Reasonable Rascal
12-26-01, 19:39
MYCOTOXINS (T2)
SUMMARY
Signs and symptoms: Exposure causes skin pain, pruritus, redness, vesicles, necrosis and sloughing of epidermis. Effects on the airway include nose and throat pain, nasal discharge, itching and sneezing, cough, dyspnea, wheezing, chest pain and hemoptysis. Toxin also produces effects after ingestion or eye contact. Severe poisoning results in prostration, weakness, ataxia, collapse, shock, and death.
Diagnosis: Should be suspected if an aerosol attack occurs in the form of "yellow rain" with droplets of yellow fluid contaminating clothes and the environment. Confirmation requires testing of blood, tissue and
environmental samples.
Treatment: There is no specific antidote. Superactivated charcoal should be given orally if the toxin is swallowed.
Prophylaxis: The only defense is to wear a protective mask and clothing during an attack. No specific immunotherapy or chemotherapy is available for use in the field.
Isolation and Decontamination: Standard Precautions for healthcare workers. Outer clothing should be removed and exposed skin should be decontaminated with soap and water. Eye exposure should be treated with copious saline irrigation. Once decontamination is complete, isolation is not required. Environmental decontamination requires the use of a hypochlorite solution under alkaline conditions such as 1% sodium hypochlorite and 0.1M NAOH with 1 hour contact time.
OVERVIEW
The trichothecene mycotoxins are low molecular weight (250-500 daltons) nonvolatile compounds produced by filamentous fungi (molds) of the genera Fusarium, Myrotecium, Trichoderma, Stachybotrys and others. The structures of approximately 150 trichothecene derivatives have been described in the literature. These substances are relatively insoluble in water but are highly soluble in ethanol, methanol and propylene glycol. The trichothecenes are extremely stable to heat and ultraviolet light inactivation. Heating to 1500o F for 30 minutes is required for inactivation, while brief exposure to NaOCl destroys toxic activity. The potential for use as a BW toxin was demonstrated to the Russian military shortly after World War II when flour contaminated with species of Fusarium was unknowingly baked into bread that was ingested by civilians. Some developed a protracted lethal illness called alimentary toxic aleukia (ATA) characterized by initial symptoms of abdominal pain, diarrhea, vomiting, prostration, and within days
fever, chills, myalgias and bone marrow depression with granulocytopenia and secondary sepsis. Survival beyond this point allowed the development of painful pharyngeal/laryngeal ulceration and diffuse bleeding into the skin (petechiae and ecchymoses), melena, bloody diarrhea, hematuria, hematemesis, epistaxis and
vaginal bleeding. Pancytopenia, and gastrointestinal ulceration and erosion were secondary to the ability of these toxins to profoundly arrest bone marrow and mucosal protein synthesis and cell cycle progression through DNA replication.
HISTORY AND SIGNIFICANCE
Mycotoxins allegedly have been used in aerosol form ("yellow rain") to produce lethal and nonlethal casualties in Laos (1975-81), Kampuchea (1979-81), and Afghanistan (1979-81). It has been estimated that there were more than 6,300 deaths in Laos, 1,000 in Kampuchea, and 3,042 in Afghanistan. The alleged victims were usually unarmed civilians or guerrilla forces. These groups were not protected with masks or chemical protective clothing and had little or no capability of destroying the attacking enemy aircraft. These attacks were alleged to have occurred in remote jungle areas which made confirmation of attacks and recovery of agent extremely difficult. Some investigators have claimed that the "yellow clouds" were, in fact, bee feces produced by swarms of migrating insects. Much controversy has centered upon the veracity of eyewitness and victim accounts, but there is evidence to make these allegations of BW agent use in these areas possible.
