-somal mixed-function oxidases to form several metabo-lites, including aflatoxin B1-8,9-epoxide that binds covalently to nucleic acids and proteins and seems to be responsible for cellular necrosis, immune suppression, mutagenesis, and neoplasms.43,49 Aflatoxicosis is a disease that predominantly affects animals that ingest grains or grain byproducts. Pigs and poultry are most often affected, but aflatoxicosis can also occur in other species including cattle (Lafluf O, Termezana A, Rivero R, et al.: 1989, Un caso de aflatoxicosis en bovinos asociado a maíz carbonoso [A case of aflatoxicosis associated with corn infected by Ustilago maydis]. Buiatrics Uruguayan XVII Conference, Paysandú, Uruguay, sección cc8, pp. 1–8).25,40,51 Young ani-mals are more susceptible than adults, and, in cattle, the disease is more common in calves and dairy cows than in adult beef cattle. Aflatoxins only cause clinical signs in calves at high doses (e.g., 0.02–0.08 mg of aflatoxin B1 per kg of body weight daily).52 However, the effects of afla-toxin poisoning in cattle depend on the aflatoxin concentra-tion in the food, the length of the feeding period, and the age of the animals. In horses, aflatoxicosis is a rare

disease,49 and the few reported cases have been reviewed.13 As in other species, aflatoxicosis in horses affects mainly the liver causing hepatocellular degeneration, necrosis, and megalocytosis, as well as bile duct proliferation and fibro-sis. Hemorrhagic enteritis and pale kidneys with protein precipitate in renal tubules are also observed.13,49 An out-break of aflatoxicosis was reported in young goats follow-ing ingestion of polkudu meal (defatted residue from grated coconut after juice extraction),73 and decreased milk pro-duction has been reported in goats following aflatoxin ingestion.28 Sheep are resistant to aflatoxins, although high concentrations (2,000 ppb) have been associated with a decrease in weight gain.25

In Uruguay, an outbreak of aflatoxicosis occurred in cattle that had been grazed for 2 weeks in a corn field in which corn was not harvested due to heavy infection by Ustilago may-dis. Out of 81 Holstein dairy cows, 10 became ill and 3 died. Aspergillus flavus was isolated from the corn, which was found to contain 2,700 ppb of aflatoxin B1. The poor condi-tion of this corn, due to U. maydis infection, favored the development of the toxigenic strains of this fungus. High infection by this fungus occurs when rainfall is scarce during the vegetative period of the plant (Lafluf O, et al.: 1989, [A case of aflatoxicosis]). In Uruguay and Brazil, outbreaks of aflatoxicosis were reported in steers that had ingested a ration constituted by 70% sorghum wet grain silage and 27% sorghum silage containing 20 ppb of aflatoxins25 and in 4-month-old calves that ingested a ration that consisted of alfalfa hay, broken corn, and milk substitute containing 5,136 ppb of aflatoxin B1.51 The mortality rates varied from 1.6% to 15%.25,51

The most frequent clinical signs of chronic aflatoxicosis, caused by ingestion of aflatoxins for weeks or months, are a decrease in milk production in dairy cattle and lower weight gains in growing animals. Some animals show signs of liver failure, including general unthriftiness, rough coats, anorexia, depression, food refusal, abdominal pain with colic, grinding of the teeth, photosensitivity, severe diar-rhea, and rectal tenesmus, sometimes with a prolapsed rec-tum.20,51 Acute aflatoxicosis is rare, but has been reported to cause anorexia, depression, jaundice, photodermatitis, sub-mandibular edema, diarrhea (sometimes bloody), nervous signs, and abortion (Lafluf O, et al.: 1989, [A case of afla-toxicosis]).40 Most likely, the most important form of afla-toxicosis is subclinical and nonspecific, causing reduced milk production, lower weight gains, and immune depres-sion associated with an increased frequency of diarrhea, respiratory disease, and mastitis. The increased serum activities of alkaline phosphatase and gamma-glutamyl transpeptidase are good indicators of liver damage due to aflatoxins.52

Gross lesions include color changes and increased consis-tency of the liver, gall bladder dilatation with wall edema, and edema of the mesentery and wall of the abomasum (Lafluf O, et al.: 1989, [A case of aflatoxicosis]).20,40 In acute





cases, there may be jaundice and bleeding of the subcutane-ous tissue, skeletal muscles, lymph nodes, pericardium, and gastrointestinal tract (Lafluf O, et al.: 1989).40 Histological changes of the liver are characterized by periportal fibrosis, bile duct cell proliferation, megalocytosis, and vacuolization or single-cell necrosis of hepatocytes (Lafluf O, et al.: 1989).20,40,51

The presumptive diagnosis of aflatoxicosis is made through epidemiological data, clinical signs, gross lesions, and primarily by the presence of histological lesions. The definitive diagnosis should rely on the detection of aflatoxins in the food and the characteristic histologic lesions. How-ever, it should be noted that the aflatoxin analysis of the sample is not representative of food consumed during the previous weeks or months and that histologic lesions are not specific. The main differential diagnosis is with poisoning by plants containing pyrrolizidine alkaloids (Senecio spp., Echium plantagineum, Erechtites hieracifolia, and Crota-laria spp. in South America). In feedlots, hay or silage should be observed to detect the possible presence of these plants. Crops can be contaminated by Crotalaria spp. seeds. In the subclinical form, other diseases and management mistakes that cause reduced production and impaired immunity should be considered.

