Mycotoxicosis in animals

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by Sunchai Luxsanakoses

 

INTRODUCTION

History

Mycotoxins may be produced on bay, cereals, pastures, or fodder, or may be present in constituents used in the manufacture of meals or pelleted animal diets. Some animal diets, especially those containing grain or nuts, may contain several toxigenic species of mould, which may produce a number of mycotoxins having different toxic or pharmacological properties. Under these situations, clinical signs and lesions found In disease outbreaks may not conform to the usual descriptions of outbreaks, or to experimental findings in animals dosed with mycotoxins isolated from pure mould cultures.

Tentative Diagnosis (Confirmation)

History
Clinical signs
Lesions

requires extraction & identification of responsible mycotoxins from suspect foodstuffs.

Treatment

Generally ineffective
But some animals recover if the source of toxin is removed
Others are stunted or die.

 

CLASSIFICATION OF MYCOTOXINS

Classified according to the main organ system, they affect.;

Hepatotoxins

Nephrotoxins

Neurotoxins

Cytotoxins (Alimentary Tract Toxins)

Estrogenic Mycotoxins

Other Mycotoxins

Discovered by:

Stevens et al. 1960: Turkey H disease outbreak Wannop, 1961; Abrams, 1965: duckling is more susceptible

Asao et al (1963): isolated the Chemical structure & referred to it as "Aflatoxin"

Harley et al (1963): found FBI, FB2, FG1, and FG2 Aflatoxicosis increases the susceptibility of turkeys to candidasis. pasteurellosis and salmonellosis, and of chicks to coccidiosis and Marek's disease: Experimental work has revealed a significant interaction between aflatoxin and vitamin D with respect to bone calcification in chicks, this increasing their vitamin D requirements. (Bird, 1978).

Vitamin A increases mortality rate in Aflatoxin chicks (Bryden et al., 1979)

Affected: Animals:

Poultry
ducks; turkey poults; pheasant chicks; chickens quail

Mammals
young pigs; pregnant sows; dogs; calves; cattle; sheep; cats; monkeys; man

Fish
Lab. animals

Cause(s):

Some strains of Aspergillus flavus & most strains of A. parasiticus

Sign(s):

a high mortality
sudden onset
inappetite
dejected appearance

Farm animals:

Other animals:

Chicken:(5)

depression, inappetence, lower growth rates, poor condition, bruising, lowered egg production, fertility, and hatchability, with high mortality. Also, ataxia, convulsion and opisthotonos are common signs.

less plasma testosterone(22)

paralysis & lameness(24)

Turkey poults & ducklings are particularly susceptible. In acute outbreaks, death occunsafter only a short period of inappetence. Subacute symptoms are more usual.

Fish

highly sensitive
1 ppb B1 - cancer in Rainbow trout(5)

Rat

highly sensitive p.(6)
1 ppb B1 - cancer in Fisher rat(5)

Severity ~ Biological Effect of Toxin(3)

Doskges:
Duration of Expose:
Species:

Sheep - highest resistance
Duck - lowest resistance & the most susceptible

breed:
Age:

young animals are more susceptible to acute effect(22)

diet:

dietary protein (11): The effect of aflatoxin is enhanced by a low protein diet.

A low fat diet also: increases the aflatoxin effect

animal's health
individual susceptibility
Type of Toxin

PM Lesion(s):

Target organs(5)

Liver- major
Kidney - minor (in some condition)
Colon - minor (in some condition)

Chich(23)

Testes
Liver

general edema with congested spleen & kidneys marked degenerative changes in the parenchymal liver cells

bile duct proliferation a membranous glomerulonephritis hyaline droplet necrosis some degree of ascites & visceral edema pale & mottled liver with widespread necrosis excessive bile production (common) marked catarrhal enteritis (characteristic) (especisily duodenum).

Diagnosis:

A. flavus may be isolated from feed.

Biological assays for the toxin (duckling/poults).

Chemical assays: fluorescent/chromatographic

techniques.

