Presumptive tremorgenic mycotoxicosis in a dog in New Zealand, after eating mouldy walnuts

CASE HISTORY: A 1-year-old, intact male Labrador-cross dog vomited after eating walnuts that had been on the ground for 5 months. The dog then developed tremors, ataxia, increased salivation, and hyperaesthesia. CLINICAL FINDINGS: The dog had marked generalised tremors, ataxia and a temperature of 39.9 degrees C. Both pupils were of normal size and normally responsive to light. Vomiting was induced, and walnut shell was visible in the vomitus. DIAGNOSIS: Due to the sudden onset of tremors, lack of exposure to other convulsive toxins, and the evidence of ingestion of walnuts, the provisional diagnosis was tremorgenic mycotoxicosis. The dog was treated symptomatically, and made a full recovery over 18 hours. Tremorgenic mycotoxins were detected within walnuts collected from the dog's environment. CLINICAL RELEVANCE: Fungi that produce tremorgenic mycotoxins are present in New Zealand. Intoxication should be suspected in dogs that suddenly develop muscle tremors, especially if there is a history of ingestion of mouldy food 2-3 hours prior to the development of tremors.     

Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs

In this report, we describe the natural intoxication of 2 dogs that consumed moldy dairy products found in the household garbage and the procedures used to identify and quantify the tremorgenic mycotoxins, roquefortine and penitrem A, in the remaining portions of ingested materials. Following the ingestion of mycotoxins, the dogs of our report developed muscle tremors or seizures that resembled clinical signs of strychnine poisoning. Roquefortine was the predominant mycotoxin in a moldy cream cheese wrapper that was found among scattered garbage consumed by the first dog. Penitrem A was the only mycotoxin detected in discarded moldy macaroni and cheese that was consumed by the second dog. Treatment of dogs with tremorgenic mycotoxin intoxication involves supportive care. Close monitoring is important because the development of aspiration pneumonia is common and has been reported as the cause of death. Clinical signs of intoxication gradually resolve within 24 to 48 hours.     

Mycotoxicosis: mechanisms of immunosuppression.

Mycotoxins are structurally diverse secondary metabolites of fungi that grow on feedstuffs consumed by animals and man. The clinical toxicologic syndromes caused by ingestion of fungal toxins have been characterized in domestic animals, poultry and laboratory animals and range from acute mortality to decreased production. Consumption of some mycotoxins, at levels that do not cause overt clinical mycotoxicosis, suppress immune functions and may decrease resistance to infectious disease. The sensitivity of the immune system to mycotoxin-induced immunosuppression arises from the vulnerability of the continually proliferating and differentiating cells that participate in immunemediated activities and regulate the complex communication network between cellular and humoral components. Mycotoxin-induced immunosuppression may be manifested as depressed T or B lymphocyte activity, suppressed immunoglobulin and antibody production, reduced complement or interferon activity, and impaired macrophage-effector cell function. Although the cellular-molecular basis for many of the specific immunosuppressive effects of mycotoxins are presently unclear, inhibition of DNA, RNA and protein synthesis via a variety of different mechanisms appears to be directly or indirectly responsible for the immunosuppressive action of many mycotoxins.     

Tremorgenic neuromycotoxicosis in 2 dogs ascribed to the ingestion of penitrem A and possibly roquefortine in rice contaminated with Penicillium crustosum

Two dogs developed alarming tremorgenic nervous stimulation shortly after ingesting discarded rice that had been forgotten in a refrigerator for an undetermined period and that was covered with a grey-green mould. Both dogs exhibited vomition followed by slight salivation, tremors and ataxia and 1 showed such severe agitation and seizures that it necessitated anaesthesia with thiopentone followed, on recovery, by xylazine. The other dog was only sedated with xylazine. They made an uneventful recovery. The rice vomitus yielded a pure culture of Penicillium crustosum. On chemical analysis it was negative for organochlorine, organophosphor and carbamate insecticides, as well as for strychnine, but contained 2.6 microg/g of the mycotoxins penitrem A as well as 34 microg/g of roquefortine as determined by LC-MS and confirmed by MS-MS. This is the 1st South African case of naturally occurring penitrem A toxicosis and also the 1st case where quantification of the levels of mycotoxins in dog vomitus is reported. The tremorgenicity of roquefortine and its contribution towards this syndrome, is questioned.     

