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RESOURCE CENTER | Biological Warefare  

A bioterrorism attack is the deliberate release of viruses, bacteria, chemical or other agent for the purpose of causing widespread illness or death. There are more than 1200 different kinds of biological agents. They include prions, microorganisms (viruses, bacteria and fungi) and some unicellular and multi-cellular eukaryotes and their associated toxins. They have the ability to adversely affect human health in many ways, ranging from allergic reactions that are relatively mild, to serious medical conditions, and even death. These organisms are ubiquitous in the natural environment; they are found in water, soil, plants, and animals. Because many biological agents reproduce rapidly and require minimal resources for preservation, they have been harnessed for their destructive powers for decades and continue to pose a viable and dangerous threat to countries around the world. They are divided into three groups:

Category A
These high-priority agents include organisms or toxins that pose the highest risk to the public and national security because they can be easily spread or transmitted from person to person. They result in high death rates and have the potential for major public health impact. They require special action for public health preparedness.

Category B
These agents are the second highest priority because they are moderately easy to spread.
They result in moderate illness and death rates. They require specific enhancements of CDC's laboratory capacity and enhanced disease monitoring.

Category C
The third highest priority agents include emerging pathogens that could be engineered for wide spread use in the future because they are easily available, they are easily produced and spread and have potential for high morbidity and mortality rates.

Anthrax: (Bacterium – Category A) 

Anthrax is an acute infectious disease caused by the bacterium Bacillus anthracis and is highly lethal in some forms. Anthrax most commonly occurs in wild and domestic ruminants, but it can also occur in humans when they are exposed to infected animals, tissue from infected animals, or high density of anthrax spores. Anthrax cannot spread from human to human. Anthrax infection is extremely rare in common domestic pets (dogs and cats) with only one documented case in the USA in the last 15 years. The word anthrax is derived from the Greek word anthrakis, or "coal", in reference to the black skin lesions victims develop. There are 89 known strains of anthrax; the most widely recognized being the virulent Ames strain used in the 2001 anthrax attacks in the United States. The Ames strain is extremely dangerous, though not quite as virulent as the Vollum strain which was successfully tested as a biological weapon during the Second World War. The Vollum strain was isolated in 1935 from a cow in Oxfordshire, UK. This is the same strain that was used during the Gruinard bio-weapons trials. A variation of Vollum known as "Vollum 1B" was used during the 1960s in the US and UK bio-weapon programs. Vollum 1B was isolated from William A. Boyles, a 46 year old USAMRIID scientist who died in 1951 after being accidentally infected with the Vollum strain. The Sterne strain, named after a South African researcher, is an attenuated strain used as a vaccine. Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous) and causes distinct clinical syndromes based on its site of entry. An infected human will generally be quarantined. However, anthrax does not usually spread from an infected human to a non-infected human. The government of the Soviet Union had an active bioweapons program that included the production of hundreds of tons of weapons-grade anthrax. An overnight accident at a weapons facility in Sverdlovsk in 1979 released weaponized anthrax into the air and resulted in the deaths of at least 60 people according to the Soviet government, but facility employees think that death toll is closer to 100. It was the largest documented human outbreak of inhalation anthrax in history. There was a plant directly across the street and all of the night shift workers got sick and most died. Since most of these people were men, there were suspicions by Western governments that the Soviet Union had developed a gender-specific weapon.

Botulism: (Bacterium – Category A)  

Botulinum is a neurotoxin protein produced by the bacterium Clostridium botulinum. It is one of the most poisonous naturally occurring substances in the world, and it is the most toxic protein. Botulinum toxin blocks the release of acetylcholine from nerve endings thus arresting their function. The Clostridium botulinum bacterium produces toxin in an anaerobic environment, and the toxin is unstable to heating, so poisoning generally occurs from the use of improperly bottled or canned foods: typical instances of botulism would be home-bottled preserves used in salads. Symptoms, usually including dry mouth, double and/or blurred vision, difficulty swallowing, muscle weakness, drooping eyelids, difficult breathing, slurred speech, vomiting, urinary incontinence and sometimes diarrhea. These symptoms may continue to cause paralytic ileus with severe constipation, and will lead to body paralysis. The respiratory muscles are affected as well, which may cause death due to respiratory failure. These are all symptoms of the muscle paralysis caused by the bacterial toxin.

