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Abhishek Singh
Medical Microbiology
MYCOTOXIN
CONTENTS
 INTRODUCTION
 HISTORY
 EPIDEMIOLOGY
 TYPES
 DETECTION OF MYCOTOXINS
 PREVENTION AND CONTROL
 TREATMENT
INTRODUCTION
 Mycotoxins are low-molecular-weight secondary
metabolites of fungi.
 These metabolites constitute a toxigenically and
chemically heterogeneous assemblage that are
grouped together only because the members can
cause disease and death in human beings and other
vertebrates.
 Mycotoxins are an important chronic dietary risk
factor.
 They occur more frequently in areas with hot and
humid climate, favorable for growth of molds; also
found in temperate zones.
 The disease produced by mycotoxins are largely
called as Mycotoxicoses.
HISTORY:
 An outbreak of aflatoxicosis was reported in 1974
in adjoining districts of gujarat and rajasthan
 Stachybotyrotoxicosis killed thousand of horses
in 1930s in USSR
 In 1960, Aflatoxicosis alone killed about 1,00,000
young turks in the UK
 From 1960-1971 US military sprayed millions
litres of toxic herbicides to destroy the vegetation
used by liberation forces for cover and food
EPIDEMIOLOGY:
 Food stored for longer periods give fungi a
greater opportunity to contaminate it
 Seen to be a significant cause of death in
developed countries
 Based on the data given by Pitt and colleagues it
was seen that a number of deaths caused by liver
cancer were due to aflatoxins in Indonesia
 Acute fatalities have been reported in India
caused by aflatoxin poisoning due to unseasonal
rains
Factors Affecting Mycotoxin
Production:
 Genetics , environmental and nutritional factors
greatly affect the formation of Mycotoxins.
 Depending on the susceptibility of the crop,
geographic and seasonal factors, as well as
cultivation, harvesting, storage, and transportation
practices, mycotoxins are found worldwide.
 In the field, weather conditions, plant stress,
invertebrate vectors, species and spore load of
infective fungi, variations within plant and fungal
species, and microbial competition all significantly
affect mycotoxin production.
7
 Physical factors such as time of exposure, temperature
during exposure, humidity, and extent of insect or other
damage to the commodity prior to exposure determine
mycotoxin contamination in the field or during storage.
 Chemical factors including the nutritional status of the
crops or chemicals (such as fungicides) used in crop
management could affect fungal populations, and
consequently toxin production
 In general, mycotoxins are optimally produced at 24–
28C, but some toxins such as T-2 toxin is maximally
produced at 15C.
 Contamination during crop storage may be affected by
changes in temperature and water activity, that allow
ecological succession of different fungi as water activity
Continue Factors Affecting…….
THE VARIOUS TYPES:
The effects produced by fungi and their
metabolites are categorised in two headings:
1. Mycotoxicoses
2. Mycetismus
MYCOTOXICOSES:
 Defined as the illness of man or domestic animal
due to ingestion of pre formed substances on a
particular food stuffs. Consumption of these
toxins lead to fatal consequences.
 Most of the significant fungi producing
mycotoxicosis mainly belong to toxigenic species
of genera Aspergillus, Fusarium, and Penicillium
 Out of all the mycotoxins- aflatoxins, fusarium
toxins and ochratoxins are considered to be
significant in humans and animals
 Production of mycotoxins depends upon factors
like temperature, moisture, aeration and substrate
on which the fungus is growing
 Most of the reported outbreaks of mycotoxicoses
were found to be as consequence to consumption
of food that is contaminated with mycotoxins
 There are four basic types: acute, chronic,
mutagenic and teratogenic
 These are a few medically important mycotoxins
which produce distinctive diseases in man and
animals:
1. Aflatoxins
2. Fumonisins
3. Tricothecenes
4. Ochratoxins
5. Cyclopyazonic acid
6. Zearalenone
7. Patulin
AFLATOXINS:
 Secondary metabolites produced by Aspergillus
flavus
 Were discovered as strange manifestations of a
mysterious disease called Turkey-X-disease
 Shows presence of B1, B2, G1 and G2 on the basis
of their metabolites which exhibit blue (B), and
green (G) fluorescence when irradiated under
ultraviolet light on thin chromatography plates
 They can be modified by bio-transformation e.g.
