Bioterrorism

BACKGROUND

Terrorism is the use of threats or violence to achieve political, social, or religious goals. Terrorism may be created by individuals or organizations, and may target civilians, political groups, or other organizations. Bioterrorism, also known as biological warfare or biological attack, is described by the U.S. Centers for Disease Control and Prevention (CDC) as a type of terrorism involving the intentional release of biological agents, such as viruses, bacteria, fungi, or toxins (poisonous substances) from living organisms that brings about illness or death in human beings, animals, or plants. Viruses, bacteria, and fungi are tiny, disease-causing, microscopic organisms that can spread from person to person through air, water, food, or soil. Biological toxins are poisonous substances produced by living cells or organisms, which are capable of causing disease or death.

The biological agents used for bioterrorism are known as bioweapons (BW) or bio arms. These agents may be in their natural form, or may be genetically manipulated to increase their disease-causing ability (virulence), resistance to the currently available drugs, or to increase their ability to disperse easily into the environment.

Biological agents may cause serious harm if used as bioweapons, especially if they are highly contagious (spread easily from person to person). Other characteristics, such as environmental stability, easy dispersion, and resistance to currently available drugs, may increase the risk of damage caused by a particular agent. Bioweapons have the potential to cause high morbidity (incidence of disease) and mortality (number of deaths), and even panic in public and health care workers.

The onset of illness from these agents is often late and takes several hours or days to show disease-specific symptoms. This may make it difficult to identify the timing and location of the bioterror attack. For instance, Francisella tularensis (tularemia-causing bacterium) causes acute, non-specific feverish illness after three to five days of exposure, and the actual disease symptoms, such as pneumonia, develop later.

The origin of biological terrorism dates back as early as ancient Roman civilization, when the Romans dumped dead and decaying animals into wells to poison their rivals' drinking water supplies. In the early 14th Century, attackers at Hainault (now Northern France) and Karlstein (Bohemia) threw human and animal cadavers over the castle walls of captive cities using catapults to spread disease and death among rival populations.

Some of the major bioterrorist activities in modern times include the RISE or Order of the Rising Sun incident in the U.S (1972), Red Army Faction incident in France (1980), Rajneeshee bioterror attack in the U.S (1984), Minnesota Patriots Council episode in the U.S (1991), Aum Shinrikyo's bioterror attack in Japan (1993, 1995), and the postal anthrax incident in the U.S (2001).

In 1972, the United States and several other nations signed the Biological and Toxic Weapons Convention (BTWC) treaty, which involved the prohibition of research and development, production, and stockpiling of bioweapons for offensive purposes.

The CDC has compiled a list of high-concern microorganisms that may adversely affect human health by causing severe illness or death. Some of these high-priority, potential biothreat agents and the diseases caused by them include Bacillus anthracis (anthrax), Clostridium botulinum toxin (botulism), Variola major (smallpox), Yersinia pestis (plague), Francisella tularensis (tularemia), and filoviruses and arenavirus (viral hemorrhagic fever).

TECHNIQUE

General: Many methods may be used to disperse bioweapons. They are most often dispersed through air, water, or food.

Biological agents: Agents used as bioweapons are most often microbes, such as viruses or bacteria. These have the potential to cause infection and spread from person to person. However, certain toxins extracted from these biological agents may also be used. These do not spread like microbes, but they may cause instant symptoms. In contrast, there is usually a symptom-free period between the time of infection and the onset of symptoms.

Bacillus anthracis: Bacillus anthracis is a spore-forming soil bacterium that causes anthrax, a severe infectious disease. Anthrax infection may occur in three forms: cutaneous anthrax, resulting from the infection of skin cuts or wounds with Bacillus anthracis; inhalation anthrax, caused by breathing in of Bacillus anthracis spores into the lungs; and gastrointestinal anthrax, resulting from consumption of food contaminated with the bacterium. Anthrax is non-contagious i.e., it does not spread from person to person. The disease could occur through contact with an infected animal or animal products, or inhalation of spores. Inhalational anthrax is the most deadly among the three anthrax infections and results in death in about 75% of cases. Spores are the dormant (inactive) stage of an organism that is capable of surviving in harsh environments; they become active on the availability of favorable environmental conditions, such as optimal temperature and moisture.