E. coli: (Bacterium – Category B)  

E. coli is a bacterium that is commonly found in the lower intestine of warm-blooded animals. Most e.Coli strains are harmless, but some, such as serotype O157:H7, can cause serious food poisoning in humans, and are occasionally responsible for costly product recalls. The harmless strains are part of the normal flora of the gut, and can benefit their hosts by producing vitamin K2, or by preventing the establishment of pathogenic bacteria within the intestine. E. coli are not always confined to the intestine, and their ability to survive for brief periods outside the body makes them an ideal indicator organism to test environmental samples for fecal contamination. The bacteria can also be grown easily and its genetics are comparatively simple and easily-manipulated, making it one of the best-studied prokaryotic model organisms, and an important species in biotechnology. E. coli was discovered by German pediatrician and bacteriologist Theodor Escherich in 1885, and is now classified as part of the Enterobacteriaceae family of gamma-proteobacteria.

Plague: (Bacterium – Category A)  

Yersinia pestiscan reproduce inside cells, so even if phagocytosed, they can still survive. Once in the body, the bacteria can enter the lymphatic system, which drains interstitial fluid. Plague bacteria secrete several toxins, one of which is known to cause dangerous beta-adrenergic blockade. Y. pestis spreads through the lymphatics of the infected human until it reaches a lymph node, where it stimulates severe hemorrhagic inflammation causing the lymph nodes to expand. The expansion of lymph nodes is the cause of the characteristic "bubo" associated with the disease. Lymphatics ultimately drain into the bloodstream and as a result the plague bacteria may enter the blood where they can travel to virtually any part of the body. In septicemic plague, there is bleeding into the skin and other organs, which creates black patches on the skin. There are bite-like bumps on the skin, commonly red and sometimes white in the center. Untreated, septicemic plague is universally fatal, but early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent. People who die from this form of plague often die on the same day symptoms first appear. The pneumonic plague infects the lungs, and with that infection comes the possibility of person-to-person transmission through respiratory droplets. The incubation period for pneumonic plague is usually between two and four days, but can be as little as a few hours. The initial symptoms, of headache, weakness, and coughing with hemoptysis, are indistinguishable from other respiratory illnesses. Without diagnosis and treatment, the infection can be fatal in one to six days; mortality in untreated cases is 50–90%.

Tularemia: (Bacterium – Category A) 

Tularemia is a serious infectious disease caused by the bacterium Francisella tularensis. The disease is endemic in North America, and parts of Europe and Asia. The primary vectors are ticks and deer flies, but the disease can also be spread through other arthropods. Animals such as rabbits, prairie dogs, hares and muskrats serve as reservoir hosts. The disease is named after Tulare County, California. Francisella tularensis was discovered in 1911 during an outburst of rabbit fever, when the disease killed a large number of ground squirrels in the area of Tulare Lake in California. Scientists determined that tularemia could be dangerous to humans; a human being may catch the infection after contacting an infected animal. The ailment soon became frequent with hunters, cooks and agricultural workers. The disease has a very rapid onset, with headache, fatigue, dizziness, muscle pains, loss of appetite and nausea. Fever is moderate or very high and tularemia bacillus can be isolated from blood cultures at this stage. Face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may suppurate (mimicking bubonic plague). Lymph node involvement is accompanied by a high fever. Death may result.

Smallpox: (Virus – Category A)

Smallpox is caused by infection with variola virus, which belongs to the genus Orthopoxvirus, the family Poxviridae, and subfamily chordopoxvirinae. Variola virus is a large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nm, with a single linear double stranded DNA genome consisting of 186 kilobase pairs (kbp) and containing a hairpin loop at each end. The two classic varieties of smallpox are variola major and variola minor. The closest viral relative is molluscum contagiosum, which like smallpox, infects only humans. However, unlike variola species, molluscum infection is benign. The lifecycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus. In order to replicate poxvirures produce a variety of specialized proteins not produced by other DNA viruses, the most important of which is a viral-associated DNA-dependent RNA polymerase. Both enveloped and nonenveloped virions are infectious. The viral envelop is made of modified membranes containing viral-specific polypeptides, including hemagglutinin. Infection with either variola major or variola minor confers immunity against the other. Four orthopoxviruses cause infection in humans: variola, vaccinia, cowpox, and monkeypox. Variola virus infects only humans in nature, although primates and other animals have been infected in a laboratory setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature.

