Use of Integrative Interactomics for Improvement of Farm Animal Health and Welfare: An Example with Fescue Toxicosis.

Rapid scientific advances are increasing our understanding of the way complex biological interactions integrate to maintain homeostatic balance and how seemingly small, localized perturbations can lead to systemic effects. The 'omics movement, alongside increased throughput resulting from statistical and computational advances, has transformed our understanding of disease mechanisms and the multi-dimensional interaction between environmental stressors and host physiology through data integration into multi-dimensional analyses, i.e., integrative interactomics. This review focuses on the use of high-throughput technologies in farm animal research, including health- and toxicology-related papers. Although limited, we highlight recent animal agriculture-centered reports from the integrative multi-'omics movement. We provide an example with fescue toxicosis, an economically costly disease affecting grazing livestock, and describe how integrative interactomics can be applied to a disease with a complex pathophysiology in the pursuit of novel treatment and management approaches. We outline how 'omics techniques have been used thus far to understand fescue toxicosis pathophysiology, lay out a framework for the fescue toxicosis integrome, identify some challenges we foresee, and offer possible means for addressing these challenges. Finally, we briefly discuss how the example with fescue toxicosis could be used for other agriculturally important animal health and welfare problems.

Claviceps purpurea e Bipolaris sp. como causa de ergotismo em bovinos no estado de Santa Catarina / Claviceps purpurea e Bipolaris sp. as a cause of ergotism in cattle in Santa Catarina State

Claviceps purpurea é o fungo associado ao ergotismo. Esta é uma enfermidade causada pela ingestão de escleródios chamados de ergot, que contém alcalóides que atuam em receptores adrenérgicos, dopaminérgicos e seratoninérgicos causando efeito direto em vasos sanguíneos, musculatura lisa e sistema nervoso central e autônomo. Descrevem-se dados epidemiológicos, sinais clínicos e lesões de uma enfermidade de bovinos caracterizada por hipertermia, taquicardia, taquipneia e ulcerações na coroa do casco de bovinos. Entre 2000 e 2014 foram diagnosticados 13 surtos, três da forma distérmica, sete da forma gangrenosa e três da forma convulsiva. Porém, em cinco destes sete surtos, nos locais onde esses animais pastoreavam havia alta incidência de inflorescências de Sporobolus indicus conhecido como "capim-mourão", infectadas por um fungo com coloração enegrecida, identificado como Bipolaris sp. A enfermidade foi reproduzida experimentalmente em cinco bovinos com a administração destas inflorescências. Os bovinos em experimentação receberam inflorescências de S. indicus respectivamente nas doses diárias de 0,1g/kg, 0,2g/kg, 0,2g/kg, 0,26g/kg e 0,34g/kg por um período de 4, 7, 9 e 30 dias. Após três a sete dias de ingestão das inflorescências infectadas, quatro dos cinco bovinos apresentaram diarreia e manifestaram taquicardia, taquipneia e hipertermia em algum período durante a ingestão. Estes sinais coincidiram com os dias mais quentes deste período. Um bovino manifestou hiperemia na coroa do casco e perda de pêlos da extremidade da cauda. Baseado na reprodução experimental é possível afirmar que o capim Sporobolus indicus infectado pelo fungo Bipolaris sp é capaz de causar diarreia, hipertermia, taquicardia, taquipneia, hiperemia na coroa do casco e perda de pêlos da extremidade da cauda.(AU)

Claviceps purpurea is the fungus associated with ergotism. Ergotism is a disease caused by the ingestion of esclerodios called ergot, which contains alkaloids that act on dopaminergic and adrenergic receptors, causing seratoninergic effect on blood vessels, smooth muscles and central nervous and autonomic system. The present study describes epidemiological data, clinical signs and lesions of a bovine cattle disease characterized by hyperthermia, tachycardia, tachypnea and injuries in the coronary band of the hooves. Initially the cause was attributed to the fungus Claviceps purpurea. Between 2000 and 2014, 13 outbreaks were described, being three of distermic form, seven of gangrenous and three of the convulsive form. However, in five out of the seven of the gangrenous form outbreaks, it has been observed a high incidence of smut grass (Sporobolus indicus) inflorescences infected by a blackened fungus, classified as Bipolaris sp., in the places where the bovine grazed. The disease was reproduced experimentally by administration of inflorescences of smut grass contaminated by Bipolaris sp. Five bovine received daily doses of 0.1g/kg, 0.2g/kg, 0.2g/kg, 0.26g/kg and 0.34g/kg during 4, 7, 9, 30 and 30 days respectively. After three to seven days of eating contaminated inflorescences four cattle had diarrhea, tachycardia, tachypnea and intermittent hyperthermia. These clinical signs happened on the warmest days and during the warmest temperatures of the day. A bovine showed hyperemia in the coronary band of the hoof and loss of tail tip hair. According to data obtained during the experimental reproduction, smut grass contaminated by Bipolaris sp. can cause hyperthermia, tachycardia, tachypnea, injuries in the coronary band of the hoof and loss of the tail tip hair in bovine cattle.(AU)

Forages and pastures symposium: managing the tall fescue-fungal endophyte symbiosis for optimum forage-animal production.