formation of hydroxylated derivates of aflatoxins
B1 and B2 as aflatoxins M1 and M2 respectively
Mycotoxins effects on peanut and
maize
CLINICAL MANIFESTATION:
 Aflatoxicosis
 Two forms are identified: acute severe
intoxication, which results in direct liver damage
and subsequent illness or death; chronic sub-
symptomatic aflatoxicosis
symptoms: lethargy, anorexia and muscle
weakness and spasm
 Other manifestations include: fever, jaundice,
hepatomegaly, ascites, portal hypertension, pedal
edema and eventually death
REYE’S SYNDROME:
 Acute aflatoxicosis in which patient presents with
signs and symptoms of encephalopathy and fatty
degeneration of viscera
 Endemic disease of children in developing
countries
 Also responsible for implicating outbreaks of
hepatitis in India
 ICC (Indian childhood cirrhosis) is also caused by
aflatoxins
PREVENTION
 Detoxification : Hydrated sodium calcium
aluminosilicate (HSCAS) can absorb aflatoxins.
 Supportive : Vitamin .E & selenium.
 Prevention
- Mold inhibitor
- Treatment of grain with anhydrous ammonia for
10-14 days.
Fumonisins:
 Mycotoxin are toxic and carcinogenic secondary
metabolites produced by many species of Fusarium.
 Common contaminant of maize and maize-based
animal feeds throughout the world .
 The mycotoxin produced by fungi known as
Fuomonisin B (FB1 to FB4 ) .
 These may cause fatal illness in some animals and are
suspected to be human oesophageal carcinogens.
 High –performance liquid chromatography with
fluorescent detection is the most widely used method.
TRICHOTHECENE:
 F. graminearum a pathogen of gramineous plants
especially wheat is known to produce
trichothecenes.
 The effect of the toxins are weight loss ,vomiting ,
feed refusal , dermatitis , diarrhoea ,
hemorrhages and necrosis of epithelium of
stomach and intestine and Immunosuppression of
lymphoid cells in thymus . Bone marrow , spleen
testis and ovary.
OCHRATOXIN:
 OA causes renal toxicity, nephropathy and
Immunosuppression in several species, and is
carcinogenic in experimental animals.
 No data are available on absorption, distribution,
metabolism and excretion of OA in humans.
CYCLOPYAZONIC ACID
 The CPA is a toxic indole tetramic acid derived
from tryptophan , produces by the species genus
of Aspergillus.
 It occurs naturally in agriculture products such as
ground nuts and corn , mostly as co-contaminant
with aflatoxin.
CLINICAL SYMPTOMS:
 Loss of weight
 Loss of appetite
 Weakness
 Vomiting
 Diarrhoea
 Dehydration
 Depression
 Convulsion and death
KODUA POISONING:
 Toxic syndrome in cattle and man often
encountered in areas where kodo millet seed is
consumed as staple food by poor people in
several region of india.
 Eating of this grain result in giddiness ,
sleepiness and tremors recovering after 1 to 3
days.
ZEARALENONE:
 Zearalenone is an estrogenic toxin and it also
produced by Fusarium species.
 This is found in variety of cereals like maize,
barely, wheat grain etc.
 In humans it causes cervical cancer and
precocious pubertal changes in children.
PATULIN:
 Patulin, is produced by many different molds but
was first isolated as an antimicrobial active
principle during the 1940s from Penicillium
patulum.
 A number of early studies were directed towards
harnessing its antibiotic activity.
 Patulin was toxic to both plants and animals,
precluding its clinical use as an antibiotic. During
the 1960s, patulin was reclassified as a
mycotoxin.
