Ergotism in Thailand caused by increased access to antiretroviral drugs: a global warning.

Ergotism is a toxic condition resulting from overexposure to the ergot compounds produced by various fungi of the genus Claviceps. Traditionally, such exposure was due to ingestion of infected grains, but long-term or excessive use of medications containing ergot derivatives or drug-drug interactions between these medications can result in ergotism. Ergotamine, typically used to treat migraine, has less than 5% bioavailability due to extensive first-pass metabolism by cytochrome P450 3A4 (CYP3A4). Concurrent intake of ergotamine and strong CYP3A4 inhibitors, such as the HIV protease inhibitors (PIs), can lead to clinical ergotism. A total of 13 cases of clinical ergotism in HIV-infected patients has been published since 1997 (most recently reviewed by Frohlich et al).

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice.

BACKGROUND: Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. METHODS: Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 mug and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. RESULTS: Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B1, B2, G1 and G2) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon beta-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. CONCLUSION: Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora.

Presumptive gangrenous ergotism in free-living moose and a roe deer.

Presumptive gangrenous ergotism in 10 moose (Alces alces) and one roe deer (Capreolus capreolus) is reported. Three of the moose came from a municipality in southeastern Norway where the disease occurred as a cluster in 1996. The other moose represented solitary or sporadic cases diagnosed in four municipalities in northwestern Norway between 1996 and 2004. Affected moose (seven calves, three yearlings) were found between October and June, showing distal limb lesions on one to three limbs. The lesions in the moose found during October and November presented as dry gangrene, whereas moose found between December and June presented with loss of the distal part of the limbs or open lesions close to sloughing. Four of the moose also had bilateral ear lesions affecting the outer third of the pinnae. A retrospective diagnosis of ergotism (June 1981) was made in a 1-yr-old roe deer from northwestern Norway showing loss of the distal part of all four limbs.

Claviceps cyperi, a new cause of severe ergotism in dairy cattle consuming maize silage and teff hay contaminated with ergotised Cyperus esculentus (nut sedge) on the Highveld of South Africa.

During December/January 1996/97 typical summer syndrome (hyperthermia and a 30% drop in milk yield) occurred in succession in two Holstein dairy herds (n=240 and n=150 milking cows, respectively) on the South African Highveld. These farms are situated in the midst of the prime maize and dairy farming areas of South Africa where this condition had never been diagnosed before. The individual components of the concentrate on both farms were negative for ergot alkaloids. Endophytic fungi and/or ergot infestation of teff and other grasses fed to the cows were then suspected of being involved, but neither endophytes nor ergot alkaloids could be implicated from these sources. By measuring the serum prolactin levels of groups of sheep (n=5) fed the first farm's total mixed ration (TMR) or its three individual fibre components for a period of 11 days, the source of the ergot alkaloids was identified. A statistically significant decrease in the level of this hormone occurred only in the group on maize silage (which constituted 28% on dry matter base of the TMR). The involvement of the maize silage was further chemically confirmed by the high levels of total ergot alkaloids, predominantly ergocryptine, found by LC-MS in the silage as well as in the TMR (115-975 ppb and 65-300 ppb, respectively). The ergot alkaloid content (mainly ergocryptine) of the maize silage on the second affected farm was 875 ppb. Withdrawal of contaminated silage resulted in gradual recovery of stock on both farms. Nut sedge (Cyperus esculentus and Cyperus rotundus of the family Cyperaceae) has a world-wide distribution and is a common weed in annual crops, and can be parasitized by Claviceps cyperi. Careful examination of the maize silage from both farms revealed that it was heavily contaminated with nut sedge and that it contained minute sclerotia, identified as those of Claviceps cyperi, originating from the latter. Nut sedge was abundant on both farms and it is believed that late seasonal rain had resulted in mature, heavily ergotised nut sedge being cut with the silage. Claviceps cyperi sclerotia, collected on the affected fields in the following autumn contained 3600-4000 ppm ergocryptine. That the dominant alkaloid produced by this particular fungus was indeed ergocryptine, was confirmed by negative ion chemical ionization MS/MS. In one further outbreak in another Holstein herd, teff hay contaminated with ergotised nut sedge and containing 1200 ppb alkaloids, was incriminated as the cause of the condition. This is the first report of bovine ergotism not associated with the Poaceae infected with Claviceps purpureum or endophytes but with the family Cyperaceae and this particular fungal phytopathogen.

