Toxins

STAPHYLOCOCCAL ENTEROTOXIN B

Staphylococcal enterotoxin B (SEB) is one of the best-studied and, therefore, best-understood toxins.

Staphylococcal enterotoxin is one of the most common causes of food poisoning. Nausea, vomiting, and diarrhea normally occur after someone eats or drinks contaminated food.

The toxin creates different symptoms when exposure is through the air in a biological warfare situation. Only a small, inhaled dose is necessary to harm people within 24 hours of inhalation.

Signs and symptoms

After exposure, signs and symptoms begin in 2-12 hours. Mild-to-moderate exposure to SEB produces fever, chills, headache, nausea, vomiting, shortness of breath, chest pain, body aches, and a nonproductive cough. Severe exposures can lead to a toxic shock -type picture and even death. Depending on the severity of exposure, the illness may last 3-10 days.

Diagnosis

Diagnosis of SEB can be difficult. Laboratory tests and a chest x-ray may be performed. Nasal swabs may show the toxin for 12-24 hours after exposure.

Treatment

Doctors provide care to relieve symptoms. Close attention to oxygenation and hydration are important. People with severe SEB may need help breathing with a ventilator. Most victims are expected to do well after the initial phase, but the time to full recovery may be long.

Prevention

No approved human vaccine exists for SEB, although human trials are ongoing. Passive immunotherapy agents have demonstrated some promise when given within 4 hours of exposure, but such therapy is still being tested.

RICIN

Ricin, a plant protein toxin derived from the beans of the castor plant, is one of the most toxic and easily produced of the plant toxins. Although the lethal toxicity of ricin is about 1000-fold less than botulinum toxin, the worldwide ready availability of castor beans and the ease with which the toxin can be produced give it significant potential as a biological weapon.

Since ancient times, more than 750 cases of ricin intoxication have been described. Ricin may have been used in the highly published killing of Bulgarian exile Georgi Markov in London in 1978. He was attacked with a device in an umbrella that implanted a ricin-containing pellet into his thigh.

Signs and symptoms

The toxicity of ricin varies greatly with the way it is given. Ricin is extremely toxic to cells and acts by inhibiting protein synthesis. Inhalation exposure causes primarily breathing and lung problems. If eaten, ricin causes symptoms in the GI tract. If injected, the reaction takes place in that area.

• Following inhalation exposure of ricin, toxicity is characterized by the sudden onset of nasal and throat congestion, nausea and vomiting, itching of the eyes, itching, and tightness in the chest. If exposure is significant, after 12-24 hours severe breathing problems may set in. In animal studies, death occurs 36-48 hours after severe exposure.
  
  
• Ingestion of ricin is generally less toxic because it is not absorbed well and may degrade in the digestive tract. Out of 751 ingestions recorded, only 14 resulted in a death.
  
  
• At low doses, injection exposures produce flulike symptoms, body aches, nausea, vomiting, and localized pain and swelling at the injection site. Severe exposure results in tissue death and GI bleeding, as well as widespread liver, spleen, and kidney problems.

Diagnosis

The diagnosis of ricin poisoning is made on the basis of symptoms and whether exposure was possible. In biological warfare, exposure is likely to occur by inhalation of a toxin aerosol.

Victims may have certain signs on a chest x-ray. The diagnosis can be confirmed by lab tests on samples from a nasal swab. Ricin can be identified for up to 24 hours after exposure.

Treatment

Treatment is mainly to relieve symptoms. If exposure was by inhalation, the person may need help breathing. Those who ingested the poison may need to have their stomachs pumped (gastric lavage), or they might be given activated charcoal to soak up the material.

Prevention

Currently, no vaccine is available for ricin exposure. Test vaccines have proven effective in animals. Other drugs are being studied as well.

BOTULINUM TOXIN

Botulinum toxins are the most deadly toxins known. Because botulinum toxin is so lethal and easy to manufacture and weaponize, it represents a credible threat as a biological warfare agent. When used in this manner, exposure is likely to occur following inhalation of aerosolized toxin or ingestion of food contaminated with the toxin or its microbial spores. Iraq admitted to active research on the offensive use of botulinum toxins and to weaponizing and deploying more than 100 munitions with botulinum toxin in 1995.

All 7 subtypes (A-G) of botulinum toxin act in similar ways. The toxin produces similar effects whether ingested, inhaled, or via a wound. The time course and severity of illness vary with route of exposure and dose received. Symptom onset is slower after inhalation exposure.