For control of aflatoxicosis, the contaminated food should be immediately removed from the diet. For preven-tion, it is important to avoid feeding animals any crops or byproducts that have been stored improperly. Surveying feed crops for the presence of aflatoxins is the best way to prevent aflatoxicosis, especially the subclinical form. Alu-minosilicate products such as hydrated calcium alumino-silicate and sodium bentonite, which are effective in binding aflatoxins and preventing their absorption, have been widely used in the pig and poultry industries to prevent aflatoxicosis.

Poisoning by Aspergillus clavatus

Poisoning by Aspergillus clavatus leads to neuromycotoxi-cosis of cattle and sheep, characterized by tremors, ataxia, weakness, paresis, and recumbence followed by death. This poisoning occurs primarily in animals that ingest malting residues contaminated with A. clavatus.32,37,55,72,74 In Brazil, this neuromycotoxicosis was reproduced in cattle19 and sheep4 fed corn contaminated with A. clavatus, which pro-duces several toxic metabolites, including patulin, trypto-quivalines, cytochalasin E, and glyantripine.55,72 Aspergillus clavatus poisoning has also been reported in animals that have ingested sprouting wheat, sprouting maize, and sor-ghum beer residues.32 In Uruguay, the disease was also reported in cattle that ingested sugar beet residues, which were widely used as animal feed in that country until the 1980s. Toxigenic strains of A. clavatus were isolated from toxic sugar beet residues stored under humidity and tempera-ture conditions suitable for fungal growth.55

The morbidity rates of poisoning by malting residues varied between 17% and 32%, and mortality ranged from 25% to 87%.19,55 In cases of poisoning by sugar beet resi-dues, morbidity rates were 35–93%, and mortality rates were 8.6–34.4%.

Clinical signs include instability, ataxia, weakness or paralysis mainly of the hind limbs, and an inability to rise (Fig. 5A, 5B). Initially, affected cattle appear normal at rest, but manifest clinical signs when stimulated. If the animals are exercised or forced to move, they display muscle trem-ors, and fall down into a position of sternal recumbence, fre-quently with the legs extended or in a dog-sitting position. After a short rest, some animals rise and walk normally, but others stay recumbent and may present mild head tremors, salivation, and loss of spinal cord reflexes. Lateral recum-bence and paddling are observed in the terminal phase.37 The clinical course of the disease varies from 2–3 days to 2 weeks. Deaths occur during a period of several weeks. The morbidity rate is 17–32%, and the mortality rate is 25–87%.19,55 A mortality rate of 97% has been reported in sheep.74

The main gross lesion is a whitish appearance of the large muscles of the fore and hind limbs (Fig. 5C). His-tologically, severe chromatolysis, paleness, vacuolation, and margination of the nuclei occur in the neurons of the midbrain, medulla oblongata, and pons and in the ventral horn of the spinal cord (Fig. 5D).37,72 Axonal degenera-tion is observed in the white matter of the central ner-vous system and in the peripheral nerves.72 Focal degeneration and necrosis are present in the skeletal muscles.

The presence of the histologic lesions described above and a history of feeding with barley or sugar beet residues are the most important criteria for the diagnosis of A. clava-tus poisoning. Aspergillus clavatus can be isolated from the food, but it is important to consider that not all strains are toxigenic. Multitoxin and patulin analysis of the contami-nated food and isolation of A. clavatus should be performed to confirm the diagnosis. The main differential diagnoses are poisoning by indole-diterpenoid mycotoxins and botu-lism. Indole-diterpenoid poisoning is a tremorgenic disease with much lower mortality rates, and the animals recover in a few days after withdrawal of the contaminated food. Clin-ically, botulism is very similar to A. clavatus poisoning, but in the latter, neuronal lesions do not occur and muscle lesions are much less common. Analysis for botulism toxin in more than 1 animal is important for diagnosis. In South America, paralytic rabies transmitted by bats causes a simi-lar disease, but with 100% fatality and typical histologic lesions.

In cases of A. clavatus poisoning, the contaminated food should be removed from the diet immediately. To prevent poisoning, barley, barley residues, or beet residues should be stored under appropriate environmental conditions to avoid fungal contamination.