Gangrenous ergotism in cattle grazing fescue (Festuca elatior L.) in South Africa.

The 1st outbreak of fescue toxicosis in South Africa was recently confirmed in a Brahman herd at Perdekop, near Standerton, in Mpumalanga province, South Africa. Within 3 weeks of being placed on a fescue pasture in mid-winter, 50 of 385 cattle developed lameness and/or necrosis of the tail. The farmer had established Festuca elatior L. (tall fescue, Iewag variety) on c. 140 ha for winter grazing. Fescue may be infected by an endophyte, Neotyphodium coenophialum, which produces ergot alkaloids, in particular ergovaline. Ergovaline concentrations in basal leaf sheaths and grass stems collected during the outbreak ranged from 1720-8170 ppb on a dry-matter basis.

Manifold manifestations of ergotism.

Vasospastic side effects leading to organic manifestations are rare in ergotamine therapy. To our knowledge, combinations of more than two signs of ergotism have rarely been described in the literature so far. We present a 65-year-old male patient who as a consequence of severe migraine had developed ergotamine abuse. He was admitted to our hospital after one week of increasing abdominal pain. During laparotomy, necrotic areas of the small intestine and the sigmoid colon were resected, which on histopathologic examination revealed severe hypertrophy of the smooth musculature of mesenteric arteries, resulting from chronic vasospasms. Postoperatively, the patient developed ischaemia of the limbs which was confirmed by angiography. Before death, the patient also showed ischaemic signs in the acrae and necrosis of the tongue.

First report of field outbreaks of ergot-alkaloid toxicity in South Africa.

Outbreaks of clinical disease caused by the ingestion of ergotized Lolium rigidum (annual ryegrass), which resulted in a substantial loss in production, have been reported. A number of outbreaks of a hyperthermia syndrome in cattle, characterized by severe loss in milk production, loss of body mass and reduced fertility, are described. In one major outbreak in March to April 1994, a milling company reported that 2,646 dairy cows on 29 farms had developed clinical signs. In this outbreak, significant levels of ergotamine, ergosine, ergocornine and ergocryptine were found in the milled dairy rations fed to the affected cows. Barley screenings containing ergotized annual-ryegrass seed was identified as the toxic component and probable source of the ergot alkaloids in the ration. The clinical syndrome was reproduced experimentally by feeding suspected feed to a group of nine high-producing Ayrshire cows. An outbreak of gangrenous necrosis of the extremities in young cattle in the winter of 1987 was also suspected of having been caused by ergot alkaloids in grain screenings.

[Ergotamine-induced anorectal lesions]. / Ergotamininduzierte anorectale Läsionen.

During the past 10 years several reports on perianal ulcerations secondary to chronic use of ergotamine suppositories were published. The present case reports deal with 2 female patients who used ergotamine suppositories for treatment of sick head aches for several years. In both cases the suppositories were used chronically. The first patient, a 60 year old woman has been treated repeatedly because of recurrent perianal ulcerations. An infection and a carcinoma could be excluded. The diagnosis of ergotamine induced ulcerations could be suspected only after a detailed work up of the patients past medical history and interview of family members. The ulcerations healed within a few months after broad excision and withdrawal of the medication. The second patient, a 51 year old woman complained of severe obstipation which occurred within a few months. The investigations showed a circular stenosis in the lower third of the rectum. The patient was treated successfully by bougienage under general anaesthesia. These case reports demonstrate the difficulties in diagnosis such lesions and emphasize the importance of a close medical follow-up when ergotamine suppositories are used for treatment of migraine. Whenever possible, a continuous treatment should be avoided.