Brucella species: Brucella causes brucellosis (also known as Malta fever, rock fever, or undulant fever), a highly contagious bacterial infection which is transmitted to humans through contact with infected animals (cattle, sheep, goat, pig, and dogs), ingestion of contaminated animal products (meat and milk and other dairy products which are not properly pasteurized), inhalation of bacteria, or through cuts or wounds. The infection may cause long-lasting symptoms like recurrent fever, fatigue, and joint pain.

Burkholderia mallei and Burkholderia pseudomallei: These bacterial species cause glanders and melioidosis, respectively. Both infections may be transmitted through direct contact with infected animals (horses, swine, cattle), ingestion of contaminated water, inhalation, or through skin cuts/wounds. In both conditions, the infection may be localized or may affect multiple organs (lungs, blood, skin, liver, and spleen). Antibiotics such as sulfadiazine, ciprofloxacin, streptomycin, novobiocin, gentamicin, and ceftazidime are effective for treating glanders. Penicillin, doxycycline, amoxicillin-clavulanic acid, azocillin, ceftriaxone and aztreonam are effective for treating melioidosis. No vaccines are available against these infections.

Clostridium botulinum (toxin): Clostridium botulinum is a spore-forming, non-contagious soil bacterium, which causes botulism. The botulinum toxin affects the nervous system, causing paralysis and lung (respiratory) failure, if untreated. Botulism occurs in three forms: food botulism, caused by the ingestion of food contaminated with botulinum toxin; wound botulism, resulting from the infection of wounds with Clostridium botulinum; and infant botulism or intestinal botulism, caused by the ingestion of spores of this bacterium, usually from honey.

Coxiella burnetii: This bacterium causes Q fever, an infection characterized by high fever, cough, diarrhea, and abdominal and chest pain. The infection may last for six months and may sometimes be long-lasting (up to 20 years). Some of the serious complications associated with Q fever include endocarditis (inflammation of heart valves) and hepatitis (liver inflammation). The infection is transmitted to humans through contact with infected animals, ingestion of contaminated milk or food, inhalation of the bacteria, and tick bites. Human-to-human transmission is very rare.

Francisella tularensis: Francisella tularensis is a bacterium that causes tularemia, also known as deerfly fever or rabbit fever. The disease is not contagious, and is transmitted to humans through contaminated food, water, soil, air, infected animal tissues, and bites from infected insects. The infection causes acute sepsis, pneumonia, and respiratory failure, if left untreated. Sepsis is a serious illness characterized by inflammation and blood clotting throughout the body, leading to multi-organ failure and death. Pneumonia is an infection of one or both lungs, usually caused by bacteria, viruses, or fungi. Symptoms of pneumonia include difficulty in breathing, cough, chills, fever, unusual rapid breathing, and chest or abdominal pain.

Hemorrhagic fever viruses (HFVs): HFVs are a group of zoonotic (animal-borne), ribonucleic acid (RNA) viruses, which cause viral hemorrhagic fever (VHF). VHF is a fatal infection associated with damage to the blood vessels (which causes bleeding), and multiple organ failure. HFVs are classified into four groups: Floriviridae (e.g. Ebola virus and Marburg virus); Arenaviridae (e.g. Lassa virus); Bunyaviridae (e.g. Crimean Congo hemorrhagic virus, Rift Valley virus); and Flaviviridae (e.g. Dengue virus, yellow fever virus, and Omsk hemorrhagic fever virus). These viruses are transmitted through infected animal or human hosts. RNA viruses are a group of viruses with RNA as its genetic material. RNA is a molecule made of a long chain of nucleotide units, with each nucleotide consisting of a nitrogenous base, ribose sugar and a phosphate molecule.

