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A REVIEW ON
MYCOTOXIN: TRICHOTHECENES AS A BIOWEAPON
PRESENTED BY
OLATEJU, ESTHER OMOTOLA.
MATRIC NUMBER: 120408026
DEPARTMENT OF BIOLOGICAL SCIENCES
MICROBIOLOGY {PROGRAMME}
1
INTRODUCTION
• Biotechnology is the use of living system and
organisms to develop or make product or any
technological application that uses biological
system, living organisms, their toxins or derivatives
thereof, to make or modify product for specific use.
• Biotechnology has been employed diversely in
biological warfare to produce biological weapons
including various microorganisms (bacteria,
viruses, fungi) and their toxins.
• A biological weapon is a harmful biological agent
(biological toxin or infectious agents such as
bacteria, viruses, and fungi) used as a weapon to
cause death or disease usually on a large scale. 2
Classification of Biological Weapons
The biological warfare agents can be classified as:
• Bacteria: Anthrax, Plague, Brucellosis, Cholera, Clostridium perf. toxin,
Staph. enterotoxin B, Melioidosis, Tularemia.
• Virus: Congo Crimen Hemorrhagic Fever, Ebola Hemorrhagic Fever,
Small Pox, Rift Valley Fever,Venezuelan Equine Encephalitis.
• Fungus: Trichothecene Mycotoxin.
• Rickettsia: Q Fever.
• Misc: Saxitoxin (derived from paralytic shellfish).
• Ricin: (cytotoxin derived from castor bean mesh).
3
Trichothecenes Mycotoxin
• A mycotoxin is a toxic secondary metabolite
produced by organisms of the fungi kingdom.
Various genera of toxigenic fungi are capable of
producing such diverse mycotoxins as the
aflatoxins, rubratoxins, ochratoxins, fumonisins,
and trichothecenes.
• The trichothecenes are a very large family of
chemically related toxins produced by various
species of Fusarium, Myrotecium, Trichoderma,
Cephalosporium, Verticimonosporium, and
Stachybotrys.
4
Cont’d
• Potentially hazardous concentrations of the
trichothecene mycotoxins can occur naturally in
moldy grains, cereals, and agricultural products.
• Trichothecenes has also been used as an agent
of biological warfare (BW) also known as germ
warfare or bioweapon.
5
History and military significance of
tricothecenes
From 1974 to 1981,trichothecene was used as
part of toxic agents used by the Soviet Union
and its client states in such Cold War sites as
Afghanistan, Laos, and Kampuchea
(Cambodia) resulting in over 10,000 deaths.
Aerosol-and-droplet clouds, described as
“yellow rain” were produced by delivery
systems in the Soviet arsenal such as aircraft
spray tanks, aircraft-launched rockets, bombs
(exploding cylinders), canisters, a Soviet hand-
held weapon (DH-10), and booby traps. 6
NATURAL PRODUCTION OF TRICHOTHECENES
• Hazardous concentrations of the trichothecene
mycotoxins can occur naturally in grains,
cereals, and agricultural products contaminated
by moulds of Fusarium, Myrotecium,
Trichoderma, Cephalosporium,
Verticimonosporium, and Stachybotrys family.
• Toxigenic species of Fusarium occur worldwide
in habitats as diverse as deserts, tidal salt flats,
and alpine mountain regions.
7
INDUSTRIAL PRODUCTION OF TRICHOTHECENES
• Trichothecene mycotoxins can be produced by a
procedure considered proprietary by industry using the
existing state-of-the-art fermentation process developed
for brewing and antibiotics.
• T-2 toxin can be produced by solid substrate
fermentation at approximately 9g/kg of substrate, with
a yield of 2 to 3g of crystalline product.
• Extraction of trichothecene mycotoxins from fungal
cultures with organic solvents yields a yellow-brown
liquid, which, if allowed to evaporate, forms a greasy,
yellow crystalline product.