Suspect: if his topath. shows that hyperplasia of

bile ducts (Common)

Chickens hepatic cells enlarged with some necrotic foci. if feed aflatoxin 25- 15,000 µg/Kg for 8wks the highest B1 residue will be found in liver (muscles)

Swine

if feed aflatoxin 300-500 ug/Kg for 4 months B1

residue can be found ~137 ug/kg in liver but if stop

feed aflatoxin for 2 wks-no liver aflatoxin residue

can be found

FDA (3)

to condemn foods with 15 ppb B1 (6)

Mild inhibitors can control the growth of A.flavus in the feed, i.e.

- 8-Hydroxyquinoline (500 ppm [0.5 gm/kg]) - Gentian violet (500-1500 ppm [0.5-1.5 g/kg]) - Propionic acid (500-1500 ppm [0.5-1.5g/kg]) - Thiabendazole (100 ppm [100 mg/kg])

Fed a high energy, good quality protein diet, increfsed water, and fat soluble vitamins.

Luteoskyrin

Animals Affected: chicken rat

Cause(s): Penicillium islandicum

PM Lesion (s): liver necrosis

Cyclochlorotine

Animals Affected: chicken rat

Cause(s):

Penicillium islandicum

PM Lesion(s): liver necrosis

Rubratoxins

Sources: maize; legume; cereal; peanut kernels; pods; sunflower seeds; bran

Charcteristics: Classification: Rubratoxin A Rubratoxin B

Animals Affected: several spp.

Cause(s):

penicillium rubrum sign(s): several organs & tissues hemorrhage, especialIy - liver

Sterigmatocystin

Sources: Green coffee/moldy wheat/Dutch cheeses Charcteristics: low acute toxicity about 1/10 as potent a carcinogen as B1 Spp. Affected: Lab. animals mice/rats Cause(s): Several spp. of Aspergillus Penicillium luteum Bipolaris sp.

NEPHROTOXINS

Ochratoxin

Sources:

Cereal grains

wheat/Barley/Oats/Corn/Dry beans/

Moldy peanuts/Cheese/Tissues of

swine

Characteristics:

Ochratoxin A-a potent nephrotoxin in

RatslDogs/swine

teratogenic to Mice; Rats, & Chicken embryos

involved in Porcine nephropathy?

Animals Affected: Poultry ducks/chickens Mammals swine/dogs/man(?)

Cause(s): Aspergillus ochraceus & related spp. Penicillium uiridicatum other Penicillium spp.

Sign(s):

3.6 mg/Kg Ochratoxin A causes 5% mortality

rate(4)

54 mg/Kg Ochratoxin B(4)

lowered growth rate

edema of visceral organs

accumulated of uric acid in

kidneys

ureters

heart

spleen

liver

suppress as blood-forming in bone marrow

suppress as lymph formation in spleen

bursa of Fabricius

highest toxicity in broiler (4)

5 ppm Ochratoxin in feed- growth rate

4-8 ppm Ochratoxin in feed-high mortality

rate

4 ppm Ochratoxin in laying hen-ceases egg

production

Citrinin

Sources:

Cereal grains wheat/Barley/Corn/Rice

Charcteristics: a yellow colored compound involved in Porcine nephropathy? lower toxicity than Ochratoxin

Animals Affected:

Mammals

swine/dogs

Lab. animals

Cause(s): several Penicillium spp. several Aspergillus spp.

NEUROTOXINS

Penitrem A

Sources: silage

Characteristics: produces neurological & renal effects

Discovered by: Wilson et al. 1968

Spp. Affected: Cattle sheep horses

Causes(s): Penicillium cyclopium

Sign(s): incoordination syndrome (staggers)

Patulin

Sources: Moldy feed/Rotted apples/Apple juice/Wheat straw residue

Characteristics: carcinogenic in mice found Pexpansum in apple & apple juice

Spp. Affected: Poultry chicken embryo/chickens/quaiI Mammals cattle/cats Lab. animals mice/rats/rabbits Aquatics brine shrimp/guppies/zebra fish larvae

Cause(s): numerous Penicillium spp. numerous Aspergillus spp. Byssochlamys nivea

Citreoviridin

Cause(s): Penicillium citreoviride

Sign(s): directly affects the central nervous system paralysis convulsion respiratory failure cardiac failure death