Avian Flu: (Virus)
 

The highly pathogenic Influenza A virus subtype H5N1 virus is an emerging avian influenza virus that has been causing global concern as a potential pandemic threat. It is often referred to simply as "bird flu" or "avian influenza" even though it is only one subtype of avian influenza causing virus. H5N1 has killed millions of poultry in a growing number of countries throughout Asia, Europe and Africa. Health experts are concerned that the co-existence of human flu viruses and avian flu viruses (especially H5N1) will provide an opportunity for genetic material to be exchanged between species-specific viruses, possibly creating a new virulent influenza strain that is easily transmissible and lethal to humans. Since the first H5N1 outbreak occurred in 1997, there has been an increasing number of HPAI H5N1 bird-to-human transmissions leading to clinically severe and fatal human infections. However, because there is a significant species barrier that exists between birds and humans, the virus does not easily cross over to humans, though some cases of infection are being researched to discern whether human to human transmission is occurring. More research is necessary to understand the pathogenesis and epidemiology of the H5N1 virus in humans. Exposure routes and other disease transmission characteristics such as genetic and immunological factors, that may increase the likelihood of infection, are not clearly understood. The Avian Flu claimed at least 200 humans in Romania, Greece, Turkey and Russia. Epidemiologists are afraid that the next time such a virus mutates, it could pass from human to human. If this form of transmission occurs, another big pandemic could result. However, disease-control centers around the world are making avian flu a top priority.

Hantavirus: (Virus – Category C)
 

Like other members of the bunyavirus family, Hantaviruses are enveloped viruses with a genome that consists of three single-stranded RNA segments designated S (small), M (medium), and L (large). All Hantaviral genes are encoded in the negative (genome complementary) sense. The S RNA encodes the nucleocapsid (N) protein. The M RNA encodes a polyprotein that is cotranslationally cleaved to yield the envelope glycoproteins G1 and G2. The L RNA encodes the L protein, which functions as the viral transcriptase/replicase. Within virions, the genomic RNAs of Hantaviruses are thought to complex with the N protein to form helical nucleocapsids, the RNA component of which circularizes due to sequence complementarities between the 5' and 3' terminal sequences of each genomic segment. Hantaviruses replicate exclusively in the host cell cytoplasm. Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent endocytosis. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the endosomal membrane. Transcription of viral genes must be initiated by association of the L protein with the three nucleocapsid species. In addition to transcriptase and replicase functions, the viral L protein is also thought to have an endonuclease activity that cleaves cellular messenger RNAs (mRNAs) for the production of capped primers used to initiate transcription of viral mRNAs. As a result of this "cap snatching," the mRNAs of Hantaviruses are capped and contain nontemplated 5' terminal extensions. The G1 (aka Gn) and G2 (Gc) glycoproteins form hetero-oligomers and are then transported from the endoplasmic reticulum to the Golgi complex, where glycosylation is completed. The L protein produces nascent genomes by replication via a positive-sense RNA intermediate. Hantavirus virions are believed to assemble by association of nucleocapsids with glycoproteins embedded in the membranes of the Golgi, followed by budding into the Golgi cisternae. Nascent virions are then transported in secretory vesicles to the plasma membrane and released by exocytosis. Hantavirus has an incubation time of 2-4 weeks in humans, before symptoms of infection occur. These symptoms can be split into five phases: Febrile phase: Symptoms include fever, chills, malaise, headaches, nausea, abdominal and back pain, respiratory problems such as the ones common in the influenza virus, as well as gastro-intestinal problems. These symptoms normally occur for 3-7 days. Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. This phase can last for 2 days. Oliguric phase: This phase lasts for 3-7 days and is characterised by the onset of renal failure and proteinuria occurs. Diuretic phase: This is characterized by diuresis of 3-6L per day, which can last for a couple of days up to weeks. Convalescent phase: This is normally when recovery occurs and symptoms begin to improve.

Viral Hemorrhagic Fevers: (Virus)
 

Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that are caused by four distinct families of RNA viruses: the Arenaviridae, Filoviridae, Bunyaviridae and Flaviviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in extreme cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, whilst others, such as the African Ebola virus, can cause severe, life-threatening disease. Symptoms of VHFs include (by definition) fever and bleeding diathesis. Manifestations of VHF often also include flushing of the face and chest, petechiae, frank bleeding, edema, hypotension, and shock. Malaise, myalgias, headache, vomiting, and diarrhea occur frequently. Definitive diagnosis is usually made at a reference laboratory with advanced biocontainment capabilities.