Signs and symptoms

Symptoms may occur hours to several days after exposure. Initial signs and symptoms include blurred vision, dilated pupils, difficulty swallowing, difficulty speaking, an altered voice, and muscle weakness. After 24-48 hours, muscle weakness and paralysis may cause the person to be unable to breathe. Varying degrees of muscular weakness may occur.

Diagnosis

Paralysis may indicate the presence of this exposure. Laboratory tests generally are not helpful. Infection by inhalation can be diagnosed from nasal swabs up to 24 hours after exposure.

Treatment

The most serious complication is respiratory failure. With attention to symptoms and help breathing, sometimes with a ventilator, death occurs in fewer than 5% of cases. For confirmed exposures, an antitoxin is available from the CDC. This antitoxin has all of the disadvantages of horse serum products, including the risks for shock and serum sickness. Skin testing is performed first by injecting a small amount of the antitoxin into the skin and then monitoring the person for 20 minutes.

Prevention

A toxoid (inactivated toxin that produces immunity) has been used in volunteers and occupationally at-risk workers. It is available through the CDC. It was used to immunize US military troops during the Persian Gulf War. The current schedule for immunization is at 0, 2, and 12 weeks with an annual booster.

MYCOTOXINS

The trichothecene mycotoxins are highly toxic compounds produced by certain species of fungi. Because these mycotoxins can cause massive organ damage, and because they are fairly easy to produce and can be dispersed by various methods (dusts, droplets, aerosols, smoke, rockets, artillery mines, portable sprays), mycotoxins have an excellent potential for weaponization.

Strong evidence suggests that trichothecenes ("yellow rain") have been used as a biological warfare agent in Southwest Asia and Afghanistan. From 1974-1981, numerous attacks resulted in a minimum of 6310 deaths in Laos, 981 deaths in Cambodia, and 3042 deaths in Afghanistan. When taken from fungal cultures, the mycotoxins yield a yellow-brown liquid that evaporates into a yellow crystalline product (thus, the "yellow rain" appearance). These toxins require certain solutions and high heat to be completely inactivated.

Signs and symptoms

After exposure to the mycotoxins, early symptoms begin within 5 minutes. Full effects take 60 minutes.

• If skin exposure occurs, the skin burns, becomes tender, swollen, and blisters. In lethal cases, large areas of skin die and slough (fall off).
  
  
• Respiratory exposure results in nasal itching, pain, sneezing, a bloody nose, shortness of breath, wheezing, cough, and blood-tinged saliva and sputum.
  
  
• If ingested, the person feels nausea and vomits, loses appetite, feels abdominal cramping, and has watery and/or bloody diarrhea.
  
  
• Following entry into the eyes, pain, tearing, redness, and blurred vision occur.
  
  
• Systemic toxicity may occur and includes weakness, exhaustion, dizziness, inability to coordinate muscles, heart problems, low or high temperature, diffuse bleeding, and low blood pressure. Death may occur within minutes to days depending on the dose and route of exposure.

Diagnosis

Diagnosis of an attack of trichothecene mycotoxin depends on the symptoms and identifying the toxin from biological and environmental samples. Many people with these symptoms may report being in a yellow rain or smoke attack.

Initial laboratory tests are not always helpful. Currently, a rapid identification kit for any of the trichothecene mycotoxins does not exist. Gas-liquid chromatography has been used in the past with great success. However, chromatographic methods lack great sensitivity, and presently alternative methods of detection are under investigation.

Treatment

Treatment is mainly to help with symptoms. The immediate use of protective clothing and mask during a mycotoxin aerosol attack should prevent illness. If a soldier is unprotected during an attack, the outer clothing should be removed within 4-6 hours and decontaminated with 5% sodium hydroxide for 6-10 hours. The skin should be washed with copious amounts of soap and uncontaminated water. The eyes, if exposed, should be washed out with large amounts of normal saline or sterile water. US military personnel can use a skin decontamination kit effectively against most chemical warfare agents, including the mycotoxins.

No specific therapy exists for a trichothecene exposure. After appropriate skin decontamination, victims of inhalation and oral exposures may be given superactivated charcoal orally. Activated charcoal removes mycotoxins from the GI tract. Some victims may need help breathing with a ventilator. Early use of steroids increases survival time by decreasing the primary injury and shock-like state that follows significant poisoning.

Prevention

No vaccine exists for trichothecene mycotoxin exposure. Currently, 2 topical skin protectants as well as vaccines are in advanced development but have not been approved yet for use in humans.