Poisoning by moldy sweet potatoes (Ipomoea batatas)

Sweet potatoes (Ipomoea batatas) infected by Fusarium solani (Fig. 6A) may contain 3-substituted furans, including 4-ipomeanol, 1-ipomeanol, 1,4-ipomeadiol, and ipomeanine, which cause acute respiratory distress in cattle. This disease is not technically a mycotoxicosis because the toxins are pro-duced by the tubercle after it has been infected by the fungi. Fusarium solani stimulates host tissues to form ipomeama-rone and 4-hydroxymyoporone; the latter is then converted to 4-ipomeanol, 1-ipomeanol, and 1,4-ipomeadiol.62 Other fungi, including Fusarium oxysporum, have been isolated from sweet potatoes in some outbreaks.26,41 Mechanical injury, chemical treatments, and parasitic infections can also induce the production of 3-substituted furans by sweet potatoes. In some regions, animals are commonly fed tubercles that are visibly moldy (Fig. 6A) or infected by parasites, as these potatoes are considered unfit for human consumption.26,41

Poisoning has been reported in Brazil26,41 and Uruguay.69 The clinical signs include severe respiratory distress with dyspnea, coughing, salivation, and dilated nostrils. Greatly

affected animals adopt a position with an extended neck and hanging head. The clinical manifestation period varies from 3–5 days.26,41,69 Necropsy lesions include distended and pale lungs with a rubbery consistency that does not collapse when the thorax is opened. Pulmonary edema and emphysema (Fig. 6B), as well as white foam, can also be observed in the airways. Sweet potato residues can be found in the rumen content. Histologically, the interlobular septa and the sub-pleural tissues are distended by edema and emphysema (Fig. 6C). Additional lesions are thickening of the alveolar walls by inflammatory cells and edema. The alveoli can be lined by type II pneumocytes, and the pulmonary lymphatic ves-sels are dilated by air.26,41 The clinical signs and pathology, as well as a history of feeding moldy sweet potatoes, usually allow diagnosis of this type of poisoning, and the macro-scopic and histological lesions are characteristic. However, there are several causes of interstitial pneumonia, grouped under the name “atypical interstitial pneumonia,” including poisoning by d-tryptophan and/or l-tryptophan in pastures, poisoning by Perilla frutescens, inhalation of irritant gasses, and lungworm infestation; all of these should be considered in the differential diagnosis because they produce clinical signs and lesions similar to those observed in poisoning by

Figure 5. Poisoning by Aspergillus clavatus. A, B, cattle poisoned by A. clavatus toxins showing weakness of the hind limbs and recumbence. C, whitish appearance of the hind limb muscles due to degeneration and necrosis. D, chromatolysis and cytoplasmatic pallor with cellular swelling of neurons is observed in the brain. Hematoxylin and eosin. Bar = 100 µm. Photos courtesy David Driemeier, Pedro Bezerra, and Alexandre Loretti.





moldy sweet potatoes. To prevent this type of poisoning, it is necessary to avoid feeding the animals with sweet potatoes if the storage conditions are not suitable and the tubercles are contaminated by fungi or parasites.

Leukoencephalomalacia

Leukoencephalomalacia (LEM) is a disease of equids caused by ingesting moldy corn contaminated by the fungus of the genera Fusarium, including Fusarium verticillioides (syn. F. moniliforme) and Fusarium proliferatum, which produce fumonisin. Many fumonisins have been identified, but only

fumonisins B1 and B2 are important as a cause of LEM. Fumonisins alter sphingolipid metabolism by inhibiting ceramide synthase, an important enzyme in the biosynthesis of sphingolipids. High doses of fumonisin B1 may cause hepatotoxicity. In Brazil, F. verticillioides has been isolated consistently from samples of corn that cause LEM.2,29,64,83 Fusarium proliferatum and Fusarium subglutinans are less frequently isolated. Levels of fumonisin B1 ranging from 10 to 500 µg/g were detected in 24 samples of corn that caused LEM.63 In another 13 samples, fumonisin B1 concentrations ranged from 0.2 mg/g to 38.5 mg/g, and fumonisin B2 con-centrations were between 0.1 and 12 µg/g.79 In Argentina, fumonisin B1 and B2 concentrations were 12.5 and 5.2 µg/g, respectively, in a feed supplement that caused LEM.27

Leukoencephalomalacia has been diagnosed in horses in all regions of Brazil,2,12,29,53,63,64,67,79,83 in Argentina27,42 and Uruguay,68 and in mules in the Brazilian states of Pernam-buco and Pará.14,67 Outbreaks occur in animals that are fed corn kernels, corn cobs, ground whole corn (a mixture of corn, corn stalks, and corn cobs), corn bran, corn screenings, or other byproducts from the processing of corn for human consumption. Corn that causes LEM may not be visibly moldy. Some outbreaks are caused by apparently normal corn contaminated by F. verticillioides. In the southern and southeastern regions of Brazil, LEM is seasonal, occurring mainly between June and September, although outbreaks have been recorded from March to December.2,63,64 In tropi-cal climates, outbreaks occur in both the dry and rainy sea-sons.14,67 Fusarium verticillioides infection of maize is more frequent when periods of drought are followed by cool, wet weather during pollination.43

In corn samples from 21 outbreaks of LEM, the moisture was 16.98 ± 2.30%. In 5 samples, the moisture was below 15%, which is in accordance with Brazilian standards for corn storage.63 In outbreaks reported in southern Brazil, LEM occurred in horses ingesting more than 1 kg of corn daily or rations containing more than 20% corn.63 Animals of different ages and both sexes can be affected. Morbidity rates are 4–100%, and case fatality rates are nearly 100%.27,63,68 Partial recovery has been reported in some cases,27 although this is rare.

