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Biological weapons include any organism such as bacteria, viruses, or fungi or toxin found in nature that can be used to kill or injure people. Toxins are poisonous compounds produced by organisms.
The act of bioterrorism can range from a simple hoax to the actual use of these biological weapons, also referred to as "agents". A number of nations have or are seeking to acquire biological warfare agents, and there are concerns that terrorist groups or individuals may acquire the technologies and expertise to use these destructive agents.
Biological agents may be used for an isolated assassination, as well as to cause incapacitation or death to thousands. If the environment is contaminated, a long-term threat to the population could be created.
The use of biological agents is not a new concept, and history is filled with examples of their use.
Attempts to use biological warfare agents date back to antiquity. Scythian archers infected their arrows by dipping them in decomposing bodies or in blood mixed with manure as far back as 400 BC. Persian, Greek, and Roman literature from 300 BC quotes examples of dead animals used to contaminate wells and other sources of water. In the Battle of Eurymedon in 190 BC, Hannibal won a naval victory over King Eumenes II of Pergamon by firing earthen vessels full of venomous snakes into the enemy ships.
During the battle of Tortona in the 12th century AD, Barbarossa used the bodies of dead and decomposing soldiers to poison wells. During the siege of Kaffa in the 14th century AD, the attacking Tatar forces hurled plague-infected corpses into the city in an attempt to cause an epidemic within enemy forces. This was repeated in 1710, when the Russians besieging Swedish forces at Reval in Estonia catapulted bodies of people who had died from plague.
During the French and Indian War in the 18th century AD, British forces under the direction of Sir Jeffrey Amherst gave blankets that had been used by smallpox victims to the Native Americans in a plan to spread the disease.
Allegations were made during the American Civil War by both sides, but especially against the Confederate Army, of the attempted use of smallpox to cause disease among enemy forces.
Modern times: Biological warfare reached sophistication during the 1900s.
During World War I, the German Army developed anthrax, glanders, cholera, and a wheat fungus specifically for use as biological weapons. They allegedly spread plague in St. Petersburg, Russia, infected mules with glanders in Mesopotamia, and attempted to do the same with the horses of the French Cavalry.
The Geneva Protocol of 1925 was signed by 108 nations. This was the first multilateral agreement that extended prohibition of chemical agents to biological agents. Unfortunately, no method for verification of compliance was addressed.
During World War II, Japanese forces operated a secret biological warfare research facility (Unit 731) in Manchuria that carried out human experiments on prisoners. They exposed more than 3000 victims to plague, anthrax, syphilis, and other agents in an attempt to develop and observe the disease. Some victims were executed or died from their infections. Autopsies were also performed for greater understanding of the effects on the human body.
In 1942, the United States formed the War Research Service. Anthrax and botulinum toxin initially were investigated for use as weapons. Sufficient quantities of botulinum toxin and anthrax were stockpiled by June 1944 to allow unlimited retaliation if the German forces first used biological agents. The British also tested anthrax bombs on Gruinard Island off the northwest coast of Scotland in 1942 and 1943 and then prepared and stockpiled anthrax-laced cattle cakes for the same reason.
The United States continued research on various offensive biological weapons during the 1950s and 1960s. From 1951-1954, harmless organisms were released off both coasts of the United States to demonstrate the vulnerability of American cities to biological attacks. This weakness was tested again in 1966 when a test substance was released in the New York City subway system.
During the Vietnam War, Viet Cong guerrillas used needle-sharp punji sticks dipped in feces to cause severe infections after an enemy soldier had been stabbed.
In 1979, an accidental release of anthrax from a weapons facility in Sverdlovsk, USSR, killed at least 66 people. The Russian government claimed these deaths were due to infected meat, and maintained this position until 1992, when Russian President Boris Yeltsin finally admitted to the accident.