Miscellaneous Neurotoxins

Cause(S): Claviceps paspali aspergillus fumigatus

Sign(s): nervous disorder: ataxialparesis/apathyl hypersensitivity/frenzy locomotor problems

CYTOTOXINS (ALIMENTARY TRACT TOXINS)

Trichothecenes

T-2 Toxin (Fusariotoxin)

Sources:

Corn/Wheat/Commercial cattle feed/Mixed feeds

Characteristics:

quite toxic to rats/trout/calves

involved in ATA (Alimentary toxic Aleukid) in human

has been implicated in "Yellow Rain" in Southeast

Asia

is not thought to be carcinogenic

is very toxic, but low contamination in foods & feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

Cause(s): Fusarium tricinctum(4) Fusarium spp.

Sign(S):

Poultry:

affect to G1 tract of broiler

1 ppm T-2 causes stomatitis

20 mg/Kg in Laying hen

stomatitis

<<appetite

wt. loss

<< egg production

soft shell

abnormal of hair coat

large doses in chickens cause

oral lesions

large intestine hemorrhage

severe ascites

neurotoxic effects

death

tibial dyschondroplasia (26)

Skin of Rabbits/Rats/& other animals (+Man) severe dermal responses

Cattle:(16) similar to other spp. coagulopathy immunosuppression hematologic changes Iymphatic necrosis or atrophy decreased feed consumption decreased weight gain

Swine:(19) anorexia lethargy posterior weakness/paresis persistent high fever decreased weight gain prominent neutrophilia decreased serum glucose/albumin/alkaline phosphatase increased serum globulin topical exposure can cause systemic effects reduced cardiac output (hypotension) (21) circulatory shock (21)

Treatment Swine superactivated charcoal with magnesium sulfate improved survival times and rates (25)

Diacetoxyscripenai

Sources:

Corn/Wheat/commercial cattle feed/Mixed feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

Neosolaniol

Sources:

Corn/Wheat/Commercial cattle feed/Mixed feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

Nivalenol

Sources:

Corn/Wheat/Commercial cattle feed/Mixed feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

Diacetyinivalenol

Sources:

Corn/Wheat/Commercial cattle feed/Mixed feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals

Deoxynivalenol (DON, vomitoxin)

Sources:

Corn/Wheat/Commercial cattle feed/Mixed feeds

Characteristics: moldy corn toxicosis of swine may have teratogenic effect unlike T-2 toxin, DON contamination in feed is significant

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

Sign(s): vomitting in animals inappetite lack of weight gain digestive disorders diarrhea death

HT-2 Toxin

Sources:

Corn/Wheat/Commercial cattle feed/mixed feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

Fusarenon H

Sources:

Corn/Wheat/Commercial cattle feed/Mixed feeds

Spp. Affected: Poultry turkey/chickens Mammals swine/cattle/horses/dogs/cats/man Lab. animals mice/rats

ESTROGENIC MYCOTOXINS

F-2 Toxin (Zearalenone)

Sources:

Corn/Oats/Barley/Wheat/Sorghum(both fresh and

stored)/Moldy hay/Pelleted commercial feed high moisture corn

Characteristics:

- a potent nonsteroidal estrogen

- one of the Resorcyclic acid lactones (RAL)

- under controlled administration; "zearalanol", a closely related RAL, is widely used in cattle as an anabolic agent

- not highly toxic

- needs 1-5 ppm to cause responses in swine

- can be transmitted to piglets via sow's milk and causes estogenism in young pigs

Spp. Affected: Poultry turkey/chickens Mammals swine/dairy cattle/lambs Lab. animals mice/rats/guinea pigs

Cause(s): Fusarium Spp.(4) primarily from F. graminearium (roseum)

Sign(S)

affect Reproductive system of mammal

Poultry:

Fusarium roseum(4)

swollen & prolapse of poultry's cloaca

bursa of Fabricius enlargement of turkey

25 ppm F-2 causes no effect to chicken

300 ppm F-2/10 days(4)

no effect to growth rate of Leghorn chicken

but found cysts in reproductive tract

Swine:(48) no effect on libido/mating behavior slight increase in sperm abnormalities vulvovaginitis & estrogenic responses in swine