8
Plate 1: Fungal cultures with colonies of fusarium sp. 9
Plate 2: Liquid mixture of trichothecene dissolved in acetone extracted
from a fungal culture 10
Weaponization
• Because of their efficacy, ease of large-
scale production, and apparent proven
delivery by various aerial dispersal
systems, the trichothecene mycotoxins
(especially T-2 toxin) have an excellent
potential for weaponization.
• Trichothecene mycotoxins can be
delivered as dusts, droplets, aerosols, or
smoke from aircraft, rockets, missiles,
artillery, mines, or portable sprayers. 11
CLINICAL DISEASE
The symptoms and clinical signs of trichothecene
intoxication can vary depending on whether the
exposure is acute or chronic. These symptoms
include:
• Nausea
• Vomiting
• Dyspnoea
• Coughing
• Sore mouth
• Bleeding gums
• Epistaxis
• Haematemesis
• Haematochezia
• Abdominal pain
• Shock
• Death
12
Battlefield Diagnosis
The following events should suggest to
medical officers that a biological warfare
attack with trichothecene mycotoxins has
occurred:
• Clinical findings that match the symptoms
listed above;
• High attack and fatality rates;
• All types of dead animals; and
• Onset of symptoms after a yellow rain or
• Red, green, or white smoke or vapor attack.
13
MEDICAL MANAGEMENT
• The immediate use of protective clothing and
mask at the first sign of a yellow rain–like
attack.
• Use of skin decontamination kits.
• Early use of high doses of systemic
glucocorticosteriods.
• Upper respiratory irritation can be relieved by
steam inhalation, codeine, or another substance
to suppress the cough.
14
Advantages of bio-weapon
• Efficiency: Biological weapons are efficient; a single
gram of biological warfare agents like trichothecenes
can kill thousands of individuals.
• Cheap cost: It would require higher cost if you opt to
use regular nuclear and chemical weapons.
• Ease of production, use and storage: a biological
weapon is easy to produce, use and store.
• Easy dispersion: In a biological warfare scenario,
weapons are dispersed easily.
15
DISADVANTAGES OF BIOWEAPONS
• Unpredictability: Bioweapons are highly
unpredictable. There have been recorded
incidents of infecting own troops.
• Longer residual effect: Biological weapons
linger for long periods of time. This
therefore signifies that the longer it stays the
more possibilities for unwanted effects.
16
CONCLUSION
• The threat of use of trichothecenes as an agent
of biological warfare agents in a terrorism-
related issue or in a warfare situation is real.
• The highly unpredictable nature of any event
involving biological warfare agents has given
rise to the need for developing rapid and
accurate detection systems.
• The current knowledge on the agents and their
detection methodologies will be highly useful
in developing a highly effective response
system through systematic planning.
17
REFERENCES
• Ciegler, A. (1975). Mycotoxins: Occurrence, chemistry, biological activity. Lloydia.;
38(1):21–35.
• Ciegler, A., Bennett J. W. (1980). Mycotoxins and mycotoxicoses.
Bioscience.;30(8):512–515.
• Godtfredsen, W. O., Grove, J.F., Tamm C. H. (1967). Trichothecenes. Hev Chim
Acta.;50:1666–1668.
• Haig, A. M. Jr. (March 22, 1982). Chemical Warfare in Southeast Asia and
Afghanistan. Washington, DC: US Government Printing Office; Report
to the Congress.
• Mirocha, C. J. (1982). Hazards of scientific investigation: Analysis of samples
implicated in biological warfare. Journal of Toxicology-Toxin
Reviews.;1(1):199–203.
• Mirocha, C. J., Pawlosky, R.A., Chatterjee, K., Watson, S., Hayes, W. (1983).
Analysis for Fusarium toxins in various samples implicated in biological
warfare in Southeast Asia. J. Assoc Of Anal Chem.; 66(6):1485–1499.
• Moss, M. O. (1989). Mycotoxins of Aspergillus and other filamentous fungi. J Appl
Bacteriol.;67(symposium suppl):69S–81S.
• Rosen, R. T, Rosen, J. D. (1982). Presence of four Fusarium mycotoxins and synthetic
material in “yellow rain”: Evidence for the use of chemical weapons in Laos.