Clinical signs of LEM appear abruptly and are character-istic of lesions of the cerebrum and brain stem, including anorexia, dullness, drowsiness, occasional hyperexcitability, muscle tremors, compulsive walking, head pressing, cir-cling, chewing difficulties, unilateral or bilateral blindness, ataxia, decreased eyelid reflex, decreased tone of the tongue and lips, loss of sensitivity of the face, paralysis of the jaw, and recumbence.2,12,27,63,64,67 The clinical manifestation period is 2–72 hr, but most affected animals die within 6–24 hr. Occasionally, the clinical course may last up to 13 days. In some outbreaks, the clinical signs may appear up to 12 days after the corn is withdrawn from the diet.

The lesions are almost bilateral, but asymmetric, with one side much more affected than the other and are located in the

Figure 6. Poisoning by moldy sweet potatoes (Ipomoea bata-tas). A, moldy sweet potatoes. B, lung with emphysema and edema. C, histologic section of the lung showing severe alveolar and inter-stitial emphysema. Hematoxylin and eosin. Bar = 100 µm.





cerebrum and/or brain stem. One of the cerebral hemispheres may be enlarged, and malacia of the white matter may be observed on the cut surface, with multifocal to coalescing foci of hemorrhage, brown-yellow discoloration, and soften-ing of the centrum semiovale and corona radiata (Fig. 7A). Cavities containing fluid are often observed in these areas. The internal capsule and thalamus are usually affected, but lesions may be observed also in the mesencephalon (Fig. 7B), cerebellar peduncles, pons, and medulla oblongata. The

macroscopic lesions are better evidenced after fixation of the central nervous system in 10–25% formalin, but cavitation, edema (yellow areas), and hemorrhages are easily observed in fresh brain tissue (Fig. 8). In some horses, the liver may be enlarged and yellowish.2,12,63,64,67,83

Histologically, malacia surrounded by edema and hemor-rhage of the neuropil are observed (Fig. 9). An additional characteristic of LEM is the presence of swollen astrocytes or oligodendrocytes, with abundant eosinophilic cytoplasm, deeply eosinophilic intracytoplasmic globules, and eccentric hyperchromatic nuclei (Fig. 9).14,27,63,67 These cells, previ-ously known as clasmatodendritic astroglia, are found in areas of hemorrhage and edema and are swollen because they have imbibed plasma protein. Additional lesions include hypertrophic and degenerative changes in the vascular endo-thelium and perivascular edema, hemorrhages, and eosino-philic globules. Some vessels have perivascular cuffing of eosinophils, neutrophils, or mononuclear cells.2,12,63,64,67,83

Figure 7. Leukoencephalomalacia in equid. A, a formalin-fixed cerebrum showing yellow areas of edema, hemorrhages, and cavitation of the white matter. Photo courtesy Dr. Jose A. B. da Silva and Ciência Animal Brasileira. B, formalin-fixed mesencephalon showing cavitation and hemorrhages.

Figure 8. Leukoencephalomalacia in equid. Fresh cerebrum showing enlarged left hemisphere with hemorrhages (arrows) and yellow discoloration of the white matter (*).

Figure 9. Equine leukoencephalomalacia; cerebral white mat-ter. Malacia (M), perivascular edema (E), and hemorrhages (H) and numerous characteristic reactive glial cells with abundant eosino-philic cytoplasm, sometimes called clasmatodendritic astroglia, are observed (arrows). Hematoxylin and eosin (HE). Bar = 100 µm. Inset: reactive glial cells (arrows). HE. Bar = 30 µm.





Affected horses may also have hepatic lesions, including vacuolization or necrosis of the hepatocytes.

The diagnosis of LEM is based on the occurrence of the disease in horses that have ingested diets containing corn or corn byproducts. The main differential diagnosis is with rabies, viral equine encephalitis, and hepatic encephalopathy, which is caused primarily by poisoning with pyrrolizidine alkaloids. Malacia of the white matter, macroscopically simi-lar to that caused by LEM, is observed in equine trypanoso-miasis caused by Trypanosoma evansi. In trypanosomiasis, however, the main histologic lesion is severe encephalitis, and the clinical manifestation period is much longer. The only way to prevent LEM is to avoid the ingestion of improperly dried corn. When the corn is properly dried, it should not con-stitute more than 20% of the dry matter.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Institute for Science and Technol-ogy for the Control of Plant Poisonings, National Council of Scien-tific and Technological Development (CNPq; grant 573534/2008-0).

References

1. Aiken GE, Sutherland BL, Fletcher LR: 2011, Haemodynamics of lambs grazing perennial ryegrass (Lolium perenne L.) either infected with AR6 novel, wild-type endophyte, or endophyte-free. N Z Vet J 59:179–184.

2. Barros CSL, Barros SS, Santos MN, et al.: 1984, Leucoencefalomalacia em eqüinos no Rio Grande do Sul [Leukoencephalomalacia in horses in southern Brazil]. Pesq Vet Bras 4:101–107. In Portuguese. Abstract in English.

3. Beck PA, Gunter SA, Lusby KS, et al.: 2008, Animal perfor-mance and economic comparison of novel and toxic endo-phyte tall fescues to cool-season annuals. J Anim Sci 86: 2043–2055.