CLINICAL FEATURES
T-2 and other mycotoxins may enter the body through the skin and digestive or respiratory epithelium. They are fast acting potent inhibitors of protein and nucleic acid synthesis. Their main effects are on rapidly proliferating tissues such as the bone marrow, skin, mucosal epithelia, and germ cells. In a successful BW attack with trichothecene toxin (T-2), the toxin(s) can adhere to and penetrate the skin, be inhaled, or can be ingested. Clothing would be contaminated and serve as a reservoir for further toxin exposure. Early symptoms beginning within minutes of exposure include burning skin pain, redness, tenderness, blistering, and progression to skin necrosis with leathery blackening and sloughing of large areas of skin in lethal cases. Nasal contact is manifested by nasal itching and pain, sneezing, epistaxis and rhinorrhea; pulmonary/tracheobronchial toxicity by dyspnea, wheezing, and cough; and mouth and throat exposure by pain and blood tinged saliva and sputum. Anorexia, nausea, vomiting and watery or bloody diarrhea with abdominal crampy pain occurs with gastrointestinal toxicity. Eye pain, tearing, redness, foreign body sensation and blurred vision may follow entry of toxin into the eyes. Skin symptoms occur in minutes to hours and eye symptoms in minutes. Systemic toxicity is manifested by weakness, prostration, dizziness, ataxia, and loss of coordination. Tachycardia, hypothermia, and hypotension follow in fatal cases. Death may occur in minutes, hours or days. The most common symptoms are vomiting, diarrhea, skin involvement with burning pain, redness and pruritus, rash or blisters, bleeding, and dyspnea.
DIAGNOSIS
Rapid onset of symptoms in minutes to hours supports a diagnosis of a chemical or toxin attack. Mustard agents must be considered but they have an odor, are visible, and can be rapidly detected by a field available chemical test. Symptoms from mustard toxicity are also delayed for several hours after which mustard can cause skin, eye and respiratory symptoms. Staphylococcal enterotoxin B delivered by an aerosol attack can cause fever, cough, dyspnea and wheezing but does not involve the skin and eyes. Nausea, vomiting, and diarrhea may follow swallowing of inhaled toxin. Ricin inhalation can cause severe respiratory distress, cough, nausea and arthralgias. Swallowed agent can cause vomiting, diarrhea, and gastrointestinal bleeding, but it spares the skin, nose and eyes. Specific diagnosis of T-2 mycotoxins in the form of a rapid diagnostic test is not presently available in the field. Removal of blood, tissue from fatal cases, and environmental samples for testing using a gas liquid chromatography -mass spectrometry technique will confirm the toxic exposure. This system can detect as little as 0.1-1.0 ppb of T-2. This degree of sensitivity is capable of measuring T-2 levels in the plasma of toxin victims.
MEDICAL MANAGEMENT
Use of a chemical protective mask and clothing prior to and during a mycotoxin aerosol attack will prevent illness. If a soldier is unprotected during an attack the outer uniform should be removed within 4 hours and decontaminated by exposure to 5% hypochlorite for 6-10 hours. The skin should be thoroughly washed with soap and uncontaminated water if available. The M291 skin decontamination kit should also be used to remove skin adherent T-2. Superactivated charcoal can absorb swallowed T-2 and should be administered to victims of an unprotected aerosol attack. The eyes should be irrigated with normal saline or water to remove toxin. No specific antidote or therapeutic regimen is currently available. All therapy is supportive.
PROPHYLAXIS
Physical protection of the skin and airway are the only proven effective methods of protection during an attack. Immunological (vaccines) and chemoprotective pretreatments are being studied in animal models, but are not available for field use by the warfighter.
PERSONAL PROTECTION
The currently fielded chemical protective equipment, which includes the protective mask, battle dress overgarment (BDO), protective gloves, and overboots will provide protection against a biological agent attack.
The M40 protective mask is available in three sizes, and when worn correctly, will protect the face, eyes, and respiratory tract. The M40 utilizes a single screw on filter element which involves two separate but complementary mechanisms: 1) impaction and adsorption of agent molecules onto ASC Whetlerite Carbon filtration media, and 2) static electrical attraction of particles initially failing to contact the filtration media. Proper maintenance and periodic replacement of the crucial filter elements are of the utmost priority. The filter MUST be replaced under these circumstances: the elements are immersed in water, crushed, cut, or otherwise damaged; excessive breathing resistance is encountered; the "ALL CLEAR" signal is given after exposure to a biological agent; 30 days have elapsed in the combat theater of operations (the filters must be replaced every 30 days); supply bulletins indicate lot number expiration; or when ordered by the unit commander. The filter element can only be changed in a non-contaminated environment. Two styles of optical inserts for the protective mask are available for soldiers requiring visual correction. The wire frame
style is considered to be the safer of the two and is more easily fitted into the mask. A prong-type optical insert is also available. A drinking tube on the mask allows the wearer to drink while in a contaminated environment. Note that the wearer should disinfect the canteen and tube by wiping with a 5 percent hypochlorite solution before use.