MYCETISMUS:
Bioterrorism
 Mycotoxins can be used as chemical warfare
agents .There is considerable evidence that Iraqi
scientists developed aflatoxins as part of their
bioweapons program during the 1980s.
 Aflatoxins seem a curious choice for chemical
warfare because the induction of liver cancer is
“hardly a knockout punch on the battlefield”.
 Unlike the aflatoxins, trichothecenes can act
immediately upon contact, and exposure to a few
milligrams of T-2 is potentially lethal.
27
Detection and Screening of
Mycotoxins:
 Because many steps are involved in the analysis, it is
not uncommon that the analytical error can amount to
20–30%
 To obtain reliable analytical data, an adequate sampling
program and an accurate analytical method are both
important.
 To minimize the errors, studies have led to many
improved and innovative analytical methods for
mycotoxin analysis over the years.
 New, more sensitive TLC, HPLC, and GLC techniques
are now available.
 New chemical methods, including capillary
 ELISA
 RIA
 Spectrophotometry
 Tissue culture
- Primary fetal bovine kidney cells
 Newer techniques have been used which include
patterns of isoenzyme electrophoresis , DNA-DNA
homology , restriction fragment length
polymorphism.
PREVENTIVE
MEASURES:
29
Management of Mycotoxin Contamination
 The economic implications of the mycotoxin problem
and its
potential health threat to humans have clearly created a
need
to eliminate or at least minimize mycotoxin
contamination of food and feed.
 While an association between mycotoxin contamination
and
inadequate storage conditions has long been
recognized,
studies have revealed that seeds are contaminated with
mycotoxins prior to harvest . Therefore, management of
TREATMENT:
 The main treatment is vigorous intravenous fluid
replacement and correction of electrolyte
disturbances and coagulopathy.
 Hameodialysis and hemoperfusion may be
effective in removing toxin if initiated within 24 hrs
of intake.
 Atropine is useful in mycetismus involving PNS in
muscarine poisoning.
 Corticosteroids may prove useful and such
patients should be given trails.
Mycotoxin presentation

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Mycotoxin presentation

  • 2. CONTENTS  INTRODUCTION  HISTORY  EPIDEMIOLOGY  TYPES  DETECTION OF MYCOTOXINS  PREVENTION AND CONTROL  TREATMENT
  • 3. INTRODUCTION  Mycotoxins are low-molecular-weight secondary metabolites of fungi.  These metabolites constitute a toxigenically and chemically heterogeneous assemblage that are grouped together only because the members can cause disease and death in human beings and other vertebrates.  Mycotoxins are an important chronic dietary risk factor.  They occur more frequently in areas with hot and humid climate, favorable for growth of molds; also found in temperate zones.  The disease produced by mycotoxins are largely called as Mycotoxicoses.
  • 4. HISTORY:  An outbreak of aflatoxicosis was reported in 1974 in adjoining districts of gujarat and rajasthan  Stachybotyrotoxicosis killed thousand of horses in 1930s in USSR  In 1960, Aflatoxicosis alone killed about 1,00,000 young turks in the UK  From 1960-1971 US military sprayed millions litres of toxic herbicides to destroy the vegetation used by liberation forces for cover and food
  • 5. EPIDEMIOLOGY:  Food stored for longer periods give fungi a greater opportunity to contaminate it  Seen to be a significant cause of death in developed countries  Based on the data given by Pitt and colleagues it was seen that a number of deaths caused by liver cancer were due to aflatoxins in Indonesia  Acute fatalities have been reported in India caused by aflatoxin poisoning due to unseasonal rains
  • 6. Factors Affecting Mycotoxin Production:  Genetics , environmental and nutritional factors greatly affect the formation of Mycotoxins.  Depending on the susceptibility of the crop, geographic and seasonal factors, as well as cultivation, harvesting, storage, and transportation practices, mycotoxins are found worldwide.  In the field, weather conditions, plant stress, invertebrate vectors, species and spore load of infective fungi, variations within plant and fungal species, and microbial competition all significantly affect mycotoxin production.