Biomed Mass Spectrom.; 9(10):443–450.
18
Thank
You
for
listening
19

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Trichothecene as a bioweapon

  • 1. A REVIEW ON MYCOTOXIN: TRICHOTHECENES AS A BIOWEAPON PRESENTED BY OLATEJU, ESTHER OMOTOLA. MATRIC NUMBER: 120408026 DEPARTMENT OF BIOLOGICAL SCIENCES MICROBIOLOGY {PROGRAMME} 1
  • 2. INTRODUCTION • Biotechnology is the use of living system and organisms to develop or make product or any technological application that uses biological system, living organisms, their toxins or derivatives thereof, to make or modify product for specific use. • Biotechnology has been employed diversely in biological warfare to produce biological weapons including various microorganisms (bacteria, viruses, fungi) and their toxins. • A biological weapon is a harmful biological agent (biological toxin or infectious agents such as bacteria, viruses, and fungi) used as a weapon to cause death or disease usually on a large scale. 2
  • 3. Classification of Biological Weapons The biological warfare agents can be classified as: • Bacteria: Anthrax, Plague, Brucellosis, Cholera, Clostridium perf. toxin, Staph. enterotoxin B, Melioidosis, Tularemia. • Virus: Congo Crimen Hemorrhagic Fever, Ebola Hemorrhagic Fever, Small Pox, Rift Valley Fever,Venezuelan Equine Encephalitis. • Fungus: Trichothecene Mycotoxin. • Rickettsia: Q Fever. • Misc: Saxitoxin (derived from paralytic shellfish). • Ricin: (cytotoxin derived from castor bean mesh). 3
  • 4. Trichothecenes Mycotoxin • A mycotoxin is a toxic secondary metabolite produced by organisms of the fungi kingdom. Various genera of toxigenic fungi are capable of producing such diverse mycotoxins as the aflatoxins, rubratoxins, ochratoxins, fumonisins, and trichothecenes. • The trichothecenes are a very large family of chemically related toxins produced by various species of Fusarium, Myrotecium, Trichoderma, Cephalosporium, Verticimonosporium, and Stachybotrys. 4
  • 5. Cont’d • Potentially hazardous concentrations of the trichothecene mycotoxins can occur naturally in moldy grains, cereals, and agricultural products. • Trichothecenes has also been used as an agent of biological warfare (BW) also known as germ warfare or bioweapon. 5
  • 6. History and military significance of tricothecenes From 1974 to 1981,trichothecene was used as part of toxic agents used by the Soviet Union and its client states in such Cold War sites as Afghanistan, Laos, and Kampuchea (Cambodia) resulting in over 10,000 deaths. Aerosol-and-droplet clouds, described as “yellow rain” were produced by delivery systems in the Soviet arsenal such as aircraft spray tanks, aircraft-launched rockets, bombs (exploding cylinders), canisters, a Soviet hand- held weapon (DH-10), and booby traps. 6
  • 7. NATURAL PRODUCTION OF TRICHOTHECENES • Hazardous concentrations of the trichothecene mycotoxins can occur naturally in grains, cereals, and agricultural products contaminated by moulds of Fusarium, Myrotecium, Trichoderma, Cephalosporium, Verticimonosporium, and Stachybotrys family. • Toxigenic species of Fusarium occur worldwide in habitats as diverse as deserts, tidal salt flats, and alpine mountain regions. 7
  • 8. INDUSTRIAL PRODUCTION OF TRICHOTHECENES • Trichothecene mycotoxins can be produced by a procedure considered proprietary by industry using the existing state-of-the-art fermentation process developed for brewing and antibiotics. • T-2 toxin can be produced by solid substrate fermentation at approximately 9g/kg of substrate, with a yield of 2 to 3g of crystalline product. • Extraction of trichothecene mycotoxins from fungal cultures with organic solvents yields a yellow-brown liquid, which, if allowed to evaporate, forms a greasy, yellow crystalline product. 8
  • 9. Plate 1: Fungal cultures with colonies of fusarium sp. 9
  • 10. Plate 2: Liquid mixture of trichothecene dissolved in acetone extracted from a fungal culture 10