Aspergillus clavatus tremorgenic neurotoxicosis in cattle fed sprouted grains

Beef and dairy cattle from four different herds in southern and central Queensland fed hydroponically-produced sprouted barley or wheat grain heavily infested with Aspergillus clavatus developed posterior ataxia with knuckling of fetlocks, muscular tremors and recumbency, but maintained appetite. A few animals variously had reduced milk production, hyperaesthesia, drooling of saliva, hypermetria of hind limbs or muscle spasms. Degeneration of large neurones was seen in the brain stem and spinal cord grey matter. The syndrome was consistent with A clavatus tremorgenic mycotoxicosis of ruminants. The cases are the earliest known to be associated with this fungus in Australia. They highlight a potential hazard of hydroponic fodder production systems, which appear to favour A clavatus growth on sprouted grain, exacerbated in some cases by equipment malfunctions that increase operating temperatures.     

Mycotoxins in fungal contaminated samples of animal feed from western Canada, 1982-1994.

Feed samples from 94 cases involving fungal contamination and suspected mycotoxicosis of farm animals in western Canada were examined during 1982-1994 to assess the incidence of mycotoxins. Samples were analyzed for aflatoxins, ochratoxin A, citrinin, sterigmatocystin, and the fungal estrogen zearalenone. Samples infected with Fusarium fungi were additionally assayed for nivalenol, deoxynivalenol, fusarenone-x, 15-acetyl-deoxynivalenol, diacetoxyscirpenol, HT-2 toxin, and T-2 toxin. Mycotoxins were found in 21 feed samples from 17 cases (18% of the reported cases), generally at levels far below those needed to induce symptoms under laboratory conditions. HT-2 toxin and other type-A trichothecenes were detected in 5 samples, deoxynivalenol and other type-B trichothecenes in 13, ochratoxin A in 5, and citrinin in 2. In 9 cases, symptoms observed in the animals were consistent with the known effects of the mycotoxin(s) found in the particular feed samples.     

Roquefortine in the stomach contents of dogs suspected of strychnine poisoning in Alberta

From April to September 1990, submissions in Alberta veterinary diagnostic laboratories for which strychnine analysis was requested were tested retrospectively for roquefortine, a diketopiperazine alkaloidal tremorgenic mycotoxin. Roquefortine was found only in strychnine-negative samples. The specific origins of the fungal-contaminated specimens could not be determined. Of the six roquefortine-positive cases, four dogs that vomited prior to treatment recovered. Two dogs which died had significant amounts of stomach contents present at the time of postmortem.

At the present time only one veterinary laboratory in Canada is routinely testing for roquefortine when samples are negative for strychnine. It appears that a low diagnostic rate for this type of poisoning may be occurring due to incomplete testing. The inability to differentiate between roquefortine and strychnine poisoning on a clinical basis in five of our six cases emphasizes that an accurate causative diagnosis requires laboratory examination.

Research in rats and sheep has shown that the tremorgenic mycotoxins penitrem A and roquefortine are excreted through bile. Although further research is required, the submission of bile and intestinal contents is recommended if stomach contents or vomitus are not available for laboratory testing. Both of these mycotoxins should be tested for when strychnine analysis is negative as fungi may produce both toxins at the same time. In this study we were unsure if roquefortine alone or in combination with other toxins was responsible for our findings.