Ebola: (Viral Hemorrhagic Fever – Category A)
 

The Ebola virus first emerged in 1976 in simultaneous outbreaks in Sudan and Zaire. Ebola is considered to be the deadliest virus of all time, but it is not as well known as Smallpox because Ebola outbreaks have been limited mainly to remote areas of the world. It is known to be a zoonotic virus as it is currently devastating the populations of lowland gorillas in Central Africa. Despite considerable effort by the World Health Organization, no animal reservoir capable of sustaining the virus between outbreaks has been identified. However, it has been hypothesized that the most likely candidate is the fruit bat. Ebola hemorrhagic fever is potentially lethal and encompasses a range of symptoms including fever, vomiting, diarrhea, generalized pain or malaise, and sometimes internal and external bleeding. Mortality rates are extremely high, with the human case-fatality rate ranging from 50% - 89%, according to viral subtype. The cause of death is usually due to hypovolemic shock or organ failure. Because Ebola is potentially lethal and since no approved vaccine or treatment is available, Ebola is classified as a bio-safety level 4 agent, as well as a Category A bioterrorism agent by the Centers for Disease Control and Prevention. It has the potential to be weaponized for use in biological warfare and was investigated for this particular use by both the Soviet Union and the United States during the Cold War. Its effectiveness as a biological-warfare agent is compromised by its extreme deadliness and its level of contagion: a typical outbreak spreads through a small village or hospital, affects the entire population, and then runs out of potential hosts, burning out before it reaches a larger community.

Mycotoxin: (Chemical Toxin)
 

Mycotoxins are toxins produced by an organism of the fungus kingdom, which includes mushrooms, molds and yeasts. Most fungi are aerobic (use oxygen). Fungi are found almost everywhere in extremely small quantities because of their spores, and are most commonly microscopically small. They consume organic matter, wherever humidity and temperature are sufficient. Where conditions are right, fungi proliferate into colonies and mycotoxin levels become high. Toxins vary greatly in their severity. Some fungi produce severe toxins only at specific levels of moisture, temperature or oxygen in the air. Some toxins are lethal, some cause identifiable diseases or health problems, some weaken the immune system without producing symptoms specific to that toxin, some act as allergens or irritants. Some mycotoxins generally have more negative impacts on farm animal populations than on humans. Some mycotoxins are harmful to other micro-organisms such as other fungi or even bacteria; penicillin is one example. Aspergillus species are highly aerobic and are found in almost all oxygen-rich environments, where they commonly grow as molds on the surface of a substrate, as a result of the high oxygen tension. Commonly, fungi grow on carbon-rich substrates such as monosaccharides (such as glucose) and polysaccharides (such as amylose). Aspergillus species are common contaminants of starchy foods (such as bread and potatoes), and grow in or on many plants and trees. In addition to growth on carbon sources, many species of Aspergillus demonstrate oligotrophy where they are capable of growing in nutrient-depleted environments, or environments in which there is a complete lack of key nutrients. A. niger is a prime example of this; it can be found growing on damp walls, as a major component of mildew.

Ricin: (Chemical Toxin)
 

Ricinus communis has an average lethal dose in humans of 0.2 milligrams (1/5,000th of a gram.) Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. Ricin is 6000 times more toxic than cyanide and 12000 times more poisonous than rattlesnake venom by weight. While there is no known antidote, the US military has developed a vaccine. Symptomatic and supportive treatment is available. Long term organ damage is likely in survivors. Ricin causes severe diarrhea and victims can die of shock. Ricin consists of two distinct protein chains that are linked to each other by a disulfide bond. Ricin is easily purified from castor-oil manufacturing waste. The seed-pulp left over from pressing for castor oil contains on average about 5% by weight of Ricin. 0.2 mg of purified Ricin constitutes a fatal dose. Symptoms of Ricin poisoning depend on the route of exposure and the dose received, though many organs may be affected in severe cases. Initial symptoms of Ricin poisoning by inhalation may occur within 8 hours of exposure. Following ingestion of Ricin, initial symptoms typically occur in less than 6 hours. Inhalation: Within a few hours of inhaling significant amounts of Ricin, the likely symptoms would be respiratory distress (difficulty breathing), fever, cough, nausea, and tightness in the chest. Heavy sweating may follow as well as fluid building up in the lungs (pulmonary edema). This would make breathing even more difficult, and the skin might turn blue. Excess fluid in the lungs would be diagnosed by x-ray or by listening to the chest with a stethoscope. Finally, low blood pressure and respiratory failure may occur, leading to death. In cases of known exposure to Ricin, people having respiratory symptoms that started within 12 hours of inhaling Ricin should seek medical care. Ingestion: If someone swallows a significant amount of Ricin, he or she would develop vomiting and diarrhea that may become bloody. Severe dehydration may be the result, followed by low blood pressure. Other signs or symptoms may include hallucinations, seizures, and blood in the urine. Within several days, the person’s liver, spleen, and kidneys might stop working, and the person could die. Skin and eye exposure: Ricin in the powder or mist form can cause redness and pain of the skin and the eyes. Death from Ricin poisoning could take place within 36 to 72 hours of exposure, depending on the route of exposure (inhalation, ingestion, or injection) and the dose received. If death has not occurred in 3 to 5 days, the victim usually recovers.

 
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