The battle dress overgarment suits come in eight sizes and are currently available in both woodland and desert camouflage patterns. The suit may be worn for 24 continuous hours in a contaminated environment, but once contaminated, it must be replaced by using the MOPP-gear exchange procedure described in the Soldier's Manual of Common Tasks. The discarded BDO must be incinerated or buried. Chemical protective gloves and overboots come in various sizes and are both made from butyl rubber. They may be decontaminated and reissued. The gloves and overboots must be visually inspected and decontaminated as needed after every 12 hours of exposure in a contaminated environment. While the protective equipment will protect against biological agents, it is important to note that even standard uniform clothing of good quality affords a reasonable protection against dermal exposure of surfaces covered.
Those casualties unable to continue wearing protective equipment should be held and/or transported within casualty wraps designed to protect the patient against further chemical-biological agent exposure. Addition
of a filter blower unit to provide overpressure enhances protection and provides cooling.
Collective protection by the use of either a hardened or unhardened shelter equipped with an air filtration unit providing overpressure can offer protection for personnel in the biologically contaminated environment. An airlock ensures that no contamination will be brought into the shelter. In the absence of a dedicated structure, enhanced protection can be afforded within most buildings by sealing cracks and entry ports, and providing air filtration with high efficiency particulate air (HEPA) filters within existing ventilation systems. The key problem is that these shelters can be very limited in military situations, very costly to produce and maintain, and difficult to deploy. Personnel must be decontaminated prior to entering the collective protection unit.
The most important route of exposure to biological agents is through inhalation. Biological warfare (BW) agents are dispersed as aerosols by one of two basic mechanisms: point or line source dissemination. Unlike some chemical threats, aerosols of agents disseminated by line source munitions (e.g., sprayed by low-flying aircraft or speedboats along the coast) do not leave hazardous environmental residua (although anthrax spores may persist and could pose a hazard near the dissemination line). On the other hand, aerosols generated by point-source munitions (i.e., stationary aerosol generator, bomblets, etc.) are more apt to produce ground contamination, but only in the immediate vicinity of dissemination. Point-source munitions leave an obvious signature that alerts the field commander that a biological warfare attack has occurred. Because point-source munitions always leave an agent residue, this evidence can be exploited for detection and identification purposes.
Aerosol delivery systems for biological warfare agents most commonly generate invisible clouds with particles or droplets of < 10 micrometers (m m). They can remain suspended for extensive periods. The major risk is pulmonary retention of inhaled particles. To a much lesser extent, particles may adhere to an individual or his clothing, thus the need for individual decontamination. The effective area covered varies with many factors, including wind speed, humidity, and sunlight. In the absence of an effective real-time alarm system or direct observation of an attack, the first clue would be mass casualties fitting a clinical pattern compatible with one of the biological agents. This may occur hours or days after the attack.
Toxins may cause direct pulmonary toxicity or be absorbed and cause systemic toxicity. Toxins are frequently as potent or more potent by inhalation than by any other route. A unique clinical picture may sometimes be seen which is not observed by other routes (e.g., pulmonary edema after staphylococcal enterotoxin B (SEB) exposure). Mucous membranes, including conjunctivae, are also vulnerable to many biological warfare agents. Physical protection is then quite important and the use of full-face masks equipped with small-particle filters, like the chemical protective masks, assumes a high degree of importance.
Other routes for delivery of biological agents are thought to be less important than inhalation, but are nonetheless potentially significant. Contamination of food and water supplies, either purposefully or incidentally after an aerosol biological warfare attack, represents a hazard for infection or intoxication by ingestion. Assurance that food and water supplies are free from contamination should be provided by
appropriate preventive medicine authorities in the event of an attack.
Intact skin provides an excellent barrier for most biological agents. T-2 mycotoxins would be an exception because of their dermal activity. However, mucous membranes and abraded, or otherwise damaged, integument can allow for passage of some bacteria and toxins, and should be protected in the event of an attack.