     

Effects of foodborne Fusarium mycotoxins with and without a polymeric glucomannan mycotoxin adsorbent on food intake and nutrient digestibility, body weight, and physical and clinicopathologic variables of mature dogs

OBJECTIVE: To investigate the effects of feeding cereal-based diets that are naturally contaminated with Fusarium mycotoxins to dogs and assess the efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) in prevention of Fusarium mycotoxicosis. ANIMALS: 12 mature female Beagles. PROCEDURES: Dogs received each of 3 cereal-based diets for 14 days. One diet was uncontaminated (control diet), and the other 2 contained contaminated grains; one of the contaminated diets also contained 0.2% GMA. Contaminants included deoxynivalenol, 15-acetyl deoxynivalenol, zearalenone, and fusaric acid. Food intake and nutrient digestibility, body weight, blood pressure, heart rate, and clinicopathologic variables of the dogs were assessed at intervals during the feeding periods. RESULTS: Food intake and body weight of dogs fed the contaminated diet without GMA were significantly decreased, compared with effects of the control diet. Reductions in blood pressure; heart rate; serum concentrations of total protein, globulin, and fibrinogen; and serum activities of alkaline phosphatase and amylase as well as increases in blood monocyte count and mean corpuscular volume were detected. Consumption of GMA did not ameliorate the effects of the Fusarium mycotoxins. For the GMA-contaminated diet, digestibility of carbohydrate, protein, and lipid was significantly higher than that associated with the control diet, possibly because of physiologic adaptation of the recipient dogs to reduced food intake. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that consumption of grains naturally contaminated with Fusarium mycotoxins can adversely affect dogs' feeding behaviors and metabolism. As a food additive, GMA was not effective in prevention of Fusarium mycotoxicosis in dogs.     

Tremorgenic syndrome in a cattle herd after feeding silage contaminated with A. clavatus

The clinical signs, pathological and laboratory findings of cattle suffering from a tremorgenic syndrome are described. Animals on a farm with a total of 22 cows, 18 heifers and 9 calves were fed mouldy grass and spent malt-grain silage. Five heifers were affected with muscular tremor, hyperexcitability and hypersensitivity. They were ataxic or in sternal recumbency, while their appetite remained normal. Haematology and blood chemistry in two heifers as well as cerebrospinal fluid from one sick animal were unremarkable. The pathological examination of one animal brought no macroscopic changes to light. Histological examination, however, revealed the degeneration of motor neurones in the midbrain, brain stem and spinal cord. Analysis of a silage sample provided evidence of the presence of Aspergillus clavatus, a mould capable of producing neurotoxic tremorgenic mycotoxins. Epidemiology, clinical findings, pathology and microbiological examination suggest that the five cattle were suffering from neuromycotoxicosis.     

霉菌毒素对动物肠道功能的影响及其作用机制研究进展

霉菌毒素属于霉菌次级代谢产物,具有种类多、分布广、毒性大的特点。霉菌毒素作为畜牧业中的“隐形杀手”,不仅严重降低了饲料品质,而且常存在于饲料原料中,影响动物机体健康,直接或间接造成食品安全问题。肠道作为消化吸收的主要场所,对霉菌毒素的刺激具有强烈的抵御和免疫作用,同时也深受霉菌毒素的损伤。玉米是主要的饲料原料之一,而黄曲霉毒素、脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮是玉米中主要出现的霉菌毒素,因此了解这3种霉菌毒素的毒性机制显得尤为重要。本文综合国内外研究进展,主要以这3种霉菌毒素为例,就霉菌毒素对肠道屏障、免疫机能、抗氧化功能、微生态平衡和营养物质代谢等的影响及其作用机制研究进行综述,为降低饲料中霉菌毒素的危害和开发降解霉菌毒素产品提供新的思路和理论依据,同时也对提升我国畜禽肉品质和粮食战略安全具有重要意义。     