Yersinia pestis infections are transmitted through the bite of rodent fleas carrying the plague bacterium, or through inhalation of respiratory droplets of an infected person. Yersinia pestis is one possible bioweapon; infection by this bacterium can cause three forms of plague: pneumonic, septicemic, and bubonic plague. According to an analysis done by the World Health Organization (WHO), aerosol dispersal of 50kg Yersinia pestis, over a city with approximately 5 million people, may result in 150,000 pneumonic plague (infected lung) cases, of whom 36,000 victims would die and 80,000 to 100,000 cases would require hospitalization.

Ricin is a toxin found in Ricinus communis (castor beans). The toxin may enter the body through inhalation, ingestion, or injection. Inhalation may result in low blood pressure and respiratory failure; ingestion could lead to severe dehydration, diarrhea (which may be bloody), multiple organ failure, and death. Injection of the toxin through the skin, muscles, or veins could cause irritation of the skin and eyes, diarrhea, heart injury, cerebral edema (excess fluid accumulation in the brain), pancreatitis, and nephritis (inflammation of the pancreas and kidney, respectively). There are no approved medications for treating ricin toxicity.

Salmonella typhimurium is the causative agent of salmonellosis, which is water- or food-borne illness that is characterized by fever, diarrhea, vomiting, dehydration, and severe stomach cramps.

Yersinia pestis: Yersinia pestis causes plague, a serious bacterial infection, which occurs in three forms: bubonic plague, occurring when the bacterium enters through the skin and infects the lymphatic system, leading to the formation of 'buboes' (swelling of lymph nodes); pneumonic plague, a rare but serious form, which occurs when the bacterium infects the lungs; and septicemia plague, which may result from bubonic or pneumonic plague, when the bacterium from the lymph or lungs enters and infects the blood. Bubonic and septicemic plagues are rarely contagious and are transmitted through the bite of rodent fleas carrying the plague bacterium. Pneumonic plague is highly contagious and is transmitted through the inhalation of respiratory droplets of an infected person. The lymphatic system consists of a complex network of fine vessels and nodes (lymph nodes) which circulates lymph (a faintly yellowish fluid consisting mainly of infection-fighting cells called lymphocytes) from body tissues to the bloodstream.

Variola major: Variola major causes smallpox, a highly contagious viral infection, which has been completely eradicated through vaccinations programs around the world. The virus may spread through close contact with an infected person for a prolonged period, or through infected body fluids, contaminated beddings, and clothing.

Aerosol dispersal: Most biological warfare programs have focused on agents that may be delivered through the air. Bioagents are released through exploding munitions (like bombs) or aerosol sprayers. Aerosol is a suspension of fine liquid droplets or minute particles in the air. In the aerosol dispersal technique, aerosolized bioagents remain suspended in the air for several hours depending on environmental conditions (such as temperature and humidity) or the properties of the bioagent. An aerosol generator-carrying aircraft could disperse 100kg of anthrax over a 300km2 area that could cause three million deaths in a population density of around 10,000 people per km2.

The bioterror incident by Aum Shinrikyo (a Japanese religious group) in 1993 used the aerosol dispersal technique. This terrorist group sprayed a liquid suspension of Bacillus anthracis spores in Kameido, Japan from their headquarters. Symptoms such as short-term loss of appetite, nausea, and vomiting were reported among the residents after exposure. No deaths were reported due to the incident. The attack failed and the reason for failure is not clear. However, it is presumed that ineffective aerosolization and unfavorable weather conditions may have contributed to the failure. The strains used may have also lacked the virulence necessary to cause disease, or the quantities may have been insufficient.

Water: Contamination of water supplies is another possible method of bioweapon dispersal. The technique may not always cause a major health impact, as municipal water systems are designed to remove impurities (especially disease-causing organisms) to safeguard public health. One bioterror incident that targeted water supplies was the RISE, or Order of the Rising Sun incident, in 1972. This terrorist group had planned to contaminate Chicago's water supplies with 30-40kgs of Salmonella typhimurium. The plan failed when the bioweapon to be used for the attack was seized. The terrorists also lacked the technical knowledge to carry out the attack successfully.