Bioterrorism and biowarfare today: A number of countries have continued offensive biological weapons research and use. Additionally, since the 1980s, terrorist organizations have become users of biological agents. Usually, these cases amount only to hoaxes. However, the following exceptions have been noted:
In 1985, Iraq began an offensive biological weapons program producing anthrax, botulinum toxin, and aflatoxin. During Operation Desert Storm, the coalition of allied forces faced the threat of chemical and biological agents. Following the Persian Gulf War, Iraq disclosed that it had bombs, Scud missiles, 122-mm rockets, and artillery shells armed with botulinum toxin, anthrax, and aflatoxin. They also had spray tanks fitted to aircraft that could distribute agents over a specific target.
In September and October of 1984, 751 people were intentionally infected with Salmonella, an agent that causes food poisoning, when followers of the Bhagwan Shree Rajneesh contaminated restaurant salad bars in Oregon.
In 1994, a Japanese sect of the Aum Shinrikyo cult attempted an aerosolized (sprayed into the air) release of anthrax from the tops of buildings in Tokyo.
In 1995, 2 members of a Minnesota militia group were convicted of possession of ricin, which they had produced themselves for use in retaliation against local government officials.
In 1996, an Ohio man attempted to obtain bubonic plague cultures through the mail.
In 2001, anthrax was delivered by mail to US media and government offices. There were 4 deaths.
In December 2002, 6 terrorist suspects were arrested in Manchester, England; their apartment was serving as a "ricin laboratory." Among them was a 27-year-old chemist who was producing the toxin. Later, on January 5, 2003, British police raided 2 residences around London and found traces of ricin, which led to an investigation of a possible Chechen separatist plan to attack the Russian embassy with the toxin; several arrests were made.
On February 3, 2004, 3 US Senate office buildings were closed after the toxin ricin was found in mailroom that serves Senate Majority Leader Bill Frist's office.
The threat that biological agents will be used on both military forces and civilian populations is now more likely than it was at any other point in history.
Biological warfare agents are easy to hide and difficult to detect or protect against. They are invisible, odorless, tasteless, and can be spread silently.
Protective measures can be taken against biological warfare agents. These should be started early, if enough warning is received, but definitely once it is suspected that a biological agent has been used.
Masks: Currently, available masks such as the military gas mask or high-efficiency particulate air (HEPA) filter masks used for tuberculosis exposure filter out most biological warfare particles delivered through the air. However, the face seals on ill-fitting masks often leak. For a mask to fit properly, it must be fitted to a person's face.
Clothing: Most biological agents in the air do not penetrate unbroken skin, and few organisms stick to skin or clothing. After an aerosol attack, the simple removal of clothing eliminates a great majority of surface contamination. Thorough showering with soap and water removes 99.99% of the few organisms that may be left on the victim's skin.
Medical protection: Health care providers treating victims of biological warfare may not need special suits but should use latex gloves and take other precautions such as wearing gowns and masks with protective eye shields. Victims would be isolated in private rooms while receiving treatment.
Antibiotics: Victims of biological warfare might be given antibiotics orally (pills) or through an IV, even before the specific agent is identified.
Vaccinations: Currently, protective vaccines (given as shots) are available for anthrax, botulinum toxin, tularemia, plague, Q fever, and smallpox. The widespread immunization of nonmilitary personnel has not been recommended by any governmental agency so far. Immune protection against ricin and staphylococcal toxins may also be possible in the near future.
Anthrax bacteria occur worldwide. The organisms known as Bacillus anthracis may ordinarily produce disease in domesticated as well as wild animals such as goats, sheep, cattle, horses, and swine. Humans become infected by contact with infected animals or contaminated animal products. Infection occurs mainly through the skin and rarely by breathing spores or swallowing them. Spores exist in the soil and become active when the organisms in the carcass are exposed to air.
Apart from biological warfare, anthrax in humans is rare. In the United States, only 127 cases of anthrax appeared in the early years of the 20th century and dropped to about 1 per year during the 1990s.
Signs and symptoms
Skin anthrax (cutaneous): Infection begins when the spores enter the skin through small cuts or abrasions. Spores then become active in the host (human or animal) and produce poisonous toxins. Swelling, bleeding, and tissue death may occur at the site of infection.