4. Bezerra PS Jr, Santos AS, Bandarra PM, et al.: 2009, Intoxicação experimental por Aspergillus clavatus em ovi-nos [Experimental poisoning by Aspergillus clavatus in sheep]. Pesq Vet Bras 29:205–210. In Portuguese. Abstract in English.

5. Bianchii P, Pugliese A, Tonolo A, et al.: 1965, La tossicita degli sclerozi naturali di Claviceps paspali Steve and Hall su alcuni animali domestici [The toxicity of natural sclero-tia of Claviceps paspali Steve Hall in domestic animals]. Zooprofilassi 2:79–98. In Italian. Abstract in English.

6. Blodgett DJ: 2001, Fescue toxicosis. Vet Clin North Am Equine Pract 17:567–577.

7. Boosinger TR, Brendemuehl JP, Bransby DL, et al.: 1995, Prolonged gestation, decreased triiodothyronine concentration, and thyroid gland histomorphologic features in newborn foals of mares grazing Acremonion coenophialum-infected fescue. Am J Vet Res 56:66–69.

8. Borges AS, Oliveira-Filho JP, Simon JJ, et al.: 2012, Slaframine toxicosis in Brazilian horses causing excessive salivation. Equine Vet Educ 24:279–283.

9. Botha CJ, Kellerman TS, Fourie N: 1996, A tremorgenic myco-toxicosis in cattle caused by Paspalum distichum (L.) infected by Claviceps paspali. J S Afr Vet Assoc 67:36–37.

10. Botha CJ, Naudé TW, Moroe ML, Rottinghaus GE: 2004, Gangrenous ergotism in cattle grazing fescue (Festuca elatior L.) in South Africa. J S Afr Vet Assoc 75:45–48.

11. Brewer D, Russell DW, deMelio Amaral RE, Aycardi ER: 1989, An examination of North and South American isolates of Pithomyces chartarum for production of sporidesmin and sporidesmolides. Proc N S Inst Sci 38:73–81.

12. Brito LAB, Nogueira RHG, Pereira JJ, et al.: 1982, Leucoencefalomalacia em eqüino associada à ingestão de milho mofado [Equine leukoencephalomalacia associated with the ingestion of moldy corn]. Arq Esc Vet UFMG 34:49–53. In Portuguese. Abstract in English.

13. Caloni F, Cortinovis C: 2011, Toxicological effects of aflatox-ins in horses. Vet J 188:270–273

14. Câmara ACL, Bastos-Alfonso JA, Riet-Correa F, et al.: 2008, Leucoencefalomalacia em eqüídeos no estado de Pernambuco [Leucoencephalomalacia in horses in Pernambuco State, Brazil]. Ciência Anim Bras 9:470–479. In Portuguese. Abstract in English.

15. Cawdell-Smith AJ, Scrivener CJ, Bryden WL: 2010, Staggers in horses grazing paspalum infected with Claviceps paspali. Aust Vet J 88:393–395.

16. Cheeke PR: 1998, Mycotoxins associated with forages. In: Natural toxicants in feeds, forages, and poisonous plants, 2nd ed., pp. 243–273. Interstate Publishers, Danville, IL.

17. Cole RJ, Dorner JW, Lansden JA, et al.: 1977, Paspalum staggers: isolation and identification of tremorgenic metabo-lites from sclerotia of Claviceps paspali. J Agric Food Chem 25:1197–1201.

18. Collin RG, Odriozola E, Towers NR: 1998, Sporidesmin pro-duction by Pithomyces chartarum isolates from Australia, Brazil, New Zealand and Uruguay. Mycol Res 102:163–166.

19. Colodel EM, Schmitz M, Traverso SD, et al.: 2004, Aspectos clínicos e patológicos da doença neurológica de bovinos reproduzida pela administração de milho contaminado com Aspergillus clavatus [Clinical and pathological aspects of the neurological disease of cattle reproduced by administration of Aspergillus clavatus contaminated corn]. Pesq Vet Bras 24(Suppl):16–17. In Portuguese.

20. Colvin BM, Harrison LR, Gosser HS, Hall RF: 1984, Aflatoxicosis in feeder cattle. J Am Vet Med Assoc 184: 956–958.

21. Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: 1995, The involvement of slaframine and swainsonine in slob-bers syndrome: a review. J Anim Sci 73:1499–1508.

22. Cunnighan IJ, Swan JB, Hopkirk CSM: 1994, The symptoms of ergot poisoning in sheep. N Z J Sci Technol 26:121–124.

23. di Menna ME, Finch SC, Popay AJ, Smith BL: 2012, A review of the Neotyphodium lolii/Lolium perenne symbiosis and its associated effects on animal and plant health, with particular emphasis on ryegrass staggers. N Z Vet J 60:315–328.

24. Evans TJ: 2011, The endocrine disruptive effects of ergopep-tine alkaloids on pregnant mares. Vet Clin North Am Equine Pract 27:165–173.





25. Fernández A, Hernández M, Verde MT, Sanz M: 2000, Effect of aflatoxin on performance, hematology, and clinical immu-nology in lambs. Can J Vet Res 64:53–58.