Food: Food contamination is another possible bioweapon dispersal method. Here, terrorists may target (contaminate) raw or uncooked foods, such as salad greens and raw fruits and vegetables. Food-borne bioterror agents may survive even after cooking. One of the prominent bioterror incidents that involved food contamination was the Rajneeshee (a religious group) attack in the U.S in 1984. This terrorist group, led by Bhagwan Shree Rajneesh, sprinkled Salmonella typhimurium on restaurant salad bars. This caused food poisoning in at least 751 people. The plot was revealed when the religious group split and its members became informants. In 1985, one of the leading cult members, Sheela, was convicted of instigating the incident. Rajneesh was later arrested for immigration violations.

Others: Non-food surfaces, such as doorknobs or drinking glasses, have also been contaminated in bioterror attacks. In the Rajneeshee bioterror attack in 1984, drinking glasses and doorknobs surfaces were also contaminated with Salmonella typhimurium.

In 1991, the Minnesota Patriots Council had planned to kill federal law enforcement government officials by applying ricin toxin on doorknobs. The plan was not successful and the perpetrators were arrested.

In a 2001 anthrax attack, letters containing anthrax spores were posted to the offices of the New York Post and to Senator Tom Daschle in Washington, D.C. When these letters were opened, they released fine-grained anthrax spores into the air. The prime suspect in this case was Dr. Bruce Edwards Ivins, a prominent biodefense researcher at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) in Fort Detrick, Maryland. Dr. Ivins committed suicide in 2008, before former charges were filed.

THEORY/EVIDENCE

General: Several bioterrorism incidents have occurred since World War I.

World War II: The Japanese army, after the invasion of Manchuria (China) during World War II, made use of Chinese prisoners to test the lethality of several bioweapons, including Bacillus anthracis, Salmonella typhimurium, Vibrio cholerae, and Yersinia pestis. The incident killed over 10,000 Chinese civilians. The Japanese army also attacked Chinese civilians by dropping paper bags containing Yersinia pestis-infected insects over Ningbo and Quzhou cities, contaminating wells. They also distributed poisoned food, which resulted in several plague outbreaks.

RISE, or the Order of the Rising Sun incident (1972): A group of students in Chicago had allegedly planned to target cities near Chicago, with an assertion that mankind was destroying itself and the planet, and that eliminating mankind (except for a minor population who live in harmony with nature) would be the only means of preserving the environment. The group had attempted to contaminate urban water supplies with 30-40kgs of Salmonella typhimurium. The plan failed when the bioweapon to be used for the attack was seized and two main perpetrators fled to Cuba. The terrorists also lacked the technical knowledge to carry out the attack successfully.

Red Army Faction incident (1980): According to the Centers for Disease Control and Prevention (CDC), the Red Army Faction group, based on Marxist revolutionary philosophy, had planned a bioweapon attack against West German officials and business leaders. This would be accomplished by illegally producing large quantities of botulinum toxin in a small laboratory in a Paris safe house, but the plans failed.

Rajneeshee bioterror attack (1984): This was one of the first and largest bioterrorist attacks in the history of the U.S. A religious group led by Bhagwan Shree Rajneesh poisoned the residents of The Dalles in Wasco County, Oregon, in an attempt to sicken the voters and win a local election. The group contaminated the local restaurant salad bars and supermarkets, drinking glasses, and doorknob surfaces with Salmonella typhimurium, which affected 751 people and hospitalized 45.

Minnesota Patriots Council (1991): An anti-government, tax protest group in Minnesota had planned to kill federal law enforcement government officials by using ricin. The group had planned to deliver ricin through an aerosol spray or by placing the toxin on doorknobs. The group members were finally sentenced under the 1989 U.S. Biological Weapons Anti-Terrorism Act, which prohibits the development, production and stockpiling of biological and toxin weapons.

Gulf War (1991): During Gulf War I, Iraq had developed and stockpiled bioweapons, like Bacillus anthracis, botulinum toxin, and ricin toxin, for offensive purposes, and tested various delivery systems, such as spray tanks, rockets, and bombs. However, there was no evidence of use of these bioweapons.