Alkaloids produced by the fungal endophyte (Neotyphodium coenophialum) that infects tall fescue [Lolium arundinaceum (Schreb.) Darbysh.] are a paradox to cattle production. Although certain alkaloids impart tall fescue with tolerances to environmental stresses, such as moisture, heat, and herbivory, ergot alkaloids produced by the endophyte can induce fescue toxicosis, a malady that adversely affects animal production and physiology. Hardiness and persistence of tall fescue under limited management can be attributed to the endophyte, but the trade-off is reduced cattle production from consumption of ergot alkaloids produced by the endophyte. Improved understanding and knowledge of this endophyte-grass complex has facilitated development of technologies and management systems that can either mitigate or completely alleviate fescue toxicosis. This review discusses the research results that have led to development of 5 management approaches to either reduce the severity of fescue toxicosis or alleviate it altogether. Three approaches manipulate the endophyte-tall fescue complex to reduce or alleviate ergot alkaloids: 1) use of heavy grazing intensities, 2) replacing the toxic endophyte with nonergot alkaloid-producing endophytes, and 3) chemical suppression of seed head emergence. The remaining 2 management options do not affect ergot alkaloid concentrations in fescue tissues but are used 1) to avoid grazing of tall fescue with increased ergot alkaloid concentrations in the late spring and summer by moving cattle to warm-season grass pasture and 2) to dilute dietary alkaloids by interseeding clovers or feeding supplements.

Epidemics of mold poisoning past and present.

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

Effect of feeding sorghum ergot (Claviceps africana) to sows during mid-lactation on plasma prolactin and litter performance.

Diets containing 3% sorghum ergot (16 mg alkaloids/kg, including 14 mg dihydroergosine/kg) were fed to 12 sows from 14 days post-farrowing until weaning 14 days later, and their performance was compared with that of 10 control sows. Ergot-fed sows displayed a smaller weight loss during lactation of 24 kg/head vs. 29 kg/head in control sows (p > 0.05) despite feed consumption being less (61 kg/head total feed intake vs. 73 kg/head by control sows; p < 0.05). Ergot-fed sows had poorer weight gain of litters over the 14-day period (16.6 kg/litter vs. 28.3 kg/litter for controls; p < 0.05) despite an increase in consumption of creep feed by the piglets from the ergot-fed sows (1.9 kg/litter compared with 1.1 kg/litter by the control; p > 0.05). Sow plasma prolactin was reduced with ergot feeding after 7 days to 4.8 microg/l compared with 15.1 microg/l in the control sows (p < 0.01) and then at weaning was 4.9 microg/l compared with 8.0 microg/l (p < 0.01) in the control sows. Two sows fed ergot ceased lactation early, and the above sow feed intakes, body weight losses with litter weight gains and creep consumption indirectly indicate an ergot effect on milk production.

Feeding sorghum ergot (Claviceps africana) to sows before farrowing inhibits milk production.

OBJECTIVE: To assess the impact of feeding different amounts of sorghum ergot to sows before farrowing. DESIGN: Fifty-one pregnant sows from a continually farrowing piggery were sequentially inducted into the experiment each week in groups of four to seven, as they approached within 14 days of farrowing. Diets containing sorghum ergot sclerotia within the range of 0 (control) up to 1.5% w/w (1.5% ergot provided 7 mg alkaloids/kg, including 6 mg dihydroergosine/kg) were randomly allocated and individually fed to sows. Ergot concentrations were varied with each subsequent group until an acceptable level of tolerance was achieved. Diets with ergot were replaced with control diets after farrowing. Post-farrowing milk production was assessed by direct palpation and observation of udders, and by piglet responses and growth. Blood samples were taken from sows on three days each week, for prolactin estimation. RESULTS: Three sows fed 1.5% ergot for 6 to 10 days preceding farrowing produced no milk, and 87% of their piglets died despite supplementary feeding of natural and artificial colostrums, milk replacer, and attempts to foster them onto normally lactating sows. Ergot inclusions of 0.6% to 1.2% caused lesser problems in milk release and neo-natal piglet mortality. Of 23 sows fed either 0.3% or 0.6% ergot, lactation of only two first-litter sows were affected. Ergot caused pronounced reductions in blood prolactin, and first-litter sows had lower plasma prolactin than multiparous sows, increasing their susceptibility to ergot. CONCLUSION: Sorghum ergot should not exceed 0.3% (1 mg alkaloid/kg) in diets of multiparous sows fed before farrowing, and should be limited to 0.1% for primiparous sows, or avoided completely.

