Health Effects of Penitrem A – Ingestion Poisoning

 

 

This page lists medical journal articles discussing ingestion poisoning with penitrem A.

The Health Effects of Penitrem A page of the Paradigm Change site provides further information on the effects of this mycotoxin.

 

Humans

Botha CJ, Visagie CM, Sulyok M. Putative neuromycotoxicoses in an adult male following ingestion of moldy walnuts. Mycotoxin Res. 2018 Aug 7. PMID: 30088215

A tremorgenic syndrome occurs in dogs following ingestion of moldy walnuts, and Penicillium crustosum has been implicated as the offending fungus. This is the first report of suspected moldy walnut toxicosis in man. An adult male ingested approximately eight fungal-infected walnut kernels and after 12 h experienced tremors, generalized pain, incoordination, confusion, anxiety, and diaphoresis. Following symptomatic and supportive treatment at a local hospital, the man made an uneventful recovery. A batch of walnuts (approximately 20) was submitted for mycological culturing and identification as well as for mycotoxin analysis. Penicillium crustosum Thom was the most abundant fungus present on walnut samples.

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Lewis Peter R., Donoghue Michael B., Hocking Ailsa D., Cook Lucy, Granger Linda V.. Tremor syndrome associated with a fungal toxin: sequelae of food contamination. The Medical journal of Australia. 2005;182:582–584. PMID: 15938687

We report on an elderly couple who presented with a syndrome that included severe generalised tremor and incoordination after eating soup from a damaged can. Black mould contaminating the can was subcultured and the fungus Penicillium crustosum was identified. This fungus usually produces a potent neurotoxin called penitrem A. The couple displayed symptoms consistent with penitrem A ingestion, all of which resolved fully.

 

Dogs

Eriksen G. S., Jäderlund K. Hultin, Moldes-Anaya A.,  Schönheit J, Bernhoft A, Jaeger G, Rundberget T, Skaar I.. Poisoning of dogs with tremorgenic Penicillium toxins. Medical mycology. 2010;48:188–196. PMID: 19886763

Fungi in the genus Penicillium, particularly P. crustosum, produce tremorgenic mycotoxins, as well as suspected tremorgenic compounds. The accidental intoxication of six dogs with such toxins are reported. The clinical signs included vomiting, convulsions, tremors, ataxia, and tachycardia, all of which are indicators of intoxications affecting the nervous system. One dog was euthanized in the acute phase, while three others recovered completely within a few days. However, neurological symptoms were still observed four months after the poisoning of two of the dogs. One of these recovered completely within the next 2-3 months, while the other still suffers from ataxia three years later. Available samples of feed, stomach content and/or tissues from the intoxications were subjected to mycological and chemical analysis. Penitrem A was found in all reported poisonings and roquefortine C in all cases when this toxin was included in the analysis.

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Young Kristin L., Villar David, Carson Thomas L., Ierman Paula M., Moore Ronda A., Bottoff Michael R.. Tremorgenic mycotoxin intoxication with penitrem A and roquefortine in two dogs. Journal of the American Veterinary Medical Association. 2003;222. PMID: 12523480

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 mycotoxinsroquefortine 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. 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.

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Walter Sean L.. Acute penitrem A and roquefortine poisoning in a dog. The Canadian veterinary journal. La revue vétérinaire canadienne. 2002;43:372–374. PMID: 12001505

Penitrem A and roquefortine poisonings were diagnosed in a Laborador retriever following garbage consumption. Clinical signs of mycotoxicosis included polypnea, tachycardia, and ataxia that quickly progressed to lateral recumbency and seizures. Removal of the mycotoxins from the stomach soon after ingestion allowed the dog to recover within 72-96 hours.

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Puschner Birgit. Mycotoxins. The Veterinary clinics of North America. Small animal practice. 2002;32:409–419. PMID: 12012744

Only aflatoxins, penitrem A, and roquefortine have been confirmed in natural mycotoxicoses in pets. Although they make up only a small portion of the cases presented to veterinarians, mycotoxicoses often require special effort. Establishing an accurate diagnosis is crucial to minimize exposure and provide adequate treatment.

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Naudé T. W., OʼBrien O. M., Rundberget T., McGregor A. D., Roux C., Flåøyen A.. Tremorgenic neuromycotoxicosis in 2 dogs ascribed to the ingestion of penitrem A and possibly roquefortine in rice contaminated with Penicillium crustosum. Journal of the South African Veterinary Association. 2002;73:211–215. PMID: 12665136

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.