  • 11. Weaponization • Because of their efficacy, ease of large- scale production, and apparent proven delivery by various aerial dispersal systems, the trichothecene mycotoxins (especially T-2 toxin) have an excellent potential for weaponization. • Trichothecene mycotoxins can be delivered as dusts, droplets, aerosols, or smoke from aircraft, rockets, missiles, artillery, mines, or portable sprayers. 11
  • 12. CLINICAL DISEASE The symptoms and clinical signs of trichothecene intoxication can vary depending on whether the exposure is acute or chronic. These symptoms include: • Nausea • Vomiting • Dyspnoea • Coughing • Sore mouth • Bleeding gums • Epistaxis • Haematemesis • Haematochezia • Abdominal pain • Shock • Death 12
  • 13. Battlefield Diagnosis The following events should suggest to medical officers that a biological warfare attack with trichothecene mycotoxins has occurred: • Clinical findings that match the symptoms listed above; • High attack and fatality rates; • All types of dead animals; and • Onset of symptoms after a yellow rain or • Red, green, or white smoke or vapor attack. 13
  • 14. MEDICAL MANAGEMENT • The immediate use of protective clothing and mask at the first sign of a yellow rain–like attack. • Use of skin decontamination kits. • Early use of high doses of systemic glucocorticosteriods. • Upper respiratory irritation can be relieved by steam inhalation, codeine, or another substance to suppress the cough. 14
  • 15. Advantages of bio-weapon • Efficiency: Biological weapons are efficient; a single gram of biological warfare agents like trichothecenes can kill thousands of individuals. • Cheap cost: It would require higher cost if you opt to use regular nuclear and chemical weapons. • Ease of production, use and storage: a biological weapon is easy to produce, use and store. • Easy dispersion: In a biological warfare scenario, weapons are dispersed easily. 15
  • 16. DISADVANTAGES OF BIOWEAPONS • Unpredictability: Bioweapons are highly unpredictable. There have been recorded incidents of infecting own troops. • Longer residual effect: Biological weapons linger for long periods of time. This therefore signifies that the longer it stays the more possibilities for unwanted effects. 16
  • 17. CONCLUSION • The threat of use of trichothecenes as an agent of biological warfare agents in a terrorism- related issue or in a warfare situation is real. • The highly unpredictable nature of any event involving biological warfare agents has given rise to the need for developing rapid and accurate detection systems. • The current knowledge on the agents and their detection methodologies will be highly useful in developing a highly effective response system through systematic planning. 17
  • 18. REFERENCES • Ciegler, A. (1975). Mycotoxins: Occurrence, chemistry, biological activity. Lloydia.; 38(1):21–35. • Ciegler, A., Bennett J. W. (1980). Mycotoxins and mycotoxicoses. Bioscience.;30(8):512–515. • Godtfredsen, W. O., Grove, J.F., Tamm C. H. (1967). Trichothecenes. Hev Chim Acta.;50:1666–1668. • Haig, A. M. Jr. (March 22, 1982). Chemical Warfare in Southeast Asia and Afghanistan. Washington, DC: US Government Printing Office; Report to the Congress. • Mirocha, C. J. (1982). Hazards of scientific investigation: Analysis of samples implicated in biological warfare. Journal of Toxicology-Toxin Reviews.;1(1):199–203. • Mirocha, C. J., Pawlosky, R.A., Chatterjee, K., Watson, S., Hayes, W. (1983). Analysis for Fusarium toxins in various samples implicated in biological warfare in Southeast Asia. J. Assoc Of Anal Chem.; 66(6):1485–1499. • Moss, M. O. (1989). Mycotoxins of Aspergillus and other filamentous fungi. J Appl Bacteriol.;67(symposium suppl):69S–81S. • Rosen, R. T, Rosen, J. D. (1982). Presence of four Fusarium mycotoxins and synthetic material in “yellow rain”: Evidence for the use of chemical weapons in Laos. Biomed Mass Spectrom.; 9(10):443–450. 18