SUMMARY
Signs and symptoms: Exposure causes skin pain, pruritus, redness, vesicles, necrosis and sloughing of epidermis. Effects on the airway include nose and throat pain, nasal discharge, itching and sneezing, cough, dyspnea, wheezing, chest pain and hemoptysis. Toxin also produces effects after ingestion or eye contact. Severe poisoning results in prostration, weakness, ataxia, collapse, shock, and death.
Diagnosis: Should be suspected if an aerosol attack occurs in the form of "yellow rain" with droplets of yellow fluid contaminating clothes and the environment. Confirmation requires testing of blood, tissue and
environmental samples.
Treatment: There is no specific antidote. Superactivated charcoal should be given orally if the toxin is swallowed.
Prophylaxis: The only defense is to wear a protective mask and clothing during an attack. No specific immunotherapy or chemotherapy is available for use in the field.
Isolation and Decontamination: Standard Precautions for healthcare workers. Outer clothing should be removed and exposed skin should be decontaminated with soap and water. Eye exposure should be treated with copious saline irrigation. Once decontamination is complete, isolation is not required. Environmental decontamination requires the use of a hypochlorite solution under alkaline conditions such as 1% sodium hypochlorite and 0.1M NAOH with 1 hour contact time.
OVERVIEW
The trichothecene mycotoxins are low molecular weight (250-500 daltons) nonvolatile compounds produced by filamentous fungi (molds) of the genera Fusarium, Myrotecium, Trichoderma, Stachybotrys and others. The structures of approximately 150 trichothecene derivatives have been described in the literature. These substances are relatively insoluble in water but are highly soluble in ethanol, methanol and propylene glycol. The trichothecenes are extremely stable to heat and ultraviolet light inactivation. Heating to 1500o F for 30 minutes is required for inactivation, while brief exposure to NaOCl destroys toxic activity. The potential for use as a BW toxin was demonstrated to the Russian military shortly after World War II when flour contaminated with species of Fusarium was unknowingly baked into bread that was ingested by civilians. Some developed a protracted lethal illness called alimentary toxic aleukia (ATA) characterized by initial symptoms of abdominal pain, diarrhea, vomiting, prostration, and within days
fever, chills, myalgias and bone marrow depression with granulocytopenia and secondary sepsis. Survival beyond this point allowed the development of painful pharyngeal/laryngeal ulceration and diffuse bleeding into the skin (petechiae and ecchymoses), melena, bloody diarrhea, hematuria, hematemesis, epistaxis and
vaginal bleeding. Pancytopenia, and gastrointestinal ulceration and erosion were secondary to the ability of these toxins to profoundly arrest bone marrow and mucosal protein synthesis and cell cycle progression through DNA replication.
HISTORY AND SIGNIFICANCE
Mycotoxins allegedly have been used in aerosol form ("yellow rain") to produce lethal and nonlethal casualties in Laos (1975-81), Kampuchea (1979-81), and Afghanistan (1979-81). It has been estimated that there were more than 6,300 deaths in Laos, 1,000 in Kampuchea, and 3,042 in Afghanistan. The alleged victims were usually unarmed civilians or guerrilla forces. These groups were not protected with masks or chemical protective clothing and had little or no capability of destroying the attacking enemy aircraft. These attacks were alleged to have occurred in remote jungle areas which made confirmation of attacks and recovery of agent extremely difficult. Some investigators have claimed that the "yellow clouds" were, in fact, bee feces produced by swarms of migrating insects. Much controversy has centered upon the veracity of eyewitness and victim accounts, but there is evidence to make these allegations of BW agent use in these areas possible.