Aum Shinrikyo (1993, 1995): Aum Shinrikyo, a Japanese religious group, had planned to attack the mass civilian population and rivals of their group by spraying a liquid suspension of Bacillus anthracis spores in Kameido, Japan, from their headquarter building. The group also tried to disperse other bioweapon agents, like botulinum toxin (a toxin released by botulism-causing bacteria, Clostridium botulinum), Coxiella burnetii (an animal-borne bacteria which causes Q fever), Ebola virus (an animal-borne virus which causes viral hemorrhagic fever, characterized by vascular damage and multiple organ failure), along with chemical agents like hydrogen cyanide, a toxic chemical. The attack was planned to eliminate rivals and seize the ruling of the Japanese government. The multiple attacks killed nearly 20 people and injured more than 1000.

Anthrax attack (2001): A few days after the attack on the World Trade Center on September 11, 2001 in the U.S., letters containing anthrax spores were posted to the offices of the New York Post, and to Senator Tom Daschle in Washington, D.C. All of the letters were assumed to have been sent from Trenton, New Jersey. Five people died from inhalation anthrax as a result of these letters, and the attack sickened 22 others, of whom 11 suffered from inhalation anthrax and others from cutaneous (skin) anthrax.

HEALTH IMPACT/SAFETY

General: Bioweapons have the capacity to generate a devastating impact on humankind. The U.S. Food and Drug Administration (FDA), together with other organizations, such as the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), the Department of Defense (DoD), and governments outside of the U.S., are working to ensure the availability of medicines in case of national emergencies through the Strategic National Stockpile (SNS) plan. SNS is a stockpile of antibiotics, antitoxins, vaccines, medical supplies, and surgical items in the United States to protect the nation's population in case of public health emergencies, such as terrorist attack, disease outbreak, or natural calamities.

The U.S. Centers for Disease Control and Prevention (CDC) has classified bioterrorism agents into three categories (A, B, and C), based on their ability to spread and cause severe illness or death.

Category A bioagents: These bioagents are easily spread from one person to another, result in high mortality (death) rates, and necessitate special attention for public health preparedness. The bioterrorism preparedness plan includes sterilization of equipments and environment, decontamination of patients and the environment to prevent and control the spread of infection, stockpiling of medicines, and improving diagnostic capacity of laboratories in order to identify and isolate bioterror agents. Examples of category A bioagents include Bacillus anthracis, Clostridium botulinum (toxin), Variola major, Yersinia pestis, Francisella tularensis, filoviruses, like Ebola virus and Marburg virus, and arenaviruses, like Lassa virus, and Machupo virus.

Category B bioagents: These bioagents are moderately spread from one person to the other, result in relatively high disease incidence rates but low death rates, and need special attention from the government for disease management. Examples of category B bioagents include Brucella species, Clostridium perfringens, Salmonella species, Escherichia coli O157:H7, Shigella, Burkholderia mallei, Burkholderia pseudomallei, Chlamydia psittaci, Coxiella burnetii, Ricinus communis toxin, Staphylococcal enterotoxin B, Rickettsia prowazekii, alphaviruses, like Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis (EEE) and western equine encephalitis (WEE), Vibrio cholerae, and Cryptosporidium parvum.

Category C bioagents: These bioagents are recently discovered and emerging infectious organisms, which are easily available in the environment, easy to produce on a large scale, and have the potential to cause a major public health impact. Some examples of Category C bioagents are Nipah virus (NiV), and Hantavirus.

Listed below is a brief overview of currently available vaccines and drugs for these high-risk biothreat agents

Bacillus anthracis : The FDA has approved antibiotics, such as ciprofloxacin, levofloxacin, and procaine penicillin G for treating inhalation anthrax, and doxycycline for all forms of anthrax infection. BioThraxTM (Anthrax Vaccine Adsorbed or AVA) is the only FDA-approved vaccine in the U.S. for inhalation anthrax. BioThraxTM is a cell-free vaccine, which contains proteins purified from weakened Bacillus anthracis strains. The vaccine is currently available for use in people (military members, laboratory workers, livestock handlers) who are at a higher risk of being exposed to Bacillus anthracis. BioThraxTM consists of six doses; the first three doses are given at two-week intervals and the next three doses at six, 12, and 18 months, following the first dose. Booster doses are recommended every year for ongoing protection.