More than 95% of the cases of anthrax involve the skin. After a person is exposed, the disease first appears in 1-5 days as a small pimple-looking sore that progresses over the next 1-2 days to contain fluid filled with many organisms. The sore is usually painless and it may have swelling around it. Sometimes the swelling affects a person's entire face or limb.
Victims may have fever, feel tired, and have a headache. Once the sore opens, it forms a black area of tissue. The black appearance of the tissue injury gives anthrax its name from the Greek word anthrakos meaning coal. After a period of 2-3 weeks, the black tissue separates, often leaving a scar. With adequate treatment, less than 1% of people infected with skin anthrax die.
Inhalation anthrax: In inhalation anthrax, the spores are inhaled into the lungs where they become active and multiply. There they produce massive bleeding and swelling inside the chest cavity. The germs then can spread to the blood, leading to shock and blood poisoning, which may lead to death.
Historically known as woolsorter's disease (because it affected people who work around sheep), inhalation anthrax can appear anywhere within 1-6 days, or as long as 60 days after exposure. Initial symptoms are general and can include headache, tiredness, body aches, and fever. The victim may have a nonproductive cough and mild chest pain. These symptoms usually last for 2-3 days.
Some people show a short period of improvement. This is followed by the sudden onset of increased trouble breathing, shortness of breath, bluish skin color, increased chest pain, and sweating. Swelling of the chest and neck may also occur. Shock and death may follow within 24-36 hours in most people with this type of infection.
Anthrax is not spread from person to person. Inhalation anthrax is the most likely form of disease to follow a military or terrorist attack. Such an attack likely will involve the aerosolized delivery of anthrax spores.
Mouth, throat, GI tract (oropharyngeal and gastrointestinal): These cases result when someone eats infected meat that has not been cooked sufficiently. After an incubation period of 2-5 days, victims with oropharyngeal disease develop a severe sore throat or sores in the mouth or on a tonsil. Fever and neck swelling may occur. The victim may have trouble breathing. GI anthrax begins with nonspecific symptoms of nausea, vomiting, and fever. These are followed in most victims by severe abdominal pain. The victim may also vomit blood and have diarrhea.
Doctors will perform various tests, especially if anthrax is suspected.
With skin anthrax, a biopsy is taken of the sore (lesion), and lab tests are performed to look at the organism under a microscope and confirm the diagnosis of anthrax.
The diagnosis of inhalation anthrax is difficult to make. A chest x-ray may show certain signs in the chest cavity. Cultures (growing the bacteria in a lab and then examining them under a microscope) are minimally helpful in making the diagnosis. Blood tests may also be performed.
GI anthrax also is difficult to diagnose because the disease is rare and symptoms are not always obvious. Diagnosis usually is confirmed only if the victim has a history of eating contaminated meat in the setting of an outbreak. Once again, cultures generally are not helpful in making the diagnosis.
Meningitis (brain swelling) from anthrax is difficult to distinguish from meningitis due to other causes. A spinal tap may be performed to look at the person's spinal fluid in identifying the organism.
The most useful microbiologic test is the standard blood culture, which is almost always positive in victims with anthrax throughout their bodies. Blood cultures should show growth in 6-24 hours and if the laboratory has been alerted to the possibility of anthrax, biochemical testing should provide a preliminary diagnosis 12-24 hours later. However, if the laboratory has not been alerted to the possibility of anthrax, there is the chance that the organism may not be identified correctly.
Rapid diagnostic tests for anthrax and its proteins include polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct fluorescent antibody (DFA) testing. Currently, these tests are only available at national reference laboratories.
Inhalation anthrax: As previously stated because inhalation anthrax moves quickly throughout the body, doctors will begin antibiotic treatment right away even before a firm diagnosis is made through lab testing;
are FDA-approved antibiotics for treatment of anthrax.
Experts currently recommend ciprofloxacin or other drugs in the same class for adults who are assumed to have inhalation anthrax infection. Penicillin and doxycycline may be used once organism culture sensitivities are known.