  • 7. 7  Physical factors such as time of exposure, temperature during exposure, humidity, and extent of insect or other damage to the commodity prior to exposure determine mycotoxin contamination in the field or during storage.  Chemical factors including the nutritional status of the crops or chemicals (such as fungicides) used in crop management could affect fungal populations, and consequently toxin production  In general, mycotoxins are optimally produced at 24– 28C, but some toxins such as T-2 toxin is maximally produced at 15C.  Contamination during crop storage may be affected by changes in temperature and water activity, that allow ecological succession of different fungi as water activity Continue Factors Affecting…….
  • 8. THE VARIOUS TYPES: The effects produced by fungi and their metabolites are categorised in two headings: 1. Mycotoxicoses 2. Mycetismus
  • 9. MYCOTOXICOSES:  Defined as the illness of man or domestic animal due to ingestion of pre formed substances on a particular food stuffs. Consumption of these toxins lead to fatal consequences.  Most of the significant fungi producing mycotoxicosis mainly belong to toxigenic species of genera Aspergillus, Fusarium, and Penicillium  Out of all the mycotoxins- aflatoxins, fusarium toxins and ochratoxins are considered to be significant in humans and animals
  • 10.  Production of mycotoxins depends upon factors like temperature, moisture, aeration and substrate on which the fungus is growing  Most of the reported outbreaks of mycotoxicoses were found to be as consequence to consumption of food that is contaminated with mycotoxins  There are four basic types: acute, chronic, mutagenic and teratogenic
  • 11.  These are a few medically important mycotoxins which produce distinctive diseases in man and animals: 1. Aflatoxins 2. Fumonisins 3. Tricothecenes 4. Ochratoxins 5. Cyclopyazonic acid 6. Zearalenone 7. Patulin
  • 12. AFLATOXINS:  Secondary metabolites produced by Aspergillus flavus  Were discovered as strange manifestations of a mysterious disease called Turkey-X-disease  Shows presence of B1, B2, G1 and G2 on the basis of their metabolites which exhibit blue (B), and green (G) fluorescence when irradiated under ultraviolet light on thin chromatography plates  They can be modified by bio-transformation e.g. formation of hydroxylated derivates of aflatoxins B1 and B2 as aflatoxins M1 and M2 respectively
  • 13. Mycotoxins effects on peanut and maize
  • 14. CLINICAL MANIFESTATION:  Aflatoxicosis  Two forms are identified: acute severe intoxication, which results in direct liver damage and subsequent illness or death; chronic sub- symptomatic aflatoxicosis symptoms: lethargy, anorexia and muscle weakness and spasm  Other manifestations include: fever, jaundice, hepatomegaly, ascites, portal hypertension, pedal edema and eventually death
  • 15. REYE’S SYNDROME:  Acute aflatoxicosis in which patient presents with signs and symptoms of encephalopathy and fatty degeneration of viscera  Endemic disease of children in developing countries  Also responsible for implicating outbreaks of hepatitis in India  ICC (Indian childhood cirrhosis) is also caused by aflatoxins
  • 16. PREVENTION  Detoxification : Hydrated sodium calcium aluminosilicate (HSCAS) can absorb aflatoxins.  Supportive : Vitamin .E & selenium.  Prevention - Mold inhibitor - Treatment of grain with anhydrous ammonia for 10-14 days.
  • 17. Fumonisins:  Mycotoxin are toxic and carcinogenic secondary metabolites produced by many species of Fusarium.  Common contaminant of maize and maize-based animal feeds throughout the world .  The mycotoxin produced by fungi known as Fuomonisin B (FB1 to FB4 ) .  These may cause fatal illness in some animals and are suspected to be human oesophageal carcinogens.  High –performance liquid chromatography with fluorescent detection is the most widely used method.
