INTRODUCTION	Section 2 of 11
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Background: Mycotoxins are naturally occurring substances produced by fungi as a secondary metabolite that typically affords the organism survival benefit (eg, penicillin). Many of these toxins are pathogenic to animals and humans. An estimated more than 300 mycotoxins are produced by some 350 species of fungi. The T-2 mycotoxin, which is classified as a trichothecene mycotoxin, is elaborated from the fusarial species of fungus. According to the current declassified literature, the T-2 mycotoxin is the only mycotoxin known to have been used as a biological weapon. The trichothecene mycotoxins are low molecular weight compounds (250-500 d, averaging 466 d) that are nonvolatile, relatively insoluble in water, and highly soluble in ethanol, methanol, and propylene glycol. The toxin is highly heat stable and resistant to UV light destabilization (2 important factors when considering an agent as a biological warfare agent).

In laboratory rats, the LD50 (dose to cause 50% lethality) is 4 mg/kg when ingested. The LD50 for dermal exposure is reportedly 2-12 mg/kg. In mice, the LD50 for aerosol exposure is 1.2 mg/kg. The trichothecene class of toxins is considered among the most potent naturally occurring toxic substances.

Most information regarding the effects of T-2 mycotoxin on humans has been collected from many incidents of accidental ingestion of moldy wheat or corn. One such incident involved the Orenburg district of Russia during World War II. Most men in the village were fighting in the war, leaving the wheat crop unharvested, which resulted in the crop remaining in the fields over the winter. It was harvested in the spring and consumed, causing the clinical syndrome alimentary toxic aleukia (ATA), with varied reports of 10-60% mortality. Some hypothesize that T-2 mycotoxin may have been the operative agent in the "plague" of Athens in 430 BC. Additional information about the clinical effects of T-2 mycotoxin has been demonstrated in the laboratory using human cell cultures and animal models.

Reports exist of T-2 mycotoxin used as a biological warfare agent. The first suspected use was in the country of Laos during the Vietnam War. The report of "yellow rain" in remote sections of jungle in Laos (1975-81), which resulted in more than 6300 deaths, has been viewed as use of T-2 mycotoxin as a biological weapon. Evidence regarding the use of the toxin in Laos remains hotly debated. Other reported uses of T-2 mycotoxin as a biological weapon concern Kampuchea (1979-81) and Afghanistan (1979-81).

It has been suggested that T-2 mycotoxin was disseminated near a US military camp in Saudi Arabia during the Desert Storm campaign. An Iraqi missile may have detonated over or near the camp. Some of the troops in the area reported immediate symptoms that could be consistent with dermal mycotoxin exposure. Evidence surrounding this incident is questionable, and the government has not verified any evidence consistent with the use of this agent. Some sources state that exposure to T-2 mycotoxins may be the cause of Gulf War syndrome. More recently, the mysterious illness of the Ukrainian President Viktor Yushchenko was thought to be the surreptitious use of either dioxin or possibly T-2 mycotoxin (personal communication).

Qualities important to producing an effective chemical or biological weapon are its ease of manufacture, ease of weaponization, durability of the organism or toxin in storage form, ease of dispersal, and chemical stability when exposed to heat and UV radiation. Other factors include ease of concealment and ability to directly obtain the agent or organism that produces the agent. In the early half of the century, biotoxins were investigated as military weapons. These types of weapons fell into disfavor primarily because of problems with weaponization of the biotoxin material. The US closed its biotoxin program in the 1960s. Interest was rekindled in the 1970s with improvements in gene technology and biotechnology. Although the US has no current offensive biological weapons capability, these agents are less expensive than nuclear and chemical weapons and therefore appeal to smaller countries or terrorist organizations.

Because of limitations in the manufacture of sufficient quantities, biotoxins are not optimal agents for mass dispersal. This agent is better suited as a small-group assassination tool, since a small amount can be dispersed effectively in enclosed areas. As an assassination tool, T-2 mycotoxins can be used as a food or water-borne poison. The T-2 mycotoxin is the only biologically active toxin effective through dermal exposure and respiratory and gastrointestinal (GI) portals. The route of entry and dose dictate the clinical course. Tissues involved in high cellular turnover (eg, GI and respiratory epithelium, bone marrow cellular elements) are most susceptible to the toxin.