Cattle:(20) abortion

OTHER MYCOTOXINS

Ergot toxin

Sources: flowers or spikelets of cereals (rye) & of grasses perennial rye grass/cocksfoot/timothy/crested dog's tail/oat grass/yorkshire fog

Characteristics: a worldwide disease of farm animals ergot contains a number of alkaloids ergotamine & ergonovine (ergometrine) are the most important alkaloids ergotamine stimulates the central nervous system

Discovered by:

Edwards (1953)

Spp. Affected: cattle swine sheep

Cause(s):

Claviceps purpurea

(ergot)

Sign(s):

Ergotamine: — Weak clonic convulsions followed by depression — lethargy — weakness —ataxia — stupor — paralysis of respiratory center — hypertension —> tone of uterus — death

Ergometrine:

—capillary endothelium damage

— blocking of capillary flow

—vascular stasis

— thrombosis in small arterioles

— dry gangrene

Cattle:

— lameness for 2-6 weeks or longer

— hindlimbs are affected before forelimbs

— high fever

— high pulse rate

— high respiration rate

— swelling & tenderness of fetlock & pastern

joints

— in 1 week, loss of sensation of the affected

area

— dry gangrene at the distal part

— sloughing of distal part

Swine: — lower feed intake — lower weight gain — lack of udder development of sow pregnacy — weak and undersized newborn piglets — low survival rate of the piglets

Sheep: — similar signs to cattle with additional, mouth ulceration

PM Lesion(s): marked intestinal inflammation in sheep

Control: immediate change to an ergot-free diet grazing or topping of pastures to reduce flower head production.

Fescue toxin (Fescue Foot/Tall Fescue Lameness)

Sources: perennial grass

Characteristics: cool season perennial grass in Australia, New Zealand, Eastern & Central USA, France, Italy

Discovered by: Case (1966) and Keyl ea at. (1967)

SDD. Affected: cattle sheep

Cause(s): unidentified, may be related to Acremonium coenophialum, Fusarium spp., and Aspergillus terreus

Sign(s): lameness in one or both hind feet may progress to necrosis of the distal part of the affected limb tail & ears may also be affected with or without lameness.

Lupins Toxin (Mycotic Lupinosis)

sources: sweet lupines

Characteristics: differs from Lupine poisoning (a nervous syndrome caused by alkaloids present in bitter lupines)

Discovered by: van Warmelo et al. (1970)

Spp. Affected: sheep cattle

Cause(s): Phomopsis leptostromiformis

Sign(s): — inappetite —listlessness — photosensitive (sheep) — ketosis (common) — lacrimation (cattle) — salivation (cattle) —jaundice — death occur in 2-14 days in acute case

PM Lesion(s):

— liver—damage, enlarge, orange-yellow, fatty (acute)

— liver - bronze-or tan -colored, firm, contracted in size, distorted and fibrosed

— copious transudates in abdominal, thoracic and pericardial sac

control:

— frequent surveillance of sheep and of lupine fodder material for characteristic black spot fungal infestation, especially after rains

—oral doses of zinc (0.5 9 or more per day) for protection from phomopsin-induced liver in jury in sheep.

REGULATION AND CONTROL

The U.S. Food, Drug & Cosmetic Act: defines food as adulterated if it contains "any poisonous or deleterious substance which may render it injurious to health". (Labuza 1982: Rodricks & Roberts, 1977)

Safe tolerance levels have not been established for any of the mycotoxins. In the absence of tolerances, FDA has set a regulation which apply to all products known to be susceptible to aflatoxin contamination, including animal feeds. In the U.S., the FDA has an action level of 20 ppb (ug/kg) for aflatoxin in susceptible commodities. Since 1984, FDA has relaxed its action level for aflatoxin levels in feed. The new aflatoxin in feed level should not exceed 100 ppb except those for dairy cows, in which the level still should not exceed 20 ppb. The action level for aflatoxin in whole milk, skim milk and low fat milk is 0.5 ppb.