Traditionally, ciprofloxacin and other antibiotics in that class are not recommended for use in children younger than 16-18 years because of a weak theoretical link to permanent joint disorders. Balancing these small risks against the risk of death and the possibility of infection with a resistant strain of anthrax, experts recommend that ciprofloxacin nonetheless be given to children in appropriate doses. Because there is a risk the infection will recur, victims are treated with antibiotics for at least 60 days.
Skin anthrax: Treatment of skin anthrax with antibiotics generally prevents the disease from progressing to the entire body although the black tissue and scar continue to form. Although previous guidelines have suggested treating skin anthrax with 7-10 days of therapy, recent recommendations suggest treatment for 60 days in the setting of bioterrorism, thus assuming the person may also have been exposed to inhalational anthrax.
In pregnant women, experts recommend that ciprofloxacin be given after exposure as a preventive medication following exposure to an anthrax attack.
After exposure, the antibiotics ciprofloxacin, or doxycycline may be prescribed by a doctor and the medications are usually taken for 60 days. A vaccination series to protect against anthrax consists of 6 injections given over a period of 18 months, followed by booster shots every year.
If a biological warfare attack is expected or may have occurred, people who have not had the vaccine may be given ciprofloxacin or doxycycline for at least 4 weeks.
The viral encephalitides, Venezuelan equine encephalitis (VEE) virus, western equine encephalitis (WEE) virus, and eastern equine encephalitis (EEE) virus, are members of the Alphavirus genus and are regularly associated with encephalitis. These viruses were recovered from horses during the 1930s. VEE was isolated in the Guajira peninsula of Venezuela in 1930, WEE in the San Joaquin Valley of California in 1930, and EEE in Virginia and New Jersey in 1933.
Although natural infections with these viruses occur following bites from mosquitos, the viruses are also highly infectious when spread through the air. If intentionally released as a small particle aerosol, this virus may be expected to infect a high percentage of people exposed within a few miles.
VEE virus has the capacity to produce epidemics. Outcomes are significantly worse for the very young and the very old. Up to 35% of people infected may die. WEE and EEE typically produce less severe and widespread disease but are associated with death rates as high as 50-75% in those with severe illness.
Signs and symptoms
VEE: After an incubation period of 2-6 days, people with VEE develop fevers, chills, headache, aches, sore throat, and sensitivity to light (eyes). They may become mildly confused, have seizures or paralysis, or go into a coma. For those who survive, their nervous system functions usually recover completely.
EEE: The incubation period for EEE varies from 5-15 days. Adults may have certain early symptoms up to 11 days before the onset of nervous system problems such as mild confusion, seizures, and paralysis. Signs and symptoms include fever, chills, vomiting, muscle rigidity, lethargy, slight paralysis, excess salivation, and difficulty breathing. Children frequently develop swelling on their face and near their eyes. Up to 30% of survivors of severe disease have permanent nervous system problems such as seizures and various degrees of confusion (dementia).
WEE: The incubation period is 5-10 days. Most people have no symptoms, or they might develop a fever. Other symptoms include nausea, vomiting, headache, a stiff neck, and drowsiness. Up to 90% of victims younger than 1 year have seizures. Typically, adults recover completely. Children, especially newborns, may have lasting nervous system problems.
Laboratory tests, including nasal swab samples, may show any of the 3 viruses.
No specific treatment is available. Doctors will help control symptoms. For some people that may include medications to control fever and seizures or help breathing.
A vaccine for VEE can be given as an injection for those at high risk, such as laboratory field personnel. About 20% of those who receive the vaccine fail to respond to it, meaning they would not be protected by the vaccine. An additional 25% of those vaccinated develop high fever, chills, and feel sick enough to be in bed.
A different vaccine was developed for those who did not develop protection from the initial activated vaccine. It is an inactivated vaccine, which produces only mild tenderness at the injection site. Shots are given at 2- and 4-week intervals until the person responds and develops antibodies as protection.
The EEE vaccine is inactivated and given as an injection (1 to start and another 28 days later). There are no serious side effects or long-term problems with this vaccine. Boosters are required.
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 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 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.
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.