Pathophysiology: The pathophysiology of T-2 mycotoxin is multifactorial. It causes DNA breaks, chromosomal abnormalities, and inhibition of protein synthesis. Inhibition of protein synthesis seems to be the primary cause of symptoms in intoxicated patients. Conflicting reports of the mechanism involving the inhibition of protein synthesis exist. One theory relates it to the toxin's affinity for the 60S ribosomal subunit, therefore inhibiting protein synthesis at the initial step. Another theory involves the inactivation of peptidyl transferase, which inhibits the terminal step of protein synthesis. The mechanism of action on DNA is not clear but is believed to be related indirectly to the cessation of protein synthesis.

Frequency:

• In the US: The only epidemiologic information available is from the ingestion of contaminated foodstuff. No well-documented epidemiologic information is available for exposure to T-2 mycotoxin as a result of bioweapon deployment.

Mortality/Morbidity: No human mortality or morbidity data are reported for T-2 mycotoxin use as a bioweapon. Information regarding mortality from ingestion of contaminated food is quite varied, with 10-60% mortality reported in Russia's Orenburg district. Mortality figures from the Kampuchea and Afghanistan uses of mycotoxin as a bioweapon do not report mortality rates, only total number of deaths. Not knowing the number of exposed individuals as related to the number of fatalities makes the calculation of mortality rates impossible.

	CLINICAL	Section 3 of 11
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History:

• Patients with cutaneous symptoms may report seeing clouds of a yellow colored smoke or aerosol, but blue and green aerosols also have been reported.

• Patients may report "yellow droplets" on clothing.

• Immediate skin pain and burning on exposed surfaces is described. Eye pain and burning also should be reported.

• Suspicion of the toxin being placed in an ingested food source may exist. Ingested toxin probably has no taste, since no documentation supports a foul odor or taste in previous epidemics of toxin ingestion. This is further supported by the historical experience that many individuals become ill when exposed to contaminated food without any suspicion of having ingested tainted food.

• The most common symptoms occurring with most exposures include skin (or oral) pain (burning) and redness or rash, vomiting, diarrhea, dyspnea, and bleeding.

Physical:

• Symptom onset usually is observed within 2-4 hours, although significant exposure can cause immediate onset of symptoms.

• The clinical syndrome of ATA represents a more chronic form of exposure to T-2 mycotoxin, and in some ways the syndrome mimics that of radiation sickness. It occurs in 4 stages.

• The first stage, which may be seen in the emergency department, refers to the acute injury of exposed cells and tissues. This phase is addressed in greater depth below. The symptoms observed in this phase depend on the form of exposure.

• The second stage, which typically occurs weeks after the exposure, represents bone marrow suppression secondary to the antimitotic effects of the toxin and includes significant leukopenia, granulocytopenia, and thrombocytopenia. Patients may feel well during this phase.

• The third stage is considered the hemorrhagic stage. In this phase, the patient experiences petechial hemorrhages, especially of the mucosal areas of the nasopharynx and oropharynx. Bleeding encountered in this phase can be fatal. Related airway edema can be present, making airway compromise a complication of this phase. The patient also is at risk for systemic infection secondary to the compromised immune system.

• The fourth stage of illness typically is referred to as the recovery phase, when all necrotic lesions heal and the bone marrow recovers, replacing essential blood elements.

• Skin

• Painful erythema is noted in exposed areas. These symptoms can progress to blistering and skin necrosis with sloughing of the epidermal layer.

• Skin symptoms can mimic acute radiation syndrome, similar to beta-particle exposure.

• Head, eyes, ears, nose, and throat

• Nasal and oral cavities are painfully erythematous.

• If the agent is inhaled through the nose, the patient experiences nasal pruritus, pain, and rhinorrhea. Sneezing, coughing, and epistaxis also are noted.

• If the agent is ingested, nasal symptoms may be sparse with more intense symptoms involving the oral cavity, throat, and esophagus. This manifests as a complaint of severe throat pain and blood-tinged saliva or sputum.

• Eye exposure results in immediate symptoms of eye pain and tearing. A sensation of a foreign body and visual blurring may be present. Scleral induration is noted.

• Respiratory: Inhalation exposure results in cough, dyspnea, and wheezing. Symptoms typically progress to hemoptysis.

• Gastrointestinal

• GI symptoms also are similar to radiation syndrome.

• Vomiting is the most common symptom. The patient also may complain of significant crampy abdominal pain.

• Watery or bloody diarrhea typically is reported with ingestion of toxin.

• Anorexia also is a typical symptom of both ingested and absorbed intoxication.

• Neurologic: No specific neurologic signs or symptoms are related to the toxin except for mild ataxia, which accompanies systemic intoxication.

• Systemic: Severe intoxication can result in early systemic effects including prostration, dizziness, and ataxia. Also noted in systemic intoxication are tachycardia, hypothermia, and vascular collapse.