CLINICAL FEATURES
T-2 and other mycotoxins may enter the body through the skin and digestive or respiratory epithelium. They are fast acting potent inhibitors of protein and nucleic acid synthesis. Their main effects are on rapidly proliferating tissues such as the bone marrow, skin, mucosal epithelia, and germ cells. In a successful BW attack with trichothecene toxin (T-2), the toxin(s) can adhere to and penetrate the skin, be inhaled, or can be ingested. Clothing would be contaminated and serve as a reservoir for further toxin exposure. Early symptoms beginning within minutes of exposure include burning skin pain, redness, tenderness, blistering, and progression to skin necrosis with leathery blackening and sloughing of large areas of skin in lethal cases. Nasal contact is manifested by nasal itching and pain, sneezing, epistaxis and rhinorrhea; pulmonary/tracheobronchial toxicity by dyspnea, wheezing, and cough; and mouth and throat exposure by pain and blood tinged saliva and sputum. Anorexia, nausea, vomiting and watery or bloody diarrhea with abdominal crampy pain occurs with gastrointestinal toxicity. Eye pain, tearing, redness, foreign body sensation and blurred vision may follow entry of toxin into the eyes. Skin symptoms occur in minutes to hours and eye symptoms in minutes. Systemic toxicity is manifested by weakness, prostration, dizziness, ataxia, and loss of coordination. Tachycardia, hypothermia, and hypotension follow in fatal cases. Death may occur in minutes, hours or days. The most common symptoms are vomiting, diarrhea, skin involvement with burning pain, redness and pruritus, rash or blisters, bleeding, and dyspnea.
DIAGNOSIS
Rapid onset of symptoms in minutes to hours supports a diagnosis of a chemical or toxin attack. Mustard agents must be considered but they have an odor, are visible, and can be rapidly detected by a field available chemical test. Symptoms from mustard toxicity are also delayed for several hours after which mustard can cause skin, eye and respiratory symptoms. Staphylococcal enterotoxin B delivered by an aerosol attack can cause fever, cough, dyspnea and wheezing but does not involve the skin and eyes. Nausea, vomiting, and diarrhea may follow swallowing of inhaled toxin. Ricin inhalation can cause severe respiratory distress, cough, nausea and arthralgias. Swallowed agent can cause vomiting, diarrhea, and gastrointestinal bleeding, but it spares the skin, nose and eyes. Specific diagnosis of T-2 mycotoxins in the form of a rapid diagnostic test is not presently available in the field. Removal of blood, tissue from fatal cases, and environmental samples for testing using a gas liquid chromatography -mass spectrometry technique will confirm the toxic exposure. This system can detect as little as 0.1-1.0 ppb of T-2. This degree of sensitivity is capable of measuring T-2 levels in the plasma of toxin victims.
MEDICAL MANAGEMENT
Use of a chemical protective mask and clothing prior to and during a mycotoxin aerosol attack will prevent illness. If a soldier is unprotected during an attack the outer uniform should be removed within 4 hours and decontaminated by exposure to 5% hypochlorite for 6-10 hours. The skin should be thoroughly washed with soap and uncontaminated water if available. The M291 skin decontamination kit should also be used to remove skin adherent T-2. Superactivated charcoal can absorb swallowed T-2 and should be administered to victims of an unprotected aerosol attack. The eyes should be irrigated with normal saline or water to remove toxin. No specific antidote or therapeutic regimen is currently available. All therapy is supportive.
PROPHYLAXIS
Physical protection of the skin and airway are the only proven effective methods of protection during an attack. Immunological (vaccines) and chemoprotective pretreatments are being studied in animal models, but are not available for field use by the warfighter.
PERSONAL PROTECTION
The currently fielded chemical protective equipment, which includes the protective mask, battle dress overgarment (BDO), protective gloves, and overboots will provide protection against a biological agent attack.
The M40 protective mask is available in three sizes, and when worn correctly, will protect the face, eyes, and respiratory tract. The M40 utilizes a single screw on filter element which involves two separate but complementary mechanisms: 1) impaction and adsorption of agent molecules onto ASC Whetlerite Carbon filtration media, and 2) static electrical attraction of particles initially failing to contact the filtration media. Proper maintenance and periodic replacement of the crucial filter elements are of the utmost priority. The filter MUST be replaced under these circumstances: the elements are immersed in water, crushed, cut, or otherwise damaged; excessive breathing resistance is encountered; the "ALL CLEAR" signal is given after exposure to a biological agent; 30 days have elapsed in the combat theater of operations (the filters must be replaced every 30 days); supply bulletins indicate lot number expiration; or when ordered by the unit commander. The filter element can only be changed in a non-contaminated environment. Two styles of optical inserts for the protective mask are available for soldiers requiring visual correction. The wire frame
style is considered to be the safer of the two and is more easily fitted into the mask. A prong-type optical insert is also available. A drinking tube on the mask allows the wearer to drink while in a contaminated environment. Note that the wearer should disinfect the canteen and tube by wiping with a 5 percent hypochlorite solution before use.