 

REFERENCES

1. Velthman JR: Reducing the effects of mycotoxins through nutrition. Texas A & M.Feed International, May 1984:33-36.

2. Casarett & Doull's Toxicology. 2nd Ed:104-105.

3. Richardson KE, Nelson LA, Hamilton PB: Effect of dietary fat levels on dose response relationships during aflatoxicosis in young chickens. Poultry science (1987) 66(9) 1470-1478.

4. Shoyinka SVO, Onyekweodiri EO: Clinicopathology of Interaction between Aflatoxin and Aspergillosis in Chickens. Dep Vet Path & Microbiol, Univ, Nsukka, Nigeria. Veterinary Bulletin. 1988 V58 #2. February.

5. Borisova L et al.: Experimental reproduction of aflatoxicosis in broilers. Borisova L, Duparinova M, Alexandrov M, Tacheva T. Dzhurov D, Chotinski D, Tsvetkov A. Tsentralen Veterinarnomed. Inst., Sofia, Bulgaria. Veterinary Bulletin. 1988 V58 # 1. January.

6. Dafalla R. Hassan YM, Adam SKI: Fatty & hemorrhagic liver & kidney syndrome in breeding hens caused by aflatoxin B1 & heat stress in the sudan. Fac Vet Sci, Univ, PO Box 32, KhartoumNorth, Sudan. Veterinary Bulletin. 1987 V57 #12. December

7. Richardson KE, Nelson LA, Hamilton PB: Interaction of dietary protein level in dose response relationships during aflatoxicosis in young chickens. Dep Poultry Sci, State Univ, Raleigh, NG 27695-608, USA Veterinary Bulletin. 1988 V58 # 1. January.

8. The Merck Vet manual. 6th Ed.1287-88 & 1365.

9. Daivi RR, Adlmoyero AA: Toxic effects of aflatoxin B1 in chickens given feed contaminated c A.flavus & reduction Of the toxicity by activated charcoal & some chemical agents. Avian Diseases (28)1 (1984)

10. Clarke Ml, Harvey DG, Humphreys DJ: Vet.Toxicology 2nd Ed.

11. Hamilton PB: Aflatoxicosis in farm animals. Aflatoxin in Maize. A proceedings of the workshop. El Batan, Mexico, April 7-11, 1986: 51 - 57.

12. Hook BS: Effects of T-2 toxin in cattle. Dissertation Abstracts International, B (1988) 48 (10): 28322833.

13. Bonnefoi M, Bezille P. Arvay O. Braun JP, Bars JLE: Economic impact of facial eczema of sheep in Basque country: preliminary study. Revue de Medecine Veterinaire (1988) 139 (5): 489 - 492.

14. Stolla R. Bauer J. Gedek B: Effect of the mycotoxin zearalenone on semen characters in boars. zuchthygiene (1987) 22 (4): 165-172.

15. Pang et al.: The toxicity of T-2 toxin in swine following topical application. Fundamental & applied toxicology (1987) 9 (1) 50-59.

16. Zhao et al.: Study of abortion in dairy cows caused by zearalenone. J. of Vet. Scs. and Tech. (1987) 5:3 - 6.

17. Lundeen GR: Systemic & regional distribution of blood flow during T-2 toxin induced shock in swine. Dissertation Abstracts International, B (1987) 48 (5): 1267.

18. Clarke RN Doerr JA, Ottinger MA: Age related changes in testicular development & reproductive endocrinology associated with aflatoxicosis in the male chicken. Biology of Reproduction (1987) 36 (1): 117-124.

19. Marvan et al.: Aflatoxin B1 residues in the organs of young poultry. Biologizace a Chemizace Zivocisne Vyroby-Veterinaria (1988) 24 (1): 85-92.

20. Okoye JOA, Asuzu IU, Gugnoni HC: Paralysis and iameness associated with afla toxicosis in broilers. Avian Pathology (1988) 17 (3) 731 - 734.

21. Poppenga RH: Effect of therapeutic intervention on pathophysiology, pathology, and survival in rats and swine following acute intravenous exposure to T-2 toxin. Dissertation Abstracts International, B (1988) 49 (1): 54.

22. Lawler EM, shivers JL, Walser MM: Acid phosphatase activity of chondroclasts from Fusarium-induced tibial dyschondroplastic cartilage. Avian Diseases (1988) 32 (2): 240-245.


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