Implications of mycotoxins in animal disease

Mycotoxins are formed on animal feeds when conditions of moisture and temperature permit the growth of naturally occurring toxigenic fungi. In general, mycotoxins are low molecular weight, nonantigenic substances, many of which are relatively heat stable. Mycotoxins can cause acute disease episodes when animals consume critical quantities of them. Specific toxins affect specific organs or tissues such as the liver, kidney, oral and gastric mucosa, brain, or reproductive tract. In acute mycotoxicoses, the signs of disease often are marked and directly referable to the affected target organs. Most frequently, however, concentrations of mycotoxin in feeds are below those that cause acute disease. At lower concentrations, the effects of mycotoxins are more protean. They reduce the growth rate of young animals, and some interfere with native mechanisms of resistance and impair immunologic responsiveness, making the animals more susceptible to infection. These effects on immunity and resistance are difficult to recognize because the signs of disease are associated with the infection rather than with the mycotoxin that predisposed the animal to infection. Animals vary in their susceptibility to some mycotoxins, according to the species and age of animal; young growing animals are more susceptible to certain mycotoxins than are adults. The major effects, sources, and dose response relationships of mycotoxins important to the health of food-producing animals are presented in accompanying tables.     

The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response

Mycotoxins are structurally diverse fungal metabolites that can contaminate a variety of dietary components consumed by animals and humans. It is considered that 25% of the world crop production is contaminated by mycotoxins. The clinical toxicological syndromes caused by ingestion of moderate to high amounts of mycotoxins and their effect on the immune system have been well characterized. However, no particular attention has been focused on the effects of mycotoxins on the local intestinal immune response. Because of their location, intestinal epithelial cells (IECs) could be exposed to high doses of mycotoxins. As a component of the innate local immune response, intestinal epithelial cells have developed a variety of mechanisms which act to reduce the risk of infection by microorganisms or intoxication by toxic compounds. This review summarises the innate immune response developed by intestinal epithelial cells and reports the literature concerning the effects of mycotoxins on them. Particularly, the effects of mycotoxins on the maintenance of a physical barrier by epithelial cells will be discussed together with their effect on extrinsic protective components of the innate intestinal immunity: mucus secretion, antimicrobial peptide generation, IgA and pro-inflammatory cytokine release.     

电化学生物传感器在真菌毒素检测中的研究进展

真菌毒素是真菌在食品或饲料中生长所产生的代谢产物,这些低分子质量化合物既是天然存在的,同时也是无法避免的。真菌通过两种途径进入食物链,一方面可以直接从受真菌毒素污染的植物性食品成分进入食物链;另一方面也可以通过食物中产毒真菌生长的间接污染进入食物链。真菌毒素广泛存在于成熟的玉米、谷物、大豆、高粱、花生和饲料作物中。食用受真菌毒素污染的食物或饲料会对人和动物造成急性或慢性毒性。真菌毒素除了有直接食用受霉菌毒素污染的食物和饲料造成的不良影响外,还有因为摄入动物源性食品,如肉类、牛奶或鸡蛋,含有真菌毒素的残留物或代谢物而引起的公众健康问题。目前虽然已经鉴定出超过400种真菌毒素,但食物中广泛存在的6种毒素：黄曲霉毒素、赭曲霉毒素、玉米赤霉烯酮、伏马菌素、呕吐毒素及T-2毒素,已在世界范围内引发了持续的食品安全问题。该论文总结了6种真菌毒素的毒性,重点分析了近年来电化学生物传感器在这几种真菌毒素检测中的研究进展,旨在通过一系列的总结分析去展望其在真菌毒素检测方面的发展前景。     

饲料中的霉菌毒素及其防制措施

霉菌毒素是由真菌或霉菌产生的次级代谢产物,在动物体中,霉菌毒素的毒性是慢性的,很少引起动物死亡。但是霉菌毒素的存在降低了饲料的营养价值,以及动物的生产性能,从而影响生产力,且霉菌毒素在畜产品(肉、奶等)中的残留会给人类健康带来严重威胁。作者主要介绍了饲料中常见的霉菌毒素(黄曲霉毒素、赭曲霉毒素、玉米赤霉烯酮、脱氧雪腐镰刀菌烯醇、T-2毒素、伏马菌素等),以及其毒性和危害,并从预防与去毒两个方面,阐述了霉菌毒素的防制措施,进而减少霉菌毒素造成的危害。     