26. Fighera RA, Rozza DB, Piazer JV, et al.: 2003, Pneumonia intersticial em bovinos associada à ingestão de batata-doce (Ipomoea batatas) mofada [Interstitial pneumonia in cattle fed moldy sweet potatoes (Ipomoea batatas)]. Pesq Vet Bras 23:161–166. In Portuguese. Abstract in English.

27. Giannitti F, Diab SS, Pacin AM, et al.: 2011, Equine leuko-encephalomalacia (ELEM) due to fumonisins B1 and B2 in Argentina. Pesq Vet Bras 31:407–412.

28. Hassan GA, El-Nouty FD, Salem MH, et al.: 1985, Effect of aflatoxins on milk yield, plasma cortisol and haematological characteristics in lactating goats. Indian J Anim Sci 55:5–10.

29. Hirooka EY, Viotti NMA, Marochi MA, et al.: 1990, Leucoencefalomalacia em eqüinos no norte do Paraná [Equine leucoencephalomalacia in the north of Parana State, Brazil]. Rev Microbiol 21:223–227. In Portuguese. Abstract in English.

30. Hovermale JT, Craig AM: 2001, Correlation of ergovaline and lolitrem B levels in endophyte-infected perennial ryegrass (Lolium perenne). J Vet Diagn Invest 13:323–327.

31. Ilha MR, Loretti AP, Barros CS: 2003, Hyperthermic syn-drome in dairy cattle associated with consumption of ergots of Claviceps purpurea in southern Brazil. Vet Hum Toxicol 45:140–145.

32. Kellerman TS, Coetzer JAW, Naudé TW, Botha CJ: 2005, Central nervous system. In: Plant poisonings and mycotoxico-ses of livestock in southern Africa, 2nd ed., pp. 91–93. Oxford University Press, Cape Town, Republic of South Africa.

33. Lehner AF, Craig M, Fannin N, et al.: 2005, Electrospray[+] tandem quadrupole mass spectrometry in the elucidation of ergot alkaloids chromatographed by HPLC: screening of grass or forage samples for novel toxic compounds. J Mass Spectrom 40:1484–1502.

34. Løken T, Ulvund MJ, Våg T: 1979, A case of gangrenous ergotism in grazing sheep. Acta Vet Scand 20:601–603.

35. Lopez TA: 1979, Pie de festuca y su relación con otras enfermedades de origen fúngica. Una revisión bibliográfica [Gangrenous ergotism caused by fescue and its relation with other fungal diseases. A review]. Rev Med Vet 60:1–32. In Spanish. Abstract in English.

36. Lopez TA, Odriozola E, Mutti G: 1985, Intoxicación de bovi-nos con Paspalum dilatatum poir (pasto miel) contaminado con Claviceps paspali Stivens et Hall [Poisoning in cattle ingesting Paspalum dilatatum contaminated by Claviceps paspali]. Vet Argentina 3:863–870. In Spanish. Abstract in English.

37. Loretti AP, Colodel EM, Driemeier D, et al.: 2003, Neurological disorder in dairy cattle associated with the consumption of beer residues contaminated with Aspergillus clavatus. J Vet Diagn Invest 15:123–132.

38. Mason RW: 1968, Axis cylinder degeneration associated with ryegrass staggers in sheep and cattle. Aust Vet J 44:428.

39. McKenzie R: 2012, Digest of poisonous cyanobacteria, algae, slime moulds, macrofungi and plants in Australia. In: Australia’s poisonous plants, fungi and cyanobacteria: a guide to species of medical and veterinary importance, pp. 645–84. CSIRO Publishing, Collingwood, Victoria, Australia.

40. McKenzie RA, Blaney BJ, Connole MD, Fitzpatrick LA: 1981, Acute aflatoxicosis in calves fed peanut hay. Aust Vet J 57:284–286.

41. Medeiros RM, Simões SV, Tabosa IM, et al.: 2001, Bovine atypical interstitial pneumonia associated with the ingestion of damaged sweet potatoes (Ipomoea batatas) in northeastern Brazil. Vet Hum Toxicol 43:205–207.

42. Monina MI, Mascotena EA, Ruager J, et al.: 1981, Leucoencefalomalacia equina: casos registrados en el país [Equine leucoencephalomalacia: cases registered in the coun-try]. Revta Mil Vet 28:13–17. In Spanish. Abstract in English.

43. Mostrom MS, Jacobsen BJ: 2011, Ruminant mycotoxicosis. Vet Clin North Am Food Anim Pract 27:315–344.

44. Moyano MR, Molina AM, Lora AJ, et al.: 2010, Tremorgenic mycotoxicosis caused by Paspalum paspaloides (Michx.) Scribner infected by Claviceps paspali: a case report. Vet Med 55:336–338.

45. Odeon A, Steffan P, Salamanco A, Odriozola E: 1983, Fotosensibilización hepatógena del ganado bovino [Hepatogenous photosensitization in cattle]. Rev Med Vet 64:110. In Spanish. Abstract in English.

46. Odriozola E, Bretschneider G, Pagalday M, et al.: 2001, Intoxicación natural con Cynodon dactylon (pata de perdiz) en un rodeo de cría [Poisoning by Cynodon dactylon in a repro-duction herd]. Vet Argentina 148:579–583.