Variola major : Dryvax© is the only smallpox vaccine currently approved by the FDA. It is a "live-virus" vaccine, which consists of vaccinia virus purified from calf lymph. No proven medications are available for smallpox treatment. Intravenous fluids and medications for pain, fever, and bacterial infection are usually administered. Vaccinia virus is closely related to Variola major, a causative agent of smallpox. Vaccinia virus given to humans in the form of vaccine helps the body to develop resistance against smallpox, without causing illness. Lymph is a faintly yellowish fluid consisting mainly of infection-fighting cells called lymphocytes.

Clostridium botulinum (toxin): Timely administration of botulinum antitoxin (before the worsening of the symptoms) is effective and reduces the severity of botulism. The symptoms of botulism begin within 12 to 36 hours. The California Department of Public Health maintains a supply of antitoxin for infant botulism, and the CDC has a stock of antitoxins to treat other forms of botulism. Currently, no licensed vaccine is available for botulism. An investigational vaccine called pentavalent botulinum toxoid is available only for military personnel and high-risk laboratory workers. Antitoxin is a compound which neutralizes the activity of a specific toxin. A toxoid is a bacterial toxin, whose toxicity is weakened by heat or chemical process.

Yersinia pestis : The FDA has approved doxycycline, streptomycin, and other tetracycline-based antibiotics for the treatment of plague. Currently, there is no vaccine available for plague.

Francisella tularensis : A vaccine for tularemia is currently under review by the FDA. The U.S. Department of Defense has designed an experimental tularemia vaccine for high-risk groups, such as military personnel and laboratory workers handling Francisella tularensis cultures. Antibiotics like doxycycline or ciprofloxacin are currently used to treat tularemia.

Hemorrhagic fever viruses (HFVs): There are no approved antiviral drugs against most of the HFVs. Ribavirin is an anti-viral drug, generally prescribed for Lassa fever and Crimean-Congo hemorrhagic fever (viral hemorrhagic fevers characterized by vascular damage, hemorrhage (bleeding) and multiple organ failure). Ribavirin is an antimetabolite drug, which interferes with the duplication of a virus' genetic material, thereby inhibiting its multiplication.

Brucella species : Pasteurization is a heat-treatment process employed to destroy disease-causing organisms in food products like milk. Antibiotics such as doxycycline and rifampin are used for six weeks to prevent recurring brucellosis infection.

Salmonella typhimurium : No vaccines are available to prevent salmonellosis; intravenous fluids and antibiotics, such as ampicillin, trimethoprim-sulfamethoxazole and ciprofloxacin, are given for treating salmonellosis.

Shigella : Antibiotics such as ampicillin, trimethoprim-sulfamethoxazole, ceftriaxone, and ciprofloxacin are prescribed to treat shigellosis. No vaccines are available.

Vibrio cholerae : Oral rehydration or intravenous fluids are given to restore fluids and salts lost through diarrhea caused by cholera. Dukoral © is a recently developed vaccine for cholera, but the CDC does not recommend its usage and it is not available in the U.S.

Salmonella typhimurium : Antibiotics such as ampicillin, trimethoprim-sulfamethoxazole, and ciprofloxacin are used for treating typhoid fever. Two vaccines are available against the disease: Ty2la and Vi capsular polysaccharide vaccine (ViCPS). These vaccines are usually given to people who stay in or travel to parts of the world where typhoid is widespread. ViCPS vaccine is administered as a single dose through skin or muscle, 14 days before traveling. Booster doses are recommended every two years. Ty2la vaccine is orally administered in four doses on alternate days. The doses are given one week prior to traveling.