Clinical presentation and management of moxidectin toxicity in two dogs

Moxidectin is a macrocyclic lactone related to ivermectin used in horses and dogs for endoparasite treatment and prophylaxis. The clinical and neurological presentation of moxidectin toxicity in two dogs following inadvertent poisoning with a moxidectin-containing equine de-worming medication is reported here. In both the dogs, the predominant clinical signs were generalised tremors and ataxia. Moxidectin exerts its neurotoxic effects in mammals by potentiating the effect of gamma-aminobutyric acid and, consistent with this, both the dogs demonstrated a poor response to treatment with diazepam. It would be more appropriate to avoid gamma-aminobutyric acid agonists, such as benzodiazepines and barbiturates, in dogs with moxidectin toxicity and consider using anaesthetic agents with a different mode of action, such as propofol. The prognosis in dogs accidentally exposed to moxidectin-containing equine de-worming medication appears to be excellent if the cause of the neurotoxicity is correctly identified and the case is appropriately managed.     

Toxicity in three dogs from accidental oral administration of a topical endectocide containing moxidectin and imidacloprid

Three dogs were presented with a history of oral administration of a topical endectocide containing imidacloprid and moxidectin. They were diagnosed with imidacloprid and moxidectin intoxication, having ingested doses ranging from 7.5 to 1.4 mg/kg of imidacloprid and 1.9 to 2.8 mg/kg of moxidectin. The three dogs were affected to different degrees of severity, but all displayed signs of ataxia, generalised muscle tremors, paresis, hypersalivation and disorientation. Temporary blindness occurred in two cases. The three dogs were tested for the presence of the multi-drug resistance 1 gene deletion, which can cause an increased sensitivity to the toxic effects of moxidectin, and were found to be negative. Treatment included gastrointestinal decontamination, intravenous fluid therapy and benzodiazepines to control muscle tremors. All three dogs made a complete recovery within 48 h of ingestion.     

Molds, mycotoxins, and mycotoxicosis

Interest in mycotoxins and mycotoxicosis in humans and animals has greatly increased in recent years. Horses have long been considered very susceptible to molds. The signs, treatment, and prevention of several conditions, such as leukoencephalomalacia, aflatoxicosis, ergotism, fescue toxicity, slobbering disease, ryegrass staggers, and moldy sweet clover disease, are discussed.     

Mycotoxins.

Horses consume feed grains and forages that can produce a range of mycotoxins resulting from mold invasion. Toxicosis of horses often occurs from fumonisins or aflatoxin in grains, from the tremorgenic mycotoxins in dallis grass, or from slaframine in red clover. Fumonisin toxicosis often is severe and fatal, and aflatoxin can be acute or chronic and debilitating. Other mycotoxins reported in horses may cause moderate to mild signs that regress when the contaminated feedstuff is removed. Overall, horses appear to have a relatively low prevalence of reported mycotoxicoses among domestic animals, but they are extremely sensitive to the fumonisins. Since there are no good therapies for mycotoxin poisoning, attention to providing high quality grains and forages to prevent mycotoxicoses is the most effective means for reducing the risk of mycotoxins in horses.     

Intoxication by tremorgenic mycotoxin (penitrem A) in a dog

A 1-year-old Siberian Husky dog presented with severe muscle tremors after ingestion of a mouldy hamburger bun. Penicillium crustosum and the tremorgenic mycotoxin penitrem A were isolated from the remaining portion of the hamburger bun. When grown in pure culture, the isolate of P. crustosum produced large amounts of penitrem A, along with other penitrem compounds. This is the first reported Australian case of toxicosis by naturally occurring penitrem A.     

牛奶中霉菌毒素共污染及联合毒理效应

霉菌毒素是由镰刀菌、曲霉和青霉等丝状真菌产生的低分子质量次级代谢产物.食品和饲料中霉菌毒素的共污染现象广泛存在,深受各国相关从业者和研究人员的重视,但直到今天,有关霉菌毒素的联合毒理效应研究仍然有所欠缺,如低毒性长期暴露的体内试验如今仍然很少.目前,世界范围内相关标准和法规的建立普遍只关注于单独霉菌毒素的毒理效应.牛奶...