47. Odriozola E, Lopez T, Campero C, Gimenez Placeres C: 1993, Ryegrass staggers in heifers: a new mycotoxicosis in Argentina. Vet Hum Toxicol 35:144–146.

48. Odriozola E, Odeón A, Canton G, et al.: 2005, Diplodia maydis: a cause of death of cattle in Argentina. N Z Vet J 53:161–163.

49. Osweiler GD: 2001, Mycotoxins. Vet Clin North Am Equine Pract 17:547–566, viii.

50. Perusia OR, Rodríguez RA: 2001, Micotoxicosis [Mycotoxicosis]. Rev Invest Vet Perú 12:87–116. In Spanish.

51. Pierezan F, Oliveira Filho JC, Carmo PM, et al.: 2010, Surto de aflatoxicose em bezerros no Rio Grande do Sul [Outbreak of aflatoxicosis in calves in southern Brazil]. Pesq Vet Bras 30:418–422. In Portuguese. Abstract in English.

52. Pierezan F, Oliveira-Filho JC, Carmo PM, et al.: 2012, Intoxicação experimental por aflatoxina em bezerros [Experimental aflatoxin poisoning in calves]. Pesq Vet Bras 32:607–618. In Portuguese. Abstract in English.

53. Rego-Chaves L: 1950, Doença de sintomatologia nervosa causada pela intoxicação pelo milho [Neurological disor-der caused by corn poisoning]. Rev Med Vet 10:199–217. In Portuguese. Abstract in English.

54. Riet-Alvariza F: 1993, Intoxicação por Pithomyces chartarum [Intoxication by Pithomyces chartarum]. In: Intoxicações por plantas e micotoxicoses em animais domésticos [Plant poison-ings and mycotoxicosis in domestic animals], ed. Riet-Correa F, Méndez MC, Schild AL, pp. 93–101. Editorial Hemisfério Sul do Brasil, Pelotas, RS, Brazil. In Portuguese.

55. Riet-Alvariza F: 1993, Intoxicação por toxinas tremorgênicas de Aspergillus spp. e Penicillium spp. [Intoxication by trem-orgenic toxins of Aspergillus spp. and Penicillium spp.]. In: Intoxicações por plantas e micotoxicoses em animais domésti-cos [Plant poisonings and mycotoxicosis in domestic animals], ed. Riet-Correa F, Méndez MC, Schild AL, pp. 137–141. Editorial Agropecuária Hemisfério Sur, Montevideo, Uruguay. In Portuguese.

56. Riet-Alvariza F, Riet-Correa F, Corbo M, et al.: 1976, Síndrome nervioso en bovinos causado por el hongo Claviceps paspali [Neurological syndrome in cattle caused by the fungus Claviceps





paspali]. Veterinaria (Uruguay) 12:82–89. In Spanish. Abstract in English.

57. Riet-Alvariza FR, Riet-Correa F, Corbo M: 1977, Sindrome nervioso en bovinos producido por la ingestión de pasto ber-muda (Cynodon dactylon) [Neurological syndrome in cattle caused by ingestion of bermuda grass (Cynodon dactylon)]. Veterinaria (Uruguay) 13:89–95. In Spanish. Abstract in English.

58. Riet-Correa B, Castro MB, Lemos RA, et al.: 2011, Brachiaria spp. poisoning of ruminants in Brazil. Pesq Vet Bras 31:183–192.

59. Riet-Correa F: 1993, Intoxicação por Claviceps purpurea [Intoxication by Claviceps purpurea]. In: Intoxicações por plantas e micotoxicoses em animais domésticos [Plant poison-ings and mycotoxicosis in domestic animals], ed. Riet-Correa F, Méndez MC, Schild AL, pp. 227–239. Editorial Hemisfério Sul do Brasil, Pelotas, RS, Brazil. In Portuguese.

60. Riet-Correa F: 1993, Intoxicação por Diplodia maydis (Diplodiose) [Intoxication by Diplodia maydis (diplodiosis)]. In: Intoxicações por plantas e micotoxicoses em animais domésticos [Plant poisonings and mycotoxicosis in domestic animals], ed. Riet-Correa F, Méndez MC, Schild AL, pp. 142–145. Editorial Hemisfério Sul do Brasil, Pelotas, RS, Brazil. In Portuguese.

61. Riet-Correa F: 1993, Intoxicação por Festuca arundinacea [Intoxication by Festuca arundinacea]. In: Intoxicações por plantas e micotoxicoses em animais domésticos [Plant poison-ings and mycotoxicosis in domestic animals], ed. Riet-Correa F, Méndez MC, Schild AL, pp. 240–245. Editorial Hemisfério Sul do Brasil, Pelotas, RS, Brazil. In Portuguese.

62. Riet-Correa F, Medeiros RMT, Pfister J, et al.: 2009, Poisonings by plants, mycotoxins and related substances in Brazilian live-stock. Pallotti, Santa Maria, RS, Brazil.

63. Riet-Correa F, Meireles M, Barros C, et al.: 1998, Equine leukoencephalomalacia in Brazil. In: Toxic plants and other natural toxicants, ed. Garland T, Barr CA, pp. 479–482. CAB International, Wallingford, Oxon, UK.