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Boysen Søren R., Rozanski Elizabeth A., Chan Daniel L., Grobe Terri L., Fallon Michael J., Rush John E.. Tremorgenic mycotoxicosis in four dogs from a single household. Journal of the American Veterinary Medical Association. 2002;221. PMID: 12458614

Mycotoxins that induce muscle tremors, ataxia, and convulsions are termed tremorgenic mycotoxins. Our report documents the clinical course of 4 dogs from a single household that were simultaneously affected by tremorgenic mycotoxins. Diagnosis of tremorgenic mycotoxicosis was confirmed by stomach content analysis from 1 of the dogs. The mycotoxins identified were penitrem A and roquefortine, which are both produced by Penicillium spp. Treatment goals following tremorgenic mycotoxin ingestion include minimizing absorption, controlling tremors and seizures with methocarbamol and pentobarbital sodium administration, and providing supportive care. Two of the affected dogs required ventilatory support. With early aggressive treatment, prognosis is good and recovery is complete without sequelae.

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Lowes N. R., Smith R. A., Beck B. E.. Roquefortine in the stomach contents of dogs suspected of strychnine poisoning in Alberta. The Canadian veterinary journal. La revue vétérinaire canadienne. 1992;33:535–538. PMID: 17424061 

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. 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.

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Hocking A. D., Holds K., Tobin N. F.. Intoxication by tremorgenic mycotoxin (penitrem A) in a dog. Australian veterinary journal. 1988;65:82–85. PMID: 3401148

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.

Richard J. L., Bacchetti P., Arp L. H.. Moldy walnut toxicosis in a dog, caused by the mycotoxin, penitrem A. Mycopathologia. 1981;76:55–58. PMID: 7312021

Penitrem A was found in moldy walnuts that were involved in an intoxication of a dog in California. Penicillium crustosum was isolated from the walnuts and penitrem A was isolated from extracts of the mycelium of this fungus when it was grown on a synthetic medium.

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Arp L. H., Richard J. L.. Intoxication of dogs with the mycotoxin penitrem A. Journal of the American Veterinary Medical Association. 1979;175:565–566. PMID: 511750

Mycotoxicosis caused by ingestion of moldy cream cheese was suspected in two dogs with severe muscle tremors and generalized seizures. Penicillium crustosum and its toxin, penitrem A, were isolated from the moldy cream cheese.

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Hayes A. W., Presley D. B., Neville J. A.. Acute toxicity of penitrem A in dogs. Toxicology and applied pharmacology. 1976;35:311–320. PMID: 1265748

 

Other Animals

Stoev S. D., Dutton M. F., Njobeh P. B., Mosonik J. S., Steenkamp P. A.. Mycotoxic nephropathy in Bulgarian pigs and chickens: complex aetiology and similarity to Balkan endemic nephropathy. Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment. 2010;27:72–88. PMID: 19753495 

Spontaneous nephropathy in Bulgaria, which is observed frequently during meat inspection and which differs morphologically from the classical description of mycotoxic porcine/chicken nephropathy as made in Denmark, was found to have a multi-mycotoxic aetiology being mainly provoked by a combined effect of ochratoxin A, penicillic acid and fumonisin B1 in addition to a not-yet-known metabolite. Some other mycotoxins with lower importance such as citrinin, penitrem A, etc., may also influence clinicopathological picture of this nephropathy.

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Arp L. H., Richard J. L.. Experimental intoxication of guinea pigs with multiple doses of the mycotoxin, penitrem A. Mycopathologia. 1981;73:109–113. PMID: 7219513

Young female guinea pigs were fed various doses of penitrem A very 3 days for 3 weeks. Guinea pigs fed penitrem A had muscle tremors, seizures, and ataxia, and total weight gains were less than those of control guinea pigs. Histologic examination of multiple tissues and electron microscopic examination of liver and kidney revealed no differences between guinea pigs fed penitrem A and controls. Sera harvested at necropsy from guinea pigs fed penitrem A and control guinea pigs did not differ significantly in mean values of two liver enzymes (ornithine carbamoyltransferase and sorbitol dehydrogenase), complement, total protein, and differential proteins (albumin; alpha 1, alpha 2, beta, and gamma globulins). Results of this study indicate that penitrem A causes only central nervous system dysfunction; evidence of cytotoxicity for extraneural tissues was not found.

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Cysewski S. J., Baetz A. L., Pier A. C.. Penitrem A intoxication of calves: blood chemical and pathologic changes. American journal of veterinary research. 1975;36:53–58. PMID: 1115418

An isolate of Penicillium puberulum, obtained from moldy silage, was found to produce a tremorgenic mycotoxin, penitrem A. Dried ground mycelium of this isolate was administered orally to calves either in increasing daily doses or in a single dose that equalled the amount given over a 3-day period in the increasing daily-dose schedule. Signs of intoxication included tremor, ataxia, muscular rigidity, and convulsive episodes. Marked increases in plasma concentrations of lactic acid, pyruvic acid, glucose, and creatine phosphokinase activity were found coincident with the development of severe tremor. The only gross or microscopic change observed in tissues of intoxicated animals was an accumulation of fat in the liver. Changes in the various plasma constituents were interpreted as a secondary effect of the intoxication.

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