Lecture Slides


Actinomycetales
Antifungal Drugs
Aspergillus
Blastomycosis
Candidiasis
Coccidioidomycosis
Cryptococcosis
Dermatophytosis
Fungal Ecology
Histoplasmosis
Mycotic Keratitis
Mycotoxins
Oportunistic Fungal Inf-
ections

Otomycosis
Sporotrichosis
Unusual Pathogens
Zygomycosis

Mycotoxins

- Some fungal secondary metabolites are toxic to animals and man.
Historically, effects of mycotoxicoses have been noted for centuries
- Middle Ages - ergotism
- Salem witchcraft trials
- 1960’s - aflatoxicosis outbreaks

Conditions for Mycotoxin Production

- Substrate
- Toxin producing fungal strain
- Temperature
- Moisture
- May be more than one toxin present
- Levels for some regulated for interstate shipment (e.g. 20 ppb for aflatoxin)

Aflatoxins

- Large, unsaturated polycyclic compounds
- AFB, AFG in grains, nuts etc.
- AFM - metabolite of AFB or AFG in meat or milk
- Usually A flavus (hence name)
- produced in peanuts, cottonseeds, corn
- Needs moderate temp., moisture greater than 13 %

Aflatoxin toxicity

- Hepatotoxicity - forms adducts with DNA
Species susceptibility
- ducklings - turkey - pigs - cattle - sheep
Acute toxicity
- Obvious in days ,or sometimes hours, after ingestion of substantial amount of AF Public Health concerns
- Concentration reduced 300-fold in milk, 10,000-fold in meat

Aflatoxicosis

Chronic toxicity
- Results from prolonged ingestion of lesser amounts
- Liver damage
- Liver cancer
- Immunosuppression - controversial
- Increased incidence of microbial infection
- Decreased productivity

Zearalenone

- Produced by Fusarium species, acts as a sex hormone, similar to 17-b-estradiol
- Corn and other grains, fairly common in WI
Estrogen-like - in pigs, not other species
- Causes precocious sexual development in prepubertal gilts
- Pseudopregnancy, anestrus in sows
- affects young males, but not mature boars

Ergot

- Produced by Claviceps purpurea
- Produces hard sclerotia that replaces seed head in rye, wheat, oats, other grasses
- Produces several alkaloids that cause vasoconstriction , smooth muscle contraction, neurological changes
- Results in necrosis, gangrene, tissue soughing, convulsions, delirium, death

Trichothecenes

- Produced by Fusarium, other species, more than 45 toxins, more than one often present
- T-2 - most toxic, radiomimetic, toxic by ingestion, inhalation, or through skin
- DON - “vomtioxin”, most prevalent
Difficult to detect specific toxin
- Biochemical separation
- Immunoassays

Trichothecenes

Cattle - “moldy corn toxicity”, T-2 & others
- Hemorrhagic lesions in g.i. tract, lungs, kidney
- Detoxified in liver in 72 hr, no residue
Swine
- Deoxynivalenol (DON)
- Feed refusal and emesis in swine (vomitoxin)
- Irritates the mucosa of g.i. tract
Poultry
- T-2 and others
- Decreased weight gain, egg production, defective bone development (TDP)

Ochratoxins A and B

- Produced by Aspergillus ochraceus
- Renal toxicity
- Reported to affect chickens, pigs, dogs
- Suspected involvement in abortion in sheep

4-Ipomeanol

- Produced during Fusarium growth on sweet potatoes, occurs in SE U.S.
- Not actually a mycotoxin, is produced by plant tissue in response to mold infection
Causes interstitial pulmonary edema
- Killed 50 of 55 head of cattle in a Georgia herd in less than 4 days.

Fumonisins

- Produced by Fusarium moniliforme on corn, corn screenings, and other grains
Equine leukoencephalomalacia
- Swelling in the brain
- Rapid onset
- Porcine pulmonary edema
- Hepatotoxic, nephrotoxic, and carcinogenic in lab rats. Carcinogenic in people?
Mode of action
- Interfere with sphingolipid metabolism
- Sphingosine decreases and sphinganine increases
- Sphigolipid metabolites (ie. ceramide) act as second messengers in cells
- Why the difference clinical response in different species?

Other Misc. Toxins

Cyanobacterial (blue-green algae) toxins
- Form when algae die, common in WI
- Can cause sever enteritis in animals and man
Fescue foot
- Fungal endophyte in the grass produces alkaloids during heat and drought stress
- Causes lameness, necrosis
- Grass is widespread throughout western US
Fungal glucans, mannans - inhalation

Case Study

- Farmer near Mayville
- Malfunction with drier, then dried to 12.8% moisture
- Corn tested at 270-280 ppb AFB1
- Neighbors had no problem
- Had 5,000 bushels worth $13,000
- Received federal aid for 90% market value
- How to get rid of “toxic waste”?

Mycotoxin Detection

Difficult to screen over 180 toxins
- UV light for AF (actually detects kojic acid)
- Chemical detection - must specify toxin
- Now have commercial immunoassays
Test for Biological activity?
- Feed some to susceptible animals

What to do about Mycotoxins?

- Prevention is best plan
- Dump contaminated feed
- Blend “bad” feed with good
- Can destroy with heat, but not practical
- Calcium aluminosilicate has been used to bind and inactivate AF

Mycetismus

- Fancy word for mushroom poisoning
- Many types of toxic mushrooms
- Store mushrooms not a problem
- Most human cases occur in mushroom "experts"

- More common in Europe
- Occasional reports in dogs- not clear how susceptible domestic animals are

Mushroom toxins

- Amanitins - Amanita sp. (Death Angel, etc.)
- Monomethylhydrazine - hemolytic toxin
- Coprine - inhibits alcohol dehydrogenase
- Muscarine - cholinergic effect
- Ibotenic acid, etc. - psychoactive
- Psilocybin - hallucinations, similar but less potent, than LSD

Mycotoxins

- Public Health Concerns
- Ingestion of Contaminated grain, nuts
- Toxin residues in meat
- Toxin residues in milk
- Mold contamination of food products at home
- What is the threat to human health?
- Not known for many, but AFB1 is carcinogenic
- Concerns about cancer, immunity, reproduction