Burkholderia mallei and Burkholderia pseudomallei : These bacterial species cause glanders and melioidosis, respectively. Both infections may be transmitted through direct contact with infected animals (horses, swine, cattle), ingestion of contaminated water, inhalation, or through skin cuts/wounds. In both conditions, the infection may be localized or may affect multiple organs (lungs, blood, skin, liver, and spleen). Antibiotics such as sulfadiazine, ciprofloxacin, streptomycin, novobiocin, gentamicin, and ceftazidime are effective for treating glanders. Penicillin, doxycycline, amoxicillin-clavulanic acid, azocillin, ceftriaxone and aztreonam are effective for treating melioidosis. No vaccines are available against these infections.

Coxiella burnetii : Doxycycline is effective against Q fever; a vaccine for Q fever has been developed in Australia that has successfully protected humans, but it is not commercially available in the United States.

Ricin toxin: There are no approved medications for treating ricin toxicity. The FDA has also cleared reactive skin decontamination lotion (RSDL) for eliminating or neutralizing fungal toxin from the skin. The product is limited to military use, however.

Advanced detection systems have been developed to provide bioterror warnings beforehand, to locate contaminated areas and high-risk populations, and to stop the spread of disease. Some of the advanced detection technologies are given below.

Handheld advanced nucleic acid analyzer (HANAA): HANAA is a real-time, polymerase chain reaction (RT-PCR) based system used for detecting disease-causing microorganisms. A polymerase chain reaction (PCR) is an enzymatic method used to copy the two DNA strands of a particular gene sequence many times for laboratory study. One of the potential uses of HANAA is to detect pathogens used in bioterrorism attacks, making it possible to deliver treatment immediately, and avoid complications related to infection. HANAA can test four samples at a time, and provides results within 30-60 minutes. The analyzer was used by United Nations inspectors in Iraq during the search for biological weapons in 2003.

Lab-on-chip (LOC) device: A LOC device is another instrument that could be used to detect bioweapons, thereby facilitating immediate treatment. A LOC device combines several laboratory functions on a single chip that is only a few millimeters to square centimeters in size. The chip contains one or more sample deposit areas, measuring devices, mixing chambers or fluid channels to move the mixtures around, and reaction chambers that are temperature-controlled. LOC devices are simple to handle, and provide fast and accurate results within 30-40 minutes using minute amounts of samples (<1 picoliter). A picoliter (pL) is a unit used to measure small volumes of liquid. One picoliter is equivalent to one trillionth (one millionth of a millionth) of a liter (L); i.e., 1pL=10-12L. Liter is defined as a unit of volume and it is equivalent to 0.001 cubic meters.

FUTURE RESEARCH OR APPLICATIONS

Scientists around the world are constantly working towards designing effective diagnostics, vaccines, and therapies to protect civilians against high-risk bioweapons.

A group of researchers from Japan has recently conducted a safety and efficacy trial on a vaccine against smallpox called LC16m8. The vaccine is prepared in vitro (in the laboratory) using rabbit kidney cells, and contains attenuated (weakened) virus. It is administered as a single dose subcutaneously (under the skin). Results from human and animal research have confirmed that the vaccine is safe and shows no adverse effects.

Some terrorist groups may use fake (harmless) bioterror agents to create public panic, which could result in considerable economic loss to a country. To solve such hoax biothreats, researchers from the U.S. Food and Drug Administration's National Center for Toxicological Research (NCTR) are designing an easy, cost-effective technique to differentiate fake substances from true bioterror agents. The test uses mass spectrometry, which compares the characteristic patterns created by an investigational substance to the patterns of known substances (true bioterror agents) that are stored in the database. The technique is fast and effective. Following about half an hour to eight hours of sample preparation, the test takes seven minutes to analyze each sample on the mass spectrometer. Mass spectrometry is an analytical tool used to determine the structure and composition of chemical/biological molecules and substances.

Researchers in the U.S. are designing innovative electronic surveillance systems to enhance early detection of bioterrorism events. A biosurveillance system collects clinical, laboratory, paramedical, and pharmacy data from various sources, like public health agencies, health care providers, academic investigators, and related industries, to analyze the onset and pace of disease outbreaks.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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