  • 18. TRICHOTHECENE:  F. graminearum a pathogen of gramineous plants especially wheat is known to produce trichothecenes.  The effect of the toxins are weight loss ,vomiting , feed refusal , dermatitis , diarrhoea , hemorrhages and necrosis of epithelium of stomach and intestine and Immunosuppression of lymphoid cells in thymus . Bone marrow , spleen testis and ovary.
  • 19. OCHRATOXIN:  OA causes renal toxicity, nephropathy and Immunosuppression in several species, and is carcinogenic in experimental animals.  No data are available on absorption, distribution, metabolism and excretion of OA in humans.
  • 20. CYCLOPYAZONIC ACID  The CPA is a toxic indole tetramic acid derived from tryptophan , produces by the species genus of Aspergillus.  It occurs naturally in agriculture products such as ground nuts and corn , mostly as co-contaminant with aflatoxin.
  • 21. CLINICAL SYMPTOMS:  Loss of weight  Loss of appetite  Weakness  Vomiting  Diarrhoea  Dehydration  Depression  Convulsion and death
  • 22. KODUA POISONING:  Toxic syndrome in cattle and man often encountered in areas where kodo millet seed is consumed as staple food by poor people in several region of india.  Eating of this grain result in giddiness , sleepiness and tremors recovering after 1 to 3 days.
  • 23. ZEARALENONE:  Zearalenone is an estrogenic toxin and it also produced by Fusarium species.  This is found in variety of cereals like maize, barely, wheat grain etc.  In humans it causes cervical cancer and precocious pubertal changes in children.
  • 24. PATULIN:  Patulin, is produced by many different molds but was first isolated as an antimicrobial active principle during the 1940s from Penicillium patulum.  A number of early studies were directed towards harnessing its antibiotic activity.  Patulin was toxic to both plants and animals, precluding its clinical use as an antibiotic. During the 1960s, patulin was reclassified as a mycotoxin.
  • 26. Bioterrorism  Mycotoxins can be used as chemical warfare agents .There is considerable evidence that Iraqi scientists developed aflatoxins as part of their bioweapons program during the 1980s.  Aflatoxins seem a curious choice for chemical warfare because the induction of liver cancer is “hardly a knockout punch on the battlefield”.  Unlike the aflatoxins, trichothecenes can act immediately upon contact, and exposure to a few milligrams of T-2 is potentially lethal.
  • 27. 27 Detection and Screening of Mycotoxins:  Because many steps are involved in the analysis, it is not uncommon that the analytical error can amount to 20–30%  To obtain reliable analytical data, an adequate sampling program and an accurate analytical method are both important.  To minimize the errors, studies have led to many improved and innovative analytical methods for mycotoxin analysis over the years.  New, more sensitive TLC, HPLC, and GLC techniques are now available.  New chemical methods, including capillary
  • 28.  ELISA  RIA  Spectrophotometry  Tissue culture - Primary fetal bovine kidney cells  Newer techniques have been used which include patterns of isoenzyme electrophoresis , DNA-DNA homology , restriction fragment length polymorphism.
  • 29. PREVENTIVE MEASURES: 29 Management of Mycotoxin Contamination  The economic implications of the mycotoxin problem and its potential health threat to humans have clearly created a need to eliminate or at least minimize mycotoxin contamination of food and feed.  While an association between mycotoxin contamination and inadequate storage conditions has long been recognized, studies have revealed that seeds are contaminated with mycotoxins prior to harvest . Therefore, management of
  • 30. TREATMENT:  The main treatment is vigorous intravenous fluid replacement and correction of electrolyte disturbances and coagulopathy.  Hameodialysis and hemoperfusion may be effective in removing toxin if initiated within 24 hrs of intake.  Atropine is useful in mycetismus involving PNS in muscarine poisoning.  Corticosteroids may prove useful and such patients should be given trails.