Histological examination of blood vessels in peripheral gangrene among patients with sporadic outbreak of ergotism.

During the academic year 1985-1986 at Gondar College of Medical Sciences Hospital gangrenous ergotism was clinically diagnosed in seven patients (5 males, 2 females) ranging in age from 20 to 45 years. Amputation and subsequent histological examination of the blood vessels revealed occluded tibial arteries by acute thrombosis without cellular reaction or inflammatory lesion of the arterial wall in 3 patients. Endangitis with organized arterial thrombosis and focal recanalization of the vessels was noted in the remaining four patients. The smaller arterial branches including the dorsal pedal artery appeared to be contracted with knobby projections into the lumen. The latter was occluded by chronic, organized thrombosis in all patients. The present finding indicates that thrombosis and its organization could be another pathogenic factor in the development of gangrene due to ergotism, which is a histological picture similar to that of thrombangitis obliterans.

Cutaneous ergotism in a herd of dairy calves.

Weather conditions in northern Illinois favored infection of pasture grasses with Claviceps purpurea. A herd of 52 Holstein heifers selectively grazed the seedheads of an orchard grassbromegrass pasture infected with C purpurea and were poisoned. Peptide alkaloids were found in the sclerotia. Clinical signs of intoxication included lameness, edema of the hind limbs, epilation, areas of skin necrosis, and diarrhea. Pathologic findings included myopachynsis of arterioles in the deep dermal areas, lungs, kidney, spleen, submucosa of small intestines and cerebral cortex, focal cracks on the hoofs, and multifocal areas of detachment of the hoof wall. Of the 52 heifers, 3 died on the farm, 1 was euthanatized, and 3 were sold. The remaining heifers conceived without difficulty, and subsequent calvings were uncomplicated.

[Guides to ergotism, a too little recognized complication of trauma]. / Hinweise zum Ergotismus, einer zu wenig erkannten traumatologischen Komplikation.

The authors present two cases of ergotism in polytraumatised patients after prophylactic treatment with the combination preparation heparin-dihydroergotamine. Attention is drawn to the severity of the possible complications. It seems that it would be quite appropriate to adopt a critical attitude towards routine therapy with combination preparations containing ergotamine for the prevention of thromboembolism in polytraumatised patients.

[Ano-cutaneous gangrenous ergotism]. / Anokutaner Ergotismus gangreanosus.

A case of ergotism by abuse of ergotamine tartrate suppositories is reported. The patient developed the clinical picture of ergotism with multiple perianal ulcers. After ergot had been withdrawn there was a spontaneous healing of these ulcers after a few weeks. It is well known that ergot abuse can develop severe vascular spasm in the arteries, but it is unknown that cutaneous ulcers may occur by topical application.

Further studies concerning the toxicity of ingested ergot sclerotia (Claviceps purpurea) to young and growing pigs.

In three experiments pigs were offered diets contaminated with milled ergot sclerotia. In a metabolism study 0-5 per cent (w/w) of American wheat ergot decreased urinary nitrogen losses and improved the efficiency of nitrogen retention. When early weaned piglets ingested a diet contaminated with 2-5 per cent of the ergot, feed intake was reduced and growth rate decreased. Reduction in growth rate was also evident in growing pigs given a diet containing ergotised English wheat. These latter pigs had lesions in stomach, intestine and liver, consistent with a toxic insult. With respect to feed intake and growth these results agreed with those of an earlier study, although a toxic response was produced by a lower dosage rate and there was additional internal evidence of toxicity. Improved nitrogen retention was contrary to earlier evidence at higher dose rates but may merely reflect a tonic action which, at higher doses, becomes toxic.