The battle dress overgarment suits come in eight sizes and are currently available in both woodland and desert camouflage patterns. The suit may be worn for 24 continuous hours in a contaminated environment, but once contaminated, it must be replaced by using the MOPP-gear exchange procedure described in the Soldier's Manual of Common Tasks. The discarded BDO must be incinerated or buried. Chemical protective gloves and overboots come in various sizes and are both made from butyl rubber. They may be decontaminated and reissued. The gloves and overboots must be visually inspected and decontaminated as needed after every 12 hours of exposure in a contaminated environment. While the protective equipment will protect against biological agents, it is important to note that even standard uniform clothing of good quality affords a reasonable protection against dermal exposure of surfaces covered.
Those casualties unable to continue wearing protective equipment should be held and/or transported within casualty wraps designed to protect the patient against further chemical-biological agent exposure. Addition
of a filter blower unit to provide overpressure enhances protection and provides cooling.
Collective protection by the use of either a hardened or unhardened shelter equipped with an air filtration unit providing overpressure can offer protection for personnel in the biologically contaminated environment. An airlock ensures that no contamination will be brought into the shelter. In the absence of a dedicated structure, enhanced protection can be afforded within most buildings by sealing cracks and entry ports, and providing air filtration with high efficiency particulate air (HEPA) filters within existing ventilation systems. The key problem is that these shelters can be very limited in military situations, very costly to produce and maintain, and difficult to deploy. Personnel must be decontaminated prior to entering the collective protection unit.
The most important route of exposure to biological agents is through inhalation. Biological warfare (BW) agents are dispersed as aerosols by one of two basic mechanisms: point or line source dissemination. Unlike some chemical threats, aerosols of agents disseminated by line source munitions (e.g., sprayed by low-flying aircraft or speedboats along the coast) do not leave hazardous environmental residua (although anthrax spores may persist and could pose a hazard near the dissemination line). On the other hand, aerosols generated by point-source munitions (i.e., stationary aerosol generator, bomblets, etc.) are more apt to produce ground contamination, but only in the immediate vicinity of dissemination. Point-source munitions leave an obvious signature that alerts the field commander that a biological warfare attack has occurred. Because point-source munitions always leave an agent residue, this evidence can be exploited for detection and identification purposes.
Aerosol delivery systems for biological warfare agents most commonly generate invisible clouds with particles or droplets of < 10 micrometers (m m). They can remain suspended for extensive periods. The major risk is pulmonary retention of inhaled particles. To a much lesser extent, particles may adhere to an individual or his clothing, thus the need for individual decontamination. The effective area covered varies with many factors, including wind speed, humidity, and sunlight. In the absence of an effective real-time alarm system or direct observation of an attack, the first clue would be mass casualties fitting a clinical pattern compatible with one of the biological agents. This may occur hours or days after the attack.
Toxins may cause direct pulmonary toxicity or be absorbed and cause systemic toxicity. Toxins are frequently as potent or more potent by inhalation than by any other route. A unique clinical picture may sometimes be seen which is not observed by other routes (e.g., pulmonary edema after staphylococcal enterotoxin B (SEB) exposure). Mucous membranes, including conjunctivae, are also vulnerable to many biological warfare agents. Physical protection is then quite important and the use of full-face masks equipped with small-particle filters, like the chemical protective masks, assumes a high degree of importance.
Other routes for delivery of biological agents are thought to be less important than inhalation, but are nonetheless potentially significant. Contamination of food and water supplies, either purposefully or incidentally after an aerosol biological warfare attack, represents a hazard for infection or intoxication by ingestion. Assurance that food and water supplies are free from contamination should be provided by
appropriate preventive medicine authorities in the event of an attack.
Intact skin provides an excellent barrier for most biological agents. T-2 mycotoxins would be an exception because of their dermal activity. However, mucous membranes and abraded, or otherwise damaged, integument can allow for passage of some bacteria and toxins, and should be protected in the event of an attack.