Use of nonergot alkaloid-producing endophytes for alleviating tall fescue toxicosis in sheep.

Nonergot alkaloid-producing endophytes from New Zealand were inserted into tall fescue (Festuca arundinacea) cultivars in an attempt to address the problem of fescue toxicosis in grazing sheep. A 3-yr grazing study was conducted to determine lamb performance and to evaluate toxicosis in lambs grazing nonergot alkaloid-producing endophyte-infected (AR542 or AR502), endophyte-free (E-), or wild-type toxic endophyte-infected (E+) Jesup tall fescue or nonergot alkaloid-producing endophyte-infected (AR542) Georgia-5 tall fescue. Replicated 0.11-ha tall fescue paddocks were established at the central Georgia Branch Station during September 1997 and stocked with lambs from spring 1998 through autumn 2000. Mean ergot alkaloid concentrations were higher (P < 0.01) in E+ forage than in AR542, AR502, and E- tall fescue, and ergot alkaloid concentrations in E- plants and plants infected with AR542 and AR502 were low. Forage availability did not differ (P = 0.92) across treatments during autumn and was higher (P < 0.05) in Georgia-5 AR542 than in Jesup AR502 and E+ pastures. Initial serum prolactin (PRL) concentrations did not differ (P = 0.58) across treatments during autumn, but were higher on Jesup AR542 than E+ during spring. Post-treatment serum PRL concentrations were depressed (P < 0.01) on E+ compared with AR542, AR502, and E- in both spring and autumn. Signs of heat stress were observed in E+ lambs during periods of high ambient temperatures. Mean post-treatment rectal temperature and mean stocking rate exhibited treatment x year interactions (P < 0.05). Lamb ADG was higher (P < 0.05) on AR542, AR502, and E- than on E+ tall fescue. Similarly, gain/hectare was higher (P < 0.015) on AR542, AR502, and E- than on E+. Tall fescue pastures containing AR542 and AR502 endophytes yielded lamb performance that did not differ from that on E- tall fescue and which was superior to performance on E+ tall fescue. Depressed PRL concentrations and elevated rectal temperatures as indicators of toxicosis were evident only in lambs grazing E+ tall fescue, suggesting that nonergot alkaloid-producing endophyte-infected tall fescue is a viable alternative for alleviating tall fescue toxicosis.

Endocrine alterations associated with ergopeptine alkaloid exposure during equine pregnancy.

Ergopeptine alkaloid exposure is common in pregnant mares. Many mares live in geographic areas where Neotyphodium coenophialum-infected tall fescue is the dominant grass in pastures and hay. A variety of grasses and cereal grains can be infected by Claviceps purpurea, and fungal sclerotia can contaminate forage and especially ground and pelleted feed. An understanding of the endocrine alterations associated with ergopeptine alkaloid exposure during pregnancy is necessary for the diagnosis of potential exposure to these compounds and for eective prophylaxis and therapy.

[Ergot in feed--the clarification of possible ergot-related infirmity cases]. / Mutterkorn in Futtermitteln--ein Beitrag zur Klärung möglicher mutterkornbedingter Schadensfälle.

Practicing veterinarians should realize that the symptoms of ergot intoxication may differ markedly. Gangrenous alterations (ears, feet, tail) as well as convulsive signs (excitability) are described as typical symptoms of ergotism. It is noteworthy that inadequate development of the udder and lactation failure may also be related to ergot contaminated diets. Ergot contamination of diets is caused by grain infection with Claviceps purpurea and sometimes by infection of grass and weed (in grain). The frequency of ergot contamination is high in rye, triticale and wheat and varies in relation to region, climatic conditions and kind of wheat. For diagnosis of ergot contamination a thorough visual inspection of the used diet is to be recommended. Due to the variation of ergots (infected grain, infected weed) it is difficult to determine the contamination in prepared feed mixtures. The anamnestic procedure, method of visual feed inspection as well as a chromatographic method for detection of ergot alkaloids in feed samples are described to facilitate the detection of possible ergot related cases.