64. Riet-Correa F, Meireles MA, Soares JM, et al.: 1982, Leucoencefalomalacia associada à ingestão de milho mofado [Leukoencephalomalacia associated with the ingestion of moldy corn]. Pesq Vet Bras 2:27–30. In Portuguese. Abstract in English.

65. Riet-Correa F, Méndez MC, Schild AL, et al.: 1988, Agalactia, reproductive problems and neonatal mortality in horses asso-ciated with the ingestion of Claviceps purpurea. Aust Vet J 65:192–193.

66. Riet-Correa F, Schild AL, Méndez MC, et al.: 1983, Intoxicação por Claviceps paspali em bovinos no Rio Grande do Sul [Intoxication by Claviceps paspali in cattle in Southern Brazil]. Pesq Vet Bras 3:59–65. In Portuguese. Abstract in English.

67. Riet-Correa G, Duarte MD, Cerqueira VD, et al.: 2007, Leucoencephalomalacia in mules in northern Brazil. In: Poisonous plants: global research and solutions, ed. Panter KE, Wierenga TL, Pfister JA, pp. 219–224. CABI Publishing, Wallingford, Oxon, UK.

68. Rivero R, Collazo S, Ugarte E, et al.: 2013, Leucoencefalomalacia en equinos en el litoral oeste de Uruguay [Leukoencephalomalacia

in horses on the west coast of Uruguay]. Veterinaria (Montevideo) 49:31–39. In Spanish. Abstract in English.

69. Rivero R, Feed O: 1993, Intoxicación por Ipomoea batata con-taminada por Fusarium solani [Intoxication by Ipomoea bata-tas contaminated by Fusarium solani]. In: Intoxicações por plantas e micotoxicoses em animais domésticos [Plant poison-ings and mycotoxicosis in domestic animals], ed. Riet-Correa F, Méndez MC, Schild AL, pp. 195–199. Editorial Hemisfério Sul do Brasil, Pelotas, RS, Brazil. In Portuguese.

70. Rivero R, Riet-Correa F, Dutra F, Matto C: 2011, Toxic plants and mycotoxins affecting cattle and sheep in Uruguay. In: Poisoning by plants, mycotoxins and related toxins, ed. Riet-Correa F, Pfister J, Schild AL, Wierenga T, pp. 25–34. CABI Publishing, Wallingford, Oxon, UK.

71. Rowan DD: 1993, Lolitrems, peramine and paxilline: myco-toxins of the ryegrass/endophyte interaction. Agric Ecosyst Environ 44:103–122.

72. Sabater-Vilar M, Maas RFM, De Bosschere H, et al.: 2004, Patulin produced by an Aspergillus clavatus isolated from feed containing malting residues associated with a lethal neurotoxi-cosis in cattle. Mycopathologia 158:419–426.

73. Samarajeewa U, Arseculeratne SN, Tennekoon GE: 1975, Spontaneous outbreak of aflatoxicosis in goats. Res Vet Sci 19:267–277.

74. Shlosberg A, Zadikov I, Perl S, et al.: 1991, Aspergillus cla-vatus as the probable cause of a lethal mass neurotoxicosis in sheep. Mycopathologia 114:35–39.

75. Smith BL, Towers NR: 2002, Mycotoxicoses of grazing ani-mals in New Zealand. N Z Vet J 50(Suppl):28–34.

76. Snyman LD, Kellerman TS, Vleggaar R, et al.: 2011, Diplonine, a neurotoxin isolated from cultures of the fungus Stenocarpella maydis (Berck) Sacc. that induces diplodiosis. J Agric Food Chem 59:9039–9044.

77. Strickland JR, Looper ML, Matthews JC, et al.: 2011, Board-invited review: St. Anthony’s Fire in livestock: causes, mecha-nisms, and potential solutions. J Anim Sci 89:1603–1626.

78. Stuedemann JA, Rumsey TS, Bond J, et al.: 1985, Association of blood cholesterol with occurrence of fat necrosis in cows and tall fescue summer toxicosis in steers. Am J Vet Res 46:1990–1995.

79. Sydenham EW, Marasas WFO, Shephard GS, et al.: 1992, Fumonisin concentrations in Brazilian feeds associated with field outbreaks of confirmed and suspected animal mycotoxi-coses. J Agric Food Chem 40:994–997.

80. Towers NR: 2006, Mycotoxin poisoning in grazing livestock in New Zealand. Proc N Z Soc Anim Prod 66:300–306.

81. Uhlig S, Botha CJ, Vrålstad T, et al.: 2009, Indole-diterpenes and ergot alkaloids in Cynodon dactylon (Bermuda grass) infected with Claviceps cynodontis from an outbreak of trem-ors in cattle. J Agric Food Chem 57:11112–11119.

82. Wijnberg ID, van der Ven PJ, Gehrmann JF: 2009, Outbreak of salivary syndrome on several horse farms in the Netherlands. Vet Rec 164:595–597.

83. Xavier JG, Brunner CHM, Sakamoto M, et al.: 1991, Equine leucoencephalomalacia: report of five cases. Braz J Vet Res Anim Sci 28:185–189.




Documents

Mycotoxicoses of ruminants and horses